MedWorm: Epithelial Cancer

Key signaling nodes in mammary gland development and cancer: Smad signal integration in epithelial cell plasticity

Breast Cancer Research — Wed, 08 Feb 2012 05:00:00 +0100

Smad proteins are the key intermediates of TGF-beta-signaling during development and in tissue homeostasis. Pertubations in TGF-beta/Smad signaling have been implicated in cancer, and other diseases. In the cell nucleus Smad complexes trigger cell type- and context-specific transcriptional programs, thereby transmitting and integrating signals from a variety of ligands of the TGF-beta-superfamily and other stimuli in the cell micro-environment. The actual transcriptional and biological outcome of Smad activation critically depends on the genomic integrity and the modification state of genome and chromatin of the cell. The cytoplasmic and nuclear Smads can also modulate the activity of other signal transducers and enzymes such as microRNA processing factors. In the case of breast cancer the...

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The role and function of cadherins in the mammary gland

Breast Cancer Research — Wed, 08 Feb 2012 05:00:00 +0100

Cadherins are transmembrane receptors that function through calcium-dependent homophilic and heterophilic interactions that provide cell-cell contact and communication in many different organ systems. In the mammary gland only a few of the cadherins that make up this large superfamily of proteins have been characterized. Frequently in metastatic breast cancer, the genes for cadherins are epigenetically silenced, mutated, or regulated differently. During epithelial mesenchymal transition, cadherins that are expressed normally in the epithelial cells are down regulated, while cadherins expressed in the mesenchyme are up regulated. This process is known as cadherin switching, and its regulation can sometime facilitates the increase motility, invasiveness and proliferation that occurs in meta...

Initiating breast cancer by PIK3CA mutation

Breast Cancer Research — Tue, 07 Feb 2012 05:00:00 +0100

PIK3CA mutations confer constitutive activation of PI3K, which initiates intracellular kinase signaling cascades that promote cell proliferation and survival. Recent studies by Meyer et al. and Liu et al. demonstrate that expression of the H1047R exon 20 mutant of PIK3CA in luminal mammary epithelial cells induces tumorigenesis, implying that PIK3CA mutations are an early event in breast cancer. PIK3CA-H1047R-initiated tumors exhibit variable dependence on the oncogene, and variable sensitivity to PI3K inhibition. Amplification of the oncogenes MYC and MET was observed in tumors which recurred following silencing of PIK3CA-H1047R, suggesting that these pathways represent mechanisms of escape from PI3K inhibition. (Source: Breast Cancer Research)

Effect of KRAS Oncogene Substitutions on Protein Behavior: Implications for Signaling and Clinical Outcome

JNCI — Tue, 07 Feb 2012 05:00:00 +0100

Conclusions Not all mutant KRas proteins affect patient survival or downstream signaling in a similar way. The heterogeneous behavior of mutant KRas proteins implies that therapeutic interventions may need to take into account the specific mutant KRas expressed by the tumor. (Source: JNCI)

Personalized therapy of lung cancer.

Onkologie — Mon, 06 Feb 2012 02:58:36 +0100

Authors: Thomas R, Wolf J Abstract The implementation of personalized approaches in the treatment of patients with non-small cell lung cancer (NSCLC) requires a precise understanding of tumor biology, a reorientation of clinical development with a strong focus on genetically stratified early phase 'proof of concept' trials, the availability of high-quality 'realtime' genetic diagnostics, and the establishment of networks for molecular screening of lung cancer patients. To achieve this goal, a close interaction between basic researchers, clinical scientists, molecular pathologists, and pharmaceutical companies is essential. We believe that this approach is worth the effort, since personalized therapy in lung cancer has the potential to substantially improve survival in an increasing...

Population‐based survival for childhood cancer patients diagnosed during 2002–2005 in Shanghai, China

Pediatric Blood and Cancer — Sun, 05 Feb 2012 12:57:12 +0100

ConclusionsThe survival rate for children aged 0–14 diagnosed with cancer in Shanghai during 2002–2005 was at the medium level. There was a substantial survival difference from childhood cancers between Shanghai and specific developed countries. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

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Protumor activity of interleukin‐22 in HPAFII human pancreatic cancer cells

Clinical and Experimental Immunology — Sun, 05 Feb 2012 11:17:35 +0100

In this report, we showed that IL‐22 stimulated production of vascular endothelial growth factor (VEGF) and the anti‐apoptotic factor Bcl‐XL in IL‐22R‐positive HPAFII human pancreatic cancer cells. Additionally, IL‐22 augmented HPAFII cell production of immunosuppressive cytokines. We further showed that IL‐22 activation of HPAFII cells diminished T cell production of IFN‐γ through the action of IL‐10. Strikingly, we showed for the first time that IL‐22 can fully protect cancer cells from NK cell‐mediated cytotoxicity by stimulating tumor production of IL‐10 and TGF‐β1. Our data supports the idea that IL‐22 may act to promote the pathogenesis of cancers rather than function in anti‐tumor immunity.© 2012 The Authors. Clinical and Experimental Immunology © 2...

Aberrant expression of nuclear vimentin and related epithelial‐mesenchymal transition markers in nasopharyngeal carcinoma

International Journal of Cancer — Sun, 05 Feb 2012 05:00:00 +0100

This study aimed to investigate the aberrant localization E‐cadherin, β‐catenin and vimentin, and their prognostic significance in 122 NPC patients by immunohistochemistry and immunofluorescence. Our results showed that both membranous and cytoplasmic localization of E‐cadherin staining were associated with lymph node metastasis (p = 0.000 and 0.005, respectively) and clinical stage (p = 0.000 and 0.007, respectively). High cytoplasmic β‐catenin correlated significantly with larger tumor size (p = 0.020), lymph node metastasis (p = 0.000) and advanced clinical stage (p = 0.036). However, no significant difference was observed between membranous β‐catenin and clinicopathologic features (p = 0.05). High nuclear vimentin expression correlated significantly with positive lymph nod...

Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors

Journal of Clinical Investigation — Fri, 03 Feb 2012 18:50:49 +0100

Appropriate localization and migration of T cells is a prerequisite for antitumor immune surveillance. Studies using fixed tumor samples from human patients have shown that T cells accumulate more efficiently in the stroma than in tumor islets, but the mechanisms by which this occurs are unknown. By combining immunostaining and real-time imaging in viable slices of human lung tumors, we revealed that the density and the orientation of the stromal extracellular matrix likely play key roles in controlling the migration of T cells. Active T cell motility, dependent on chemokines but not on β1 or β2 integrins, was observed in loose fibronectin and collagen regions, whereas T cells migrated poorly in dense matrix areas. Aligned fibers in perivascular regions and around tumor epi...

Aggressive Management of Peritoneal Carcinomatosis from Mucinous Appendiceal Neoplasms

Annals of Surgical Oncology — Fri, 03 Feb 2012 07:21:20 +0100

Conclusions Aggressive management of PC from mucinous appendiceal neoplasms, by experienced surgeons, to achieve complete cytoreduction provides long-term survival with low major morbidity. Content Type Journal ArticleCategory Regional Cancer TherapiesPages 1-8DOI 10.1245/s10434-012-2241-6Authors Frances Austin, Division of Surgical Oncology, University of Pittsburgh, Pittsburgh, PA, USAArun Mavanur, Division of Surgical Oncology, University of Pittsburgh, Pittsburgh, PA, USAMagesh Sathaiah, Division of Surgical Oncology, University of Pittsburgh, Pittsburgh, PA, USAJennifer Steel, Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USADiana Lenzner, Biostatistics Facility, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USALekshmi Ramali...

Cytoreductive Surgery with Selective Versus Complete Parietal Peritonectomy Followed by Hyperthermic Intraperitoneal Chemotherapy in Patients with Diffuse Malignant Peritoneal Mesothelioma: A Controlled Study

Annals of Surgical Oncology — Fri, 03 Feb 2012 07:21:17 +0100

Conclusions CPP improved survival in patients with DMPM undergoing combined treatment. This information may contribute to standardize surgical options for DMPM and other peritoneal malignancies. Content Type Journal ArticleCategory Regional Cancer TherapiesPages 1-9DOI 10.1245/s10434-012-2237-2Authors Dario Baratti, Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyShigeki Kusamura, Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyAntonello Domenico Cabras, Department of Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyMarcello Deraco, Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy Journal Annals of Surgical OncologyOnline ISSN 1534-4681Print ISSN 1068...

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The hexosamine biosynthetic pathway and O-GlcNAcylation drive the expression of {beta}-catenin and cell proliferation

AJP: Endocrinology and Metabolism — Fri, 03 Feb 2012 05:00:00 +0100

The short half-life protooncogene β-catenin acquires a remarkable stability in a large subset of cancers, mainly from mutations affecting its proteasomal degradation. In this sense, colorectal cancers (CRC) form a group of pathologies in which early steps of development are characterized by an aberrant expression of β-catenin and an uncontrolled proliferation of epithelial cells. Diet has long been described as an influence in the emergence of CRC, but the molecular events that link metabolic disorders and CRC remain elusive. Part of the explanation may reside in hexosamine biosynthetic pathway (HBP) flux. We found that fasted mice being force-fed with glucose or glucosamine leads to an increase of β-catenin and O-GlcNAcylation levels in the colon. MCF7 cells possessing inta...

A ZEB1-HDAC pathway enters the epithelial to mesenchymal transition world in pancreatic cancer

Gut — Fri, 03 Feb 2012 05:00:00 +0100

Epithelial to mesenchymal transition (EMT) correlates with high-grade malignancy including the competence to form metastases. In addition, EMT has recently been linked to cellular self-renewal programmes of cancer stem cells and apoptosis/anoikis resistance, which are all features of therapeutic resistance. The EMT programme is driven by several transcription factors (TFs), such as the transcriptional regulators SNAIL, SLUG, ZEB1 and ZEB2 and the basic helix–loop–helix factors E47 and TWIST. These proteins target and repress the CDH1 gene, which encodes for E-cadherin, an important caretaker of the epithelial state. Expression studies in human pancreatic cancer showed expression of SNAIL in 78% and of SLUG in 50% of cases.1 Although no or low levels of TWIST are expressed in pa...

Synergistic tumour suppressor activity of E-cadherin and p53 in a conditional mouse model for metastatic diffuse-type gastric cancer

Gut — Fri, 03 Feb 2012 05:00:00 +0100

Conclusion This mouse line is the first genetically engineered mouse model of DGC and is very useful for clarifying the mechanism underlying gastric carcinogenesis, and provides a new approach to the treatment and prevention of DGC. (Source: Gut)

Recruitment of histone deacetylases HDAC1 and HDAC2 by the transcriptional repressor ZEB1 downregulates E-cadherin expression in pancreatic cancer

Gut — Fri, 03 Feb 2012 05:00:00 +0100

Conclusions These findings imply an important role for histone deacetylation in the downregulation of E-cadherin in human pancreatic cancer. Recruitment of HDACs to the CDH1 promoter is regulated by the transcription factor ZEB1, and inhibition of HDACs may be a promising antitumour therapy for pancreatic cancer. (Source: Gut)

Hyperplastic polyposis syndrome and the risk of colorectal cancer

Gut — Fri, 03 Feb 2012 05:00:00 +0100

I read with great interest the two reports by Boparai and coworkers in Gut on the increased risk of colorectal carcinoma (CRC) in 77 hyperplastic/serrated polyposis syndrome (HPS) patients during follow-up1 and in 347 HPS first-degree relatives (FDRs).2 To date, follow-ups have been performed in only 43/308 (14.0%) HPS patients and HPS coexistence with CRC in FDRs has been analysed in only 29/308 (9.4%) HPS patients described up to the end of 2009 (table 1). Nevertheless, there are some points to be explained:The term ‘(sessile) serrated adenoma’ should be abbreviated as SSA, instead of SA (serrated adenoma). SSA, characterised by abnormal proliferation, is included in the non-dysplastic group contrary to SA, which belongs to the dysplastic serrated polyp category because of th...

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Cancer stem cells and EMT in carcinoma

Cancer and Metastasis Reviews — Thu, 02 Feb 2012 18:16:20 +0100

Abstract The majority of deaths from carcinoma are caused by secondary growths that result from tumour invasion and metastasis. The importance of epithelial-to-mesenchymal transition (EMT) as a driver of invasion and metastasis is increasingly recognised, and recent evidence has highlighted a link between EMT and the cancer stem cells that initiate and maintain tumours and have also been implicated in invasion and metastasis. Here, we review cancer stem cells and their link with EMT, and explore the importance of this link in metastasis and therapeutic resistance of tumours. We also discuss new evidence from our laboratory demonstrating that cancer stem cells display a remarkable phenotypic plasticity that enables them to switch between an epithelial phenotype that drives ...

Estrogen suppresses expression of the matrix metalloproteinase inhibitor reversion-inducing cysteine-rich protein with Kazal motifs (RECK) within the mouse uterus

Endocrine — Thu, 02 Feb 2012 18:15:13 +0100

Abstract RECK (reversion-inducing cysteine-rich protein with Kazal motifs) is a membrane-anchored glycoprotein which regulates MMP2 and MMP9 activity and has been proposed to play a role in embryo implantation while misexpression of RECK has been associated with a variety of carcinomas. Unfortunately, understanding on the steroidal regulation of uterine RECK is lacking. To address this gap in our knowledge, we examined steroidal regulation and cellular expression of Reck mRNA and protein within the mouse uterus in vivo. Uterine Reck mRNA and protein were decreased by estrogen, while progesterone alone had no effect. The estrogen-induced down regulation could be partially blocked by progesterone. RECK was localized primarily to luminal and glandular epithelial cells and the ...

Predicting platinum resistance in primary advanced ovarian cancer patients with an in vitro resistance index

Cancer Chemotherapy and Pharmacology — Thu, 02 Feb 2012 18:11:01 +0100

Conclusions This in vitro assay predicted primary platinum resistance, without misclassification of sensitive OC patients, and the results were significantly associated with PFS. We suggest that samples from primary tumor and metastatic samples have different responses to chemotherapy and that exposure to chemotherapy might induce in vitro platinum resistance. Content Type Journal ArticleCategory Original ArticlePages 1-8DOI 10.1007/s00280-012-1835-9Authors Thea Eline Hetland, Departement of Gynecologic Oncology, Norwegian Radium Hospital, Oslo University Hospital, 0424 Oslo, NorwayJanne Kærn, Departement of Gynecologic Oncology, Norwegian Radium Hospital, Oslo University Hospital, 0424 Oslo, NorwayMartina Skrede, Departement of Pathology, Norwegian Radium Hospital...

Long-term follow-up of invasive ocular surface squamous cell carcinoma treated with excision, cryotherapy, and topical mitomycin C

Graefe's Archive for Clinical and Experimental Ophthalmology — Thu, 02 Feb 2012 06:54:32 +0100

Conclusion The combination of surgical excision, cryotherapy, and post-operative topical mitomycin-C was effective treatment for ocular surface invasive SCC in long-term follow-up. Content Type Journal ArticleCategory OncologyPages 1-6DOI 10.1007/s00417-012-1931-xAuthors Mohsen Bahmani Kashkouli, Eye Research Center, Rassoul Akram Hospital, Tehran University of Medical Sciences, Sattarkhan-Niayesh Street, Tehran, 14455-364 IranAbtin Heirati, Eye Research Center, Rassoul Akram Hospital, Tehran University of Medical Sciences, Sattarkhan-Niayesh Street, Tehran, 14455-364 IranFarzad Pakdel, Eye Research Center, Rassoul Akram Hospital, Tehran University of Medical Sciences, Sattarkhan-Niayesh Street, Tehran, 14455-364 IranVictoria Kiavash, Eye Research Center, Rassoul Akr...

Ber‐EP4 is a useful marker for follicular germinative cell differentiation of cutaneous epithelial neoplasms

The Journal of Dermatology — Thu, 02 Feb 2012 05:00:00 +0100

In this study, we performed immunohistochemical staining of 31 cases of basal cell carcinoma (BCC); 20 cases of trichoblastoma (TB), including ten cases of nodular type, eight cases of cribriform type (trichoepithelioma) and two cases of columnar type (desmoplastic trichoepithelioma); 16 cases of actinic keratosis (AK); and 10 cases each of Bowen’s disease, poroma and seborrheic keratosis. Six cases of BCC and AK were co‐lesions of both neoplasms. In normal skin tissue, Ber‐EP4 reacted positively with the secretory portion of eccrine glands and follicular germinative cells at the lower end of catagen hairs. Neoplastic cells in 97% of cases with BCC reacted positively with Ber‐EP4 in at least 5% of neoplastic cells. Those in 90% with nodular type TB and 50% with trichoepithelioma al...

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Increased radioresistance via G12S K‐Ras by compensatory upregulation of MAPK and PI3K pathways in epithelial cancer

Head and Neck — Thu, 02 Feb 2012 05:00:00 +0100

ConclusionWith our data we confirmed our hypothesis of postradiogenic constitutive activation of the 2 pathways both required for Ras‐mediated radioresistance in epithelial cells. If this effect should prove itself as a general mechanism in Ras‐mutated tumors, application of specific inhibitors to block both cascades in parallel could contribute to enhance radiosensitivity in these types of cancer. © 2012 Wiley Periodicals, Inc. Head Neck, 2012 (Source: Head and Neck)

Differences in Gene Expression and Cytokine Production by Crystalline vs. Amorphous Silica in Human Lung Epithelial Cells

Particle and Fibre Toxicology — Thu, 02 Feb 2012 05:00:00 +0100

Background: Exposure to respirable crystalline silica particles, as opposed to amorphous silica, is associated with lung inflammation, pulmonary fibrosis (silicosis), and potentially with lung cancer. We used Affymetrix/GeneSifter microarray analysis to determine whether gene expression profiles differed in a human bronchial epithelial cell line (BEAS 2B) exposed to cristobalite vs. amorphous silica particles at non-toxic and equal surface areas (75 and 150x10^6um^2/cm^2). Bio-Plex analysis was also used to determine profiles of secreted cytokines and chemokines in response to both particles. Finally, primary human bronchial epithelial cells (NHBE) were used to comparatively assess silica particle-induced alterations in gene expression. Results: Microarray analysis at 24 hours in BEAS 2B ...

Gut bacteria in health and disease: a survey on the interface between intestinal microbiology and colorectal cancer.

Biological Reviews of the Cambridge Philosophical Society — Thu, 02 Feb 2012 05:00:00 +0100

Authors: Boleij A, Tjalsma H Abstract A healthy human body contains at least tenfold more bacterial cells than human cells and the most abundant and diverse microbial community resides in the intestinal tract. Intestinal health is not only maintained by the human intestine itself and by dietary factors, but is also largely supported by this resident microbial community. Conversely, however, a large body of evidence supports a relationship between bacteria, bacterial activities and human colorectal cancer. Symbiosis in this multifaceted organ is thus crucial to maintain a healthy balance within the host-diet-microbiota triangle and accordingly, changes in any of these three factors may drive a healthy situation into a state of disease. In this review, the factors that sustain health...

Tocotrienol as a potential anticancer agent

Carcinogenesis — Thu, 02 Feb 2012 05:00:00 +0100

Vitamin E is composed of two structurally similar compounds: tocopherols (TPs) and tocotrienols (T3). Despite being overshadowed by TP over the past few decades, T3 is now considered to be a promising anticancer agent due to its potent effects against a wide range of cancers. A growing body of evidence suggests that in addition to its antioxidative and pro-apoptotic functions, T3 possesses a number of anticancer properties that make it superior to TP. These include the inhibition of epithelial-to-mesenchymal transitions, the suppression of vascular endothelial growth factor tumor angiogenic pathway and the induction of antitumor immunity. More recently, T3, but not TP, has been shown to have chemosensitization and anti-cancer stem cell effects, further demonstrating the potential of T3 as ...

Decorin-mediated inhibition of colorectal cancer growth and migration is associated with E-cadherin in vitro and in mice

Carcinogenesis — Thu, 02 Feb 2012 05:00:00 +0100

Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27kip1 and E-cadherin and an upregulation of β-catenin signaling [Bi,X. et al. (2008) Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis, 29, 1435–1440]. However, the regulation of E-cadherin by decorin and its implication in cancer formation and metastasis is largely unknown. Using a decorin knockout mouse model (Dcn–/– mice) and manipulated expression of decorin in human colorectal cancer cells, we found that E-cadherin, a prote...

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Expression of putative stem marker nestin and CD133 in advanced serous ovarian cancer.

Neoplasma — Thu, 02 Feb 2012 05:00:00 +0100

The objective of the studies was to explore if the stem cell biomarkers could be used to predict the tumor chemotherapy-resistance in serous ovarian cancer patients. Expression of two putative stem cell markers CD133 and nestin, and vascular epithelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) were detected in 123 cases of advanced serous ovarian cancer specimens by immunohistochemistry. To estimate intra-tumoral microvessel density (MVD), CD34 immunostaining was also performed. CD133 and nestin were defined to be positive in 35.0% and 32.5% of the serous ovarian carcinoma tissues, respectively. It was observed that overexpression of nestin but not CD133 was associated with the cisplatin-based chemotherapy resistance and shorter overall survival of the patients, and ...

[Comment] A tale of two tumours and a plea for progress

The Lancet Oncology — Wed, 01 Feb 2012 05:00:00 +0100

Melanoma and acute myeloid leukaemia (AML) share important characteristics: both are non-epithelial malignancies and affect a substantial proportion of young people, with roughly a third of patients diagnosed younger than 60 years. Notably, the incidence of primary melanoma is rising faster than that of any other common cancer and has quadrupled since the 1970s. Although most people with primary melanoma are cured, the incidence of metastatic disease is roughly equal to that of acute myeloid leukaemia, with about 2000 new cases per year in the UK. (Source: The Lancet Oncology)

An analysis of five clear cell papillary cystadenomas of mesosalpinx and broad ligament: four associated with von Hippel‐Lindau disease and one aggressive sporadic type

Histopathology — Wed, 01 Feb 2012 05:00:00 +0100

Conclusion: The VHLD‐associated cases appeared to be benign, but the sporadic case exhibited a low malignant potential. CCPCs show histological and immunophenotypical similarities with the recently reported clear cell papillary RCC, although the previously unreported apical CD10 and nuclear PAX2 expression may be related to their mesonephric origin. CCPC has a distinctive sub‐epithelial vascular pattern that is consistent with its pathogenesis. (Source: Histopathology)

Gastrin-releasing peptide receptor expression in non-cancerous bronchial epithelia is associated with lung cancer: a case-control study

Respiratory Research — Wed, 01 Feb 2012 05:00:00 +0100

Conclusions: GRPR expression in non-cancerous bronchial epithelium was significantly associated with the presence of lung cancer in never and former smokers. The association in never and former smokers was found in males and females. Association with lung cancer did not differ by sex in any smoking group. (Source: Respiratory Research)

Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer [RESEARCH]

Genome Research — Wed, 01 Feb 2012 05:00:00 +0100

While genetic mutation is a hallmark of cancer, many cancers also acquire epigenetic alterations during tumorigenesis including aberrant DNA hypermethylation of tumor suppressors, as well as changes in chromatin modifications as caused by genetic mutations of the chromatin-modifying machinery. However, the extent of epigenetic alterations in cancer cells has not been fully characterized. Here, we describe complete methylome maps at single nucleotide resolution of a low-passage breast cancer cell line and primary human mammary epithelial cells. We find widespread DNA hypomethylation in the cancer cell, primarily at partially methylated domains (PMDs) in normal breast cells. Unexpectedly, genes within these regions are largely silenced in cancer cells. The loss of DNA methylation in these re...

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Gut bacteria in health and disease: a survey on the interface between intestinal microbiology and colorectal cancer

Biological Reviews — Wed, 01 Feb 2012 05:00:00 +0100

A healthy human body contains at least tenfold more bacterial cells than human cells and the most abundant and diverse microbial community resides in the intestinal tract. Intestinal health is not only maintained by the human intestine itself and by dietary factors, but is also largely supported by this resident microbial community. Conversely, however, a large body of evidence supports a relationship between bacteria, bacterial activities and human colorectal cancer. Symbiosis in this multifaceted organ is thus crucial to maintain a healthy balance within the host‐diet‐microbiota triangle and accordingly, changes in any of these three factors may drive a healthy situation into a state of disease. In this review, the factors that sustain health or drive this complex intestinal system i...

Sef Downregulation by Ras Causes MEK1/2 to Become Aberrantly Nuclear Localized Leading to Polyploidy and Neoplastic Transformation.

Cell Research — Wed, 01 Feb 2012 05:00:00 +0100

In this study, we show how Ras activation causes aberrant nuclear localization of phosphorylated mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK; MEK) MEK1/2 to drive neoplastic transformation. Phosphorylated MEK1/2 was aberrantly located within the nucleus of primary colorectal tumors and human colon cancer cells, and oncogenic activation of Ras was sufficient to induce nuclear accumulation of phosphorylated MEK1/2 and ERK1/2 in intestinal epithelial cells. Enforced nuclear localization of MEK1 in epithelial cells or fibroblasts was sufficient for hyperactivation of ERK1/2, thereby driving cell proliferation, chromosomal polyploidy, and tumorigenesis. Notably, Ras-induced nuclear accumulation of activated MEK1/2 was reliant on downregulation of the spatial regul...

The miRNA-200 family and miRNA-9 exhibit differential expression in primary versus corresponding metastatic tissue in breast cancer

Breast Cancer Research and Treatment — Tue, 31 Jan 2012 16:48:05 +0100

Abstract Metastases are the major cause of cancer-related deaths, but the mechanisms of the metastatic process remain poorly understood. In recent years, the involvement of microRNAs (miRNAs) in cancer has become apparent, and the objective of this study was to identify miRNAs associated with breast cancer progression. Global miRNA expression profiling was performed on 47 tumor samples from 14 patients with paired samples from primary breast tumors and corresponding lymph node and distant metastases using LNA-enhanced miRNA microarrays. The identified miRNA expression alterations were validated by real-time PCR, and tissue distribution of the miRNAs was visualized by in situ hybridization. The patients, in which the miRNA profile of the primary tumor and corresponding dist...

The adhering junctions of valvular interstitial cells: molecular composition in fetal and adult hearts and the comings and goings of plakophilin-2 in situ, in cell culture and upon re-association with scaffolds

Cell and Tissue Research — Tue, 31 Jan 2012 07:12:12 +0100

Abstract The interstitial cells of cardiac valves represent one of the most frequent cell types in the mammalian heart. In order to provide a cell and molecular biological basis for the growth of isolated valvular interstitial cells (VICs) in cell culture and for the use in re-implantation surgery we have examined VICs in situ and in culture, in fetal, postnatal and adult hearts, in re-associations with scaffolds of extracellular matrix (ECM) material and decellularized heart valves. In all four mammalian species examined (human, bovine, porcine and ovine), the typical mesenchymal-type cell-cell adherens junctions (AJs) connecting VICs appear as normal N-cadherin based puncta adhaerentia. Their molecular ensemble, however, changes under various growth conditions insofar as...

Down-Regulation of Claudin-3 Is Associated with Proliferative Potential in Early Gastric Cancers

Digestive Diseases and Sciences — Tue, 31 Jan 2012 07:08:55 +0100

Conclusions The down-regulation of claudin-3 was associated with the proliferative potential of GC cells, indicating that claudins may have a pivotal role in the progression of GC. Content Type Journal ArticleCategory Original ArticlePages 1-6DOI 10.1007/s10620-012-2043-5Authors Takuya Okugawa, Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, JapanTadayuki Oshima, Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, JapanXin Chen, Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, JapanKazutoshi ...

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Sef Downregulation by Ras Causes MEK1/2 to Become Aberrantly Nuclear Localized Leading to Polyploidy and Neoplastic Transformation

Cancer Research — Tue, 31 Jan 2012 05:00:00 +0100

Genetic Determinants for Promoter Hypermethylation in the Lungs of Smokers: A Candidate Gene-Based Study

Cancer Research — Tue, 31 Jan 2012 05:00:00 +0100

The detection of tumor suppressor gene promoter methylation in sputum-derived exfoliated cells predicts early lung cancer. Here, we identified genetic determinants for this epigenetic process and examined their biologic effects on gene regulation. A two-stage approach involving discovery and replication was used to assess the association between promoter hypermethylation of a 12-gene panel and common variation in 40 genes involved in carcinogen metabolism, regulation of methylation, and DNA damage response in members of the Lovelace Smokers Cohort (N = 1,434). Molecular validation of three identified variants was conducted using primary bronchial epithelial cells. Association of study-wide significance (P < 8.2 × 10−5) was identified for rs1641511, rs3730859, and rs1883264 in TP53, LIG1...

Differential regulation of the activity of deleted in liver cancer 1 (DLC1) by tensins controls cell migration and transformation [Biochemistry]

Proceedings of the National Academy of Sciences — Tue, 31 Jan 2012 05:00:00 +0100

The epithelial growth factor receptor plays an important role in cell migration and cancer metastasis, but the underlying molecular mechanism is not fully understood. We show here that differential regulation of the rhodopsin-GTPase-activating (Rho-GAP) activity of deleted in liver cancer 1 (DLC1) by tensin3 and COOH-terminal tensin-like protein (cten) controls EGF-driven cell migration and transformation. Tensin3 binds DLC1 through its actin-binding domain, a region that is missing in cten, and thereby releases an autoinhibitory interaction between the sterile alpha motif and Rho-GAP domains of DLC1. Consequently, tensin3, but not cten, promotes the activation of DLC1, which, in turn, leads to inactivation of RhoA and decreased cell migration. Depletion of endogenous tensin3, but not cten...

Brush border Myosin Ia has tumor suppressor activity in the intestine [Cell Biology]

Proceedings of the National Academy of Sciences — Tue, 31 Jan 2012 05:00:00 +0100

The loss of the epithelial architecture and cell polarity/differentiation is known to be important during the tumorigenic process. Here we demonstrate that the brush border protein Myosin Ia (MYO1A) is important for polarization and differentiation of colon cancer cells and is frequently inactivated in colorectal tumors by genetic and epigenetic mechanisms. MYO1A frame-shift mutations were observed in 32% (37 of 116) of the colorectal tumors with microsatellite instability analyzed, and evidence of promoter methylation was observed in a significant proportion of colon cancer cell lines and primary colorectal tumors. The loss of polarization/differentiation resulting from MYO1A inactivation is associated with higher tumor growth in soft agar and in a xenograft model. In addition, the progre...

Cross-talk between TGF{beta}1 and EGFR signaling pathways induces TM4SF5 expression and Epithelial-Mesenchymal Transition

BJ Gene — Tue, 31 Jan 2012 05:00:00 +0100

The epithelial-mesenchymal transition (EMT) is involved in fibrosis and cancer, and regulated by different signaling pathways mediated through soluble factors, actin reorganization, and transcription factor actions. Because tetraspan(in) transmembrane 4 L6 family member 5 (TM4SF5) is highly expressed in hepatocellular carcinoma and induces EMT, understanding how TM4SF5 expression in hepatocytes is regulated is important. We explored the mechanisms that induce TM4SF5 expression and whether impaired signaling pathways for TM4SF5 expression inhibit acquisition of mesenchymal cell features, using human and mouse normal hepatocytes. We found that transforming growth factor beta 1 (TGFβ1)-mediated Smad activation caused TM4SF5 expression and EMT, and activation of the epidermal growth fac...

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Identification of novel biomarkers for early detection of human lung squamous cell cancer by quantitative proteomics.

Molecular and Cellular Proteomics : MCP — Tue, 31 Jan 2012 05:00:00 +0100

Authors: Zeng GQ, Zhang PF, Deng XM, Yu FL, Li C, Xu Y, Yi H, Li MY, Hu R, Zuo JH, Li XH, Wan XX, Qu JQ, He QY, Li JH, Ye X, Chen Y, Li JY, Xiao ZQ Abstract To discover novel biomarkers for early detection of human lung squamous cell cancer (LSCC) and explore possible mechanisms of LSCC carcinogenesis, iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed proteins in human bronchial epithelial carcinogenic process using laser capture microdissection-purified normal bronchial epithelium (NBE), squamous metaplasia (SM), atypical hyperplasia (AH), carcinoma in situ (CIS) and invasive LSCC. As a result, 102 differentially expressed proteins were identified, and three differential proteins (GSTP1, HSPB1 and CKB) showing progressively expressional...

Desmoplastic trichoepithelioma with perineural involvement: a series of seven cases.

Journal of Cutaneous Pathology — Mon, 30 Jan 2012 06:28:50 +0100

We present a series of seven desmoplastic trichoepitheliomas with otherwise typical presentation and morphology, nevertheless demonstrating epithelium present in the perineural spaces of adjacent small dermal nerves. Patients ranged in age from 14 to 66 years (mean 44 years). All seven tumors were restricted to dermis, showed strands of basaloid epithelium in desmoplastic stroma, and contained CK20‐positive cells. Additionally, five of five examined tumors displayed diffuse expression of p75 neurotrophin receptor. Five patients were followed‐up clinically (follow‐up time range: 2 months ‐ 4 years). No tumor recurrence was observed in any of these patients. We postulate that perineural involvement is an unusual feature of desmoplastic trichoepithelioma that should not be equated wit...

Prognostic and predictive value of CA-125 in the primary treatment of epithelial ovarian cancer: potentials and pitfalls

Clinical and Translational Oncology — Sat, 28 Jan 2012 16:53:14 +0100

Abstract The serum cancer antigen 125 (CA-125) remains a reliable biomarker in the therapeutic management of epithelial ovarian cancer (EOC). Monitoring the efficacy of cytotoxic chemotherapy (CT) and the early detection of relapse during the follow up of patients in remission represent the two most common clinical situations where the CA-125 has been successfully applied. There are however other scenarios along the course of the disease where the CA-125 can potentially aid in the decision-making process. Preoperative levels of CA-125 can help in selecting a subset of patients where an optimal cytoreduction may not be easily achieved. Perioperative variations in the CA-125 levels after primary surgery and, more importantly, the nadir value of the CA-125 after primary chemot...

Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance

BMC Cancer — Sat, 28 Jan 2012 05:00:00 +0100

Conclusions: We characterized a self-renewing subpopulation of CICs found among four well known human cancer-derived cell lines (HeLa, SiHa, Ca Ski and C-4 I) and found that they express characteristic markers of stem cell, EMT and radioresistance. The fact that CICs demonstrated a higher degree of resistance to radiation than differentiated cells suggests that specific detection and targeting of CICs could be highly valuable for the therapy of tumors from the uterine cervix. (Source: BMC Cancer)

Physiological and pathological role of local and immigrating colonic stem cells.

World Journal of Gastroenterology : WJG — Sat, 28 Jan 2012 05:00:00 +0100

Authors: Sipos F, Valcz G, Molnár B Abstract The latest avenue of research is revealing the existence of and role for the colonic stem cells in the physiological renewal of the mucosa and in pathological circumstances where they have both positive and negative effects. In the case of human colon, different levels of stem cell compartments exist. First, the crypt epithelial stem cells, which have a role in the normal crypt epithelial cell dynamics and in colorectal carcinogenesis. Close to the crypts, the second layer of stem cells can be found; the local subepithelial stem cell niche, including the pericryptic subepithelial myofibroblasts that regulate the epithelial cell differentiation and have a crucial role in cancer progression and chronic inflammation-related fibrosis. The t...

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The novel expression of Oct3/4 and Bmi1 in the root development of mouse molars

Cell and Tissue Research — Fri, 27 Jan 2012 17:54:29 +0100

This study aimed to investigate the characteristics of the cells involved in the root elongation. Octamer-binding factor 3/4 (Oct3/4) is known as one of the key regulators in maintaining the pluripotency and self-renewal properties of embryonic stem cells. Bmi1, the polycomb-group transcriptional repressor, has emerged as a key regulator in several cellular processes including stem cell self-renewal and cancer cell proliferation. At the beginning of root formation, ameloblasts expressed Oct3/4 in the nucleus, except in the apex of the cervical loop, in which Bmi1and cyclinD were expressed. At PN6, the expression of Oct3/4 in the ameloblasts shifted from the nucleus to the cytoplasm, whereas ameloblastin-negative Hertwig’s epithelial root sheath (HERS) cells expressed Bmi1 and cycli...

Gene expressional changes in prostate fibroblasts from cancerous tissue

APMIS — Fri, 27 Jan 2012 09:28:49 +0100

Prostate cancer is the most common type of cancer in men. It is assumed that the tumor microenvironment of the prostate contributes to invasion and metastasis. Stroma‐epithelial crosstalk has shown to change with progression of prostate cancer, and thereby the stromal compartment might be an attractive target in diagnostic and therapeutic approaches to prostate cancer. The purpose of this project was to study the reciprocal influence between fibroblasts and cancer cells in prostate cancer. Prostate fibroblast primary cultures from areas with cancer and hyperplasia were cocultivated with cells of the PC‐3 lineage. Gene expression profiles of both cell types were studied to reveal possible associations to cancer invasion and metastasis. There were 383 differentially expressed genes betwe...

Plakophilin-2: a cell-cell adhesion plaque molecule of selective and fundamental importance in cardiac functions and tumor cell growth

Cell and Tissue Research — Fri, 27 Jan 2012 06:53:49 +0100

Abstract Within the characteristic ensemble of desmosomal plaque proteins, the armadillo protein plakophilin-2 (Pkp2) is known as a particularly important regulatory component in the cytoplasmic plaques of various other cell–cell junctions, such as the composite junctions (areae compositae) of the myocardiac intercalated disks and in the variously-sized and -shaped complex junctions of permanent cell culture lines derived therefrom. In addition, Pkp2 has been detected in certain protein complexes in the nucleoplasm of diverse kinds of cells. Using a novel set of highly sensitive and specific antibodies, both kinds of Pkp2, the junctional plaque-bound and the nuclear ones, can also be localized to the cytoplasmic plaques of diverse non-desmosomal cell–cell junction struct...

Patients with thymomas have an increased risk of developing additional malignancies: lack of immunological surveillance?

Histopathology — Fri, 27 Jan 2012 05:24:13 +0100

Conclusions: Patients affected by thymomas showed a significantly higher risk of developing additional malignancies than those in the control groups, and cases that exhibited a predominantly cortical component were more likely to develop other neoplasms. This may be related to the functions of cortical thymic epithelial cells in providing for T lymphocyte maturation through interaction with major histocompatibility complexes. (Source: Histopathology)

Expression and clinical significance of extracellular matrix protein 1 and vascular endothelial growth factor-C in lymphatic metastasis of human breast cancer

BMC Cancer — Fri, 27 Jan 2012 05:00:00 +0100

Conclusions: Both ECM1 and VEGF-C were overexpressed in breast cancer tissue samples. ECM1 expression was positively correlated with estrogen responsiveness and the metastatic properties of breast cancer. We conclude, therefore, that ECM1 and VEGF-C may have a synergistic effect on lymphangiogenesis to facilitate lymphatic metastasis of breast cancer. (Source: BMC Cancer)

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Randomized, Double-Blind, Placebo-Controlled Phase II Study of AMG 386 Combined With Weekly Paclitaxel in Patients With Recurrent Ovarian Cancer [Gynecologic Cancer]

Journal of Clinical Oncology — Fri, 27 Jan 2012 05:00:00 +0100

Conclusion AMG 386 combined with weekly paclitaxel was tolerable, with a manageable and distinct toxicity profile. The data suggest evidence of antitumor activity and a dose-response effect, warranting further studies in ovarian cancer. (Source: Journal of Clinical Oncology)

Discovery of Dachshund 2 protein as a novel biomarker of poor prognosis in epithelial ovarian cancer

Journal of Ovarian Research — Fri, 27 Jan 2012 05:00:00 +0100

Conclusions: This study provides a first demonstration of DACH2 protein being expressed in human fallopian tubes and EOC, with the highest expression in serous carcinoma where DACH2 was found to be an independent biomarker of poor prognosis. Future research should expand on the role of DACH2 in ovarian carcinogenesis and chemotherapy resistance. (Source: Journal of Ovarian Research)

Carcinoma ex pleomorphic adenoma of the parotid gland.

Acta Radiologica — Fri, 27 Jan 2012 05:00:00 +0100

ConclusionAn invasive parotid mass co-existing with a round encapsulated component is suggestive of carcinoma ex pleomorphic adenoma. PMID: 22287150 [PubMed - as supplied by publisher] (Source: Acta Radiologica)

Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma

BioMed Central — Thu, 26 Jan 2012 05:00:00 +0100

Conclusions: These data reveal insight into genes and molecular pathways mediating ESCC development and provide information potentially useful in designing novel therapeutic interventions for this tumor type. (Source: BioMed Central)

TGF-{beta}-induced epithelial-mesenchymal transition of A549 lung adenocarcinoma cells is enhanced by pro-inflammatory cytokines derived from RAW 264.7 macrophage cells

Journal of Biochemistry — Wed, 25 Jan 2012 05:00:00 +0100

Cancer cells undergo epithelial-mesenchymal transition (EMT) during invasion and metastasis. Although transforming growth factor-β (TGF-β) and pro-inflammatory cytokines have been implicated in EMT, the underlying molecular mechanisms remain to be elucidated. Here, we studied the effects of proinflammatory cytokines derived from the mouse macrophage cell line RAW 264.7 on TGF-β-induced EMT in A549 lung cancer cells. Co-culture and treatment with conditioned medium of RAW 264.7 cells enhanced a subset of TGF-β-induced EMT phenotypes in A549 cells, including changes in cell morphology and induction of mesenchymal marker expression. These effects were increased by the treatment of RAW 264.7 cells with lipopolysaccharide, which also induced the expression of various proinfl...

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Metastasis is an early event in mouse mammary carcinomas and is associated with cells bearing stem cell markers

Breast Cancer Research — Wed, 25 Jan 2012 05:00:00 +0100

Conclusions: The tumorigenic and metastatic potential of a subpopulation of mammary epithelial/tumor cells in MMT mice is endowed relatively early in mammary neoplasms and suggests a potential role for cancer stem cell sub-populations in metastasis. (Source: Breast Cancer Research)

Human papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization.

Virology — Wed, 25 Jan 2012 05:00:00 +0100

Authors: Vandermark ER, Deluca KA, Gardner CR, Marker DF, Schreiner CN, Strickland DA, Wilton KM, Mondal S, Woodworth CD Abstract The NF-kB family of transcription factors regulates important biological functions including cell growth, survival and the immune response. We found that Human Papillomavirus type 16 (HPV-16) E7 and E6/E7 proteins inhibited basal and TNF-alpha-inducible NF-kB activity in human epithelial cells cultured from the cervical transformation zone, the anatomic region where most cervical cancers develop. In contrast, HPV-16 E6 regulated NF-kB in a cell type- and cell growth-dependent manner. NF-kB influenced immortalization of cervical cells by HPV16. Inhibition of NF-kB by an IkB alpha repressor mutant increased colony formation and immortalization by HPV-16. I...

Spermine synthase overexpression in vivo does not increase susceptibility to DMBA/TPA skin carcinogenesis or Min-Apc intestinal tumorigenesis.

Cancer Biology and Therapy — Tue, 24 Jan 2012 21:12:20 +0100

Authors: Welsh P, Sass-Kuhn S, Prakashagowda C, McCloskey D, Feith D Abstract Numerous studies have demonstrated a link between elevated polyamine biosynthesis and neoplastic growth, but the specific contribution of spermine synthase to epithelial tumor development has never been explored in vivo. Mice with widespread overexpression of spermine synthase (CAG-SpmS) exhibit decreased spermidine levels, increased spermine and a significant rise in tissue spermine:spermidine ratio. We characterized the response of CAG-SpmS mice to two-stage skin chemical carcinogenesis as well as spontaneous intestinal carcinogenesis induced by loss of the Apc tumor suppressor in ApcMin/+ (Min) mice. CAG-SpmS mice maintained the canonical increases in ornithine decarboxylase (ODC) activity, polyamine c...

Functions of thymic stromal lymphopoietin in immunity and disease

Immunologic Research — Tue, 24 Jan 2012 18:13:52 +0100

Abstract Thymic stromal lymphopoietin (TSLP) is an interleukin 7-like cytokine expressed mainly by epithelial cells. Current studies provide compelling evidence that TSLP is capable of activating dendritic cells to promote T helper (Th) 2 immune responses. TSLP has also been shown to directly promote Th2 differentiation of naïve CD4+ T cell and activate natural killer T cells, basophils and other innate immune cells at the initial stage of inflammation. In addition, TSLP affects B cell maturation and activation and can also influence regulatory T (Treg) cell differentiation and development. TSLP-induced Th2 responses are associated with the pathogenesis of allergic inflammatory diseases, including atopic dermatitis, asthma, and rhinitis. Based on recent findings in humans ...

Stromal–epithelial interactions modulate cross-talk between prolactin receptor and HER2/Neu in breast cancer

Breast Cancer Research and Treatment — Tue, 24 Jan 2012 07:35:07 +0100

In conclusion, CAFs play a critical role in bridging the cross-talk between PRL and HER2/Neu in both mouse and human models of breast cancer. The inhibitory effects of G129R on p-Neu and on tumor growth are dependent upon interactions of tumor epithelial cells with CAFs. Content Type Journal ArticleCategory Preclinical studyPages 1-13DOI 10.1007/s10549-012-1954-3Authors Cong Xu, Department of Biological Sciences, Clemson University, Clemson, SC 29634, USAJohn F. Langenheim, Department of Biological Sciences, Clemson University, Clemson, SC 29634, USAWen Y. Chen, Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA Journal Breast Cancer Research and TreatmentOnline ISSN 1573-7217Print ISSN 0167-6806 (Source: Breast Cancer Research and Treatment)

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Dormant but migratory tumour cells in desmoplastic stroma of invasive ductal carcinomas

Clinical and Experimental Metastasis — Tue, 24 Jan 2012 06:54:48 +0100

This study has important connotations for a role of SPCs in local recurrence. Content Type Journal ArticleCategory Research PaperPages 1-20DOI 10.1007/s10585-011-9450-4Authors Vanisri Raviraj, Australian Centre for Microscopy and Microanalysis (ACMM), AMMRF, The University of Sydney, Madsen Building F09, Room 243, Sydney, NSW 2006, AustraliaHui Zhang, Australian Centre for Microscopy and Microanalysis (ACMM), AMMRF, The University of Sydney, Madsen Building F09, Room 243, Sydney, NSW 2006, AustraliaHsin-ya Chien, Australian Centre for Microscopy and Microanalysis (ACMM), AMMRF, The University of Sydney, Madsen Building F09, Room 243, Sydney, NSW 2006, AustraliaLouise Cole, Advanced Microscopy Facility, Bosch Institute, The University of Sydney, Sydney, NSW 2006, AustraliaErik W. Th...

Suppression of the Epidermal Growth Factor Receptor Inhibits Epithelial–Mesenchymal Transition in Human Pancreatic Cancer PANC-1 Cells

Digestive Diseases and Sciences — Tue, 24 Jan 2012 06:48:48 +0100

Conclusion Suppression of EGFR expression can significantly inhibit EMT of pancreatic cancer PANC-1 cells. The mechanism may be related with the down-regulation of the expression of transcription factors snail and slug. Content Type Journal ArticleCategory Original ArticlePages 1-9DOI 10.1007/s10620-012-2036-4Authors Zhi-Gang Chang, Department of General Surgery, Peking University First Hospital, 8th Xishiku Street, Xicheng District, Beijing, 100034 People’s Republic of ChinaJun-Min Wei, Department of General Surgery, Beijing Hospital, Ministry of Health, 1st Dahua Rd. Dongdan, Beijing, 100730 People’s Republic of ChinaChang-Fu Qin, Department of General Surgery, Peking University First Hospital, 8th Xishiku Street, Xicheng District, Beijing, 100034 People’s Re...

Women with certain type of ovarian cancer and BRCA gene mutation have improved survival at 5 years

EurekAlert! - Social and Behavioral Science — Tue, 24 Jan 2012 05:00:00 +0100

(JAMA and Archives Journals) Among women with invasive epithelial ovarian cancer, patients having a germline (gene change in a reproductive cell that could be passed to offspring) mutation in the BRCA1 or BRCA2 genes was associated with improved five-year overall survival, with BRCA2 carriers having the best prognosis, according to a study in the Jan. 25 issue of JAMA. (Source: EurekAlert! - Social and Behavioral Science)

Microenvironmental Control of the Breast Cancer Cell Cycle

Tue, 24 Jan 2012 05:00:00 +0100

AbstractThe mammary gland is one of the best‐studied examples of an organ whose structure and function are influenced by reciprocal signaling and communication between cells and their microenvironment. The mammary epithelial cell (MEC) microenvironment includes stromal cells and extracellular matrix (ECM). Abundant evidence shows that the ECM and growth factors co‐operate to regulate cell cycle progression, and that the ECM is altered in breast tumors. In particular, mammographically dense breast tissue is a significant risk factor for developing breast carcinomas. Dense breast tissue is associated with increased stromal collagen and epithelial cell content. In this article, we overview recent studies addressing the effects of ECM composition on the breast cancer cell cycle. Although t...

Maximal Standardized Uptake Value on FDG-PET Is Correlated With Cyclooxygenase-2 Expression in Patients With Lung Adenocarcinoma [ORIGINAL ARTICLES: GENERAL THORACIC]

The Annals of Thoracic Surgery — Tue, 24 Jan 2012 05:00:00 +0100

Conclusions The expression of COX-2 in primary tumors is as strongly correlated with a worse clinical outcome as is increased FDG uptake in cases of lung adenocarcinoma. These findings indicate that the SUVmax of primary tumors might reflect the biological malignant potential in lung adenocarcinomas. (Source: The Annals of Thoracic Surgery)

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Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors

BMC Cancer — Tue, 24 Jan 2012 05:00:00 +0100

Conclusions: Data presented here identify a novel role for macrophages in EMT-promoted tumor progression. The observation that TAMs cluster with intra-epithelial fibroblastoid cells suggests that the role of macrophages in tumor-EMT extends beyond the invasive front. As macrophage infiltration and pronounced EMT tumor phenotype correlate with increased grade in NSCLC patients, we propose that TAMs also promote tumor progression by inducing EMT locally in tumors. (Source: BMC Cancer)

Association Between BRCA1 and BRCA2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer [Original Contribution]

JAMA — Tue, 24 Jan 2012 05:00:00 +0100

Conclusion Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis. (Source: JAMA)

CD146, an epithelial-mesenchymal transition inducer, is associated with triple-negative breast cancer [Cell Biology]

Proceedings of the National Academy of Sciences — Tue, 24 Jan 2012 05:00:00 +0100

The epithelial-mesenchymal transition (EMT) plays an important role in breast cancer metastasis, especially in the most aggressive and lethal subtype, “triple-negative breast cancer” (TNBC). Here, we report that CD146 is a unique activator of EMTs and significantly correlates with TNBC. In epithelial breast cancer cells, overexpression of CD146 down-regulated epithelial markers and up-regulated mesenchymal markers, significantly promoted cell migration and invasion, and induced cancer stem cell-like properties. We further found that RhoA pathways positively regulated CD146-induced EMTs via the key EMT transcriptional factor Slug. An orthotopic breast tumor model demonstrated that CD146-overexpressing breast tumors showed a poorly differentiated phenotype and displayed increased tumor i...

Application of RNA-Seq Transcriptome Analysis: CD151 is an Invasion/Migration Target in All Stages of Epithelial Ovarian Cancer

Journal of Ovarian Research — Tue, 24 Jan 2012 05:00:00 +0100

Conclusion: Taken together, these findings provide the first proof-of-principle demonstration for a next generation sequencing approach to identifying candidate therapeutic targets and reveal CD151 to play a role in EOC dissemination. (Source: Journal of Ovarian Research)

Bevacizumab (Avastin®) approved in the EU for ovarian cancer

NeLM - News — Mon, 23 Jan 2012 05:00:00 +0100

Source: Personal communication (Roche) Area: News The European Medicines Agency has approved an additional indication for bevacizumab (Avastin®) - for use in combination with carboplatin and paclitaxel for the front-line treatment of advanced (FIGO stages III B, III C and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer. (Source: NeLM - News)

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Ovarian Actions of Estrogen Receptor-β: An Update

Seminars in Reproductive Medicine — Mon, 23 Jan 2012 05:00:00 +0100

Semin Reprod Med 2012; 30: 32-38DOI: 10.1055/s-0031-1299595Estrogen is essential for folliculogenesis with independent roles attributed to each of the two estrogen receptors (ERs). ERβ, expressed predominantly by the ovarian granulosa cells, is required for antrum formation, preovulatory follicle maturation, expression of genes involved in ovarian differentiation (luteinizing hormone, aromatase, etc.), and follicle rupture during ovulation. Ovulatory dysfunction is associated with polymorphisms of the ERβ gene, and endocrine disruptors that selectively activate ERβ cause reproductive dysfunction and impairment fertility. ERβ may also exhibit antitumorigenic properties, with a decline in ERβ levels in epithelial ovarian cancers associated with more severe disease and poor prognosis. In...

Intestinal spirochaetosis associated with hyperplastic and adenomatous colonic polyps.

Pathology, Research and Practice — Mon, 23 Jan 2012 05:00:00 +0100

This report could stimulate microbiological investigations during the follow-up of colonic polyps in order to explain whether the persistence of abdominal symptoms in such patients could be caused by a colonic spirochaetosis susceptible to eradication by a targeted therapy. PMID: 22277793 [PubMed - as supplied by publisher] (Source: Pathology, Research and Practice)

SKI-606, a Src inhibitor, reduces tumor growth, invasion, and distant metastasis in a mouse model of thyroid cancer.

Clinical Cancer Research — Mon, 23 Jan 2012 05:00:00 +0100

CONCLUSIONS: Our findings suggest that Src is critical in the progression of thyroid cancer, making oral SKI-606 a promising treatment strategy for refractory thyroid cancer. PMID: 22271876 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Multi-pathway network analysis of mammalian epithelial cell responses in inflammatory environments.

Biochemical Society Transactions — Sun, 22 Jan 2012 22:28:54 +0100

Authors: Clarke DC, Lauffenburger DA Abstract Inflammation is a key physiological response to infection and injury and, although usually beneficial, it can also be damaging to the host. The liver is a prototypical example in this regard because inflammation helps to resolve liver injury, but it also underlies the aetiology of pathologies such as fibrosis and hepatocellular carcinoma. Liver cells sense their environment, including the inflammatory environment, through the activities of receptor-mediated signal transduction pathways. These pathways are organized in a complex interconnected network, and it is becoming increasingly recognized that cellular adaptations result from the quantitative integration of multi-pathway network activities, rather than isolated pathways causing par...

Contribution of cell blocks obtained through endobronchial ultrasound-guided transbronchial needle aspiration to the diagnosis of lung cancer

BMC Cancer — Sat, 21 Jan 2012 05:00:00 +0100

Conclusions: Cell-block preparation from EBUS-TBNA samples is a simple way to provide additional information in lung cancer diagnosis. Analysis of cell blocks increases the diagnostic yield of the procedure by nearly seven per cent and allows for genetic analysis in a sixty per cent of the patients with metastatic adenocarcinoma. (Source: BMC Cancer)

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Ovarian cancer: current management and future directions

Obstetrics, Gynaecology and Reproductive Medicine — Sat, 21 Jan 2012 03:20:54 +0100

Abstract: Ovarian cancer has the highest mortality of all the gynaecological malignancies. Epithelial ovarian cancer is the most common subtype. Approximately 5–10% occur in women with an inherited predisposition. These patients may benefit from prophylactic surgery. Diagnosis involves measurement of CA 125 and ultrasound. The results of both are combined to give a risk of malignancy index; this is used to decide where treatment takes place. Treatment of advanced epithelial ovarian cancer usually involves debulking surgery and chemotherapy. The correct order of these treatments is currently being evaluated. There are survival benefits if surgery is performed by a specialist gynaecological oncologist. Current standard chemotherapy for epithelial ovarian cancer is carboplatin with paclitax...

Free peritoneal tumor cells detection in gastric and colorectal cancer patients

Journal of Surgical Oncology — Fri, 20 Jan 2012 13:16:52 +0100

ConclusionsEpithelial immunoenrichment and immunofluorescence analysis allows unequivocal identification of the FPTC. The real time qRT‐PCR showed higher sensitivity for the detection of CEA and CK20 mRNA levels and confirmed its prognostic value in gastrointestinal cancers. J. Surg. Oncol © 2012 Wiley Periodicals, Inc. (Source: Journal of Surgical Oncology)

miR-200b regulates cell migration via Zeb family during mouse palate development

Histochemistry and Cell Biology — Fri, 20 Jan 2012 07:07:57 +0100

Abstract Palate development requires coordinating proper cellular and molecular events in palatogenesis, including the epithelial–mesenchymal transition (EMT), apoptosis, cell proliferation, and cell migration. Zeb1 and Zeb2 regulate epithelial cadherin (E-cadherin) and EMT during organogenesis. While microRNA 200b (miR-200b) is known to be a negative regulator of Zeb1 and Zeb2 in cancer progression, its regulatory effects on Zeb1 and Zeb2 in palatogenesis have not yet been clarified. The aim of this study is to investigate the relationship between the regulators of palatal development, specifically, miR-200b and the Zeb family. Expression of both Zeb1 and Zeb2 was detected in the mesenchyme of the mouse palate, while miR-200b was expressed in the medial edge epithelium. Aft...

Epithelial Myoepithelial Carcinoma of Head and Neck Region

Indian Journal of Otolaryngology and Head and Neck Surgery — Fri, 20 Jan 2012 07:07:43 +0100

The objective of the study is to document the clinical, histopathological and immunological findings of epithelial myoepithelial carcinoma (EMEC) which is an uncommon neoplasm. The tumour represents less than 0.5–1% of all salivary gland neoplasms. As per literature, it involves the parotid gland most frequently and rarely, the minor salivary glands. We are reporting a series of four cases of EMEC over a period of one and half years, three from minor salivary glands at different sites and one from the deep lobe of parotid. Interestingly, the pre operative FNAC of all the cases revealed benign pathology. Recurrence occurred in three of them after tumour excision. One patient was subjected to post operative radiotherapy and one patient to chemotherapy. Histopathology and immunohistoc...

The anti-adhesive mucin podocalyxin may help initiate the transperitoneal metastasis of high grade serous ovarian carcinoma

Clinical and Experimental Metastasis — Fri, 20 Jan 2012 07:04:39 +0100

Abstract High grade serous ovarian tumors often metastasize transperitoneally, a process that begins when small tumor nodules de-adhere and are released into the fluid of the abdominal cavity where they float freely to reach new sites on the peritoneal wall. Podocalyxin, a small anti-adhesive sialomucin, has been shown to contribute to non-adhesive membrane domain formation in some epithelia and is overexpressed in a variety of cancers. We therefore assessed podocalyxin expression on a previously characterized tissue microarray and found that 87% (169/194) of high grade serous epithelial ovarian carcinomas were positive for podocalyxin. In addition, cell surface localization of podocalyxin was associated with a significant decrease in disease-free survival in these tumors....

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Expression of stem cell and epithelial-mesenchymal transition markers in primary breast cancer patients with circulating tumor cells.

Breast Cancer Research — Fri, 20 Jan 2012 05:00:00 +0100

Conclusion: Our data indicate that (1) a subset of primary breast cancer patients shows EMT and stem cell characteristics and (2) the currently used detection methods for CTC are not efficient to identify a subtype of CTC which underwent EMT. (3) The clinical relevance on prognosis and therapy response has to be further evaluated in a prospective trial. (Source: Breast Cancer Research)

Avastin 25mg/ml concentrate for solution for infusion (Bevacizumab)-Revised SPC

NeLM - SPC Changes — Fri, 20 Jan 2012 05:00:00 +0100

Source: eMC (electronic Medicines Compendium) Area: Other Library Updates > SPC Changes There have been significant updates to several sections of the SPC, including the following: Changes to section 4.1- Therapeutic indication Avastin, in combination with carboplatin and paclitaxel is indicated for the front-line treatment of advanced (FIGO stages III B, III C and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer. Please refer to SPC link below for full information on all changes. (Source: NeLM - SPC Changes)

Aberrant Expression of miR-638 Contributes to Benzo(a)pyrene-Induced Human Cell Transformation

Toxicological Sciences — Fri, 20 Jan 2012 05:00:00 +0100

Identification of aberrant microRNA (miRNA) expression during chemical carcinogen–induced cell transformation will lead to a better understanding of the substantial role of miRNAs in cancer development. To explore whether aberrant miRNAs expression can be used as biomarkers of chemical exposure in risk assessment of chemical carcinogenesis, we analyzed miRNA expression profiles of human bronchial epithelial cells expressing an oncogenic allele of H-Ras (HBER) at different stages of transformation induced by benzo(a)pyrene (BaP) by miRNA array. It revealed 12 miRNAs differentially expressed in HBER cells at both pretransformed and transformed stages. Differentially expressed miRNAs were confirmed in transformed cells and examined in 50 pairs of primary human non–small-cell lung ...

An NF-{kappa}B-Independent and Erk1/2-Dependent Mechanism Controls CXCL8/IL-8 Responses of Airway Epithelial Cells to Cadmium

Toxicological Sciences — Fri, 20 Jan 2012 05:00:00 +0100

Airway epithelial cells in the lung are the first line of defense against pathogens and environmental pollutants. Inhalation of the environmental pollutant cadmium has been linked to the development of lung cancer and chronic obstructive pulmonary disease, which are diseases characterized by chronic inflammation. To address the role of airway epithelial cells in cadmium-induced lung inflammation, we investigated how cadmium regulates secretion of interleukin 8 (IL-8) by airway epithelial cells. We show that exposure of human airway epithelial cells to subtoxic doses of cadmium in vitro promotes a characteristic inflammatory cytokine response consisting of IL-8, but not IL-1β or tumor necrosis factor-alpha. We also found that intranasal delivery of cadmium increases lung levels of the ...

Autoregulation of IGF-IR Gene Expression [Molecular Bases of Disease]

Journal of Biological Chemistry — Fri, 20 Jan 2012 05:00:00 +0100

We describe here a novel mechanism of autoregulation of IGF-IR gene expression by cellular IGF-IR, which is seemingly dependent on ER status. Regulation of the IGF-IR gene by IGF-IR protein is mediated at the level of transcription, as demonstrated by 1) binding assays (DNA affinity chromatography and ChIP) showing specific IGF-IR binding to IGF-IR promoter DNA and 2) transient transfection assays showing transactivation of the IGF-IR promoter by exogenous IGF-IR. The IR is also capable of translocating to the nucleus and binding the IGF-IR promoter in ER-depleted, but not in ER-positive, cells. However, transcription factors IGF-IR and IR display diametrically opposite activities in the context of IGF-IR gene regulation. Thus, whereas IGF-IR stimulated IGF-IR gene expression, IR inhibited...

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STAT1-deficient mice spontaneously develop estrogen receptor alpha-positive luminal mammary carcinomas

Breast Cancer Research — Fri, 20 Jan 2012 05:00:00 +0100

Conclusions: Our findings demonstrate that STAT1 suppresses mammary tumor formation and its expression is frequently lost during breast cancer progression. Spontaneous mammary tumors that develop in STAT1-/- mice closely recapitulate the progression, ovarian hormone responsiveness, and molecular characteristics of human luminal breast cancer, the most common subtype of human breast neoplasms, and thus represent a valuable platform for testing novel treatments and detection modalities. (Source: Breast Cancer Research)

IGFBP-4 tumor and serum levels are increased across all stages of epithelial ovarian cancer.

Journal of Ovarian Research — Fri, 20 Jan 2012 05:00:00 +0100

Background: We sought to identify candidate serum biomarkers for the detection and surveillance of EOC. Based on RNA-Seq transcriptome analysis of patient-derived tumors, highly expressed secreted proteins were identified using a bioinformatic approach. Methods: RNA-Seq was used to quantify papillary serous ovarian cancer transcriptomes. Paired end sequencing of 22 flash frozen tumors was performed. Sequence alignments were processed with the program ELAND, expression levels with ERANGE and then bioinformatically screened for secreted protein signatures. Serum samples from women with benign and malignant pelvic masses and serial samples from women during chemotherapy regimens were measured for IGFBP-4 by ELISA. Student's t Test, ANOVA, and ROC curves were used for statistical analysis. Res...

Multimarker Gene Analysis of Circulating Tumor Cells in Pancreatic Cancer Patients: A Feasibility Study.

Oncology — Fri, 20 Jan 2012 05:00:00 +0100

Conclusion: Our results suggest that in addition to the current prognostic methods, CTC analysis represents a potential complementary tool for prediction of outcome in pancreatic cancer patients. PMID: 22270149 [PubMed - as supplied by publisher] (Source: Oncology)

Targeted Cryoablation Boosts Survival in Ovarian CancerTargeted Cryoablation Boosts Survival in Ovarian Cancer

Medscape Today Headlines — Thu, 19 Jan 2012 17:18:24 +0100

With cryoablation of metastatic epithelial ovarian cancer, 5-year survival is 30%, with an estimated cost of $26,806 per life-year gained. Medscape Medical News (Source: Medscape Today Headlines)

Correlation of HLA-A02* genotype and HLA class I antigen down-regulation with the prognosis of epithelial ovarian cancer

Cancer Immunology, Immunotherapy — Thu, 19 Jan 2012 06:53:39 +0100

Conclusions HLA-A02* is a valuable prognostic biomarker in epithelial ovarian cancer. HLA class I HC loss and/or down-regulation was significantly more frequent in tumour tissues from HLA-A02* positive patients with serous adenocarcinoma surgical stage III–IV. In multivariate analysis, we show that the prognostic impact is reasonably correlated to the HLA genetic rather than to the expression of its protein products. Content Type Journal ArticleCategory Original ArticlePages 1-11DOI 10.1007/s00262-012-1201-0Authors Emilia Andersson, Department of Oncology-Pathology, Karolinska Institute, Radiumhemmet, Karolinska University Hospital, 171 76 Stockholm, SwedenLisa Villabona, Department of Oncology-Pathology, Karolinska Institute, Radiumhemmet, Karolinska University ...

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Intraductal Papillary Mucinous Neoplasm (IPMN) with Extra-Pancreatic Mucin: A Case Series and Review of the Literature

Journal of Gastrointestinal Surgery — Thu, 19 Jan 2012 06:48:11 +0100

Conclusions At this time, there is scant reporting and consensus for the treatment of IPMN with extra-pancreatic mucin. Content Type Journal ArticleCategory Original ArticlePages 1-9DOI 10.1007/s11605-012-1823-8Authors Laura H. Rosenberger, Department of Surgery, University of Virginia Health System, Medical Research Building #4, Room 3116, P.O. Box 801359, Charlottesville, VA 22908, USALouis H. Stein, Department of Surgery, Yale–New Haven Hospital, New Haven, CT, USAAgnieszka K. Witkiewicz, Department of Pathology, Thomas Jefferson University, Philadelphia, PA, USAEugene P. Kennedy, Department of Surgery, and the Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA, USACharles J. Yeo, Department of Surgery, and the Jeff...

Epithelial-mesenchymal transition, cancer stem cells and treatment resistance

Breast Cancer Research — Thu, 19 Jan 2012 05:00:00 +0100

Mortality from breast cancer has steadily been declining over the last decade, primarily due to earlier detection, adjuvant therapies and the advent of targeted therapies for ER positive and HER2 positive cancers [1, 2]. Despite these advances, a large number of patients relapse after an initial response to standard of care therapy. Novel therapies that prevent breast cancer relapse and metastasis are needed. An emerging hypothesis is that tumors contain a subpopulation of cells, called cancer stem cells (CSCs), which have the ability to self renew and regenerate the tumor. Increasingly, clinical evidence points to an intrinsic resistance to endocrine therapy and chemotherapy of this subpopulation of cancer stem cells [3]. The residual tumors after chemotherapy are enriched for CSCs and ha...

Selective inhibition of NF‐κB suppresses bone invasion by oral squamous cell carcinoma in vivo

International Journal of Cancer — Thu, 19 Jan 2012 05:00:00 +0100

AbstractNuclear factor‐κB (NF‐κB) is constitutively activated in many cancers, including oral squamous cell carcinoma (OSCC), and is involved in the invasive characteristics of OSCC, such as growth, anti‐apoptotic activity and protease production. However, the cellular mechanism underlying NF‐κB's promotion of bone invasion by OSCC is unclear. Therefore, we investigated the role of NF‐κB in bone invasion by OSCC in vivo. Immnunohistochemical staining of OSCC invading bone in 10 patients indicated that the expression and nuclear translocation of p65, a main subunit of NF‐κB, was increased in OSCC compared with normal squamous epithelial cells. An active form of p65 phosphorylated at serine 536 was present mainly in the nucleus in not only differentiated tumor cells but also...

Histologic pattern, bilaterality and clinical evaluation of 957 ovarian neoplasms: A 10-year study in a tertiary hospital of eastern India

Journal of Cancer Research and Therapeutics — Thu, 19 Jan 2012 05:00:00 +0100

Conclusion: We noted an earlier age at presentation of malignant tumors. Mature teratoma was found to be the second most common benign tumor (after serous cystadenoma). We also noted a lower percentage of endometrioid tumors. Lower number of stage IV tumors was noted, with a significant number of malignant ovarian tumors presenting at an earlier age. (Source: Journal of Cancer Research and Therapeutics)

Displaced ovarian granulosa cells mimicking metastatic lobular carcinoma of the breast

Journal of Clinical Pathology — Thu, 19 Jan 2012 05:00:00 +0100

We read with interest the review by Clarke and McCluggage on iatrogenic lesions and artefacts in gynaecological pathology and in particular displaced ovarian granulosa cells and wish to report a further case in which displaced ovarian granulosa cells caused diagnostic difficulty.1 A 49-year-old Caucasian woman underwent a wide local excision for grade 2 lobular carcinoma of the breast with sentinel lymph node biopsy, which revealed no evidence of metastatic disease. Two years later, she underwent a therapeutic bilateral oophorectomy. The right ovary was entirely normal histologically but in the peripheral cortex of the left ovary, adjacent to an ovarian follicle, there were clusters of fairly uniform small round cells with variable nuclear chromasia, stippled nuclear chromatin and scanty e...

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Distribution of aldehyde dehydrogenase 1‐positive stem cells in benign mammary tissue from women with and without breast cancer

Histopathology — Thu, 19 Jan 2012 05:00:00 +0100

Conclusions: This study provides further evidence for the stem cell character of ALDH1+ cells, here in benign breast tissue of cancer and non‐cancer patients throughout non‐lactating adult life, and contributes evidence of benign stromal ALDH1+ cells. The distribution of ductular ALDH1+ stem cells appears to be influenced by hormonal status. (Source: Histopathology)

Loss of membrane‐bound serine protease inhibitor HAI‐1 induces oral squamous cell carcinoma cells invasiveness

The Journal of Pathology — Thu, 19 Jan 2012 05:00:00 +0100

AbstractA loss of balance between cell membrane‐associated proteases and their inhibitors may underlie cancer invasion and metastasis. We analyzed the roles of a membrane‐ associated serine protease inhibitor, HAI‐1, in oral squamous cell carcinoma (OSCC). While membranous HAI‐1 was widely observed in cancer cells of human OSCC tissues, this was significantly reduced at the infiltrative invasion front. In vitro, HAI‐1 was detected in all eight OSCC cell lines examined, in which its cognate membrane protease, matriptase was also expressed. HAI‐1 expression knock down (KD) in OSCC lines, SAS and HSC‐3, reduced growth of both lines in vitro, but significantly enhanced SAS tumorigenicity in vivo, which was accompanied by histological changes suggestive of the epithelial to mesenc...

Imaging Features and Management of High-Risk Lesions on Contrast-Enhanced Dynamic Breast MRI

American Journal of Roentgenology — Thu, 19 Jan 2012 05:00:00 +0100

CONCLUSION. To our knowledge, no studies to date show definitive and specific characteristics for high-risk lesions. Underestimation of malignancy on MRI-guided biopsy currently warrants surgical management for all high-risk lesions. There is a need for prospective larger power studies. (Source: American Journal of Roentgenology)

Paediatric malignant liver tumours.

Bulletin du Cancer — Thu, 19 Jan 2012 05:00:00 +0100

Authors: Brugières L, Branchereau S, Laithier V Abstract Tumours and pseudotumours of the liver are a heterogeneous group of neoplasm including 60% of malignant tumours. Malignant liver tumours account for less than 2% of the lesions in children and vary considerably in incidence throughout the paediatric age range, with hepatoblastoma, rhabdoid tumour of the liver, hemangioendothelioma, biliary tract rhabdomysosarcoma and mesenchymal hamartoma in the first two years of life and hepatocellular carcinoma, focal nodular hyperplasia, and undifferentiated sarcoma in older children and adolescents. Treatment of malignant epithelial tumours is based on the surgical resection of the tumour associated with pre- and postoperative chemotherapy including cisplatinum. Modalities of the treatm...

DNA Methylation Profiling Defines Clinically Relevant Biological Subsets of Non-small Cell Lung Cancer.

Clinical Cancer Research — Thu, 19 Jan 2012 05:00:00 +0100

CONCLUSIONS: Our data demonstrate that patterns of DNA methylation can divide NSCLCs into two phenotypically distinct subtypes of tumors and provide proof of principle that differences in DNA methylation can be used for predictive biomarker discovery and development. PMID: 22261801 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

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The Impact of the Activated Stroma on Pancreatic Ductal Adenocarcinoma Biology and Therapy Resistance.

Current Molecular Medicine — Thu, 19 Jan 2012 05:00:00 +0100

Authors: Erkan M, Reiser-Erkan C, Michalski CW, Kong B, Esposito I, Friess H, Kleeff J Abstract Around 95% of patients diagnosed with pancreatic cancer will die of their disease within 5 years, three quarters within a year. The major hurdle in improving prognosis is the lack of a therapeutic time window. Early cancerous lesions are far beneath our threshold of detection. Therefore, at the time of diagnosis even early (T1) tumors can be metastatic and resistant to conventional treatments. Several therapies targeting epithelial tumor cells-all showing impressive results in vitro and in animal experiments-have failed to show relevant effects in clinical trials. This discrepancy between experimental data and clinical reality results mostly from the inefficiency of our current experimen...

The prostate cancer-up-regulated long noncoding RNA PlncRNA-1 modulates apoptosis and proliferation through reciprocal regulation of androgen receptor.

Urologic Oncology — Thu, 19 Jan 2012 05:00:00 +0100

CONCLUSIONS: Our study suggests reciprocal regulation of PlncRNA-1 and androgen receptor contribute to CaP pathogenesis and that PlncRNA-1 is a potential therapy target. PMID: 22264502 [PubMed - as supplied by publisher] (Source: Urologic Oncology)

Fiber-optic bronchoscope and detection of lung cancer: A five year study.

Neoplasma — Thu, 19 Jan 2012 04:30:02 +0100

Authors: Gao L, Asmitanand T, Ren H, Wu F, Zhang Y, Li X, DI L, Song Z, Yang T, Chen T, Merrilees M, Wu L, Chen M Abstract White light bronchoscopy [WLB] has been used for identification and localization of intra-epithelial pre-neoplastic and neoplastic lesions within the bronchus. Aim of the study was to evaluate the uses of WLB to detect and localize the precancerous and cancerous lesions, and in addition to analyze morphologic presentation, and association to histological type and the variation between genders.A total of 4983 patients were examined by WLB from 2004 to 2009 in a local tertiary teaching hospital. The following parameters were collected: morphological presentation, biopsy sites, histology. The patients' records of age, sex, smoking status, blood-gas, X-RAY/CT, CB...

Thymosin beta 4 in colorectal cancer is localized predominantly at the invasion front in tumor cells undergoing epithelial mesenchymal transition.

Cancer Biology and Therapy — Thu, 19 Jan 2012 00:12:48 +0100

Conclusions: Our data show that Tβ4 is expressed in the majority of colon cancers, with preferential immunoreactivity in deep tumor regions. The preferential expression of the peptide and the increase in intensity of the immunostaining at the invasion front suggests a possible link between the peptide and the process of epithelial mesenchymal transition, suggesting a role for Tβ4 in colorectal cancer invasion and metastasis. PMID: 22233609 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy)

Fibroblast activation protein: A potential therapeutic target in cancer.

Cancer Biology and Therapy — Thu, 19 Jan 2012 00:12:39 +0100

Authors: Liu R, Li H, Liu L, Yu J, Ren X Abstract The concept of targeting antigens selectively expressed on the surface of tumor capillary endothelial cells or in tumor stroma has emerged as a promising strategy for cancer therapeutics. Identification of stromal targets for anticancer therapy and development of selective inhibitors of these targets are of great clinical interest. Fibroblast activation protein (FAP), a member of the serine protease family, selectively expressed in the stromal fibroblasts associated with epithelial cancers, whereas with low or undetectable expression in the resting fibroblasts of normal adult tissues. The proteolytic activity of FAP has been shown to support tumor growth and proliferation, making it a potential target for novel anticancer...

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Elevated expression of eukaryotic translation initiation factor 4E is associated with proliferation, invasion and acquired resistance to erlotinib in lung cancer.

Cancer Biology and Therapy — Thu, 19 Jan 2012 00:12:30 +0100

In this study, we detected increased levels of eIF4E in 16 human NSCLC cell lines compared with their normal bronchial epithelial cells. Consistently, human tissue array analysis showed that eIF4E expression was significantly higher in human NSCLC tissues than normal tissues. Inhibition of eIF4E using eIF4E siRNA inhibited the growth and invasion of NSCLC cells. These data suggest that eIF4E overexpression plays a crucial role in positive regulation of the growth and invasion of NSCLC cells. By proteomics, we found that eIF4E levels were elevated in erlotinib-resistant cell lines compared with the sensitive parental cell line. In agreement, assembly of the eIF4F cap complex and several oncogenic proteins regulated by the cap-dependent translation mechanism, were also increased in erlotinib...

HIPK2 downregulates vimentin and inhibits breast cancer cell invasion.

Cancer Biology and Therapy — Thu, 19 Jan 2012 00:12:21 +0100

This study, by starting with a microarray analysis, demonstrates that HIPK2 downregulates vimentin expression in invasive, vimentin-positive, MDA-MB-231 breast cancer cells and in the non invasive MCF7 breast cancer cells subjected to chemical hypoxia, a drive for mesenchymal shift and tumor invasion. At functional level, vimentin downregulation by HIPK2 correlates with inhibition of breast tumor cell invasion. Together, these data show that vimentin is a novel target for HIPK2 repressor function and that HIPK2-mediated vimentin downregulation can contribute to inhibition of breast cancer cells invasion that might be applied in clinical therapy. PMID: 22236966 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy)

ICB3E induces iNOS expression by ROS-dependent JNK and ERK activation for apoptosis of leukemic cells

Apoptosis — Wed, 18 Jan 2012 06:49:15 +0100

Abstract The role of c-Jun N terminal Kinase (JNK) has been well documented in various cellular stresses where it leads to cell death. Similarly, extracellular signal-regulated kinase (ERK) which was identified as a signalling molecule for survival pathway has been shown recently to be involved in apoptosis also. Recently we reported that ICB3E, a synthetic analogue of Piper betle leaf-derived apoptosis-inducing agent hydroxychavicol (HCH), possesses anti-chronic myeloid leukemia (CML) acitivity in vitro and in vivo without insight on mechanism of action. Here we report that ICB3E is three to four times more potent than HCH in inducing apoptosis of leukemic cells without having appreciable effects on normal human peripheral blood mononuclear cells, mouse fibroblast cell lin...

Rab25 increases cellular ATP and glycogen stores protecting cancer cells from bioenergetic stress

EMBO Molecular Medicine — Wed, 18 Jan 2012 05:00:00 +0100

AbstractCancer cells are metabolically stressed during tumour progression due to limited tumour vascularity and resultant nutrient, growth factor and oxygen deficiency that can induce cell death and inhibit tumour growth. We demonstrate that Rab25, a small GTPase involved in endosomal recycling, that is genomically amplified in multiple tumour lineages, is a key regulator of cellular bioenergetics and autophagy. RAB25 enhanced survival during nutrient stress by preventing apoptosis and autophagy via binding and activating AKT leading to increased glucose uptake and improved cellular bioenergetics. Unexpectedly, Rab25 induced the accumulation of glycogen in epithelial cancer cells, a process not previously identified. Strikingly, an increase in basal ATP levels combined with AKT‐dependent...

Depletion of the actin bundling protein SM22/transgelin increases actin dynamics and enhances the tumourigenic phenotypes of cells

BMC Cell Biology - Latest articles — Wed, 18 Jan 2012 05:00:00 +0100

Conclusions: These findings suggest that depletion of SM22 could contribute to tumourigenic properties of cells. Reduction in SM22 levels would tend to promote cell survival when cells are under stress, such as in a hypoxic tumour environment, and may also contribute to increases in actin dynamics that favour metastatic potential. (Source: BMC Cell Biology - Latest articles)

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Rapid Radiographic and Clinical Improvement After Treatment of a MET-Amplified Recurrent Glioblastoma With a Mesenchymal-Epithelial Transition Inhibitor [DIAGNOSIS IN ONCOLOGY]

Journal of Clinical Oncology — Wed, 18 Jan 2012 05:00:00 +0100

(Source: Journal of Clinical Oncology)

Carcinogens induce loss of the primary cilium in proximal tubular epithelial cells independent of effects on cell cycle.

Am J Physiol Renal P... — Wed, 18 Jan 2012 05:00:00 +0100

Discussion: The primary cilium represents a unique physical checkpoint with relevance to carcinogenesis. The results of this study suggest that the renal carcinogens OTA and KBrO3 caused significant deciliation in tubular epithelial cells. With KBrO3, this was followed by re-entry into the cell cycle, however deciliation did not coincide with re-entry into the cell cycle following OTA exposure. Transcriptomic analysis identified dysregulation of Wnt signalling and ciliary trafficking in response to OTA and KBrO(3) exposure. PMID: 22262483 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)

Elucidating prognosis and biology of breast cancer arising in young women using gene expression profiling.

Clinical Cancer Research — Wed, 18 Jan 2012 05:00:00 +0100

CONCLUSIONS: Proliferation-related prognostic gene signatures can aid treatment decision-making for young women. However, breast cancer arising at a young age appears to be biologically distinct beyond subtype distribution. Separate therapeutic approaches such as targeting RANKL or mammary stem cells could be therefore needed. PMID: 22261811 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Expression of Interleukin-4 Receptor Alpha by Human Pleura Mesothelioma is Associated with Poor Survival and Promotion of Tumor Inflammation.

Clinical Cancer Research — Wed, 18 Jan 2012 05:00:00 +0100

CONCLUSIONS: Tumor expression of IL-4Ra is inversely correlated with survival in patients undergoing surgical resection for epithelial MPM. Tumor-infiltrating T cells in MPM are polarized to produce IL-4 and may provide endogenous activation signals to MPM tumor cells in situ. The IL-4/IL-4 receptor axis is a potential therapeutic target in human MPM. PMID: 22261806 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

BMP signalling controls the malignant potential of ascites-derived human epithelial ovarian cancer spheroids via AKT kinase activation

Clinical and Experimental Metastasis — Tue, 17 Jan 2012 07:13:02 +0100

Abstract Epithelial ovarian cancer (EOC) cells have the ability to form multi-cellular aggregates in malignant ascites which dramatically alters cell signalling, survival, and metastatic potential. Herein, we demonstrate that patient ascites-derived EOC cells down-regulate endogenous bone morphogenetic protein (BMP) signalling by decreasing BMP ligand expression when grown in suspension culture to form spheroids. Enforced BMP signalling in these cells via constitutively-active BMP type I ALK3QD receptor expression causes the formation of smaller, more loosely-aggregated spheroids. Additionally, ALK3QD-expressing spheroids have an increased rate of adhesion and dispersion upon reattachment to substratum. Inhibition of endogenous BMP signalling using recombinant Noggin or smal...

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Rab25 is overexpressed in Müllerian serous carcinoma compared to malignant mesothelioma

Virchows Archiv — Tue, 17 Jan 2012 07:07:42 +0100

The objective of this study was to validate this finding at the mRNA and protein level. Quantitative PCR analysis of 112 Müllerian serous carcinomas (84 effusions, 28 primary ovarian carcinomas) and 22 malignant mesotheliomas (19 effusions, 3 solid specimens) showed significantly higher RAB25 mRNA expression in the former tumor (p < 0.001). Immunohistochemical analysis of Rab25 protein expression in 245 effusions showed significantly higher expression of this protein in Müllerian serous carcinoma compared to malignant mesothelioma (189/209 vs. 12/36 positive tumors, respectively; p < 0.001). Immunostaining of 101 patient-matched solid Müllerian carcinoma specimens (34 primary carcinomas, 67 metastases) showed expression levels comparable to effusions (94/101 positive...

Breast cancer spread triggered by a cleaver-wielding protein on cancer cell's surface

EurekAlert! - Medicine and Health — Tue, 17 Jan 2012 05:00:00 +0100

(University of Helsinki) Scientists from the University of Helsinki, Finland, and from UCSF have exposed a cell pathway that breast tumor cells use to destruct local tissue neighborhood. Cancer cells may use this pathway to free themselves from mammary epithelial tissue architecture, to spread to surrounding tissues. The findings could lead to a therapy for limiting the spread of breast cancer. (Source: EurekAlert! - Medicine and Health)

Collective and single cell behavior in epithelial contact inhibition [Cell Biology]

Proceedings of the National Academy of Sciences — Tue, 17 Jan 2012 05:00:00 +0100

Control of cell proliferation is a fundamental aspect of tissue physiology central to morphogenesis, wound healing, and cancer. Although many of the molecular genetic factors are now known, the system level regulation of growth is still poorly understood. A simple form of inhibition of cell proliferation is encountered in vitro in normally differentiating epithelial cell cultures and is known as “contact inhibition.” The study presented here provides a quantitative characterization of contact inhibition dynamics on tissue-wide and single cell levels. Using long-term tracking of cultured Madin-Darby canine kidney cells we demonstrate that inhibition of cell division in a confluent monolayer follows inhibition of cell motility and sets in when mechanical constraint on local expansion cau...

Topical vitamin A treatment of recalcitrant common warts

Virology Journal — Tue, 17 Jan 2012 05:00:00 +0100

Conclusion: Retinoids should be further investigated in controlled studies to determine their effectiveness in treating common warts and the broad range of other benign and cancerous lesions induced by HPVs. (Source: Virology Journal)

Matrix metalloproteinase (MMP-2 and MMP-9) and steroid receptor expressions in feline mammary tumors.

Biotechnic and Histochemistry — Tue, 17 Jan 2012 05:00:00 +0100

Authors: Akkoc A, Inan S, Sonmez G Abstract We evaluated the presence of estrogen (ER) and progesterone (PR) receptors, and matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) enzymes in 18 feline mammary tubulopapillary carcinomas. Immunohistochemistry was performed to localize ER, PR, MMP-2 and MMP-9 in situ. Western blotting and zymographic analyses also were performed to investigate the presence and activities of MMP-2 and MMP-9 enzymes in fresh tissue homogenates. ER immune expression was detected in five samples (27.7%) and PR was positive in sixteen (88.8%) samples. Diffuse cytoplasmic staining of MMP-2 and MMP-9 in neoplastic mammary epithelial cells, stromal fibroblasts and inflammatory cell was evident. MMP-2 and MMP-9 staining was observed also in m...

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Evaluation of in vitro cytotoxicity of one-dimensional chain [Fe(salen)(L)](n) complexes against human cancer cell lines.

Toxicology in Vitro — Tue, 17 Jan 2012 05:00:00 +0100

Authors: Dvořák Z, Starha P, Sindelář Z, Trávníček Z Abstract The 1d-polymeric iron(III) complexes [Fe(salen)(μ-L)](n) (1-6), involving a deprotonated form of the N-donor heterocyclic compounds (l) imidazole (complex 1), 1,2,4-triazole (2), benztriazole (3), 5-methyltetrazole (4), 5-aminotetrazole (5) and 5-phenyltetrazole (6), were studied for their in vitro cytotoxic activity against human cancer cell lines including lung carcinoma (A549), cervix epithelial carcinoma (HeLa), osteosarcoma (HOS), malignant melanoma (G361), breast adenocarcinoma (MCF7), ovarian carcinoma (A2780) and cisplatin-resistant ovarian carcinoma (A2780cis). Cytotoxicity in vitro (IC(50)=0.39-0.48μM) was achieved for 2-6 against A2780 (IC(50) of cisplatin equals 11.5μM) as well as for 5 and 6 agains...

Breast cancer spread triggered by a cleaver-wielding protein on cancer cell's surface

ScienceDaily Headlines — Tue, 17 Jan 2012 01:06:06 +0100

Scientists have exposed a cell pathway that breast tumor cells use to destruct local tissue neighborhood. Cancer cells may use this pathway to free themselves from mammary epithelial tissue architecture, to spread to surrounding tissues. The cell pathway, the researchers found, is a biochemical chain of events leading to activation of a protein-cleaving enzyme on the surface of the tumor cells. (Source: ScienceDaily Headlines)

Pericyte Depletion Results in Hypoxia-Associated Epithelial-to-Mesenchymal Transition and Metastasis Mediated by Met Signaling Pathway

Cancer Cell — Tue, 17 Jan 2012 00:00:00 +0100

Vesselina G. Cooke, Valerie S. LeBleu, Doruk Keskin, Zainab Khan, Joyce T. O'Connell, Yingqi Teng, Michael B. Duncan, Liang Xie, Genta Maeda, Sylvia Vong, Hikaru Sugimoto, Rafael M. Rocha, Aline Damascena, Ricardo R. Brentani, Raghu Kalluri. The functional role of pericytes in cancer progression remains unknown. Clinical studies suggest that low numbers of vessel-associated pericytes correlated with a drop in overall survival of patie.... (Source: Cancer Cell)

Role of JNK in Mammary Gland Development and Breast Cancer

Cancer Research — Mon, 16 Jan 2012 05:00:00 +0100

In this study, we employed a compound deletion of the murine Jnk1 and Jnk2 genes in the mammary gland to evaluate the requirement for these ubiquitously expressed genes in breast development and tumorigenesis. JNK1/2 was not required for breast epithelial cell proliferation or motility. However, JNK1/2 deficiency caused increased branching morphogenesis and defects in the clearance of lumenal epithelial cells. In the setting of breast cancer development, JNK1/2 deficiency significantly increased tumor formation. Together, these findings established that JNK signaling is required for normal mammary gland development and that it has a suppressive role in mammary tumorigenesis. Cancer Res; 72(2); 472–81. ©2011 AACR. (Source: Cancer Research)

Androgen Deprivation Causes Epithelial-Mesenchymal Transition in the Prostate: Implications for Androgen-Deprivation Therapy

Cancer Research — Mon, 16 Jan 2012 05:00:00 +0100

Androgen deprivation is currently a standard-of-care, first-line therapy for prostate cancer in the United States. Although this regimen effectively regresses androgen-dependent disease, relapse often occurs in an androgen-independent manner and is associated with poor prognosis. Such castration-resistant prostate cancer represents a major clinical challenge, and the mechanisms underlying castration resistance are not fully understood. Epithelial–mesenchymal transition (EMT) is a key developmental process and has also been implicated in cancer metastasis and therapeutic resistance in recent years. However, the factors contributing to EMT in human cancers remain unclear. Here, we show that both normal mouse prostate tissue and human LuCaP35 prostate tumor explants display an EMT as well a...

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New Gastroprotective Labdeneamides from (4S,9R,10R) Methyl 18-carboxy-labda-8,13(E)-diene-15-oate

Planta Medica — Mon, 16 Jan 2012 05:00:00 +0100

Planta MedDOI: 10.1055/s-0031-1280453AbstractStarting from the diterpene (4S,9R,10R) methyl 18-carboxy-labda-8,13(E)-dien-15-oate (PMD) and its 8(9)-en isomer [PMD 8(9)-en], 11 amides were prepared and assessed for a gastroprotective effect in the ethanol/HCl-induced gastric lesions model in mice. Basal cytotoxicity of the compounds was determined on the following human cell lines: normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), and hepatocellular carcinoma (Hep G2). All compounds are described for the first time. At the single oral dose of 0.1 mg/kg, compounds 1, 10, and 11 presented a strong gastroprotective effect, at least comparable with that of the reference compound lansoprazole at 1 mg/kg, reducing gastric lesions by 76.7, 67.7, and 77.2 %, respectiv...

Pre-Treatment Tumor Expression of ERCC1 in Women with Advanced Stage Epithelial Ovarian Cancer is Not Predictive of Clinical Outcomes: A Gynecologic Oncology Group Study.

Gynecologic Oncology — Mon, 16 Jan 2012 05:00:00 +0100

CONCLUSIONS: ERCC1 expression, measured by IHC in pre-treatment tumor specimens, using a highly specific antibody, has limited clinical value in patients with advanced EOC treated with platinum and taxane based chemotherapy. PMID: 22261301 [PubMed - as supplied by publisher] (Source: Gynecologic Oncology)

ERα, microRNAs, and the epithelial-mesenchymal transition in breast cancer.

Trends in Endocrinology and Metabolism: TEM — Mon, 16 Jan 2012 05:00:00 +0100

Authors: Guttilla IK, Adams BD, White BA Abstract The most common form of breast cancer, luminal A, is estrogen receptor α (ERα)-positive and epithelial, but nevertheless can metastasize. The process of epithelial-mesenchymal transition (EMT) is probably the first step in the metastasis of epithelial cancers. We discuss the characteristics of EMT, including factors that induce EMT, and the relationship of EMT to cancer stem cells (CSCs). Estrogen/ERα signaling maintains an epithelial phenotype and suppresses EMT. An overview of microRNAs in breast cancer is presented, including how microRNA biogenesis is altered in cancer and regulated by ERα. We also discuss the role of the miR-200 family in opposing EMT. Finally, we discuss specific microRNAs that target ERα and regulate EMT...

Label-free multiphoton imaging and photoablation of preinvasive cancer cells

Applied Physics Letters — Mon, 16 Jan 2012 03:35:18 +0100

Shuangmu Zhuo, Jianxin Chen, Guizhu Wu, Xiaoqin Zhu, Xingshan Jiang et al. Detection and treatment of early lesions in epithelial tissue offer several possibilities for curing cancer, but it is challenging. Here, we present an optical technique, the combination of multiphoton imaging and absorption, to label-freely detect and ablate preinvasive cancer cells in epithelial t ... [Appl. Phys. Lett. 100, 023703 (2012)] published Tue Jan 10, 2012. (Source: Applied Physics Letters)

Epithelial Sarcomas: Experience From a Single Institution

Journal of Surgical Research — Sat, 14 Jan 2012 22:29:58 +0100

Conclusions: Our study reveals that patients with epithelioid sarcomas can have long-term survival following surgical resection. Neither radiation nor chemotherapy affect outcome or recurrence. Importantly, patients with multiple recurrences continued to benefit from aggressive surgical treatment. Unlike prior reports, patients with lung metastasis did not have worse outcomes in our study. Epitheloid sarcomas are unique as they metastasize to regional nodal basins and all patients undergoing wide local excision should undergo simultaneous exploration of local lymph nodes. (Source: Journal of Surgical Research)

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MicroRNA-101 (miR-101) Promotes Expression of E-cadherin (E-Cad) By Relieving Epigenetic Repression in Epithelial Ovarian Cancer (EOC)

Journal of Surgical Research — Sat, 14 Jan 2012 22:29:58 +0100

Conclusions: miR-101 re-expression appears to have antitumor effects by enhancing the expression of E-Cad via down-regulation of Snail-1 and EzH2, paving the way for a possible therapeutic approach to EOC. (Source: Journal of Surgical Research)

IL-27 Mediated Inhibition of Epithelial to Mesenchymal Transition is Augmented by STAT1 Activator, 2-(1,8-naphthyridin-2-yl)phenol (2-NP) in Human Non-small Cell Lung Cancer

Journal of Surgical Research — Sat, 14 Jan 2012 22:29:06 +0100

Conclusions: We demonstrated that IL-27 activated both STAT1 and STAT3, but inhibited epithelial to mesenchymal transition in human lung cancer in a STAT1-dependent manner. IL-27-mediated inhibition of EMT is augmented by 2-NP through increased STAT1 and decreased STAT3 activation. We conclude that a STAT1 dominant pathway is important in modulation of EMT in carcinogenesis. (Source: Journal of Surgical Research)

RNA-Binding Protein TIA-1 Regulates Intestinal Epithelial Cell Apoptosis

Journal of Surgical Research — Sat, 14 Jan 2012 22:29:04 +0100

Conclusions: Therefore, our findings both identify miR-503 as novel regulator of TIA-1 and define a novel role for TIA-1 as a modulator of intestinal epithelial apoptosis. (Source: Journal of Surgical Research)

Human Mesenchymal Stem Cell and Epithelial Hepatic Carcinoma Cell Lines in Admixture: A Novel Method Demonstrating Concurrent Stimulation of CAF and EMT Markers

Journal of Surgical Research — Sat, 14 Jan 2012 22:28:56 +0100

(Source: Journal of Surgical Research)

Histomorphometry, apoptosis and cell proliferation in cervical intraepithelial neoplasia

Jornal Brasileiro de Patologia e Medicina Laboratorial — Sat, 14 Jan 2012 16:50:49 +0100

CONCLUSION: These data indicate that the pre-neoplastic process is dynamic and is concomitant with apoptosis and mitosis. (Source: Jornal Brasileiro de Patologia e Medicina Laboratorial)

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Characterization of gastric cancer models from different cell lines orthotopically constructed using improved implantation techniques.

World Journal of Gastroenterology : WJG — Sat, 14 Jan 2012 05:00:00 +0100

CONCLUSION: Models using the SGC-7901 and BGC-823 cell lines were established which could function in gastric cancer research on carcinogenesis mechanism and drug discovery. The two models showed different tumor behavior and the latter was more malignant than the former. PMID: 22253519 [PubMed - in process] (Source: World Journal of Gastroenterology : WJG)

Genome-wide analysis of HMGA2 transcription factor binding sites by ChIP on chip in gastric carcinoma cells.

Molecular and Cellular Biochemistry — Sat, 14 Jan 2012 05:00:00 +0100

Authors: Zha L, Wang Z, Tang W, Zhang N, Liao G, Huang Z Abstract High mobility group protein A2 (HMGA2) is an architectural transcription factor that plays an important role in development and progression of malignant neoplasias. Recently, some studies reported that HMGA2 is also implicated in epithelial-mesenchymal transitions (EMT) and cancer stem cells. But the underlying mechanisms of these conditions are poorly understood. Therefore, we established an EMT model of gastric carcinoma cells by overexpressing HMGA2 in vitro, then global mapping of HMGA2 potential transcription factor binding sites was identified by promoter microarray in these cells, and the date obtained from the microarrays were validated via chromatin immunoprecipitation-PCR (ChIP-PCR) and real-time PCR. HMGA2...

Minocycline inhibits growth of epithelial ovarian cancer.

Gynecologic Oncology — Sat, 14 Jan 2012 05:00:00 +0100

CONCLUSION: These findings provide the initial basis for further evaluation of minocycline in the treatment of ovarian cancer. PMID: 22252097 [PubMed - as supplied by publisher] (Source: Gynecologic Oncology)

An integrative genomic approach identifies p73 and p63 as activators of miR-200 microRNA family transcription

Nucleic Acids Research — Fri, 13 Jan 2012 05:00:00 +0100

This study delineates an integrative approach that can be applied to discover transcriptional regulatory mechanisms in other biological settings where analogous genomic data are available. (Source: Nucleic Acids Research)

Thymoma and thymic carcinoma

General Thoracic and Cardiovascular Surgery — Thu, 12 Jan 2012 06:43:57 +0100

Abstract Thymic tumors comprise a heterogeneous group of neoplasms with a wide spectrum of clinical presentations. The evolution of the disease is often unpredictable, ranging from an indolent attitude to the possibility of intra- and extrathoracic spread. From the histological point of view, thymoma and thymic carcinoma are the most frequent subtypes and arise only from thymic epithelial cells. Other histological types are even more rare and are usually considered separately. A number of prognostic factors have been validated as predictors of outcome: staging, World Health Organization histological classification, diameter of the tumor, associated paraneoplastic syndromes, completeness of resection, and early onset of recurrence. Complete surgical resection is the key fac...

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Molecular Pathogenesis of Granulosa Cell Tumors of the Ovary.

ENDOCR REV — Thu, 12 Jan 2012 05:00:00 +0100

Authors: Jamieson S, Fuller PJ Abstract Granulosa cell tumors of the ovary (GCT) comprise a distinct subset of ovarian cancers that account for approximately 5% of all ovarian malignancies. They are thought to arise from normal proliferating granulosa cells of the late preovulatory follicle and exhibit many morphological and biochemical features of these cells. GCT are distinct from other ovarian carcinomas in their hormonal activity; their ability to secrete estrogen, inhibin, and Müllerian inhibiting substance accounts for some of the clinical manifestations of the disease and also provides useful tumor markers for disease surveillance. Although considered to be of low malignant potential, GCT are commonly associated with slow, indolent disease progression, and frequent yet long...

Identification of mammary epithelial cells subject to chronic oxidative stress in mammary epithelium of young women and teenagers living in USA: Implication for breast carcinogenesis.

Cancer Biology and Therapy — Thu, 12 Jan 2012 04:00:43 +0100

Authors: Weisz J, Shearer DA, Murata E, Patrick SD, Han B, Berg A, Clawson GA Abstract Current knowledge of changes in the mammary epithelium relevant to breast carcinogenesis is limited to when histological changes are already present because of a lack of biomarkers needed to identify where such molecular changes might be ongoing at earlier during the of decades-long latent stages of breast carcinogenesis. Breast reduction tissues from young women and teenagers, representative of USA's high breast cancer incidence population, were studies using immunocytochemistry and targeted PCR arrays in order to learn whether a marker of chronic oxidative-stress [protein adducts of 4-hydroxy-2-nonenal (4HNE)] can identify where molecular changes relevant to carcinogenesis might be taking place...

Adenovirus-mediated expression of p33ING1b induces apoptosis and inhibits proliferation in gastric adenocarcinoma cells in vitro

Gastric Cancer — Wed, 11 Jan 2012 17:52:12 +0100

Conclusions Down-regulation of p33ING1b might play an important role in the development of gastric adenocarcinoma. Targeted local expression of p33ING1b may offer a promising alternative therapeutic measure for gastric cancer. Content Type Journal ArticleCategory Original articlePages 1-8DOI 10.1007/s10120-011-0123-4Authors Yifei Lv, Department of Gastroenterology, 1st Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, 710061 Xi’an, ChinaBibek Kumar Purbey, Department of Gastroenterology, 1st Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, 710061 Xi’an, ChinaYanhua Huang, Department of Gastroenterology, 1st Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, 710061 Xi’an, ChinaShuang Li, Department of Ga...

Generation of SV40-transformed rabbit tracheal-epithelial-cell-derived blastocyst by somatic cell nuclear transfer

Cell and Tissue Research — Wed, 11 Jan 2012 06:56:09 +0100

This study describes the successful establishment and characterization of two SV40-transformed rabbit tracheal epithelial cell lines. These cell lines, 5RTEo- and 9RTEo-, express the CF transmembrane conductance regulator (CFTR) gene, retain epithelial-specific differentiated morphology and show CFTR-based cAMP-dependent Cl− ion transport across the apical membrane of a confluent monolayer. Immunocytochemical analysis indicates the presence of airway cytokeratins and tight-junction proteins in the 9RTEo- cell line after multiple generations. However, the tight junctions appear to diminish in their efficacy in both cell lines after at least 100 generations. Initial SCNT studies with the 9RTEo- cells have revealed that SV40-transformed rabbit airway epithelial donor cells can be ...

Altered CXCR3 Isoform Expression Regulates Prostate Cancer Cell Migration and Invasion

Molecular Cancer — Wed, 11 Jan 2012 05:00:00 +0100

CONCLUSION: These data suggest that the aberrant expression of CXCR3A and down-regulation of CXCR3B may switch a progression "stop" to a "go" signal to promote prostate tumor metastasis via stimulating cell migration and invasion. (Source: Molecular Cancer)

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Matrix rigidity regulates a switch between TGF-β1-induced apoptosis and epithelial-mesenchymal transition.

Mol Biol Cell — Wed, 11 Jan 2012 05:00:00 +0100

Authors: Leight JL, Wozniak MA, Chen S, Lynch ML, Chen CS Abstract The transforming growth factor-β (TGF-β) signaling pathway is often misregulated during cancer progression. In early stages of tumorigenesis, TGF-β acts as a tumor suppressor by inhibiting proliferation and inducing apoptosis. However, as the disease progresses, TGF-β switches to promote tumorigenic cell functions, such as epithelial-mesenchymal transition (EMT) and increased cell motility. Dramatic changes in the cellular microenvironment are also correlated with tumor progression, including an increase in tissue stiffness. However, it is unknown if these changes in tissue stiffness can regulate the effects of TGF-β. To this end, we examined NMuMG and MDCK epithelial cells cultured on polyacrylamide gels with ...

Fer kinase regulates cell migration through α-dystroglycan glycosylation.

Mol Biol Cell — Wed, 11 Jan 2012 05:00:00 +0100

Authors: Yoneyama T, Angata K, Bao X, Courtneidge S, Chanda S, Fukuda M Abstract Glycans of α-dystroglycan (α-DG), which is expressed at the epithelial cell-basement membrane (BM) interface, play an essential role in epithelium development and tissue organization. Laminin-binding glycans on α-DG expressed on cancer cells suppress tumor progression by attenuating tumor cell migration from the BM. However, mechanisms controlling laminin-binding glycan expression are not known yet. Here, we used siRNA library screening and identified Fer kinase, a non-receptor type tyrosine kinase, as a key regulator of laminin-binding glycan expression. Fer overexpression decreased laminin-binding glycan expression, while siRNA-mediated down-regulation of Fer kinase increased glycan expression on ...

Radiosensitizing effect of epothilone B on human epithelial cancer cells

Strahlentherapie und Onkologie — Tue, 10 Jan 2012 17:00:57 +0100

Conclusion The results of this study showed that epothilone B displays cytotoxic antitumor activity at low nanomolar concentrations and also enhances the radiation response in the tumor cells tested; this may be induced by a reduced DNA repair capacity triggered by epothilone B. It was also demonstrated that epothilone B in fact targets microtubules in a more effective manner than paclitaxel. Content Type Journal ArticleCategory Original articlePages 1-9DOI 10.1007/s00066-011-0029-4Authors T. Baumgart, Department of Radiotherapy and Radiation Oncology, University of Rostock, Südring 75, 18059 Rostock, GermanyG. Klautke, Department of Radiation Oncology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, GermanyS. Kriesen, Department of Radi...

Regulation of the metabolism of polyunsaturated fatty acids and butyrate in colon cancer cells.

Current Pharmaceutical Biotechnology — Tue, 10 Jan 2012 15:30:48 +0100

Authors: Hofmanová J, Vaculová A, Kozubík A Abstract Experimental and epidemiological evidence supports the idea that dietary fat and fiber influence colon carcinogenesis. Particularly, their components, n-3 polyunsaturated fatty acids (PUFAs) and butyrate, have been proven to exhibit beneficial effects on colon epithelial cell metabolism, signaling, and kinetics, thus preventing colon inflammation and cancer. Moreover, these effects may be strengthened by PUFA and butyrate combination. It appears that administration of these compounds might be a relatively nontoxic form of supportive therapy improving cancer treatment outcomes and slowing down or preventing recurrence of certain types of cancer. However, their efficient application has to be based on solid scientific evidence o...