MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Cancer Science' source. Wed, 08 Feb 2012 08:41:22 +0100 http://www.medworm.com/index.php?rid=5666698&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2012.02201.x Endometrial cancer is the most common malignancy of the female genital tract and is associated with poor prognosis. It is primarily a hormone‐dependent cancer that is regulated by steroid hormones, including estrogen and progesterone. Forkhead box A1 (FOXA1) is a member of the forkhead box transcription factor family and functions as a pioneer factor in estrogen receptor (ER)‐positive breast cancer. In the present study, we investigated the expression of FOXA1 in endometrial cancers by immunohistochemical analysis. Nuclear immunoreactivity for FOXA1 was detected in 40 of 109 cases (37%), and was found to be negatively associated with lymph node status (P = 0.033). In ER‐positive Ishikawa endometrial cancer cells, small interfering RNA‐mediated downregulation of FOXA1 promoted cel... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5666698 Tue, 07 Feb 2012 05:00:00 +0100 5666698 http://www.medworm.com/index.php?rid=5646945&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2012.02200.x Thromboxane A2 (TXA2) is a prostanoid formed by thromboxane synthase using the cyclooxygenase product, prostaglandin H(2), as the substrate. TXA2 was shown to enhance tumor metastasis, but the underlying mechanism remains unclear. B16F1 melanoma cells were intravenously injected into TXA2 receptor (TP) knockout mice (TP−/−) and wild‐type littermates (WT). TP−/− showed a reduction in B16F1 lung colonization and mortality rate, which were associated with a decreased number of platelets. Platelet activation as assessed by P‐selectin expression was suppressed in TP−/−. A selective P‐selectin neutralizing antibody decreased the lung colonization in WT mice, but not in TP−/−. The expression of P‐selectin glycoprotein ligand‐1 in B16F1 and HUVEC were enhanced by treatmen... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5646945 Thu, 02 Feb 2012 05:00:00 +0100 5646945 http://www.medworm.com/index.php?rid=5646951&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02136.x Echinoderm microtubule‐associated protein‐like 4 and anaplastic lymphoma kinase (EML4–ALK) and kinesin family member 5B (KIF5B)–ALK are newly identified transforming fusion oncogenes causing non‐small‐cell lung cancers. These molecular abnormalities have become detectable using not only molecular biological methods, but also highly sensitive immunohistochemistry. During the immunohistochemical study of ALK expression in adenocarcinoma of the lung, we unexpectedly discovered that a small bronchioloalveolar carcinoma (BAC) showed strong ALK immunoreactivity. However, FISH studies failed to reveal EML4–ALK and KIF5B–ALK fusion genes in this BAC. These findings suggest the possibility that a novel or unknown ALK fusion gene plays a crucial role in BAC development. (Cancer Sci 2... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5646951 Wed, 01 Feb 2012 05:00:00 +0100 5646951 http://www.medworm.com/index.php?rid=5646950&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02068.x (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5646950 Wed, 01 Feb 2012 05:00:00 +0100 5646950 http://www.medworm.com/index.php?rid=5646949&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02188.x (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5646949 Wed, 01 Feb 2012 05:00:00 +0100 5646949 http://www.medworm.com/index.php?rid=5628059&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2012.02205.x (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5628059 Wed, 25 Jan 2012 05:00:00 +0100 5628059 http://www.medworm.com/index.php?rid=5571872&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02106.x A patient with pulmonary metastasis of colon cancer was treated with artificially synthesized helper/killer‐hybrid epitope long peptide (H/K‐HELP) of MAGE‐A4 cancer antigen. The patient was vaccinated with MAGE‐A4‐H/K‐HELP combined with OK432 and Montanide ISA‐51. There were no severe side‐effects except for a skin reaction at the injection site. MAGE‐A4‐H/K‐HELP induced MAGE‐A4‐specific Th1 and Tc1 immune responses and the production of MAGE‐A4‐specific complement‐fixing IgG antibodies. Tumor growth and carcinoembryonic antigen tumor marker were significantly decreased in the final diagnosis. This is the first report that artificially synthesized MAGE‐A4‐H/K‐HELP induces Th1‐dependent cellular and humoral immune responses in a human cancer patient. ... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5571872 Sun, 01 Jan 2012 05:00:00 +0100 5571872 http://www.medworm.com/index.php?rid=5571871&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02067.x (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5571871 Sun, 01 Jan 2012 05:00:00 +0100 5571871 http://www.medworm.com/index.php?rid=5571870&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02146.x (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5571870 Sun, 01 Jan 2012 05:00:00 +0100 5571870 http://www.medworm.com/index.php?rid=5659367&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02199.x Our previous studies have shown that epithelial–mesenchymal transition (EMT) may be involved in the vasculogenic mimicry (VM) formation in hepatocellular carcinoma. Here, we hypothesize that zinc finger E‐box binding homeobox 1 (ZEB1) promotes VM formation in colorectal carcinoma (CRC) by inducing EMT. We identified VM in 39 (19.2%) out of 203 CRC patients. The presence of VM was associated with aggressive biological behavior and was an unfavorable prognostic indicator. By immunohistochemical analysis, we found that the VM‐positive CRC samples showed increased ZEB1 expression compared with the VM‐negative samples and the ZEB1 expression occurred concomitantly with features of EMT. In vitro, knockdown of ZEB1 in poorly differentiated HCT116 CRC cells destroyed the vessel‐like stru... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5659367 Wed, 28 Dec 2011 05:00:00 +0100 5659367 http://www.medworm.com/index.php?rid=5646947&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02195.x The so‐called “seed and soil” hypothesis proposed by Stephen Paget in 1889 to explain the metastatic behavior of cancer cells and the homing of certain cancers to “selected” sites has been a well‐recognized phenomenon for over a century. What advances have been made to increase our understanding of this phenomenon and what does it really implicate in terms of targets for therapy? (Cancer Sci, doi: 10.1111/j.1349‐7006.2011.02195.x, 2012) (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5646947 Wed, 28 Dec 2011 05:00:00 +0100 5646947 http://www.medworm.com/index.php?rid=5551958&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02195.x AbstractThe so‐called “Seed and Soil” hypothesis proposed by Stephen Paget in 1889 to explain the metastatic behavior of cancer cells and the homing of certain cancers to “selected” sites has been a well‐recognized phenomenon for over a century. What advances have been made to increase our understanding of this phenomenon and what does it really implicate in terms of targets for therapy?© 2011 Japanese Cancer Association (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5551958 Wed, 28 Dec 2011 05:00:00 +0100 5551958 http://www.medworm.com/index.php?rid=5659366&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02197.x Tumor recurrence is the most common cause of disease failure after surgical resection in early‐stage lung adenocarcinoma. Identification of clinically relevant prognostic markers could help to predict patients with high risk of disease recurrence. A meta‐analysis of available lung adenocarcinoma microarray datasets revealed that T‐LAK cell‐originated protein kinase (TOPK), a serine/threonine protein kinase, is overexpressed in lung cancer. Using stable cell lines with overexpression or knockdown of TOPK, we have shown that TOPK can promote cell migration, invasion, and clonogenic activity in lung cancer cells, suggesting its crucial role in lung tumorigenesis. To evaluate the prognostic value of TOPK expression in resected stage I lung adenocarcinoma, a retrospective analysis of 20... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5659366 Thu, 22 Dec 2011 05:00:00 +0100 5659366 http://www.medworm.com/index.php?rid=5537406&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02197.x SummaryTumor recurrence is the most common cause of disease failure after surgical resection in early‐stage lung adenocarcinoma. Identification of clinical relevant prognostic markers may help to predict patients with high risk of disease recurrence. A meta‐analysis of available lung adenocarcinoma microarray datasets revealed that T‐LAK Cell‐Originated Protein Kinase (TOPK), a serine/threonine protein kinase, is overexpressed in lung cancer. Using stable cell lines with overexpression or knockdown of TOPK, we have demonstrated TOPK can promote cell migration, invasion and clonogenic activity in lung cancer cells, suggesting its crucial role in lung tumorigenesis. To evaluate the prognostic value of TOPK expression in resected stage I lung adenocarcinoma, a retrospective analysis o... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5537406 Thu, 22 Dec 2011 05:00:00 +0100 5537406 http://www.medworm.com/index.php?rid=5524029&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02172.x (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5524029 Wed, 21 Dec 2011 05:00:00 +0100 5524029 http://www.medworm.com/index.php?rid=5646948&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02192.x Hypoxia inducible factor‐1α (HIF‐1α) has a central role in cellular oxygen‐sensing, and its overexpression in many types of cancer is considered important in tumor progression. Thus, targeting HIF‐1α production and activity has been of great therapeutic interest. In normoxic conditions, HIF‐1α is hydroxylated by oxygen‐dependent prolyl‐hydroxylases, which require ferrous iron for its activity. The tumor suppressor protein von Hippel Lindau binds to the hydroxylated HIF‐1α, which is then ubiquitinated and degraded by proteasomes. We focused on the physiological degradation machinery of HIF‐1α mediated by prolyl hydroxylases. Previously, we identified a small molecule, LS081, that is capable of stimulating iron uptake into cells. In the present study, we aimed to inhi... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5646948 Mon, 19 Dec 2011 05:00:00 +0100 5646948 http://www.medworm.com/index.php?rid=5524028&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02194.x AbstractAngiogenesis plays a key role in the development and treatment response of various tumors. The signaling transductions mediated by the binding of VEGF to its receptor KDR is the most important pathway in tumor angiogenesis. Single nucleotide polymorphisms (SNPs) in VEGF have been extensively implicated in the etiology and treatment outcome of colorectal cancer (CRC). However, no study has been reported evaluating the role of KDR SNPs in CRC prognosis. We herein assessed the association between four potentially functional KDR SNPs and tumor recurrence in a Chinese population with 408 surgically resected CRC patients. The most significant SNP was for rs10013228 located in KDR gene promoter. Compared to the homozygous wild‐type genotype, the variant‐containing genotypes of this SN... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5524028 Mon, 19 Dec 2011 05:00:00 +0100 5524028 http://www.medworm.com/index.php?rid=5524027&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02191.x SummaryHSP90, a ubiquitously expressed chaperone, is of considerable interest as an oncology target since tumor cells and oncogenic proteins are acutely dependent on its activity. AT13387 is a novel, high affinity, HSP90 inhibitor currently being tested in the clinic, which shows activity against a wide array of tumor cell lines including lung cancer cell lines. AT13387 induced the degradation of specific HSP90 client proteins for up to 7 days in tumor cell lines in vitro. The primary driver of cell growth (mutant EGFR) in the NCI‐H1975 non‐small lung cancer cell line was particularly sensitive to HSP90 inhibition. The long duration of client protein knockdown and suppression of phospho‐signalling seen in vitro, after treatment with AT13387, was also apparent in vivo with client prot... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5524027 Mon, 19 Dec 2011 05:00:00 +0100 5524027 http://www.medworm.com/index.php?rid=5524026&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02193.x AbstractProstate cancer (PC) is the most common malignancy observed in men. It is evident that genetic factors play some important roles in PC etiology. Recently, genome‐wide association studies (GWAS) in diverse ethnic groups have identified more than 40 germline variants of various genes or chromosome loci that are significantly associated with PC susceptibility, including multiple 8q24 loci, prostate‐specific genes, metabolic and hormone‐related genes, and many regions where no coding gene is annotated. However, there are only a few variants or genes for which biological significance or functions have been elucidated so far. The greatest challenge related to GWAS loci in prostate genomics is to understand the functional consequences of these PC‐associated loci, and their involve... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5524026 Mon, 19 Dec 2011 05:00:00 +0100 5524026 http://www.medworm.com/index.php?rid=5524025&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02192.x SummaryHypoxia inducible factor‐1α (HIF‐1α) has a central role in cellular oxygen‐sensing and its overexpression in many types of cancer is considered important in tumor progression. Thus targeting HIF‐1α production/activity has been of great therapeutic interest. In normoxic condition, HIF‐1α is hydroxylated by oxygen‐dependent prolyl hydroxylases (PHDs), which require a ferrous iron for its activity. The tumor suppressor protein von Hippel Lindau (VHL) binds to the hydroxylated‐HIF‐1α, which is then ubiquitinated and degraded by proteasomes. We focused on the physiological HIF‐1α degradation machinery mediated by PHDs. Previously, we identified a small molecule, LS081 that is capable of stimulating iron uptake into cells. In the present study, we aimed to inhibit ... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5524025 Mon, 19 Dec 2011 05:00:00 +0100 5524025 http://www.medworm.com/index.php?rid=5608006&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02190.x In conclusion, C‐ion irradiation is effective in suppressing the invasive potential of several pancreatic tumor cell lines, but not PANC‐1; this is the first study showing that C‐ion irradiation induces the invasive potential of a tumor cell line. Further in vivo studies are required to examine the therapeutic effectiveness of radiotherapy combined with inhibitors of both mesenchymal and amoeboid modes of tumor cell motility. (Cancer Sci, doi: 10.1111/j.1349‐7006.2011.02190.x, 2012) (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5608006 Thu, 15 Dec 2011 05:00:00 +0100 5608006 http://www.medworm.com/index.php?rid=5596869&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02186.x Activation‐induced cytidine deaminase (AID/AICDA) is required for somatic hypermutation and class‐switch recombination of the immunoglobulin gene, and for c‐myc translocation of germinal center‐derived B‐cell lymphoma. In the present study, we attempted to clarify the significance of AID associated with c‐myc in the progression of follicular lymphoma (FL) using RT‐PCR and quantitative real‐time PCR. Tissues from the patients with grade 3 FL expressed relatively higher levels of c‐myc and AID. The samples taken from a patient with FL who died within 2 years after the start of treatment showed either no or low expression of AID, despite expressing high levels of c‐myc. In order to examine the role of AID expression in rapidly progressive FL, the full‐length AID transc... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5596869 Thu, 15 Dec 2011 05:00:00 +0100 5596869 http://www.medworm.com/index.php?rid=5580886&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02185.x Gastric carcinogenesis is a multistep process involving genetic and epigenetic alteration of protein‐coding proto‐oncogenes and tumor‐suppressor genes. Microribonucleic acids (miR) are a recently‐described class of genes encoding small non‐coding RNA molecules, which primarily act by downregulating the translation of target mRNA. It has become apparent that miR are also key factors in cancer, playing both oncogenic and tumor‐suppressing roles in gastric cancer. Recent studies have shown that a substantial number of miR show differential expression in gastric cancer tissues, and they are turning out to be just like any other regulatory gene. In this connection, miR dysregulation are reported to be associated with incidence, early diagnosis and prognosis of gastric cancer. Theref... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5580886 Thu, 15 Dec 2011 05:00:00 +0100 5580886 http://www.medworm.com/index.php?rid=5514991&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02189.x This study aimed to examine the role of Runx1 in tumor development in epithelial cells of the gastrointestinal tract. Conditional knockout mice were generated that lacked Runx1 expression in epithelial cells of the GI tract. These mice were crossed onto the ApcMin background, sacrificed, and their intestinal tumor phenotypes were compared with ApcMinRunx1 wildtype control mice. Apc‐wildtype Runx1‐mutant mice were also examined for tumor development. Colons from Runx1 knockout and wildtype mice were used for genome‐wide mRNA expression analyses followed by gene‐specific quantitative RT‐PCR of whole colon and colon epithelium, to identify Runx1 target genes. Runx1 deficiency in intestinal epithelial cells significantly enhanced tumorigenesis in ApcMin mice. Notably, epithelial Runx... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5514991 Thu, 15 Dec 2011 05:00:00 +0100 5514991 http://www.medworm.com/index.php?rid=5504266&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02185.x SummaryGastric carcinogenesis is a multistep process involving genetic and epigenetic alteration of protein‐coding proto‐oncogenes and tumor‐suppressor genes.MicroRNAs are a recently described class of genes, encoding small non‐coding RNA molecules, which primarily act by down‐regulating the translation of target mRNAs. It has become apparent that miRs are also key factors in cancer, playing both oncogenic and tumor‐suppressing roles in gastric cancer. Recent studies revealed that a substantial number of microRNAs show differential expression in gastric cancer tissues and they are turning out to be just like any other regulatory gene. In this connection, microRNAs dysregulation are reported to be associated incidence, early diagnosis and prognosis of gastric cancer. Therefore, ... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5504266 Thu, 15 Dec 2011 05:00:00 +0100 5504266 http://www.medworm.com/index.php?rid=5504265&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02186.x SummaryActivation‐induced cytidine deaminase (AID/AICDA) is required for somatic hyper‐mutation and class‐switch recombination of the immunoglobulin gene, and for c‐myc translocation of germinal center‐derived B‐cell lymphoma. In the present study, we attempted to clarify the significance of AID associated with c‐myc in the progression of follicular lymphoma (FL) using RT‐PCR and quantitative real‐time PCR. Tissues from the patients with grade 3 FL expressed relatively higher levels of c‐myc and AID. Interestingly, The samples taken from a patient with FL who died within two years after the start of treatment, showed either no or low expression of AID, despite expressing high levels of c‐myc. In order to examine the role of AID expression in rapidly progressive FL, th... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5504265 Thu, 15 Dec 2011 05:00:00 +0100 5504265 http://www.medworm.com/index.php?rid=5494548&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02183.x SummaryBreast cancer remains the leading cause of morbidity and second leading cause of death in women. Despite efforts to uncover new targeted therapies, a vast amount of women die due to refractory or recurrent breast tumors. Most breast cancer studies have focused on the intrinsic characteristics of breast tumor cells, including altered growth, proliferation, and metabolism. However, emerging research suggests that the tumor microenvironment can substantially affect relapse rates and therapeutic responses. In this review, we discuss the interactions between the tumor and microenvironment in breast cancer, with regard to mutational profiles and altered metabolism that could serve as potential therapeutic targets. We also describe current technologies available to study these interactions... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5494548 Mon, 12 Dec 2011 05:00:00 +0100 5494548 http://www.medworm.com/index.php?rid=5628057&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02182.x The drug delivery system to tumors is a critical factor in upregulating the effect of anticancer drugs and reducing adverse events. Recent studies indicated selective migration of bone marrow‐derived endothelial progenitor cells (EPC) into tumor tissues. Cytosine deaminase (CD) transforms nontoxic 5‐fluorocytosine (5‐FC) into the highly toxic 5‐fluorouracil (5‐FU). We investigated the antitumor effect of a new CD/5‐FC system with CD cDNA transfected EPC for hepatocellular carcinoma (HCC) in mice. We used human hepatoma cell lines (HuH‐7, HLF, HAK1‐B, KYN‐2, KIM‐1) and a rat EPC cell line (TR‐BME‐2). Escherichia coli CD cDNA was transfected into TR‐BME‐2 (CD‐TR‐BME). The inhibitory effect of 5‐FU on the proliferation of hepatoma cell lines and the inhibitor... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5628057 Thu, 08 Dec 2011 05:00:00 +0100 5628057 http://www.medworm.com/index.php?rid=5580889&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02181.x It is important to properly identify aggressive tumors among differentiated thyroid cancers that are most often indolent. By comparison of a tumorigenic clone with an originally less tumorigenic papillary thyroid carcinoma (PTC) cell line, we looked for markers involved in the aggressive biology of thyroid cancer. Human PTC cell lines BHP10‐3 and its tumorigenic subclone BHP10‐3SCmice were compared using microarray analysis. Upregulated genes in the tumorigenic clone were selected for RT‐PCR, immunoblot analysis and immunohistochemistry in human tissue. Hypoxia‐inducible factor (HIF)‐1α and its chaperone protein heat shock protein (HSP)90 showed significantly increased expression in BHP10‐3SCmice and human PTC tissue. These two genes, HIF‐1α and HSP90, were further validate... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5580889 Thu, 08 Dec 2011 05:00:00 +0100 5580889 http://www.medworm.com/index.php?rid=5486307&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02181.x SummaryIt is important to properly identify aggressive tumors among differentiated thyroid cancers which are most often indolent. By comparison of tumorigenic clone with originally less‐tumorigenic papillary thyroid carcinoma(PTC) cell line, we looked for markers involved in aggressive biology of thyroid cancer. Human PTC cell lines BHP10‐3 and its tumorigenic subclone BHP10‐3SCmice were compared using microarray analysis. Upregulated genes in the tumorigenic clone were selected for RT‐PCR, immunoblot analysis, and immunohistochemistry in human tissue. HIF‐1α and its chaperone protein HSP90 showed significantly increased expression in BHP10‐3SCmice and human PTC tissue. Two candidate genes, HIF‐1α and HSP90, were further validated using siRNA gene knockdown, pharmacologic i... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5486307 Thu, 08 Dec 2011 05:00:00 +0100 5486307 http://www.medworm.com/index.php?rid=5646946&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02179.x Olaparib (AZD2281) is an orally active Poly(ADP‐ribose) polymerase (PARP) inhibitor with favorable antitumor activity in advanced ovarian and breast cancers with BRCA1/2 mutations in Western (USA and European) studies. This Phase I dose‐finding study evaluated the tolerability, pharmacokinetics, PARP inhibitory activity, and antitumor activity of olaparib in Japanese patients with solid tumors. Olaparib was administered as a single‐dose on day 1, followed by twice‐daily dosing for 28 days from 48 h after a single dose. Doses were escalated from 100 mg b.i.d. in successive cohorts, up to a maximum of 400 mg b.i.d. The present study enrolled 12 patients (n = 3, 3, and 6 in 100, 200 and 400‐mg b.i.d. levels, respectively). The most common adverse events were nausea, incr... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5646946 Wed, 07 Dec 2011 05:00:00 +0100 5646946 http://www.medworm.com/index.php?rid=5486309&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02179.x SummaryOlaparib (AZD2281) is an orally active Poly(ADP‐ribose) polymerase (PARP) inhibitor with favorable antitumor activity in advanced ovarian and breast cancers with BRCA1/2 mutations in Western studies. This Phase I dose‐finding study evaluated the tolerability, pharmacokinetics, PARP inhibitory activity, and antitumor activity of olaparib in Japanese patients with solid tumors. Olaparib was administered as a single‐dose on day 1, followed by twice‐daily dosing for 28 days from 48 hours after single‐dose. Doses were escalated from 100 mg bid in successive cohorts, up to a maximum of 400 mg bid. Twelve patients (n=3, 3, and 6 in 100, 200 and 400 mg bid levels, respectively) were enrolled. The most common adverse events were nausea, increased blood creatinine, decreased hematoc... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5486309 Wed, 07 Dec 2011 05:00:00 +0100 5486309 http://www.medworm.com/index.php?rid=5486308&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02180.x SummaryMalignant pleural mesothelioma (MPM) usually develops pleural fluid. We investigated the value of DNA methylation in the pleural fluid for differentiating MPM from lung cancer (LC). Pleural fluid was collected from 39 patients with MPM, 46 with LC, 25 with benign asbestos pleurisy (BAP), and 30 with other causes. The methylation of O6‐methylguanine‐DNA methyltransferase (MGMT), p16INK4a, ras association domain family 1A (RASSF1A), death‐associated protein kinase (DAPK), and retinoic acid receptor ß (RARß) was examined using quantitative real‐time PCR. DNA methylation of RASSF1A, p16INK4a, RARß, MGMT, and DAPK was detected in 12 patients (30.8%), 3(7.7%), 11(28.2%), 0(0.0%), and 5(12.8%) with MPM, and in 22 patients (47.8%), 14(30.4%), 24(52.2%), 1(2.2%), and 6(13.0%) with... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5486308 Wed, 07 Dec 2011 05:00:00 +0100 5486308 http://www.medworm.com/index.php?rid=5596870&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02178.x The enhanced permeability and retention (EPR) effect is a unique pathophysiological phenomenon of solid tumors that sees biocompatible macromolecules (>40 kDa) accumulate selectively in the tumor. Various factors have been implicated in this effect. Herein, we report that heme oxygenase‐1 (HO‐1; also known as heat shock protein 32) significantly increases vascular permeability and thus macromolecular drug accumulation in tumors. Intradermal injection of recombinant HO‐1 in mice, followed by i.v. administration of a macromolecular Evans blue–albumin complex, resulted in dose‐dependent extravasation of Evans blue–albumin at the HO‐1 injection site. Almost no extravasation was detected when inactivated HO‐1 or a carbon monoxide (CO) scavenger was injected instead. Because... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5596870 Tue, 06 Dec 2011 05:00:00 +0100 5596870 http://www.medworm.com/index.php?rid=5580887&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02177.x The hypoxic microenvironment inside solid tumors, including hepatocellular carcinoma (HCC), is a major cause of tumor resistance to chemotherapy. The recently identified hypoxia‐inducible factor (HIF)‐2 executes the hypoxia response. Its expression feature and transcriptional targets indicate a possible dominance of HIF‐2 in regulating genes in HCC. The aim of the present study was to determine whether transfection of siRNA targeting HIF‐2α could enhance the efficacy of doxorubicin, the most commonly used drug in the treatment of HCC. Transfection of HIF‐2 siRNA into human HCC cells downregulated the expression of HIF‐2α, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)‐α, and cyclin D1, but had little effect on the expression of HIF‐1α, fms�... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5580887 Tue, 06 Dec 2011 05:00:00 +0100 5580887 http://www.medworm.com/index.php?rid=5476101&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02176.x AbstractThe purpose of this study was to determine the genomic profile of renal cell carcinoma in end‐stage renal disease (RCC‐ESRD) by analysis of genomic copy number aberrations (CNAs). Seventy‐nine tumor samples from 63 patients with RCC‐ESRD were analyzed by array comparative genomic hybridization (array CGH) using the Agilent Whole Human Genome 4×44K Oligo Micro Array. Unsupervised hierarchical clustering analysis revealed that the 63 cases were divisible into two groups: clusters A and B. Cluster A comprised mainly clear cell RCCs (CCRCCs), whereas cluster B comprised mainly papillary RCCs (PRCCs), acquired cystic disease (ACD)‐associated RCCs and clear cell papillary RCCs. Analysis of the averaged frequencies revealed that the genomic profiles of clusters A and B resemble... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5476101 Tue, 06 Dec 2011 05:00:00 +0100 5476101 http://www.medworm.com/index.php?rid=5476100&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02177.x SummaryHypoxic microenvironment inside solid tumors including hepatocellular carcinoma (HCC) is a major cause of tumor‐resistance to chemotherapy. A recently identified hypoxia‐inducible factor (HIF), HIF‐2, executes the hypoxia response. Its expression feature and transcriptional targets indicate the possible HIF‐2 dominance in regulating genes in HCC. The aim of this study was to determine whether transfection of small interfering RNA (siRNA) targeting HIF‐2α could enhance the efficacy of doxorubicin, the most commonly used chemotherapeutic drug for treating HCC. Transfection of HIF‐2 siRNA into human HCC cells downregulated the expression of HIF‐2α, VEGF, transforming growth factor (TGF)‐α and cyclin D1, but had little effect on the expression of HIF‐1α, fms‐rela... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5476100 Tue, 06 Dec 2011 05:00:00 +0100 5476100 http://www.medworm.com/index.php?rid=5608007&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02170.x This study explored the combined effect of number and pattern of mutations in the X/precore regions of the hepatitis B virus (HBV) genome, mutational complex genotype (MCG), on hepatocellular carcinoma (HCC) development. Sequence variations were determined by direct sequencing and multiplex restriction fragment mass polymorphism analysis in 150 age‐, sex‐ and hepatitis B e antigen (HBeAg) status‐matched patients with and without HCC. In addition, a longitudinal study and an external validation of MCG were conducted. All were HBV subgenotype C2. Eight high‐frequency mutations (G1613A, C1653T, T1753V, A1762T, G1764A, A1846T, G1896A and G1899A) were significantly associated with HCC. Whereas C1653T, T1753V, G1764A and A1846T were independent mutational factors for HCC, the significanc... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5608007 Fri, 02 Dec 2011 05:00:00 +0100 5608007 http://www.medworm.com/index.php?rid=5596871&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02174.x Nuclear factor‐κB (NF‐κB) activation contributes to the development of metastasis, thus leading to a poor prognosis in many cancers, including OSCC. However, little in vivo experimental data are available about the effects of NF‐κB inhibition on OSCC metastasis. OSCC sublines were established from a GFP‐expressing parental cell line, GSAS, and designated GSAS/N3 and N5 according to the in vivo passage number after cervical lymph node metastasis by a serial orthotopic transplantation model. In vitro migration and invasion were assessed in these cells, and the NF‐κB activities and expression of NF‐κB‐regulated metastasis‐related molecules were also examined. In in vivo experiments, the metastasis and survival of tumor‐engrafted mice were monitored. Furthermore, the eff... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5596871 Fri, 02 Dec 2011 05:00:00 +0100 5596871 http://www.medworm.com/index.php?rid=5580888&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02171.x The present study examined long‐term efficacy outcomes in a subgroup of postmenopausal, estrogen receptor‐positive Japanese breast cancer patients from the Pre‐Operative “Arimidex” Compared with Tamoxifen trial, following pre‐operative (3 months) and post‐operative (5 years) adjuvant treatment with either anastrozole or tamoxifen. Patients with large, potentially operable, locally‐advanced breast cancer were randomized to receive anastrozole (1 mg/day) plus tamoxifen placebo or tamoxifen (20 mg/day) plus anastrozole placebo pre‐operatively. After surgery at 3 months, patients continued on the same study medication as adjuvant therapy for up to 5 years or until recurrence, intolerable toxicity or withdrawal of patient consent. Recurrence‐free survival and ove... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5580888 Fri, 02 Dec 2011 05:00:00 +0100 5580888 http://www.medworm.com/index.php?rid=5468358&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02170.x This study explored the combined effect of number and pattern of mutations in the X/precore regions of the hepatitis B virus (HBV) genome, mutational complex genotype (MCG), on hepatocellular carcinoma (HCC) development. Sequence variations were determined by direct sequencing and multiplex restriction fragment mass polymorphism analysis in 150 age‐, sex‐, and hepatitis B e antigen (HBeAg) status‐matched patients with and without HCC. Additionally, a longitudinal study and an external validation of MCG were conducted. All were HBV subgenotype C2. Eight high‐frequency mutations (G1613A, C1653T, T1753V, A1762T, G1764A, A1846T, G1896A, and G1899A) were significantly associated with HCC. Whereas C1653T, T1753V, G1764A, and A1846T were independent mutational factors for HCC, the signifi... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5468358 Fri, 02 Dec 2011 05:00:00 +0100 5468358 http://www.medworm.com/index.php?rid=5468357&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02171.x SummaryTo examine long‐term efficacy outcomes in a subgroup of postmenopausal, estrogen receptor‐positive, Japanese, breast cancer patients, from the Pre‐Operative ‘Arimidex’® Compared with Tamoxifen trial, following pre‐operative (3 months) and post‐operative (5 years) adjuvant treatment with either anastrozole or tamoxifen.Patients with large, potentially operable, locally‐advanced breast cancer were randomized to receive anastrozole (1 mg/day) plus tamoxifen placebo or tamoxifen (20 mg/day) plus anastrozole placebo pre‐operatively. After surgery at 3 months, patients continued on the same study medication as adjuvant therapy for up to 5 years or until recurrence, intolerable toxicity, or withdrawal of patient consent. Recurrence‐free survival and overall survival ... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5468357 Fri, 02 Dec 2011 05:00:00 +0100 5468357 http://www.medworm.com/index.php?rid=5468356&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02175.x SummaryMutations in IDH1 and IDH2 are found frequently in malignant gliomas and are likely involved in early gliomagenesis. To understand the prevalence of these mutations and their relationship to other genetic alterations and impact on prognosis for Japanese glioma patients, we analyzed 250 glioma cases. Mutations of IDH1 and IDH2 were found in 73 (29%) and 2 (1%) cases, respectively. All detected mutations were heterozygous, and most mutations were Arg132His (G395A) substitution. IDH mutations were frequent in oligodendroglial tumors (37/52, 71%) and diffuse astrocytomas (17/29, 59%), and were less frequent in anaplastic astrocytomas (8/29, 28%) and glioblastomas (13/125, 10%). The pilocytic astrocytomas and gangliogliomas did not have mutation. Notably, 28 of 30 oligodendroglial tumors... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5468356 Fri, 02 Dec 2011 05:00:00 +0100 5468356 http://www.medworm.com/index.php?rid=5468355&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02174.x In conclusion, our results suggest that the selective inhibition of NF‐κB activation by NBD peptide may provide an effective approach for the treatment of highly metastatic OSCC.© 2011 Japanese Cancer Association (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5468355 Fri, 02 Dec 2011 05:00:00 +0100 5468355 http://www.medworm.com/index.php?rid=5551957&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02199.x SummaryVasculogenic mimicry(VM) is related to more aggressive behaviors and shorter survival time. Our previous studies have shown that epithelial–mesenchymal transition(EMT) may be involved in the VM formation in hepatocellular carcinoma (HCC). Here, we hypothesize that ZEB1 (zinc finger E‐box binding homeobox 1), a crucial EMT‐inducer, would promote VM formation in colorectal carcinoma (CRC) via inducing EMT. We identified VM in 39 (19.2%) out of 203 CRC patients and the presence of VM was associated with aggressive biological behaviors as well as an unfavorable prognostic indicator. By immunohistochemical (IHC) analysis, we found that the VM‐positive CRC samples showed increased ZEB1 expression compared with the VM‐negative ones and the ZEB1 expression occurred concomitantly w... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5551957 Thu, 01 Dec 2011 05:00:00 +0100 5551957 http://www.medworm.com/index.php?rid=5537405&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02198.x AbstractGlioblastoma (GBM) is a highly aggressive brain tumor characterized by increased proliferation and resistance to chemotherapy and radiotherapy. Recently, a growing body of evidence suggests that glioma‐initiating cells (GICs) are responsible for the initiation and recurrence of GBM. However, the factors determining the differential development of GICs remain poorly defined. In the present study, we show that curcumin, a natural compound with low toxicity in normal cells, significantly induced differentiation of GICs in vivo and in vitro by inducing autophagy. Moreover, curcumin also suppressed tumor formation upon intracranial GICs implantation into mice. Our results suggest that autophagy plays an essential role in the regulation of GICs self‐renewal, differentiation and tumor... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5537405 Thu, 01 Dec 2011 05:00:00 +0100 5537405 http://www.medworm.com/index.php?rid=5524024&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02196.x The constituents of the oncogene signal transduction pathway are promising targets for anti‐cancer drugs. Despite the wealth of available knowledge regarding their molecular properties, the spatiotemporal regulation of the signaling molecules remains elusive. Biosensors based on the principle of Förster (or fluorescence) resonance energy transfer (FRET) have been developed to visualize the activities of the signaling molecules in living cells. However, difficulties in the development of sensitive FRET biosensors have prevented their widespread use in cancer research. Furthermore, the lack of cell lines constitutively expressing a FRET biosensor has also limited their use. In this review, we will introduce the principle of FRET‐based biosensors, describe an optimized backbone of the FR... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5524024 Thu, 01 Dec 2011 05:00:00 +0100 5524024 http://www.medworm.com/index.php?rid=5514990&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02190.x In conclusion, C‐ion irradiation is effective in suppressing the invasive potential of several pancreatic tumor cell lines but not PANC‐1; this is the first study indicating that C‐ion irradiation induces invasive potential of tumor cell line. Further in vivo studies are required to examine the therapeutic effectiveness of radiotherapy combined with inhibitors of both mesenchymal and amoeboid modes of tumor cell motility.© 2011 Japanese Cancer Association (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5514990 Thu, 01 Dec 2011 05:00:00 +0100 5514990 http://www.medworm.com/index.php?rid=5504264&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02187.x SummaryMulticellular tumor spheroids (MTSs) are gaining increased recognition as valuable tools and key elements in anti‐cancer drug discovery and tumor therapy test programs. However, the lack of reproducible and uniform MTS sizes is a major problem for pharmaceutical assays. Here, we demonstrate the usefulness of duplex microcapsules with a Ca‐alginate gel membrane as a platform for producing MTSs with a highly homogeneous size distribution. HeLa cells were enclosed with 86.9% viability within the microcapsules. The enclosed cells grew and formed MTSs with the same size as the cavity of the microcapsules by arresting their growth with the microcapsule membrane. The cells in the resultant MTSs had a higher proportion in the G0/G1 phase (71.2%) than 2D cultured cells in the stationary ... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5504264 Thu, 01 Dec 2011 05:00:00 +0100 5504264 http://www.medworm.com/index.php?rid=5494547&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02184.x We present the current knowledge of the possible applications of cell reprogramming in reducing aggressive phenotype expression, which can induce tumor cell hibernation and maintain appropriate phenotypes, thereby minimizing relapse and metastasis after surgical resection of gastrointestinal cancer.© 2011 Japanese Cancer Association (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5494547 Thu, 01 Dec 2011 05:00:00 +0100 5494547 http://www.medworm.com/index.php?rid=5486306&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02182.x SummaryThe drug delivery system to tumor is a critical factor in up‐regulating the effect of anti‐cancer drugs and reducing adverse events. Recent studies indicated selective migration of bone marrow‐derived endothelial progenitor cells (EPC) into tumor tissues. Cytosine deaminase (CD) transforms nontoxic 5‐fluorocytosine (5‐FC) into the highly toxic 5‐fluorouracil (5‐FU). We investigated the anti‐tumor effect of a new CD/5‐FC system with CD cDNA transfected EPC for hepatocellular carcinoma (HCC) in mice.We used human hepatoma cell lines (HuH‐7, HLF, HAK1‐B, KYN‐2, KIM‐1) and rat EPC cell line (TR‐BME‐2). E. coli CD cDNA was transfected into TR‐BME‐2 (CD‐TR‐BME). The inhibitory effect of 5‐FU on the proliferation of hepatoma cell lines and the inhibi... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5486306 Thu, 01 Dec 2011 05:00:00 +0100 5486306 http://www.medworm.com/index.php?rid=5476099&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02178.x We report here that heme oxygenase‐1 (HO‐1; also called Hsp32), significantly increased vascular permeability and thus macromolecular drug accumulation in tumors. Intradermal injection of recombinant HO‐1 followed by i.v. administration of a macromolecular Evans blue‐albumin complex in vivo resulted in dose‐dependent extravasation of Evans blue‐albumin at the HO‐1 injection site. Almost no extravasation was detected when inactivated HO‐1 or a carbon monoxide (CO) scavenger was injected. Because HO‐1 generates CO, these data led to the reasonable to conclusion that CO plays a key role in vascular leakage. This conclusion was supported by results after intratumor administration of a CO‐releasing agent (tricarbonyldichlororuthenium(II) dimer) in the same experimental setti... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5476099 Thu, 01 Dec 2011 05:00:00 +0100 5476099 http://www.medworm.com/index.php?rid=5468354&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02173.x In this study, we investigated the association of two regulatory variants in caspase‐3 and the risk of esophageal squamous cell carcinoma (ESCC) in 1026 cases and 1270 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed by logistic regression. The function of the Caspase‐3 829A>C polymorphism was examined by Luciferase reporter assay and real‐time PCR. A significant increased risk of ESCC was found for the caspase‐3 829 AC and CC genotypes with OR (95% CI), 1.53 (1.26‐1.89) and 1.42 (1.11‐1.82), respectively. When stratified by age and gender, the risk of ESCC was more significant in younger (<=57y) and male individuals. No significantly changed risk of ESCC was related to 20541 C>T variant. Luciferase reporter assay showed 829 A>C v... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5468354 Thu, 01 Dec 2011 05:00:00 +0100 5468354 http://www.medworm.com/index.php?rid=5456881&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02169.x This study was to retrospectively stratify the risks of malignancy according to the mammographic characteristics of Japanese women. We studied mammographic findings of 1267 Japanese women. We characterized malignant phenotypes according to mass shape, margin and mass density, and by shape and distribution of calcified foci, and to obtain possible predictors for malignancies according to the age groups. Lobular and irregular mass shape, no circumscribed margin and higher density turned out to be more powerful predictors for malignancy than other radiological factors (P<0.001, respectively). The ratio of the cases detected as mass between 21 and 49 years was lower than that of other age groups. In addition, the presence of calcifications and no mammographic abnormalities turned out as one... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5456881 Thu, 01 Dec 2011 01:16:16 +0100 5456881 http://www.medworm.com/index.php?rid=5580890&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02167.x To identify potential molecular targets for diagnosis, treatment and/or prevention of lung and esophageal carcinomas, we screened for genes that were overexpressed in tumors through gene expression analyses of 120 lung cancers and 19 esophageal squamous‐cell carcinomas using a cDNA microarray consisting of 27 648 cDNA or expressed sequence tags. In this process, we identified a gene, Opa interacting protein 5 (OIP5), to be highly transactivated in the majority of lung and esophageal cancers. Immunohistochemical staining using 336 archived non‐small cell lung cancers and 305 esophageal squamous‐cell carcinomas specimens demonstrated that OIP5 expression was significantly associated with poor prognosis of lung and esophageal cancer patients (P = 0.0053 and 0.0168, respectively), ... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5580890 Wed, 30 Nov 2011 05:00:00 +0100 5580890 http://www.medworm.com/index.php?rid=5456883&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02167.x SummaryTo identify potential molecular targets for diagnosis, treatment, and/or prevention of lung and esophageal carcinomas, we screened for genes that were overexpressed in the tumors through gene expression analyses of 120 lung cancers and 19 esophageal squamous‐cell carcinomas (ESCCs) using a cDNA microarray consisting of 27,648 cDNAs or expressed sequence tags. In this process, we identified a gene, opa interacting protein 5 (OIP5), to be highly transactivated in the majority of lung and esophageal cancers. Immunohistochemical staining using 336 archived non‐small cell lung cancers (NSCLCs) and 305 ESCC specimens demonstrated that OIP5 expression was significantly associated with poor prognosis of lung and esophageal cancer patients (P = 0.0053 and 0.0168, respectively), and multi... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5456883 Wed, 30 Nov 2011 05:00:00 +0100 5456883 http://www.medworm.com/index.php?rid=5456882&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02168.x SummaryWe evaluated the impact of functional polymorphisms in the VEGFA and VEGFR2 genes on the survival of patients with DLBCL. Five potentially functional polymorphisms in the VEGFA (rs699947, rs2010963 and rs3025039) and VEGFR2 (rs1870377 and rs2305948) genes were assessed in 494 DLBCL patients treated with rituximab plus CHOP chemotherapy. The associations of genotype and haplotype with overall survival (OS) and progression‐free survival (PFS) were analyzed. Of the five polymorphisms, VEGFR2 rs1870377T>A was significantly associated with both OS and PFS; in the dominant model, patients with the AA+TA genotypes had significantly better OS (P=0.002) and PFS (P=0.004) than those with the TT genotype. The association between significantly better OS and the AA+TA genotypes was observed... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5456882 Wed, 30 Nov 2011 05:00:00 +0100 5456882 http://www.medworm.com/index.php?rid=5596872&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02164.x Primary gastrointestinal (PGI) diffuse large B cell lymphoma (DLBCL) is a relatively common disease. Recent studies indicate that measurement of maximum standardized uptake value (SUVmax) on pretreatment for 18F‐fluorodeoxyglucose PET is an important prognostic factor in PGI DLBCL. However, there is still an association between initial tumor burden and prognosis. Thus, in the present study, we investigated whether tumor volume by PET could have a potential prognostic value to predict the outcome. From 2006 to 2009, 165 Stage I E/II E PGI DLBCL patients were enrolled in the study. One hundred and five patients received cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R‐CHOP) only, whereas 60 patients underwent surgery plus R‐CHOP. Metabolic tumor volume (MTV) was... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5596872 Tue, 29 Nov 2011 05:00:00 +0100 5596872 http://www.medworm.com/index.php?rid=5596868&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02163.x Wilms’ tumor gene 1 (WT1) protein is a promising tumor‐associated antigen. In patients with WT1‐expressing malignancies, WT1‐specific CTLs are spontaneously induced as a result of an immune response to the WT1 protein. In the present study, we performed single cell‐level comparative analysis of T cell receptor β‐chain variable region (TCR‐BV) gene families of a total of 750 spontaneously induced WT1126 peptide (amino acids 126–134, WT1126)‐specific CTLs in both HLA‐A*0201+ patients with solid tumors and healthy donors (HDs). This is the first report of direct usage analysis of 24 kinds of TCR‐BV gene families of WT1126‐specific CTLs at the single cell level. Usage analysis with single‐cell RT‐PCR of TCR‐BV gene families of individual FACS‐sorted WT1126 tetr... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5596868 Tue, 29 Nov 2011 05:00:00 +0100 5596868 http://www.medworm.com/index.php?rid=5537407&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02166.x Overexpression of epidermal growth factor receptor (EGFR) is common in colorectal cancer. However, cetuximab as an EGFR‐targeting drug is useful only for a subset of patients and currently no single predictor other than V‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status has been established. In the present study, we investigated cetuximab accumulation in colorectal tumors and major organs using 111In‐DOTA‐cetuximab. We also evaluated the potential of positron emission tomography (PET) imaging of 64Cu‐DOTA‐cetuximab. Colorectal tumor xenografts with a different EGFR expression level and KRAS mutation status were subjected to in vivo biodistribution study and PET imaging at 48 h post‐injection of radiolabeled cetuximab. The EGFR expression levels on... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5537407 Tue, 29 Nov 2011 05:00:00 +0100 5537407 http://www.medworm.com/index.php?rid=5456887&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02166.x In this study, we investigated the cetuximab accumulation in colorectal tumors and major organs using 111In‐DOTA‐cetuximab. We also evaluated the potential of positron emission tomography (PET) imaging of 64Cu‐DOTA‐cetuximab. Colorectal tumor xenografts with different EGFR expression level and KRAS mutation status were subjected to in vivo biodistribution study and PET imaging at 48 hours post injection of radiolabeled cetuximab. EGFR expression levels on colorectal tumors were determined by ex vivo immunoblotting and ELISA. We found that KRAS wild type tumors had significantly higher 111In‐DOTA‐cetuximab accumulation than KRAS mutant tumors (P<0.001). Based on KRAS mutation status, a strong correlation was found between 111In‐DOTA‐cetuximab tumor uptake and EGFR express... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5456887 Tue, 29 Nov 2011 05:00:00 +0100 5456887 http://www.medworm.com/index.php?rid=5456886&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02163.x SummaryWT1 (Wilms’ tumor gene 1) protein is a promising tumor associated antigen and WT1‐specific cytotoxic T lymphocytes (CTLs) are spontaneously induced in patients with WT1‐expressing malignancies as a result of immune response to WT1 protein. We performed a single‐cell level comparative analysis of T cell receptor β‐chain variable region (TCR‐BV) gene families of a total of 750 spontaneously induced WT1126 peptide (a.a.126‐134, WT1126)‐specific CTLs in HLA‐A*0201+ patients with solid tumors and healthy donors (HDs). This is the first report of direct usage analysis of 24 kinds of TCR‐BV gene families of WT1126‐specific CTLs at single‐cell level. Usage analysis using single‐cell RT‐PCR of TCR‐BV gene families of individual FACS‐sorted WT1126 tetramer+ CD... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5456886 Tue, 29 Nov 2011 05:00:00 +0100 5456886 http://www.medworm.com/index.php?rid=5456885&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02164.x AbstractPrimary gastrointestinal (PGI) diffuse large B cell lymphoma (DLBCL) is a relatively common disease. Recent studies showed that measurement of maximum standardized uptake value (SUVmax) on pretreatment in Fluorine‐18 fluorodeoxyglucose (18F‐FDG) positron emission tomography (PET) was an important prognostic factor in PGI DLBCL. However, initial tumor burden is still importantly associated with prognosis. From 2006 to 2009, 165 stage I E/II E PGI DLBCL patients were enrolled. Sixty patients received R‐CHOP only and 105 patients underwent surgery plus R‐CHOP. Metabolic tumor volume (MTV) was defined initial tumor burden as target lesion above SUV, 2.5. For median follow‐up period of 36.6 months, 160.1cm3 was the best cut‐off value of MTV and 12.0 was the value of SUVmax i... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5456885 Tue, 29 Nov 2011 05:00:00 +0100 5456885 http://www.medworm.com/index.php?rid=5456884&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02165.x SummaryWe retrospectively investigated malignant mesothelioma (MM) cases in Japan. We extracted 6,030 cases of death due to MM between 2003 and 2008 to clarify the clinical features of MM including the association with asbestos exposure (AE). Among them, clinical diagnosis of MM was confirmed in 929 cases. The origin of MM included the pleura in 794(85.5%) cases, the peritoneum in 123(13.2%) cases, the pericardium in 7(0.8%) cases, and the testicular tunica vaginalis in 5(0.5%) cases. The histological subtype of MM included 396(55.9%) epithelioid, 154(21.7%) sarcomatoid, 126(17.8%) biphasic, and 33(4.7%) cases classified as other types. AE was indicated in 76.8% and pleural plaques were detected in 34.2% of all MM cases. Asbestos particles were determined in 103 MM cases. More than 1,000 a... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5456884 Tue, 29 Nov 2011 05:00:00 +0100 5456884 http://www.medworm.com/index.php?rid=5449499&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02162.x AbstractCo‐expression of membrane‐type matrix metalloproteinase‐1 (MT1‐MMP) with hepatocyte growth factor (HGF) activator inhibitor‐1 (HAI‐1) in HEK293T cells resulted in cleavage of HAI‐1 to produce 3 fragments. Recombinant MT1‐MMP was shown to cleave HAI‐1 protein in vitro. HAI‐1 was initially identified as the cognate inhibitor of matriptase, which is a transmembrane serine protease and processes urokinase‐type plasminogen activator (uPA). Co‐expression of HAI‐1 with matriptase suppressed matriptase protease activity, and co‐expression of MT1‐MMP with them resulted in recovery of matriptase activity by stimulating shedding of HAI‐1 fragments. Matriptase protein was detected in squamous carcinoma‐derived HSC‐4 cells, however, matriptase protease activi... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5449499 Mon, 28 Nov 2011 01:20:06 +0100 5449499 http://www.medworm.com/index.php?rid=5571869&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02160.x Toll‐like receptors (TLRs) function as pattern‐reorganization receptors in mammals and play an essential role in innate immunity. After recognizing certain ligands, TLRs activate a cascade of signal pathways to establish a guard environment. For the first time, we report that in vitro treatment with recombinant calcineurin subunit B (CNB) upregulated several TLR‐related genes. Calcineurin subunit B interacted with the ectodomain of TLR4 in vitro. On further investigation, phosphorylation of interferon regulatory factor 3 and degradation of IκB‐α were observed by CNB stimulation. In addition to pro‐inflammatory cytokines, transcription and production of β‐interferon were also enhanced after CNB stimulation. Thus, CNB could be further explored as a cancer and virus immunothera... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5571869 Sat, 26 Nov 2011 05:00:00 +0100 5571869 http://www.medworm.com/index.php?rid=5449501&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02161.x This study sought to elucidate the clinicopathological characteristics in patients with PTC regarding the expression of Notch1/Notch3 receptors and BRAFV600Emutation. Clinicopathological characteristics were evaluated according to the Notch1/Notch3 receptors and BRAFV600Emutation in 187 patients with PTC who underwent definitive surgery. Expression of the Notch1 receptor was significantly associated with poor prognostic markers including large tumor size, nodal metastasis, capsular invasion, and extrathyroidal extension. However, there was no significant association between the clinicopathological characteristics and Notch3 receptor expression/BRAFV600Emutation. In multivariate analysis, Notch1 receptor expression showed a significant relationship with lymph node metastasis (p = 0.04). Not... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5449501 Sat, 26 Nov 2011 05:00:00 +0100 5449501 http://www.medworm.com/index.php?rid=5449500&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02160.x AbstractToll like receptors (TLRs) function as pattern‐reorganization receptors in mammals and play an essential role in innate immunity. After recognizing certain ligands, TLRs activate a cascade of signal pathways to establish a guard environment. Here for the first time, we report that in vitro treatment of recombinant calcineurin subunit B (CNB) up‐regulated several TLR related genes. CNB interacted with ectodomain of TLR4 in vitro. Upon further investigation, phosphorylation of IRF3 and degradation of IκB‐α were observed by CNB stimulation. Besides pro‐inflammatory cytokines, transcription and production of IFN‐β were also enhanced after CNB stimulation. Thus, CNB can be further explored as a cancer and virus immune therapy drug. (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5449500 Sat, 26 Nov 2011 05:00:00 +0100 5449500 http://www.medworm.com/index.php?rid=5440267&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02159.x SummaryHigh‐mobility group A1 (Hmga1) protein is an architectural chromatin factor, and aberrant Hmga1 expression in mice causes hematopoietic malignancies with defects in cellular differentiation. However, the functional involvement of Hmga1 in hematopoietic development and leukemia cells remains to be elucidated. Using Hmga1‐green fluorescent protein (GFP) knock‐in mice that endogenously express an Hmga1‐GFP fusion protein, we examined Hmga1 expression in undifferentiated and differentiated populations of hematopoietic cells. During early T cell development in the thymus, Hmga1 is highly expressed in Cd4/Cd8‐double negative (DN) cells and is transiently down‐regulated in Cd4/Cd8‐double positive (DP) cells. Consistently, Hmga1 directly binds to cis‐regulatory elements in t... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5440267 Fri, 25 Nov 2011 01:17:25 +0100 5440267 http://www.medworm.com/index.php?rid=5537408&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02158.x There is no specific marker to evaluate the immuno‐suppressive status of cancer patients. Several markers, such as CD124, latency‐associated peptide (LAP), arginase I, indole‐amine‐2,3‐dioxygenase (IDO) and inducible nitric oxide synthase (iNOS), are known to be associated with immune suppression. However, there is little research regarding the change in these parameters after chemotherapy. The present study enrolled 23 chemo‐naïve non‐small cell lung cancer (NSCLC) patients and 19 healthy donors. From the 23 NSCLC patients, 11 post‐chemotherapy samples were collected. Surface and functional markers were analyzed by flow‐cytometry. The mean fluorescence intensities (MFI) of iNOS were higher and the MFI of LAP were lower in NSCLC patient than in healthy donors (P <�... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5537408 Tue, 22 Nov 2011 05:00:00 +0100 5537408 http://www.medworm.com/index.php?rid=5440268&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02158.x SummaryThere is no specific marker to evaluate the immuno‐suppressive status of cancer patients. Several markers such as CD124, latency‐associated peptide(LAP), arginase I(ARGI), indole‐amine‐2,3‐dioxygenase(IDO) and inducible nitric oxide synthase(iNOS) are known to be associated with immune suppression. However, few have been studied regarding any change of these parameters after chemotherapy.Twenty three chemo‐naïve, non‐small cell lung cancer (NSCLC) patients and 19 healthy donors were enrolled in this study. 11 post‐chemotherapy samples out of 23 were collected. Surface and functional markers were analyzed by flow‐cytometry.The mean fluorescence intensities (MFIs) of iNOS were higher and the MFIs of LAP were lower in NSCLC than in healthy donors (p<0.05). In a co... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5440268 Tue, 22 Nov 2011 05:00:00 +0100 5440268 http://www.medworm.com/index.php?rid=5431314&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02118.x (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5431314 Tue, 22 Nov 2011 01:18:27 +0100 5431314 http://www.medworm.com/index.php?rid=5431311&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02157.x SummaryIt is widely accepted that blood vessels in the tumor microenvironment are immature because mural cell (MC) adhesion to endothelial cell (EC) is broadly lacking. Hyperpermeability of the tumor vasculature then results in interstitial hypertension that mitigates against penetration of anti‐cancer drugs into the depths of the tumor. It has been suggested that treatment with angiogenesis inhibitors normalizes blood vessels, resulting in restoration of normal permeability and improved drug delivery. However, recent reports suggest that cancer cell invasion is induced from the edge of the tumor into peripheral areas after treatment with angiogenesis inhibitors. Therefore, it is important to assess the status of blood vessels in the fibrous cap at the tumor rim after anti‐angiogenesis... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5431311 Tue, 22 Nov 2011 01:17:03 +0100 5431311 http://www.medworm.com/index.php?rid=5580891&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02155.x Cancer metastasis remains the primary cause of pain, suffering, and death in cancer patients, and even the most current therapeutic strategies have not been highly successful in preventing or inhibiting metastasis. In most patients with scirrhous gastric cancer (one of the most aggressive of diffuse‐type gastric cancer), recurrence occurs even after potentially curative resection, most frequently in the form of peritoneal metastasis. Given that the occurrence of diffuse‐type gastric cancers has been increasing, the development of new strategies to combat metastasis of this disease is critically important. Plasminogen activator inhibitor‐1 (PAI‐1) is a critical factor in cancer progression; thus, PAI‐1 RNAi may be an effective therapy against cancer metastasis. In the present stud... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5580891 Sun, 20 Nov 2011 05:00:00 +0100 5580891 http://www.medworm.com/index.php?rid=5537409&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02156.x Mitochondrial transcription factor A (mtTFA) is necessary for both transcription and maintenance of mitochondrial DNA (mtDNA). Recently, we reported that mtTFA is expressed not only in mitochondria, but also in nuclei. However, the function of mtTFA in the nucleus has not been clearly elucidated. In the present study, we examined nuclear mtTFA expression in 60 tissue samples of serous ovarian cancer using immunohistochemical analysis and found that 56.7% of serous ovarian cancer patients were positive for mtTFA, whereas 43.3% were negative. Univariate survival analysis showed that the overall 5‐year survival rate was significantly worse for patients with mtTFA‐positive cancer compared with mtTFA‐negative cancer (32%vs 42%, respectively; P = 0.021). To elucidate the function of mt... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5537409 Sun, 20 Nov 2011 05:00:00 +0100 5537409 http://www.medworm.com/index.php?rid=5524030&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02157.x It is widely accepted that blood vessels in the tumor microenvironment are immature because mural cell (MC) adhesion to endothelial cells (ECs) is broadly lacking. Hyperpermeability of the tumor vasculature then results in interstitial hypertension that mitigates against penetration of anticancer drugs into the depths of the tumor. It has been suggested that treatment with angiogenesis inhibitors normalizes blood vessels, resulting in restoration of normal permeability and improved drug delivery. However, recent reports suggest that cancer cell invasion is induced from the edge of the tumor into peripheral areas after treatment with angiogenesis inhibitors. Therefore, it is important to assess the status of blood vessels in the fibrous cap at the tumor rim after antiangiogenesis therapy. I... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5524030 Sun, 20 Nov 2011 05:00:00 +0100 5524030 http://www.medworm.com/index.php?rid=5431313&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02155.x AbstractCancer metastasis remains the primary cause of pain, suffering and death in cancer patients and even the most current therapeutic strategies have not been highly successful in preventing or inhibiting metastasis. In most patients with scirrhous gastric cancer (one of the most aggressive diffuse type gastric cancer), recurrence of cancers occurs even after potentially curative resection, and recurrence most frequently occurs in the form of peritoneal metastasis. Given that the occurrence of diffuse type gastric cancers has been increasing, development of new strategies for combating metastasis of this disease is critically important. Plasminogen activator inhibitor‐1 (PAI‐1) is a critical factor in cancer progression; thus, PAI‐1 RNA interference (RNAi) might be an effective t... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5431313 Sun, 20 Nov 2011 05:00:00 +0100 5431313 http://www.medworm.com/index.php?rid=5431312&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02156.x We examined nuclear mtTFA expression in 60 tissue samples of serous ovarian cancer using immunohistochemical analysis. mtTFA was positive in 56.7% and negative in 43.3% of serous ovarian cancer patients. A univariate survival analysis showed that the 5‐year overall survival rate of the patients with mtTFA‐positive cancer was significantly worse than that of the patients with mtTFA‐negative cancer (32% vs. 42%, P=0.021). To elucidate the function of mtTFA in the nucleus, we investigated BCL2L1, a target gene of mtTFA. Nuclear expression of mtTFA significantly correlated with BCL2L1 expression in not only seven ovarian cancer cell lines but also clinical ovarian cancer specimens. Cellular BCL2L1 was downregulated following transfection of siRNA against mtTFA. BCL2L1 promoter activity w... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5431312 Sun, 20 Nov 2011 05:00:00 +0100 5431312 http://www.medworm.com/index.php?rid=5421499&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02130.x (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5421499 Thu, 17 Nov 2011 05:00:00 +0100 5421499 http://www.medworm.com/index.php?rid=5580892&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02153.x We previously prepared a tumor necrosis factor (TNF)‐α mutant (rmhTNF‐α) that showed higher antitumor activity and lower systemic toxicity compared with native TNF‐α. The safety profile and the pharmacokinetic characteristics of rmhTNF‐α were suited for clinical use according to biological Investigational New Drug application, a standard guideline for new drug investigation in China. Here, we evaluate the activity and safety of rmhTNF‐α combined with chemotherapies in head/neck, lung, colorectal, stomach, and renal cancer patients. Ninety‐five eligible patients received i.m. rmhTNF‐α treatment combined with standard chemotherapies. Another 95 patients were treated with standard chemotherapies. After two treatment cycles, one patient achieved a complete response and 24 p... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5580892 Tue, 15 Nov 2011 05:00:00 +0100 5580892 http://www.medworm.com/index.php?rid=5504268&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02152.x Centrosome amplification (also known as centrosome overduplication) is common in cancer cells and can be induced by DNA damaging agents. However, the mechanism and significance of centrosome amplification during carcinogenesis or after DNA damage are not clear. Previously, we showed that centrosome amplification could be induced by 3‐aminobenzamide (3‐AB), an inhibitor of poly(ADP‐ribose) polymerases (PARPs) in mouse embryonic fibroblasts. In this paper, we determined if the effect of 3‐AB on centrosome amplification was dependent on DNA damage in CHO‐K1 cells. We used the well‐known mutagen/carcinogen N‐methyl‐N’‐nitro‐N‐nitrosoguanidine (MNNG). Ten micromolar MNNG and 10 mM 3‐AB induced significant centrosome amplification in 18.1 ± 1.1% and 19.4 ± 1... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5504268 Tue, 15 Nov 2011 05:00:00 +0100 5504268 http://www.medworm.com/index.php?rid=5407023&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02153.x SummaryWe have previously prepared a TNF‐α mutant (rmhTNF‐α) which exhibited a higher anti‐tumor activity and a lower systemic toxicity compared with that of native TNF‐α. The safety profile and the pharmacokinetic characteristics of the rmhTNF‐α were suited for clinical use according to biological Investigational New Drug application. Here, we evaluated the activity and safety of rmhTNF‐α combined with chemotherapies in head/neck, lung, colorectal, stomach and renal cancer patients. 95 eligible patients received i.m. rmhTNF‐α treatment combined with standard chemotherapies. Another 95 patients were treated by standard chemotherapies. After two cycles, one patient achieved a complete response (CR) and 24 patients had partial response (PR), yielding an overall response r... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5407023 Tue, 15 Nov 2011 05:00:00 +0100 5407023 http://www.medworm.com/index.php?rid=5504270&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02150.x We examined the effect of aclarubicin (ACR), an anthracycline, in combination with TRAIL. The combination of TRAIL and ACR synergistically induced apoptosis in human acute lymphoblastic leukemia Jurkat cells and human lung cancer A549 cells. In contrast, another anthracycline, doxorubicin (DOX), only slightly sensitized Jurkat cells and A549 cells to TRAIL‐induced apoptosis, with weaker enhancement of death receptor 5 (DR5) expression than ACR. The RNase protection assay, real time RT‐PCR and western blot demonstrated that ACR upregulated the expression of a TRAIL receptor, DR5. Caspase inhibitors and dominant negative DR5 efficiently reduced the apoptotic response to the treatment with ACR and TRAIL, indicating that the combined effect depends on caspase activities and the interaction... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5504270 Sat, 12 Nov 2011 05:00:00 +0100 5504270 http://www.medworm.com/index.php?rid=5400016&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02150.x We examined the effect of aclarubicin (ACR), an anthracycline, in combination with TRAIL. The combination of TRAIL and ACR synergistically induced apoptosis in human acute lymphoblastic leukemia Jurkat cells and human lung cancer A549 cells. In contrast, another anthracycline, doxorubicin (DOX), only slightly sensitized Jurkat cells and A549 cells to TRAIL‐induced apoptosis with weaker enhancement of DR5 expression than ACR. The RNase protection assay, real time RT‐PCR and western blot demonstrated that ACR up‐regulated the expression of a TRAIL receptor, death receptor 5 (DR5). Caspase inhibitors and dominant negative DR5 efficiently reduced the apoptotic response to the treatment with ACR and TRAIL, indicating that the combined effect depends on caspase activities and the interacti... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5400016 Sat, 12 Nov 2011 05:00:00 +0100 5400016 http://www.medworm.com/index.php?rid=5400017&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02149.x SummaryCarcinogenetic roles of human papillomavirus (HPV) in mobile tongue cancer are unclear because currently available results are widely dissimilar. This wide disparity is suggested to be dependent on employing diverse varieties of samples and methods. Furthermore, despite increasing tendency of mobile tongue cancer among young adults, there are only a few reports on young patients. We enrolled 32 patients, including 6 in twenties, to our study and genotyped the prevalence of HPV with a highly sensitive detection tool using fresh‐frozen materials of surgical specimens and a novel detection device with electrochemical DNA chip and loop‐mediated isothermal amplification method. Additionally, we confirmed the HPV prevalence by using in situ hybridization and immunohistochemistry for p... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5400017 Wed, 09 Nov 2011 05:00:00 +0100 5400017 http://www.medworm.com/index.php?rid=5504267&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02147.x Attenuated Salmonella typhimurium (S. typhimurium) strains can selectively grow and express exogenous genes in tumors for targeted therapy. We engineered S. typhimurium strain VNP20009 to secrete tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) under the control of a hypoxia‐induced nirB promoter and examined the efficacy of Salmonella‐mediated targeted expression of TRAIL in mice bearing melanoma tumor and in TRAIL‐resistant RM‐1 tumor. We found that VNP preferentially accumulated in tumor tissues and the nirB promoter effectively drove targeted expression of TRAIL. Compared with recombinant TRAIL protein and VNP20009 combination therapy, VNP20009 expressing TRAIL significantly suppressed melanoma growth but failed to suppress RM‐1 tumor growth. Furthermore,... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5504267 Sun, 06 Nov 2011 04:00:00 +0100 5504267 http://www.medworm.com/index.php?rid=5486310&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02148.x Several models for predicting the risk of non‐sentinel lymph node (NSLN) metastasis in breast cancer patients with positive sentinel lymph nodes (SLNs) have been developed. The purpose of this study was to validate and compare these models in Chinese patients. A total of 159 breast cancer patients with positive SLNs treated at our institution were included. Among them, 81 (50.9%) patients had at least one NSLN involvement. The Cambridge, Mou, Mayo, Tenon, MDA, Memorial Sloan‐Kettering Cancer Center (MSKCC), Ljubljana, SNUH, Turkish, Louisville, Stanford, and Saidi models were evaluated and compared using receiver operating characteristic (ROC) curves, calibration plots, and false negative (FN) rates. The Cambridge and Mou models outperformed the others, both with area under the ROC cur... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5486310 Sun, 06 Nov 2011 04:00:00 +0100 5486310 http://www.medworm.com/index.php?rid=5384366&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02147.x AbstractAttenuated Salmonella typhimurium (S. typhimurium) strains could selectively grow and express exogenous genes in tumors for targeted therapy. Here, we engineered S. typhimurium strain VNP20009 to secrete tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) under the control of a hypoxia‐induced nirB promoter and examined the efficacy of Salmonella‐mediated targeted expression of TRAIL in mice bearing melanoma tumor and in TRAIL‐resistant RM‐1 tumor. We found that VNP preferentially accumulated in tumor tissues and the nirB promoter effectively drove targeted expression of TRAIL. Compared with combinational therapy of recombinant TRAIL protein with VNP20009, VNP20009 expressing TRAIL significantly suppressed the melanoma growth but failed in suppressing ... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5384366 Sun, 06 Nov 2011 04:00:00 +0100 5384366 http://www.medworm.com/index.php?rid=5384365&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02148.x SummarySeveral models for predicting the risk of nonsentinel lymph node (NSLN) metastasis in breast cancer patients with positive sentinel lymph nodes (SLNs) have been developed. The purpose of this study was to validate and compare these models in Chinese patients. A total of 159 breast cancer patients with positive SLNs treated at our institution were included. Among them, 81 (50.9%) patients had at least one NSLN involvement.The Cambridge, Mou, Mayo, Tenon, MDA, MSKCC, Ljubljana, SNUH, Turkish, Louisville, Stanford and Saidi models were evaluated and compared using ROC curves, calibration plots and false negative (FN) rates. The Cambridge and Mou models outperformed the others, both with AUCs of 0.73. The other models performed as follows: the Mayo, Tenon, MDA, MSKCC, Turkish, Ljubljana... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5384365 Sun, 06 Nov 2011 04:00:00 +0100 5384365 http://www.medworm.com/index.php?rid=5504269&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02144.x Heat shock protein 90 (Hsp90), a molecular chaperone that plays a significant role in the stability and maturation of client proteins, including oncogenic targets for cell transformation, proliferation, and survival, is an attractive target for cancer therapy. We identified the novel Hsp90 inhibitor, CH5164840, and investigated its induction of oncogenic client protein degradation, antiproliferative activity, and apoptosis against an NCI‐N87 gastric cancer cell line and a BT‐474 breast cancer cell line. Interestingly, CH5164840 demonstrated tumor selectivity both in vitro and in vivo, binding to tumor Hsp90 (which forms active multiple chaperone complexes) in vitro, and being distributed effectively to tumors in a mouse model, which, taken together, supports the decreased levels of pho... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5504269 Thu, 03 Nov 2011 04:00:00 +0100 5504269 http://www.medworm.com/index.php?rid=5456892&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02143.x The steroid and xenobiotic receptor (SXR) regulates cytochrome P450 (CYP) enzymes, which are key inactivators of testosterone in the liver and prostate. In the present study, we investigated SXR expression in human prostate tissues. We determined SXR immunoreactivity using an anti‐SXR antibody in benign (n = 78) and cancerous (n = 106) tissues obtained by radical prostatectomy. Stained slides were evaluated for the proportion and staining intensity of immunoreactive cells. Total immunoreactivity (IR) scores (range: 0–8) were calculated as the sum of the proportion and intensity scores. Associations between the clinicopathological features of the patients, SXR status, and CYP3A4 immunoreactivity were analyzed. Western blot analyses validated the specificity of the anti‐SXR ant... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5456892 Thu, 03 Nov 2011 04:00:00 +0100 5456892 http://www.medworm.com/index.php?rid=5384369&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02142.x SummaryWe have recently demonstrated that overexpression of the nucleolar GTP‐binding protein nucleostemin drives the fraction of genetically defined tumor cells that exhibit markers and tumorigenic properties of tumor initiating cells. More specifically, cells that constitutively express elevated levels of nucleostemin exhibit increased TWIST expression, expression of genes that induce pluripotent stem cells (iPS), enhanced radioresistance, form tumors even when small numbers of cells are implanted, and exhibit an increased propensity to metastasize. Immunohistochemical analysis of cancer stem cell markers, such as nucleostemin and TWIST has not been evaluated in surgically resected esophageal squamous cell carcinoma after neoadjuvant chemotherapy. Here we examined the expression of CD1... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5384369 Thu, 03 Nov 2011 04:00:00 +0100 5384369 http://www.medworm.com/index.php?rid=5384368&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02143.x AbstractThe steroid and xenobiotic receptor (SXR) regulates cytochrome P450 (CYP) enzymes, which are key inactivators of testosterone in the liver and prostate. In the present study, we investigated SXR expression in human prostate tissues.We determined SXR immunoreactivity using an anti‐SXR antibody in benign (n = 78) and cancerous (n = 106) tissues obtained by radical prostatectomy. Stained slides were evaluated for the proportion and staining intensity of immunoreactive cells. Total immunoreactivity scores (IR scores; range, 0–8) were calculated as the sum of the proportion and intensity scores. Associations between the clinicopathological features of the patients, SXR status, and CYP3A4 immunoreactivity were analyzed.Western blot analyses validated the specificity of anti‐SXR ant... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5384368 Thu, 03 Nov 2011 04:00:00 +0100 5384368 http://www.medworm.com/index.php?rid=5384367&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02144.x SummaryHeat shock protein 90 (Hsp90), a molecular chaperone that plays a significant role in the stability and maturation of client proteins, including oncogenic targets for cell transformation, proliferation, and survival, is an attractive target for cancer therapy. We identified the novel Hsp90 inhibitor, CH5164840, and investigated its induction of oncogenic client protein degradation, antiproliferative activity, and apoptosis against an NCI‐N87 gastric cancer cell line and a BT‐474 breast cancer cell line. Interestingly, CH5164840 demonstrated tumor selectivity both in vitro and in vivo, binding to tumor Hsp90 (which forms active multi‐chaperone complexes) in vitro, and being distributed effectively to tumor in a mouse model, which taken together support the decreased levels of p... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5384367 Thu, 03 Nov 2011 04:00:00 +0100 5384367 http://www.medworm.com/index.php?rid=5504271&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02138.x Insulin‐like growth factor (IGF)‐I receptor (IGF‐IR) signaling is required for carcinogenicity and progression of several cancers but the function of this pathway and its utility as a therapeutic target have not been studied comprehensively in biliary tract carcinomas (BTC). We investigated the immunohistochemical expression of elements of the IGF axis, matrilysin, overexpression of p53 and the methylation status of the IGFBP‐3 promoter in 80 surgically resected BTC. We also assessed the effect of IGF‐IR blockade on signal transduction, proliferation and survival in three BTC cell lines using a new tyrosine kinase inhibitor, BMS‐536924, and dominant negative IGF‐IR (IGF‐IR/dn). The effects of IGF‐IR blockade was also studied in nude mouse xenograft models. IGF‐I was exp... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5504271 Wed, 02 Nov 2011 04:00:00 +0100 5504271 http://www.medworm.com/index.php?rid=5476106&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02141.x FMS‐related tyrosine kinase 3 (FLT3) is a class III receptor tyrosine kinase that plays important roles in hematopoiesis, including early progenitors and dendritic cell development. FLT3 is expressed at high levels in 70–100% of cases of AML and in virtually all cases of B‐lineage acute lymphoblastic leukemia. FLT3 is regarded as a molecular target in the development of novel therapies for acute leukemia patients. Currently, many small‐molecule FLT3 inhibitors have been developed, but clinical trials have resulted in limited antileukemia effects because of off‐target toxicities and drug resistance. The development of anti‐FLT3 Abs might overcome these difficulties and enhance the antileukemia efficacy of FLT3 inhibitors. In the present study, we demonstrate the isolation of nov... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5476106 Wed, 02 Nov 2011 04:00:00 +0100 5476106 http://www.medworm.com/index.php?rid=5384373&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02138.x SummaryInsulin‐like growth factor (IGF)‐I receptor (IGF‐IR) signaling is required for carcinogenicity and progression of several cancers but the function of this pathway and its utility as a therapeutic target has not been well studied in biliary tract carcinomas. We investigated the immunohistochemical expression of elements of the IGF axis, matrilysin, overexpression of p53, and the methylation status of the IGFBP‐3 promoter in 80 surgically resected biliary tract carcinomas. We also assessed the effect of IGF‐IR blockade on signal transduction, proliferation, and survival in 3 biliary tract cancer cell lines using a new tyrosine kinase inhibitor, BMS‐536924, and dominant negative IGF‐IR (IGF‐IR/dn). The effects of IGF‐IR blockade was also studied in nude mouse xenograf... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5384373 Wed, 02 Nov 2011 04:00:00 +0100 5384373 http://www.medworm.com/index.php?rid=5384372&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02139.x This study aimed to evaluate the risk of CNS event in patients with diffuse large B‐cell lymphoma (DLBCL) in the rituximab era. We performed a retrospective survey of Japanese patients diagnosed with DLBCL who underwent primary therapy with R‐CHOP chemoimmunotherapy between September 2003 and December 2006. Patients who received any prophylactic CNS treatment were excluded. Clinical data from 1,221 patients were collected from 47 institutions. The median age was 64 years (range, 15‐91 years). We noted 82 CNS events (6.7%) and the cumulative 5‐year probability of CNS event was 8.4%. Patients with a CNS event demonstrated significantly worse overall survival (OS) (P < 0.001). The 2‐year OS rate after a CNS event was 27.1%. In multivariate analysis, involvement of breast (relativ... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5384372 Wed, 02 Nov 2011 04:00:00 +0100 5384372 http://www.medworm.com/index.php?rid=5384371&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02140.x SummaryPancreatic cancer is characterized by oncogenic activation of K‐Ras and inactivation of the cell cycle inhibitor p16INK4a. We previously demonstrated that reintroduction of p16INK4a reversed anoikis resistance and clonogenicity of human pancreatic cancer cells, properties commonly attributed to the transforming potential of oncogenic K‐Ras. We therefore aimed to determine the role of Ras after p16INK4a reexpression. Here, we show that restitution of p16INK4a in pancreatic cancer cell lines elicits a profound suppression of K‐Ras activity. A more detailed analysis in p16INK4a reconstituted Capan‐1 cells indicated a selective reduction of both K‐Ras activity and protein stability. Reexpression of K‐Ras in p16INK4a restituted Capan‐1 cells reversed the anoikis‐sensitive... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5384371 Wed, 02 Nov 2011 04:00:00 +0100 5384371 http://www.medworm.com/index.php?rid=5384370&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02141.x SummaryFLT3 is a class III receptor tyrosine kinase that plays important roles in hematopoiesis including early progenitors and dendritic cell development. FLT3 is expressed at high levels in 70‐100% of cases of acute myelogenous leukemia (AML) and in virtually all cases of B‐lineage acute lymphoblastic leukemia. FLT3 is regarded as a molecular target in the development of novel therapies for acute leukemia patients. Currently, many small molecule FLT3 inhibitors have been developed, but clinical trials have resulted in limited anti‐leukemia effects because of off‐target toxicities and drug resistance. The development of anti‐FLT3 antibodies may overcome these difficulties and enhance the anti‐leukemia efficacy of FLT3 inhibitors. Here, we demonstrate the isolation of novel hum... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5384370 Wed, 02 Nov 2011 04:00:00 +0100 5384370 http://www.medworm.com/index.php?rid=5421497&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02154.x SummaryThe Notch signaling pathway has been implicated in both developmental processes and tumorigenesis. Aberrant Notch signaling has been repeatedly demonstrated to facilitate the proliferation and survival of glioma cells by regulating downstream effectors or other signaling pathways. In glioblastoma multiforme specimens from 59 patients, Notch1 was highly expressed in the tumor tissues compared to the normal brain tissues, and this expression was correlated with elevated AKT phosphorylation and Snail expression. Increased nuclear localization of β‐catenin and p50 as well as enhanced IKKα/AKT interaction were also observed in glioma tissues. In U87MG cells, the activation of Notch1 by DLL4 stimulation or by the over‐expression of NICD resulted in AKT activation and thereby promote... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5421497 Tue, 01 Nov 2011 04:00:00 +0100 5421497 http://www.medworm.com/index.php?rid=5407022&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02152.x SummaryCentrosome amplification (also known as centrosome overduplication) is common in cancer cells and can be induced by DNA damaging agents. However the mechanism and significance of centrosome amplification during carcinogenesis or after DNA damage are not clear. Previously, we showed that centrosome amplification could be induced by 3‐aminobenzamide (3‐AB), an inhibitor of poly(ADP‐ribose) polymerases (PARPs) in mouse embryonic fibroblasts. In this paper, we determined if the effect of 3‐AB on centrosome amplification was dependent on DNA damage in CHO‐K1 cells. We used the well‐known mutagen/carcinogen N‐methyl‐N’‐ nitro‐N‐nitrosoguanidine (MNNG). Ten μM MNNG and 10 mM 3‐AB induced significant centrosome amplification in 18.1±1.1% and 19.4±1.8% of CHO‐K... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5407022 Tue, 01 Nov 2011 04:00:00 +0100 5407022 http://www.medworm.com/index.php?rid=5400015&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02151.x SummaryTriple negative breast cancer (TNBC) is a heterogeneous, aggressive cancer for which there is no effective chemotherapy or targeted therapy. We aimed to evaluate L‐type amino acid transporter (LAT) 1 and CD98 expression immunohistochemically in patients with breast cancer, especially TNBC. Out of 129 patients, LAT1 was positive in 56 patients (43.4%), and CD98 was positive in 41 patients (31.8%). The positive ratio of LAT1 expression in luminal A cases was 7.9%, 30.0% in luminal B cases, 71.4% in HER2 cases, and 64.0% in TN cases. HER2 and TN subtypes expressed LAT1 and CD98 at higher levels than luminal A and B subtypes (both P<0.001). LAT1 and CD98 expression correlated with tumor size (LAT1, P=0.010; CD98, P=0.007), nuclear grade (LAT1, P<0.001; CD98, P<0.001) and Ki67... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5400015 Tue, 01 Nov 2011 04:00:00 +0100 5400015 http://www.medworm.com/index.php?rid=5384364&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02145.x SummaryAs of 2011, population‐based cancer registries are operated by over 80% of prefectures in Japan. However, only a limited proportion of the registries can provide long‐term incidence data. Here, we aimed to establish a method for monitoring cancer incidence trends in Japan using data from selected prefectures. Based on the availability of long‐term (≥20 years) high‐quality data, we collected incidence data from five prefectures (Miyagi, Yamagata, Fukui, Osaka, and Nagasaki), which included annual average of 54 539 primary cancer cases diagnosed between 1985‐2004. Cancer mortality data in 1995‐2004 were obtained from the vital statistics. Representativeness and homogeneity of the trends were examined by funnel plot analysis of log‐linear regression coefficients calcula... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5384364 Tue, 01 Nov 2011 04:00:00 +0100 5384364 http://www.medworm.com/index.php?rid=5384374&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02137.x This study demonstrates that drug‐resistance is caused by a combination of mechanisms. (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5384374 Mon, 31 Oct 2011 04:00:00 +0100 5384374 http://www.medworm.com/index.php?rid=5359817&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02135.x SummaryWeekly PCb (Paclitaxel + Carboplatin) in neoadjuvant chemotherapy (NCT) for breast cancer has a high pCR (pathological complete remission) rate. The present study was to identify pCR predictive biomarkers and to test whether integrating candidate molecular biomarkers can improve the pCR predictive accuracy. 91 breast cancer patients treated with weekly PCb NCT were retrospectively analyzed. 11 candidate molecular biomarkers including Tau, β‐Tubulin III, PTEN, MAP4, Thioredoxin, multidrug resistance‐1, Ki67, p53, Bcl‐2, BAX and ERCC1 were detected by immunohistochemistry in pre‐NCT core needle biopsy specimens and analyzed the relationship between these biomarkers and pCR. Univariate analysis showed that estrogen receptor (ER), progesterone receptor (PR), molecular class... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5359817 Sun, 30 Oct 2011 23:47:55 +0100 5359817 http://www.medworm.com/index.php?rid=5456889&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02133.x Transforming growth factor‐β (TGF‐β) is involved in the regulation of cell proliferation, differentiation, and apoptosis and is associated with epithelial–mesenchymal transition (EMT). Inhibition of the TGF‐β pathway is an attractive strategy for the treatment of cancer. We recently screened for novel TGF‐β inhibitors among commercially available drugs and identified protein‐bound polysaccharide (PSK) as a strong inhibitor of the TGF‐β‐induced reporter activity of 3TP‐lux, a TGF‐β1‐responsive luciferase reporter. Protein‐bound polysaccharide is used as a non‐specific immunostimulant for the treatment of gastric and colorectal cancers in Japan. The anticancer activity of this agent may involve direct regulation of growth factor production and enzyme activity ... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5456889 Sat, 29 Oct 2011 04:00:00 +0100 5456889 http://www.medworm.com/index.php?rid=5456888&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02135.x Weekly PCb (paclitaxel + carboplatin) in neoadjuvant chemotherapy (NCT) for breast cancer has a high pathological complete remission (pCR) rate. The present study was to identify pCR predictive biomarkers and to test whether integrating candidate molecular biomarkers can improve the pCR predictive accuracy. Ninety‐one breast cancer patients treated with weekly PCb NCT were retrospectively analyzed. Eleven candidate molecular biomarkers (Tau, β‐tubulin III, PTEN, MAP4, thioredoxin, multidrug resistance‐1, Ki67, p53, Bcl‐2, BAX, and ERCC1) were detected by immunohistochemistry in pre‐NCT core needle biopsy specimens. We analyzed the relationship between these biomarkers and pCR. Univariate analysis showed that estrogen receptor, progesterone receptor, molecular classificat... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5456888 Sat, 29 Oct 2011 04:00:00 +0100 5456888 http://www.medworm.com/index.php?rid=5359819&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02133.x AbstractTransforming growth factor‐β (TGF‐ß) is involved in the regulation of cell proliferation, differentiation, and apoptosis and is associated with the epithelial–mesenchymal transition (EMT). Inhibition of the TGF‐ß pathway is an attractive strategy for the treatment of cancer. We recently screened for novel TGF‐ß inhibitors among commercially available drugs and identified protein‐bound polysaccharide (PSK) as a strong inhibitor of the TGF‐β‐induced reporter activity of 3TP‐lux, a TGF‐ß1‐responsive luciferase reporter. PSK is used as a nonspecific immunostimulant for the treatment of gastric and colorectal cancers in Japan. The anti‐cancer activity of this agent may involve direct regulation of growth factor production and enzyme activity in tumors in ad... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5359819 Sat, 29 Oct 2011 04:00:00 +0100 5359819 http://www.medworm.com/index.php?rid=5359818&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02134.x This study aimed to investigate their impact on temozolomide chemosensitivity and relationship with MGMT promoter methylation in secondary glioblastoma. Search for IDH1 and IDH2 mutations, 1p19q codeletion, O(6)‐methylguanine DNA methyltransferase (MGMT) promoter methylation, and p53 expression was performed in a series of 86 secondary glioblastomas and correlated with progression‐free survival and overall survival. Response to temozolomide was evaluated by progression‐free survival, as well as by tumor size on successive MRI scans, and then correlated with molecular alterations. IDH (IDH1 or IDH2) mutations were found in 58/79 patients (73.4%). IDH mutation, MGMT promoter methylation, and 1p19q codeletion were associated with prolonged progression‐free survival in univariate (P &l... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5359818 Sat, 29 Oct 2011 04:00:00 +0100 5359818 http://www.medworm.com/index.php?rid=5359820&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02132.x In conclusion, we identified several abnormal transcripts and genomic alterations in gastric and colorectal cancer cells using an integrated analysis. Our approach may enable genetic changes to be identified more efficiently, and the present results warrant further investigation using clinical samples and integrated analyses. (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5359820 Fri, 28 Oct 2011 04:00:00 +0100 5359820 http://www.medworm.com/index.php?rid=5346818&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02084.x (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5346818 Wed, 26 Oct 2011 03:07:16 +0100 5346818 http://www.medworm.com/index.php?rid=5346814&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02131.x AbstractAim of the study is to understand the importance of Wnt/β‐catenin pathway in the development of breast carcinoma (BC) and its association with different clinicopathological parameters. Alterations (deletion/methylation/expression) of some Wnt/β‐catenin pathway antagonists like APC, SFRP1/2, CDH1 and activator β‐catenin were analyzed in primary BC of Indian patients. High frequencies (65‐70%) of overall alterations (deletion/methylation) of the antagonists were seen in the BC samples. Also 99% (156/158) of the samples showed alterations in any one of the genes indicating importance of this pathway in development of this tumor. Co‐alterations of these genes were observed in 30% of the samples with significantly high alterations in late‐onset (37%) and ER‐/PR‐ (37%)... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5346814 Wed, 26 Oct 2011 03:02:06 +0100 5346814 http://www.medworm.com/index.php?rid=5486311&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02131.x The aim of the study is to understand the importance of the Wnt/β‐catenin pathway in the development of breast cancer (BC) and its association with different clinicopathological parameters. Alterations (deletion/methylation/expression) of some Wnt/β‐catenin pathway antagonists like APC, SFRP1/2, CDH1 and activator β‐catenin (CTNNB1) were analyzed in primary BC in Indian patients. High frequencies (65–70%) of overall alterations (deletion/methylation) of the antagonists were seen in the BC samples. Also, 99% (156/158) of the samples showed alterations in any one of the genes, indicating the importance of this pathway in the development of this tumor. Co‐alterations of these genes were observed in 30% of samples, with significantly high alterations in late‐onset (37%) and estr... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5486311 Tue, 25 Oct 2011 04:00:00 +0100 5486311 http://www.medworm.com/index.php?rid=5346816&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02128.x In this study, we evaluated octreotide‐PEG liposomes loaded with irinotecan in terms of the biodistribution of irinotecan and active metabolite of it, and the therapeutic efficacy, compared with PEGylated liposomes. Furthermore, to elucidate the effect of octreotide ligand after cellular association, we assessed the cytotoxicity in the tumor cells and the inhibition of protein phosphorylation in the tumor cells and xenografts using empty octreotide‐PEG liposomes, which were loaded with no drug. In a therapeutic study, octreotide‐PEG liposomes loaded with irinotecan significantly improved median survival compared with PEGylated liposomes. In tumor tissue at 6 h after injection, octreotide‐PEG liposomes‐treated mice showed significantly higher concentrations of irinotecan and 7‐e... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5346816 Mon, 24 Oct 2011 04:00:00 +0100 5346816 http://www.medworm.com/index.php?rid=5346815&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02129.x SummarySeveral studies have found that promoter CpG island is frequently methylated in gastric cancer. CpG island methylator phenotype (CIMP) defines concordant methylation of multiple promoter CpG island loci in a subset of gastric cancer. However, it is unknown regarding the relationship between CIMP and lymph node metastasis of gastric cancer. Our study aimed to characterize role of CIMP in lymph node metastasis. The clinical specimens from 120 patients were analyzed. The MethyLight PCR was used to detect the methylation status of five genes (ALX4, TMEFF2, CHCHD10, IGFBP3, and NPR1). We measured the level of mRNAs for five genes by real‐time RT‐PCR. Microsatellite instability and Helicobacter pylori infection status were assayed by capillary electrophoresis and real‐time PCR, resp... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5346815 Mon, 24 Oct 2011 04:00:00 +0100 5346815 http://www.medworm.com/index.php?rid=5440269&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02127.x Epstein–Barr virus (EBV), which infects B cells, T cells, and natural killer (NK) cells, is associated with multiple lymphoid malignancies. Recently, histone deacetylase (HDAC) inhibitors have been reported to have anticancer effects against various tumor cells. In the present study, we evaluated the killing effect of valproic acid (VPA), which acts as an HDAC inhibitor, on EBV‐positive and ‐negative T and NK lymphoma cells. Treatment of multiple T and NK cell lines (SNT13, SNT16, Jurkat, SNK6, KAI3 and KHYG1) with 0.1‐5 mM of VPA inhibited HDAC, increased acetylated histone levels and reduced cell viability. No significant differences were seen between EBV‐positive and ‐negative cell lines. Although VPA induced apoptosis in some T and NK cell lines (SNT16, Jurkat and KHYG1) an... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5440269 Fri, 21 Oct 2011 04:00:00 +0100 5440269 http://www.medworm.com/index.php?rid=5335017&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02126.x In conclusion, the combination of ZDHHC8 siRNA and X‐irradiation has the potential to improve the therapeutic efficacy of radiation therapy for malignant mesothelioma. (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5335017 Fri, 21 Oct 2011 04:00:00 +0100 5335017 http://www.medworm.com/index.php?rid=5456890&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02125.x In experimental models, mucin‐depleted foci (MDF), formed by dysplastic crypts devoid of mucin production have been recognized to be correlated with colorectal carcinogenesis and to serve as preneoplastic lesions of colorectal cancer (CRC). In humans, there is only one report of identification of MDF in patients with familial adenomatous polyposis and CRC; however, the histological characteristics of human MDF are not discussed extensively in the report. In the present study, colonic samples from 53 patients with sporadic CRC were stained with Alcian blue and examined for the presence of MDF. Subsequently, the samples were examined for the presence of aberrant crypt foci (ACF) by methylene blue staining. We classified MDF into two categories: flat‐MDF and protruded‐MDF (having the ch... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5456890 Thu, 20 Oct 2011 04:00:00 +0100 5456890 http://www.medworm.com/index.php?rid=5335019&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02124.x SummaryFas ligand (CD95L/APO‐1) is considered as a potent anti‐tumor agent due to its mediated cell death properties. We have designed a polymeric microencapsulation system, which encapsulates soluble FasL secreting cells. The encapsulated cells continuously release soluble FasL (sFasL) at the tumor site, while the device protects the encapsulated cells from the host immune system. The potential and efficacy of this system are demonstrated in‐vitro and in‐vivo for tumor inhibition. Polymeric microcapsules composed of Alginate Poly‐l‐lysine (PLL) were optimized to encapsulate L5 secreting sFasL cells. The expression and anti‐tumor activities of the sFasL were confirmed in‐vitro and tumor inhibition was studied in‐vivo in SCID mice bearing subcutaneous lymphoma tumors. In�... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5335019 Thu, 20 Oct 2011 04:00:00 +0100 5335019 http://www.medworm.com/index.php?rid=5335018&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02125.x In this study, colonic samples from 53 patients with sporadic CRC were stained with Alcian blue and examined for the presence of MDF. Subsequently, the samples were also examined for the presence of ACF by methylene blue staining. We classified MDF into two categories, namely, flat‐MDF and protruded‐MDF (having the characteristics of both ACF and MDF). We found a total of 354, 41 and 19 colonic mucosal lesions with a mean multiplicity of 44, 38.9 and 66.9 crypts (ACF, flat‐MDF and protruded‐MDF, respectively). The density of MDF was 0.0082 lesions/cm2. The ACF identified in sporadic CRC patients corresponded to hyperplastic or non‐dysplasic lesions. On the other hand, MDF identified in these patients corresponded to low‐grade dysplasia. In addition, we found that Paneth cell me... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5335018 Thu, 20 Oct 2011 04:00:00 +0100 5335018 http://www.medworm.com/index.php?rid=5456891&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02123.x Human T‐cell leukemia virus type 1 (HTLV‐1) is a causative agent of adult T‐cell leukemia, and it immortalizes and transforms human T cells in both an interleukin (IL)‐2‐dependent and ‐independent manner. HTLV‐1 encodes Tax, which plays crucial roles in HTLV‐1‐mediated immortalization and transformation of human T cells. A previous study showed that Tax can transform a mouse T‐cell line, CTLL‐2, from having IL‐2‐dependent growth to IL‐2‐independent growth. Given that the Akt/mTOR pathway is essential for IL‐2‐induced cell growth in T cells, we examined whether the Akt/mTOR pathway is involved in Tax‐induced transformation to IL‐2‐independent growth. The stable and transient expression of Tax in CTLL‐2 induced the phosphorylation of p70S6 kinase and... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5456891 Wed, 19 Oct 2011 04:00:00 +0100 5456891 http://www.medworm.com/index.php?rid=5421500&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02122.x In this report, we provide evidence substantiating an important role of autocrine TNF‐α in potentiation of cisplatin‐induced apoptosis by recombinant soluble CD40 ligand (rsCD40L) in different human cancer cell lines. Activation of CD40 by rsCD40L induces two phases of autocrine TNF‐α: the rapid early phase involving p38 MAP kinase and the robust and persistent late phase through enhanced tnf‐α gene transcription. Blocking TNF‐α with either a specific TNFR1 siRNA or a neutralizing anti‐TNF‐α antibody dramatically attenuated the potentiation effect of rsCD40L on cisplatin‐induced cancer cell death. These results reveal an important role of TNF‐α induction in CD40’s chemosensitization activity and suggest that modulating TNF‐α autocrine from cancer cells is an ef... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5421500 Wed, 19 Oct 2011 04:00:00 +0100 5421500 http://www.medworm.com/index.php?rid=5335021&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02122.x In this report, we provide evidence substantiating an important role of autocrine TNF‐α in potentiation of cisplatin‐induced apoptosis by recombinant soluble CD40 ligand (rsCD40L) in different human cancer cell lines. Activation of CD40 by rsCD40L induces two phases of TNF‐α autocrine: the rapid early phase involving p38 MAP kinase and the robust and persistent late phase through enhanced tnf‐α gene transcription. Blocking TNF‐α with either a specific TNFR1 siRNA or a neutralizing anti‐TNF‐α antibody dramatically attenuated the potentiation effect of rsCD40L on cisplatin‐induced cancer cell death. These results reveal an important role of TNF‐α induction in CD40’s chemosentization activity and suggest that modulating TNF‐α autocrine from cancer cells is an effe... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5335021 Wed, 19 Oct 2011 04:00:00 +0100 5335021 http://www.medworm.com/index.php?rid=5335020&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02123.x SummaryHuman T‐cell leukemia virus type 1 (HTLV‐1) is a causative agent of adult T‐cell leukemia (ATL), and it immortalizes and transforms human T cells in both interleukin(IL)‐2‐dependent and independent manners, respectively. HTLV‐1 encodes Tax, which plays crucial roles in HTLV‐1‐mediated immortalization and transformation of human T cells. A previous study showed that Tax can transform a mouse T cell line, CTLL‐2, from having IL‐2‐dependent growth to IL‐2 independent growth. Given that the Akt/mTOR pathway is essential for IL‐2‐induced cell growth in T cells, we examined whether the Akt/mTOR pathway is involved in Tax‐induced transformation to IL‐2‐independent growth. The stable and transient expression of Tax in CTLL‐2 induced the phosphorylation of... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5335020 Wed, 19 Oct 2011 04:00:00 +0100 5335020 http://www.medworm.com/index.php?rid=5323603&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02115.x (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5323603 Mon, 17 Oct 2011 04:00:00 +0100 5323603 http://www.medworm.com/index.php?rid=5421498&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02119.x In this study, we identified nucleobindin 2 (NUCB2) as a gene associated with recurrence based on microarray data of estrogen receptor (ER)‐positive breast carcinoma cases (n = 10), and subsequent in vitro study showed that NUCB2 expression was upregulated by estradiol in ER‐positive MCF‐7 cells. However, NUCB2 has not yet been examined in breast carcinoma, and its significance remains unknown. Therefore, we further examined the biological functions of NUCB2 in breast carcinoma using immunohistochemistry and in vitro studies. NUCB2 immunoreactivity was detected in carcinoma cells in 77 of 161 (48%) breast cancer cases, and positively associated with lymph node metastasis and ER status of the patients. In addition, NUCB2 status was significantly associated with an increased risk o... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5421498 Tue, 11 Oct 2011 04:00:00 +0100 5421498 http://www.medworm.com/index.php?rid=5400018&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02120.x Our previous case–control study suggested that equol, a metabolite of isoflavone, has a preventive effect on prostate cancer. To examine the prostate cancer risk based on isoflavone intake and equol production, we carried out a phase II, randomized, double‐blind, placebo‐controlled trial of oral isoflavone (60 mg/day) for 12 months. The inclusion criteria were Japanese men between 50 and 75 years of age, a serum prostate‐specific antigen level of 2.5–10.0 ng/mL, and a single, negative prostate biopsy within 12 months prior to enrollment. The study included 158 men in eight Japanese centers. Their median age was 66.0 years, and the numbers of equol producers and non‐producers were 76 (48%) and 82 (52%), respectively. The majority of adverse events were mild or modera... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5400018 Tue, 11 Oct 2011 04:00:00 +0100 5400018 http://www.medworm.com/index.php?rid=5304020&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02119.x In this study, we identified nucleobindin 2 (NUCB2) as a gene associated with recurrence based on microarray data of estrogen receptor (ER)‐positive breast carcinoma cases (n = 10), and subsequent in vitro study demonstrated that NUCB2 expression was up‐regulated by estradiol in ER‐positive MCF‐7 cells. NUCB2, however, has not yet been examined in breast carcinoma, and its significance remains unknown. Therefore, we further attempted to examine biological functions of NUCB2 in the breast carcinoma using immunohistochemistry and in vitro studies. NUCB2 immunoreactivity was detected in carcinoma cells in 77 (48%) out of 161 breast cancer cases, and positively associated with lymph node metastasis and ER status of the patients. In addition, NUCB2 status was significantly associated wi... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5304020 Tue, 11 Oct 2011 04:00:00 +0100 5304020 http://www.medworm.com/index.php?rid=5384376&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02117.x Pim‐3, a proto‐oncogene with serine/threonine kinase activity, is aberrantly expressed in malignant lesions, but not in normal tissues, of endoderm‐derived organs, including the pancreas, liver, colon, and stomach. Furthermore, the development of hepatocellular carcinoma is accelerated in mice expressing Pim‐3 transgene selectively in the liver when these mice are treated with a hepatocarcinogen. These observations suggest that a chemical targeting Pim‐3 kinase may be a novel type of anticancer drug. In the present study, we screened low molecular weight chemicals and observed that the phenanthrene derivative T26 potently inhibited Pim‐3 and Pim‐1, but only weakly inhibited Pim‐2. Moreover, T26 markedly inhibited the in vitro growth of human pancreatic cancer cell lines by ... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5384376 Mon, 10 Oct 2011 04:00:00 +0100 5384376 http://www.medworm.com/index.php?rid=5304021&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02117.x AbstractPim‐3, a proto‐oncogene with serine/threonine kinase activity, was aberrantly expressed in malignant lesions but not normal tissues of endoderm‐derived organs, including the pancreas, liver, colon, and stomach. Concomitantly, hepatocellular carcinoma development was accelerated in mice expressing Pim‐3 transgene selectively in liver, when these mice were treated with a hepatocarcinogen. These observations suggest that a chemical targeting Pim‐3 kinase may be a novel type of anti‐cancer drug. Here, we conducted a screening of low‐molecular chemicals and observed that a phenanthrene derivative, T26, inhibited potently Pim‐3 and Pim‐1 but weakly Pim‐2. Moreover, T26 inhibited markedly in vitro growth of human pancreatic cancer cell lines by inducing apoptosis and G... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5304021 Mon, 10 Oct 2011 04:00:00 +0100 5304021 http://www.medworm.com/index.php?rid=5384377&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02116.x We examined the MDCT findings based on mass shape classified into well, moderate, poorly and scattered demarcated shapes, the enhancement pattern classified into homogenous, heterogeneous, rim and poor, and mass density classified into high, intermediate or low. We subsequently compared these radiological findings with the histological characteristics and clinical outcome. Poorly demarcated types were higher in ER+/HER2− (P = 0.008), while the well‐demarcated type was higher in ER−/HER2− and ER−/HER2+ (P < 0.001 and P = 0.010). Rim pattern was higher in ER−/HER2− (P < 0.001). Intermediate or low density was higher in ER−/HER2− (P < 0.001, respectively). Further analysis based on histological grade, mitotic counts and lymphovascular invasion d... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5384377 Sat, 08 Oct 2011 04:00:00 +0100 5384377 http://www.medworm.com/index.php?rid=5335016&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02127.x AbstractEpstein‐Barr virus (EBV), which infects not only B cells but also T cells and natural killer (NK) cells, is associated with multiple lymphoid malignancies. Recently, histone deacetylase (HDAC) inhibitors have been reported to have anticancer effects on various tumor cells. We evaluated the killing effect of valproic acid (VPA), which has been found to act as an HDAC inhibitor, on EBV‐positive and ‐negative T and NK lymphoma cells. First, we found that VPA inhibited HDAC and increased acetylated histone levels in T and NK cell lines. VPA treatment reduced the viability of multiple T and NK cell lines. No significant difference was observed between EBV‐positive and EBV‐negative cell lines. VPA induced apoptosis and cell cycle arrest in some T and NK cell lines, but did not ... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5335016 Sat, 01 Oct 2011 04:00:00 +0100 5335016 http://www.medworm.com/index.php?rid=5323602&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02121.x SummaryThe expression of BMI‐1 is well correlated with disease progression in cancer patients. We showed that ectopic expression of BMI‐1 in B‐cell lymphoma cell lines, HT and RL, conferred resistance to etoposide and oxaliplatin, known to enhance sensitivity by targeting the survivin gene, but not to irinotecan, which is not relevant to the downregulation of survivin expression. The expression of survivin was not only augmented in cells transduced with BMI‐1, but persisted in the presence of etoposide in cells overexpressing BMI‐1. By contrast, the mock‐transduced cells succumbed in the medium with anti‐cancer drugs with an accompanying decrease in BMI‐1 and survivin expression. BMI‐1 overexpression stabilized survivin post‐translationally without an accompanying rise ... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5323602 Sat, 01 Oct 2011 04:00:00 +0100 5323602 http://www.medworm.com/index.php?rid=5304019&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02120.x SummaryOur previous case‐control study suggested that equol, a metabolite of isoflavone, has a preventive effect on prostate cancer. To examine the prostate cancer risk based on isoflavone intake and equol production, we conducted a phase II, randomized, double‐blind, placebo‐controlled trial of oral isoflavone (60 mg/day) for 12 months. The inclusion criteria were Japanese men between 50 and 75 years of age, a serum PSA level of 2.5–10.0 ng/mL, and a single, negative prostate biopsy within 12 months prior to enrollment. The study included 158 men in 8 Japanese centers. Their median age was 66.0 years (range: 50‐75 years), and the numbers of equol producers and non‐producers were 76 (48%) and 82 (52%), respectively. The majority of adverse events were mild or moderate in severi... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5304019 Sat, 01 Oct 2011 04:00:00 +0100 5304019 http://www.medworm.com/index.php?rid=5296519&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02116.x We examined the MDCT findings based on mass shape classified into well, moderate, poorly and scattered demarcated shapes, enhancement pattern classified into homogenous, heterogeneous, rim and poor, and mass density classified into high, intermediate or low. We subsequently compared these radiological findings with the histological characteristics and clinical outcome. Poorly demarcated types were higher in ER+/HER2‐ (P=0.008), while well‐demarcated type was higher in ER‐/HER2‐ and ER‐/HER2+ (P<0.001 and P=0.010). Rim pattern was higher in ER‐/HER2‐ (P<0.001). Intermediate or low density was higher in ER‐/HER2‐ (P<0.001, respectively). Further analysis based on histological grade, mitotic counts and lymphovascular invasion demonstrated that well demarcated shape ... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5296519 Sat, 01 Oct 2011 04:00:00 +0100 5296519 http://www.medworm.com/index.php?rid=5273113&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02044.x (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5273113 Sat, 01 Oct 2011 04:00:00 +0100 5273113 http://www.medworm.com/index.php?rid=5273110&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02114.x Respiratory motion considerably influences dose distribution and thus clinical outcomes in radiotherapy for lung cancer. Breath‐holding, breath‐coaching, respiratory gating with external surrogates, and mathematical predicting models all have inevitable uncertainty due to the unpredictable variations of internal tumor motion. The amplitude of the same tumor can vary with standard deviations > 5mm occurring in 23% of T1‐2N0M0 non‐small cell lung cancers. Residual motion varied 1 to 6 mm (95th percentile) for the 40% duty cycle of respiratory gating with external surrogates. The four‐dimensional computed tomography are all vulnerable to problems relating to the external surrogates. Real‐time four‐dimensional radiotherapy (4DRT), where the temporal changes in anatomy during t... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5273110 Sat, 01 Oct 2011 04:00:00 +0100 5273110 http://www.medworm.com/index.php?rid=5407025&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02114.x Respiratory motion considerably influences dose distribution, and thus clinical outcomes in radiotherapy for lung cancer. Breath holding, breath coaching, respiratory gating with external surrogates, and mathematical predicting models all have inevitable uncertainty due to the unpredictable variations of internal tumor motion. The amplitude of the same tumor can vary with standard deviations >5 mm occurring in 23% of T1–2N0M0 non‐small cell lung cancers. Residual motion varied 1–6 mm (95th percentile) for the 40% duty cycle of respiratory gating with external surrogates. The 4‐D computed tomography is vulnerable to problems relating to the external surrogates. Real‐time 4‐D radiotherapy (4DRT), where the temporal changes in anatomy during the delivery of radiotherapy are... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5407025 Thu, 29 Sep 2011 04:00:00 +0100 5407025 http://www.medworm.com/index.php?rid=5407024&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02109.x We have previously shown that inhibition of intracellular signaling pathways by treatment with quercetin induced the expression of natural killer cell group 2D (NKG2D) ligands on cancer cells and made the cells sensitive to natural killer (NK)‐cell mediated cytotoxicity. In the present study, we investigated whether epidermal growth factor receptor (EGFR) inhibitors could induce the expression of NKG2D ligands in colon cancer cells. Treatment with EGFR inhibitors predominantly increased the levels of mRNA transcripts and surface protein of UL16‐binding protein‐1 (ULBP1) in various colon cancer cells, including KM12, Caco‐2, HCT‐15, and HT‐29, which express EGFR, and increased susceptibility of these colon cancer cells to NK‐92 cells. The expression of ULBP1 was not induced by... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5407024 Fri, 23 Sep 2011 04:00:00 +0100 5407024 http://www.medworm.com/index.php?rid=5400019&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02111.x Adoptive cell therapy with lymphocytes that have been genetically engineered to express tumor‐reactive T‐cell receptors (TCR) is a promising approach for cancer immunotherapy. We have been exploring the development of TCR gene therapy targeting cancer/testis antigens, including melanoma‐associated antigen (MAGE) family antigens, that are ideal targets for adoptive T‐cell therapy. The efficacy of TCR gene therapy targeting MAGE family antigens, however, has not yet been evaluated in vivo. Here, we demonstrate the in vivo antitumor activity in immunodeficient non‐obese diabetic/SCID/γcnull (NOG) mice of human lymphocytes genetically engineered to express TCR specific for the MAGE‐A4 antigen. Polyclonal T cells derived from human peripheral blood mononuclear cells were transduced... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5400019 Fri, 23 Sep 2011 04:00:00 +0100 5400019 http://www.medworm.com/index.php?rid=5346817&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02112.x Heat shock protein 90 (Hsp90), a conserved molecular chaperone for a specific set of proteins critical for signal transduction including several oncogenic proteins, has been recognized as a promising target for anticancer therapy. Hsp90 inhibition also sensitizes cancer cells to DNA damage. However, the underlying mechanisms are not fully understood. Here, we provide evidence that Hsp90 is a general regulator of phosphatidylinositol 3‐kinase‐related protein kinase (PIKK) family proteins, central regulators of stress responses including DNA damage. Inhibition of Hsp90 causes a reduction of all PIKK and suppresses PIKK‐mediated signaling. In addition, Hsp90 forms complexes with RUVBL1/2 complex and Tel2 complex, both of which have been shown to interact with all PIKK and control their ... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5346817 Fri, 23 Sep 2011 04:00:00 +0100 5346817 http://www.medworm.com/index.php?rid=5250185&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02109.x This study suggests that EGFR inhibitors can enhance the susceptibility to NK cell‐mediated lysis of colon cancer cells by induction of ULBP1 via inhibition of PKC pathway. (Source: Cancer Science) Cancer Science journals http://www.medworm.com/rss/comments.php?id=5250185 Fri, 23 Sep 2011 04:00:00 +0100 5250185 http://www.medworm.com/index.php?rid=5250184&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02110.x AbstractAdult T‐cell leukemia (ATL) is a fatal T‐cell malignancy associated with human T‐cell leukemia virus type I (HTLV‐I) infection. Aberrant expression of nuclear factor‐κB (NF‐κB) is considered to contribute to the malignant phenotype and chemo‐resistance of ATL cells. Because of the poor prognosis of ATL, development of new therapeutic strategies is direly needed. Here we show that an novel IκB kinase 2 (IKK2) inhibitor IMD‐0354 efficiently inhibited the survival of CD4+CD25+ primary ATL cells and prevented the growth of or induced apoptosis of patient‐derived ATL cell lines. Assays of transcription with integrated forms of reporter genes revealed that IMD‐0354 suppressed NF‐κB‐dependent transcriptional activity. Moreover, daily administration of IMD‐035... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5250184 Fri, 23 Sep 2011 04:00:00 +0100 5250184 http://www.medworm.com/index.php?rid=5250183&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02111.x SummaryAdoptive cell therapy with lymphocytes that have been genetically engineered to express tumor‐reactive T cell receptors (TCR) is a promising approach for cancer immunotherapy. We have been exploring the development of TCR gene therapy targeting cancer/testis antigens, including MAGE family antigens, that are ideal targets for adoptive T cell therapy. The efficacy of TCR gene therapy targeting MAGE family antigens, however, has not yet been evaluated in vivo. Here, we demonstrate the in vivo anti‐tumor activity in immunodeficient NOD/SCID/γcnull (NOG) mice of human lymphocytes genetically engineered to express TCR specific for MAGE‐A4 antigen. Polyclonal T cells derived from human peripheral blood mononuclear cells (PBMCs) were transduced with the αβ TCR genes specific for M... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5250183 Fri, 23 Sep 2011 04:00:00 +0100 5250183 http://www.medworm.com/index.php?rid=5384378&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02108.x Transforming growth factor‐β (TGF‐β)‐stimulated clone‐22 (TSC‐22), also called TSC22D1‐2, is a putative tumor suppressor. We previously identified TSC‐22 downstream of an active mutant of fms‐like tyrosine kinase‐3 (Flt3). Here, we show that TSC‐22 works as a tumor suppressor through inhibiting Ras/Raf signaling. Notably, TSC‐22 was upregulated by Ras/Raf activation, whereas its upregulation was inhibited by concurrent STAT5 activation. Although TSC‐22 was normally retained in the cytoplasm by its nuclear export signal (NES), Ras/Raf activation caused nuclear translocation of TSC‐22, but not TSC22D1‐1. Unlike glucocorticoid‐induced leucine zipper (GILZ/TSC22D3‐2) previously characterized as a negative regulator of Ras/Raf signaling, TSC‐22 failed to inte... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5384378 Thu, 22 Sep 2011 04:00:00 +0100 5384378 http://www.medworm.com/index.php?rid=5384375&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02107.x Alcoholic extract of Piperbetle (Piper betle L.) leaves was recently found to induce apoptosis of CML cells expressing wild type and mutated Bcr‐Abl with imatinib resistance phenotype. Hydroxychavicol (HCH), a constituent of the alcoholic extract of Piper betle leaves, was evaluated for anti‐CML activity. Here, we report that HCH and its analogues induce killing of primary cells in CML patients and leukemic cell lines expressing wild type and mutated Bcr‐Abl, including the T315I mutation, with minimal toxicity to normal human peripheral blood mononuclear cells. HCH causes early but transient increase of mitochondria‐derived reactive oxygen species. Reactive oxygen species‐dependent persistent activation of JNK leads to an increase in endothelial nitric oxide synthase‐mediated n... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5384375 Thu, 22 Sep 2011 04:00:00 +0100 5384375 http://www.medworm.com/index.php?rid=5250187&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02107.x AbstractAlcoholic extract of Piper betle leaves (PBL) was recently found to induce apoptosis of chronic myeloid leukemia (CML) cells expressing wild type and mutated Bcr‐Abl having imatinib resistance phenotype. Hydroxychavicol (HCH), a constituent of the alcoholic extract of PBL, was evaluated for anti‐CML activity. Here we report that HCH and its analogues induce killing of primary cells from CML patients and leukemic cell lines expressing wild type and mutated Bcr‐Abl including T315I mutation with minimal toxicity on normal human peripheral blood mononuclear cells. HCH causes early but transient increase of mitochondria‐derived reactive oxygen species (ROS). ROS dependent persistent activation of c‐Jun‐N‐terminal‐kinase (JNK) leads to increase in eNOS‐mediated nitric o... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5250187 Thu, 22 Sep 2011 04:00:00 +0100 5250187 http://www.medworm.com/index.php?rid=5250186&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02108.x SummaryTransforming growth factor‐β (TGF‐β)‐stimulated clone‐22 (TSC‐22), also called TSC22D1‐2, is a putative tumor suppressor. We previously identified TSC‐22 downstream of an active mutant of fms‐like tyrosine kinase‐3 (Flt3). Here, we show that TSC‐22 works as a tumor suppressor through inhibiting Ras/Raf signaling. Notably, TSC‐22 was up‐regulated by Ras/Raf activation, while its up‐regulation was inhibited by concurrent STAT5 activation. Although TSC‐22 was normally retained in the cytoplasm by its nuclear export signal (NES), Ras/Raf activation caused nuclear translocation of TSC‐22, but not TSC22D1‐1. Unlike glucocorticoid‐induced leucine zipper (GILZ/TSC22D3‐2) previously characterized as a negative‐regulator of Ras/Raf signaling, TSC‐22 f... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5250186 Thu, 22 Sep 2011 04:00:00 +0100 5250186 http://www.medworm.com/index.php?rid=5313814&cid=s_31105_6_f&fid=31105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1349-7006.2011.02105.x The recent advent of whole exon (exome)‐capture technology, coupled with second‐generation sequencers, has made it possible to readily detect genomic alterations that affect encoded proteins in cancer cells. Such target resequencing of the cancer genome, however, fails to detect most clinically‐relevant gene fusions, given that such oncogenic fusion genes are often generated through intron‐to‐intron ligation. To develop a resequencing platform that simultaneously captures point mutations, insertions–deletions (indels), and gene fusions in the cancer genome, we chose cDNA as the input for target capture and extensive resequencing, and we describe the versatility of such a cDNA‐capture system. As a test case, we constructed a custom target‐capture system for 913 cancer‐rela... Cancer Science journals http://www.medworm.com/rss/comments.php?id=5313814 Tue, 20 Sep 2011 04:00:00 +0100 5313814