MedWorm: Epithelial Cancer

Metabolomic Changes Accompanying Transformation and Acquisition of Metastatic Potential in a Syngeneic Mouse Mammary Tumor Model [Genomics and Proteomics]

Journal of Biological Chemistry — Fri, 19 Mar 2010 13:36:02 +0100

Breast cancer is the most common cancer type for women in the western world. Despite decades of research, the molecular processes associated with breast cancer progression are still inadequately defined. Here, we focus on the systematic alteration of metabolism by using the state of the art metabolomic profiling techniques to investigate the changes of 157 metabolites during the progression of normal mouse mammary epithelial cells to an isogenic series of mammary tumor cell lines with increasing metastatic potentials. Our results suggest a two-step metabolic progression hypothesis during the acquisition of tumorigenic and metastatic abilities. Metabolite changes accompanying tumor progression are identified in the intracellular and secreted forms in several pathways, including glycolysis, ...

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The A61G EGF polymorphism is associated with development of extraaxial nervous system tumors but not with overall survival

Cancer Genetics and Cytogenetics — Thu, 18 Mar 2010 16:03:03 +0100

Abstract: Epidermal growth factor can activate several signaling pathways, leading to proliferation, differentiation, and tumorigenesis of epithelial tissues by binding with its receptor. The EGF protein is involved in nervous system development, and polymorphisms in the EGF gene on chromosome band 4q25 are associated with brain cancers. The purpose of this study was to investigate the association between the single-nucleotide polymorphism of EGF+61G/A and extraaxial brain tumors in a population of the southeast of Brazil. We analyzed the genotype distribution of this polymorphism in 90 patients and 100 healthy subjects, using the polymerase chain reaction–restriction fragment length polymorphism technique. Comparison of genotype distribution revealed a significant difference between pat...

Dynamic Regulation of CD24 and the Invasive, CD44posCD24neg Phenotype in Breast Cancer Cell Lines

Medscape Today Headlines — Thu, 18 Mar 2010 11:04:28 +0100

Investigators demonstrated that noninvasive, epithelial-like CD44posCD24pos cells readily give rise to invasive, mesenchymal CD44posCD24neg progeny in vivo and in vitro. Breast Cancer Research (Source: Medscape Today Headlines)

Study Finds Link Between Healthy Diets, Length Of Ovarian Cancer Survival

Health News from Medical News Today — Thu, 18 Mar 2010 11:00:00 +0100

Diets full of fruits, vegetables and healthy grains may be associated with higher rates of ovarian cancer survival, according to a study recently published in the Journal of the American Dietetic Association, the Los Angeles Times' "Booster Shots" reports. Researchers at the University of Illinois-Chicago examined a longitudinal study on the self-reported diets of 351 women for the three to five years prior to being diagnosed with epithelial ovarian cancer.The study found that eating more fruits, vegetables and healthy grains was associated with longer survival times... (Source: Health News from Medical News Today)

Functional Remodeling Of Benign Human Prostatic Tissues In Vivo By Spontaneously Immortalized Progenitor And Intermediate Cells

Health News from Medical News Today — Thu, 18 Mar 2010 07:00:00 +0100

UroToday.com - Adult tissue regeneration or remodeling is suggested to initiate from multipotent stem and/or progenitor cells. We recently reported two new human adult non-tumorigenic prostatic epithelial cell lines NHPrE1 and BHPrE1, which were generated and characterized in our laboratory. NHPrE1 cells were designated as putative progenitor cells, showing high expression levels of stem cells-associated proteins CD133, CD44, OCT4 and PTEN as detected by immunofluorescence (IF) staining and Western blotting... (Source: Health News from Medical News Today)

Functional Remodeling Of Benign Human Prostatic Tissues In Vivo By Spontaneously Immortalized Progenitor And Intermediate Cells

Prostate News From Medical News Today — Thu, 18 Mar 2010 07:00:00 +0100

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Effects of UVB-induced oxidative stress on protein expression and specific protein oxidation in normal human epithelial keratinocytes: a proteomic approach

BioMed Central — Thu, 18 Mar 2010 00:00:00 +0100

Conclusions: Despite a wide and well orchestrated cellular response, a relevant oxidation of specific proteins concomitantly occurs in UVB-irradiated human epithelial Keratinocytes. These modified (i.e. likely dysfunctional) proteins might result in cell homeostasis impairment and therefore eventually promote cellular degeneration, senescence or carcinogenesis. (Source: BioMed Central)

New Ovarian Cancer Study Results Reported From University of Miami

Cancercompass News: Gynecological Cancer — Thu, 18 Mar 2010 00:00:00 +0100

According to recent research published in the journal Gynecologic Oncology, Current treatment options for epithelial ovarian cancer are limited and therapeutic development for recurrent and drug-resistant ovarian cancer is an urgent agenda. We investigated the potential use of genetically engineered Vesicular Stomatitis Virus (VSV) to treat ovarian cancer patients who fail to respond to available therapies. (Source: Cancercompass News: Gynecological Cancer)

Kruppel-like factor 5 is a crucial mediator of intestinal tumorigenesis in mice harboring combined ApcMin and KRASV12 mutations

Molecular Cancer — Thu, 18 Mar 2010 00:00:00 +0100

Conclusions: Results of the current study confirm the cumulative effect of Apc loss and oncogenic KRAS activation on intestinal tumorigenesis. The drastic reduction in tumor number and size due to Klf5 heterozygosity in ApcMin/KRASV12 mice indicate a critical function of KLF5 in modulating intestinal tumor initiation and progression. (Source: Molecular Cancer)

Molecular signaling of the epithelial to mesenchymal transition in generating and maintaining cancer stem cells.

Cellular and Molecular Life Sciences : CMLS — Thu, 18 Mar 2010 00:00:00 +0100

Authors: Ouyang G, Wang Z, Fang X, Liu J, Yang CJ The epithelial to mesenchymal transition (EMT) is a highly conserved cellular program that allows polarized, well-differentiated epithelial cells to convert to unpolarized, motile mesenchymal cells. EMT is critical for appropriate embryogenesis and plays a crucial role in tumorigenesis and cancer progression. Recent studies revealed that there is a direct link between the EMT program and the gain of epithelial stem cell properties. EMT is sufficient to induce a population with stem cell characteristics from well-differentiated epithelial cells and cancer cells. In this review, we briefly introduce the biology of EMT inducers and transcription factors in tumorigenesis and then focus on the role of these key players of the EMT in generati...

AuNP-DG: Deoxyglucose-Labeled Gold Nanoparticles as X-ray Computed Tomography Contrast Agents for Cancer Imaging

Molecular Imaging and Biology — Wed, 17 Mar 2010 15:51:05 +0100

Conclusions Results from this study demonstrate enhanced uptake of 2-DG-labeled gold nanoparticle by cancer cells in vitro and warrant further experiments to study the exact molecular mechanism by which the AuNP-DG is internalized and retained in the tumor cells. Content Type Journal ArticleCategory Rapid CommunicationDOI 10.1007/s11307-010-0299-8Authors Bulent Aydogan, The University of Chicago Department of Radiation and Cellular Oncology Chicago IL USAJi Li, The University of Chicago Department of Radiation and Cellular Oncology Chicago IL USATijana Rajh, Argonne National Laboratory Center for Nanoscale Materials Argonne IL USAAhmed Chaudhary, The University of Chicago Department of Radiation and Cellular Oncology Chicago IL USASteven J. Chmura, The University of ...

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Epithelial Protein Lost in Neoplasm alpha (Eplin-alpha) is transcriptionally regulated by G-actin and MAL/MRTF coactivators

Molecular Cancer — Wed, 17 Mar 2010 00:00:00 +0100

Epithelial Protein Lost in Neoplasm alpha is a novel cytoskeleton-associated tumor suppressor whose expression inversely correlates with cell growth, motility, invasion and cancer mortality. Here we show that Eplin-alpha transcription is regulated by actin-MAL-SRF signalling. Upon signal induction, the coactivator MAL/MRTF is released from a repressive complex with monomeric actin, binds the transcription factor SRF and activates target gene expression. In a transcriptome analysis with a combination of actin binding drugs which specifically and differentially interfere with the actin-MAL complex (Descot et al., 2009), we identified Eplin to be primarily controlled by monomeric actin. Further analysis revealed that induction of the Eplin-alpha mRNA and its promoter was sensitive to drugs an...

High-throughput analysis of chromosome translocations and other genome rearrangements in epithelial cancers

BioMed Central — Wed, 17 Mar 2010 00:00:00 +0100

Genes that are broken or fused by structural changes to the genome are an important class of mutation in the leukemias and sarcomas but have been largely overlooked in the common epithelial cancers. Large-scale sequencing is changing our perceptions of the cancer genome, and it is now being applied to structural changes, using the 'paired end' strategy. This reveals more clearly than before the extent to which many cancer genomes are rearranged and how much these rearrangements contribute to the mutational burden of epithelial tumors. In particular, there are probably many fusion genes, analogous to those found in leukemias, to be found in common cancers, such as breast carcinoma, and some of these will prove to be important in cancer diagnosis and treatment. (Source: BioMed Central)

Reduced uptake of the proliferation-seeking radiotracer technetium-99m-labelled pentavalent dimercaptosuccinic acid in a 47-year-old woman with severe breast epithelial hyperplasia taking ibuprofen: a case report

BioMed Central — Wed, 17 Mar 2010 00:00:00 +0100

Conclusion: In proliferating breast lesions, scintigraphically displayed reduction in Technetium-99m-labelled pentavalent dimercaptosuccinic acid uptake may indicate inhibition by ibuprofen in the pathway of malignant epithelial cell transformation. (Source: BioMed Central)

Mesothelioma Subtypes: Do They Really Affect Prognosis?

Asbestos and Mesothelioma News — Tue, 16 Mar 2010 22:40:46 +0100

In conclusion, the researchers found, “The extremely poor prognosis of sarcomatoid malignant pleural mesothelioma is independent of the extent of surgery unlike other cell types. Patients with sarcomatoid histology should therefore be considered separately in trials evaluating radical procedures and adjuvant treatment. The treatment of biphasic pleural mesothelioma remains debatable.” Additional information on mesothelioma may be found through the Mesothelioma Center. (Source: Asbestos and Mesothelioma News)

Dose-dependent induction of distinct phenotypic responses to Notch pathway activation in mammary epithelial cells [Cell_Biology]

Proceedings of the National Academy of Sciences — Tue, 16 Mar 2010 19:33:04 +0100

Aberrant activation of Notch receptors has been implicated in breast cancer; however, the mechanisms contributing to Notch-dependent transformation remain elusive... (Source: Proceedings of the National Academy of Sciences)

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Genetic and epigenetic silencing of the beclin 1 gene in sporadic breast tumors

BMC Cancer — Tue, 16 Mar 2010 00:00:00 +0100

Conclusions: : These data indicated that LOH and aberrant DNA methylation might be the possible reasons of the decreased expression of beclin 1 in the breast tumors. The findings here shed some new light on the regulatory mechanisms of beclin 1 in breast cancer. (Source: BMC Cancer)

Flavokawain B, a kava chalcone, induces apoptosis via up-regulation of death-receptor 5 and Bim expression in androgen receptor negative, hormonal refractory prostate cancer cell lines and reduces tumor growth

International Journal of Cancer — Tue, 16 Mar 2010 00:00:00 +0100

Limited success has been achieved in extending the survival of patients with metastatic and hormone-refractory prostate cancer (HRPC). There is a strong need for novel agents in the treatment and prevention of HRPC. We have shown that flavokawain B (FKB), a kava chalcone, is about 4- to 12-fold more effective in reducing the cell viabilities of androgen receptor (AR)-negative, HRPC cell lines DU145 and PC-3 than AR-positive, hormone-sensitive prostate cancer cell lines LAPC4 and LNCaP, with minimal effect on normal prostatic epithelial and stromal cells. FKB induces apoptosis with an associated increased expression of proapoptotic proteins: death receptor-5, Bim and Puma and a decreased expression of inhibitors of apoptosis protein: XIAP and survivin. Among them, Bim expression was signifi...

Cardiovascular Effects in Rats following Exposure to a Receptor Tyrosine Kinase Inhibitor.

Toxicologic Pathology — Tue, 16 Mar 2010 00:00:00 +0100

Authors: Aguirre SA, Heyen JR, Collette W, Bobrowski W, Blasi ER The receptor tyrosine kinase receptor (RTK) signaling pathway, mesenchymal-epithelial transition factor (c-Met)/hepatocyte growth factor receptor (HGFR), has been implicated in oncogenesis and is a target of interest in cancer therapy. PF-04254644 is a potent and selective inhibitor of c-Met/HGFR. Wide ligand binding profiling of PF-04254644 revealed a potentially significant interaction with phosphodiesterase (PDE) 3, and follow-up PDE enzyme activity assays confirmed PF-04254644 as a potent inhibitor of PDE3 as well as other PDEs (1, 2, 5, 10, and 11). Clinical observations, laboratory, and echocardiography parameters were recorded in Sprague-Dawley (SD) rats that received PF-04254644 oral dosing for up to seven consecu...

Forkhead Box F1 Regulates Tumor-Promoting Properties of Cancer-Associated Fibroblasts in Lung Cancer.

Cell Research — Tue, 16 Mar 2010 00:00:00 +0100

Authors: Saito RA, Micke P, Paulsson J, Augsten M, Peña C, Jönsson P, Botling J, Edlund K, Johansson L, Carlsson P, Jirström K, Miyazono K, Ostman A Cancer-associated fibroblasts (CAF) attract increasing attention as potential cancer drug targets due to their ability to stimulate, for example, tumor growth, invasion, angiogenesis, and metastasis. However, the molecular mechanisms causing the tumor-promoting properties of CAFs remain poorly understood. Forkhead box F1 (FoxF1) is a mesenchymal target of hedgehog signaling, known to regulate mesenchymal-epithelial interactions during lung development. Studies with FoxF1 gain- and loss-of-function fibroblasts revealed that FoxF1 regulates the contractility of fibroblasts, their production of hepatocyte growth factor and fibr...

Tumor-Suppressive Functions of Leucine Zipper Transcription Factor-Like 1.

Cell Research — Tue, 16 Mar 2010 00:00:00 +0100

Authors: Wei Q, Zhou W, Wang W, Gao B, Wang L, Cao J, Liu ZP Human leucine zipper transcription factor-like 1 (LZTFL1) is a novel gene with unknown biological functions. It is located in the chromosome region 3p21.3, a hotspot for tumor suppressor genes. To understand the biological functions of LZTFL1, we surveyed the expression level of LZTFL1 in tumor and normal samples in tissue microarrays and a clinical archive of 84 gastric cancer specimens using immunohistochemistry. We found that LZTFL1 is expressed highly in the epithelial cells of normal tissues and is significantly downregulated in the corresponding tumor samples. The expression level of LZTFL1 correlated significantly with the survival outcomes of the patients and had significant inverse correlation with tumor metastasis. ...

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A NADPH Oxidase-Dependent Redox Signaling Pathway Mediates the Selective Radiosensitization Effect of Parthenolide in Prostate Cancer Cells.

Cell Research — Tue, 16 Mar 2010 00:00:00 +0100

Authors: Sun Y, St Clair DK, Xu Y, Crooks PA, St Clair WH Cancer cells are usually under higher oxidative stress compared with normal cells. We hypothesize that introducing additional reactive oxygen species (ROS) insults or suppressing antioxidant capacity may selectively enhance cancer cell killing by oxidative stress-generating agents through stress overload or stress sensitization, whereas normal cells may be able to maintain redox homeostasis under exogenous ROS by adaptive response. Here, we show that parthenolide, a sesquiterpene lactone, selectively exhibits a radiosensitization effect on prostate cancer PC3 cells but not on normal prostate epithelial PrEC cells. Parthenolide causes oxidative stress in PC3 cells but not in PrEC cells, as determined by the oxidation of the ROS-s...

Mesothelioma Treatment: Potential Vaccination to Combat Asbestos Cancer

Asbestos and Mesothelioma News — Mon, 15 Mar 2010 17:42:51 +0100

Recent findings from a study that have been published in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine have indicated a potential vaccine that can be safely used to combat mesothelioma cancer. The vaccine helps combine a patient’s own dentritic cells (DC) with an antigen from the patient’s mesothelioma tumor. As a result, a T-cell response against the mesothelioma tumor can be generated. According to Joachim G Aerts, a researcher and pulmonary physician at Erasmus Medical Center in the Netherlands, “This is the first human study on DC-based immunotherapy in patients with mesothelioma.” While previous research showed dentritic cell vaccinations could cause anti-tumor immunity and improved survival in mice, Dr. Aerts and colleagues s...

LYN Is a Mediator of Epithelial-Mesenchymal Transition and a Target of Dasatinib in Breast Cancer

Cancer Research — Mon, 15 Mar 2010 04:07:28 +0100

Findings suggest how to focus an attack on ‘triple-negative’ breast cancers, which presently lack effective treatment options. (Source: Cancer Research)

Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer

Oncogene — Mon, 15 Mar 2010 00:00:00 +0100

Authors: K-S Lee, Y-S Lee, J-M Lee, K Ito, S Cinghu, J-H Kim, J-W Jang, Y-H Li, Y-M Goh, X-Z Chi, H Wee, H-W Lee, A Hosoya, J-H Chung, J-J Jang, J K Kundu, Y-J Surh, W-J Kim, Y Ito, H-S Jung & S-C Bae (Source: Oncogene)

Overexpression of dicer as a result of reduced let-7 MicroRNA levels contributes to increased cell proliferation of oral cancer cells

Genes, Chromosomes and Cancer — Mon, 15 Mar 2010 00:00:00 +0100

Recent reports have demonstrated that Dicer, an RNase III endonuclease required for microRNA (miRNA) maturation, is aberrantly expressed in different types of cancer. Furthermore, Dicer has been reported to be regulated by the let-7 family of miRNA genes. We hypothesize that Dicer is aberrantly expressed in oral cancer cells due to altered expressions of let-7 and that Dicer contributes to the development and progression of the disease. Western blot examination of Dicer protein levels in four head and neck squamous cell carcinoma (HNSCC) cell lines, including two oral cancer cell lines, demonstrated that Dicer had between 4- and 24-fold higher expression levels when compared to normal human primary gingival epithelial cells. Furthermore, five of six oral cancer tissues analyzed by indirect...

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Transcriptional regulation of Rex1 (zfp42) in normal prostate epithelial cells and prostate cancer cells

Journal of Cellular Physiology — Mon, 15 Mar 2010 00:00:00 +0100

Rex1 (zfp42) was identified by our laboratory because of its reduced expression in F9 teratocarcinoma stem cells after retinoic acid (RA) treatment. The Rex1 (Zfp42) gene is currently widely used as a marker of embryonic stem cells. We compared the transcriptional regulation of the human Rex1 gene in NTera-2 (NT-2) human teratocarcinoma, normal human prostate epithelial cells (PrEC), and prostate cancer cells (PC-3) by promoter/luciferase analyses. Oct4, Sox2, Nanog, and Dax1 transcripts are expressed at higher levels in NT-2 and PrEC cells than in PC-3 cells. Co-transfection analyses showed that YY1 and Rex1 are positive regulators of hRex1 transcription in NT-2 and PrEC cells, whereas Nanog is not. Serial deletion constructs of the hRex1 promoter were created and analyzed, by which we id...

Small cell carcinoma of the brain without extracranial involvement by serial CT, MRI and PET.

International Journal of Clinical and Experimental Pathology — Sun, 14 Mar 2010 20:24:03 +0100

Authors: Terada T The author reports herein a case of small cell carcinoma of the brain without extracranial tumors by serial imaging modalities. A 75-year-old man presented with headache. Brain CT and MRI revealed a solitary cystic tumor (5 x 6 x 7 cm) in the left occipital lobe. Blood laboratory test revealed no significant findings. Preoperative diagnosis was a primary or metastatic brain tumor. Preoperative systemic examinations including CT, MRI and PET revealed no extracranial tumors. Tumorectomy was performed. Pathologically, the tumor was small cell carcinoma positive for four types of pancytokeratins, cytokeratin (CK) 7, CK 18, thyroid transcriptional factor-1 (TTF-1), CD56, chromogranin, synaptophysin, neuron-specific enolase, p53 protein, KIT, PDGFRA, and Ki-67 antigen (labe...

Sarcomatoid carcinoma of the prostate: a case report.

International Journal of Clinical and Experimental Pathology — Sun, 14 Mar 2010 20:24:03 +0100

We report a case of a 76-year old Caucasian man who underwent transurethral resection of the prostate for the treatment of bladder outlet obstruction. Histopathologic examination revealed a tumor with malignant epithelial and sarcomatous elements. The malignant epithelial component consisted of poorly differentiated adenocarcinoma (Gleason score 5+4=9/10) and the sarcomatous component was mainly composed of undifferentiated spindle cells. On immunohistochemistrythe latter expressed a positive staining for vimentin. Several cells were positively stained for cytockeratin AE3 and myoD1 while all were negative for actin, desmin and myogenin. The diagnosis of sarcomatoid carcinoma was finally made. Although sarcomatoid carcinoma of the prostate is a highly aggressive neoplasm and patients have ...

Nicotine-induced human breast cancer cell proliferation attenuated by garcinol through down-regulation of the nicotinic receptor and cyclin D3 proteins

Breast Cancer Research and Treatment — Sun, 14 Mar 2010 11:26:12 +0100

Abstract Previous studies have demonstrated that the persistent exposure of human bronchial epithelial cells to nicotine (Nic) through nicotinic acetylcholine receptors increases cyclin D1 promoter activity and protein expression. The main purpose of this study is to elucidate the carcinogenic role of cyclin D3, which is involved in breast tumorigenesis when induced by Nic. Real-time PCR analysis revealed that cyclin D3 is highly expressed at the mRNA level in surgically dissected breast tumor tissue, compared to the surrounding normal tissue (tumor/normal fold ratio = 17.93, n = 74). To test whether Nic/nicotinic acetylcholine receptor (nAChR) binding could affect cyclin D3 expression in human breast cancer cells, the transformed cell line MCF-10A-Nic (...

Dihydroartemisinin upregulates death receptor 5 expression and cooperates with TRAIL to induce apoptosis in human prostate cancer cells.

Cancer Biology and Therapy — Sun, 14 Mar 2010 07:02:04 +0100

Authors: He Q, Shi J, Shen XL, An J, Sun H, Wang L, Hu YJ, Sun Q, Fu LC, Sheikh MS, Huang Y Dihydroartemisinin (DHA) is a derivative of artemisinin and is an effective anti-malaria therapeutic used worldwide. In this paper, we report that DHA is as a potential anti-cancer drug for prostate cancer. Our data indicate that DHA suppresses the PI3-K/Akt and ERK cell survival pathways and triggers the induction of death receptor DR5 and activation of extrinsic and intrinsic cell death signaling. DHA-mediated DR5 induction appears to occur via increased transcriptional activity of DR5 promoter. Our data also show that, while DHA has strong cytotocixity in tumor cells, it exhibits minimal cytotoxic effects on normal prostate epithelial cells. Our studies also demonstrate that DHA worked cooper...

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The role of activation-induced cell death in the higher onset of spontaneous apoptosis of NK cell subsets in patients with metastatic epithelial cancer.

Cellular Immunology — Sun, 14 Mar 2010 06:34:03 +0100

Authors: Stanzer S, Janesch B, Resel M, Augustin T, Samonigg H, Bauernhofer T To address the question whether the higher onset of apoptosis of circulating NK cell subsets might be activation induced in cancer patients, surface expression of NKG2D and serum (s) levels of MHC class I chain-related (MIC) proteins in relation to apoptosis marker and CD95 expression on NK cells were evaluated. Patients showed a significantly higher onset of spontaneous apoptosis of CD56dim NK cells. No difference in the CD95 expression could be detected between patients and normal controls (NCs). Patients' CD56bright NK cells demonstrated a higher expression of NKG2D compared to CD56dim NK cells. The sMICB levels showed a higher level in patients versus NCs. No correlation between sMIC protein levels with b...

Northwestern profiling of potential translation-regulatory proteins in human breast epithelial cells and malignant breast tissues: Evidence for pathological activation of the IGF1R IRES.

Experimental and Molecular Pathology — Sat, 13 Mar 2010 00:00:00 +0100

Authors: Blume SW, Jackson NL, Frost AR, Grizzle WE, Shcherbakov OD, Choi H, Meng Z Genes involved in the control of cell proliferation and survival (those genes most important to cancer pathogenesis) are often specifically regulated at the translational level, through RNA-protein interactions involving the 5'-untranslated region of the mRNA. IGF1R is a proto-oncogene strongly implicated in human breast cancer, promoting survival and proliferation of tumor cells, as well as metastasis and chemoresistance. Our lab has focused on the molecular mechanisms regulating IGF1R expression at the translational level. We previously discovered an internal ribosome entry site (IRES) within the 5'-untranslated region of the human IGF1R mRNA, and identified and functionally characterized two individu...

Epithelial Cell Adhesion Molecule Regulation Is Associated with the Maintenance of the Undifferentiated Phenotype of Human Embryonic Stem Cells [Cell Biology]

Journal of Biological Chemistry — Fri, 12 Mar 2010 14:36:06 +0100

Human embryonic stem cells (hESCs) are unique pluripotent cells capable of self-renewal and differentiation into all three germ layers. To date, more cell surface markers capable of reliably identifying hESCs are needed. The epithelial cell adhesion molecule (EpCAM) is a type I transmembrane glycoprotein expressed in several progenitor cell populations and cancers. It has been used to enrich cells with tumor-initiating activity in xenograft transplantation studies. Here, we comprehensively profile the expression of EpCAM by immunofluorescence microscopy, Western blotting, and flow cytometry using an anti-EpCAM monoclonal antibody (mAb) OC98-1. We found EpCAM to be highly and selectively expressed by undifferentiated rather than differentiated hESCs. The protein and transcript level of EpCA...

Biological and clinical implications of nicastrin expression in invasive breast cancer

Breast Cancer Research and Treatment — Thu, 11 Mar 2010 18:24:24 +0100

Abstract Nicastrin is an essential component of the gamma secretase (GS) enzyme complex, required for its synthesis and recognition of substrates for proteolytic cleavage. The purpose of this study was to investigate whether nicastrin has prognostic value or potential as a therapeutic target in breast cancer (BC). The suitability of nicastrin as a target in BC was assessed using BC tissue microarrays (TMAs) (n = 1050), and its biological role in vitro was evaluated in BC cell lines following gene silencing. Nicastrin blocking antibodies were developed and evaluated for their suitability as potential clinical therapeutics. TMA and cell line analysis confirmed that nicastrin expression was upregulated in BC compared to normal breast cells. In TMA patient samples, hi...

Novel Therapies Against Aggressive and Recurrent Epithelial Cancers by Molecular Targeting Tumor- and Metastasis-Initiating Cells and Their Progenies

Thu, 11 Mar 2010 13:49:34 +0100

(Source: Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents))

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Association of circulating tumor cells with tumor-related methylated DNA in patients with hormone-refractory prostate cancer

International Journal of Urology — Thu, 11 Mar 2010 00:00:00 +0100

Conclusions: Hormone refractory prostate cancer patients with circulating tumor cells and/or tumor-related methylated DNA show a significantly poorer outcome than those without these blood markers. (Source: International Journal of Urology)

Phase 2 study of canfosfamide in combination with pegylated liposomal doxorubicin in platinum and paclitaxel refractory or resistant epithelial ovarian cancer

Journal of Hematology and Oncology — Thu, 11 Mar 2010 00:00:00 +0100

Conclusions: Canfosfamide in combination with PLD is well tolerated and active in platinum and paclitaxel refractory or resistant ovarian cancer. A randomized phase 3 study was conducted based on this supportive phase 2 study.Trial Registration: This study was registered at www.clinicaltrials.gov: NCT00052065. (Source: Journal of Hematology and Oncology)

A case of rapidly growing pulmonary carcinosarcoma

International Journal of Clinical Oncology — Wed, 10 Mar 2010 16:13:28 +0100

We report herein a case of rapidly growing pulmonary carcinosarcoma, a rare and highly malignant lung neoplasm characterized by a biphasic histopathological pattern consisting of both epithelial and sarcomatous components, and we also summarize the clinical features of this entity based on previously reported cases. A 65-year-old man was referred for further examination of a lung tumor after a routine chest X-ray (CXR) showed a tumor shadow in the right upper lung zone. Chest computed tomography (CT) found a 2.0 cm pulmonary mass with suspected chest wall invasion in the right upper lobe, although cytological evidence of malignancy could not be obtained despite repeated preoperative bronchoscopy. The tumor grew rapidly, indicating the possibility of lung cancer. A right upper lo...

Targeting monoamine oxidase A in advanced prostate cancer

Journal of Cancer Research and Clinical Oncology — Wed, 10 Mar 2010 16:10:15 +0100

Conclusion Our results support the possibility that anti-depressant drugs that target MAOA might find a new application in treating PCa. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00432-010-0835-6Authors Vincent Flamand, Stanford University School of Medicine Department of Urology, Stanford Medical Center Stanford CA 94305-5118 USAHongjuan Zhao, Stanford University School of Medicine Department of Urology, Stanford Medical Center Stanford CA 94305-5118 USADonna M. Peehl, Stanford University School of Medicine Department of Urology, Stanford Medical Center Stanford CA 94305-5118 USA Journal Journal of Cancer Research and Clinical OncologyOnline ISSN 1432-1335Print ISSN 0171-5216 (Source: Journal of Cancer Research and Clinical Oncology)

Sorafenib in combination with carboplatin and paclitaxel as neoadjuvant chemotherapy in patients with advanced ovarian cancer

Cancer Chemotherapy and Pharmacology — Wed, 10 Mar 2010 15:56:03 +0100

Conclusion The addition of sorafenib to carboplatin/paclitaxel chemotherapy was not feasible within this neoadjuvant regimen in primary advanced ovarian cancer. Although the occurrence of serious adverse events might have emerged at random, a detrimental effect of preoperative study medication could not be denied. Further evaluations of sorafenib in ovarian cancer are warranted. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00280-010-1276-2Authors Martin Pölcher, University Hospital of Bonn Department of Gynecology and Obstetrics, Center for Integrated Oncology, Bonn University Medical Center Sigmund-Freud-Str. 25 53105 Bonn GermanyMeike Eckhardt, University Hospital of Bonn Department of Gynecology and Obstetrics, Center for Integrated Oncol...

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Mesenchymal-to-epithelial transition determinants as characteristics of ovarian carcinoma effusions

Clinical and Experimental Metastasis — Wed, 10 Mar 2010 15:31:00 +0100

Abstract The present study investigated the intracellular regulation of E-cadherin in ovarian carcinoma. E-cadherin expression and regulation by Snail and Pak1 were studied in ES-2 and OVCAR-3 ovarian cancer cells in vitro. Twist1, Zeb1 and Vimentin mRNA expression and HIF-1α protein expression were analyzed in 80 and 189 clinical specimens, respectively. OVCAR-3 cells incubated with an anti-E-cadherin antibody formed smaller and looser spheroids compared to controls. Snail silencing using Small Hairpin RNA in ES-2 cells reduced invasion and MMP-2 activity, with unaltered cellular morphology. Using dominant negative (DN) and constitutively active (CA) Pak1 constructs, we found that DN Pak1 ES-2 and OVCAR-3 clones had reduced attachment to matrix proteins, invasion and MMP-...

Loss of ICAM-1 signaling induces psoriasin (S100A7) and MUC1 in mammary epithelial cells

Breast Cancer Research and Treatment — Wed, 10 Mar 2010 13:17:34 +0100

Abstract Psoriasin (S100A7), a member of the S100 gene family, is highly expressed in high-grade comedo ductal carcinoma in situ (DCIS), with a higher risk of local recurrence. Psoriasin is, therefore, a potential biomarker for DCIS with a poor prognosis. High-grade DCIS is characterized by a high proliferation rate and crowded cells, consequently, lose contact with the extracellular matrix. The aim of this study was, therefore, to elucidate the involvement of adhesion signals in the regulation of psoriasin. Protein expression was evaluated by Western blotting, flow cytometry, and immunohistochemistry, and using breast carcinoma SAGE databases available from the CGAP website. Intercellular adhesion molecule 1 (ICAM-1) was down-regulated in MCF10A cells using short hairpin ...

Novel in vitro assays for the characterization of EMT in tumourigenesis.

Cellular Oncology — Wed, 10 Mar 2010 13:06:02 +0100

Conclusion: The Spindle Index and the novel chemoattractant assay are valuable adjunctive assays for objective characterization of EMT changes during tumourigenesis. PMID: 20208135 [PubMed - in process] (Source: Cellular Oncology)

Improvement of tissue preparation for laser capture microdissection: application for cell type-specific miRNA expression profiling in colorectal tumors

BioMed Central — Wed, 10 Mar 2010 00:00:00 +0100

Background: Laser capture microdissection (LCM) has successfully isolated pure cell populations from tissue sections and the combination of LCM with standard genomic and proteomic methods has revolutionized molecular analysis of complex tissue. However, the quantity and quality of material recovered after LCM is often still limited for analysis by using whole genomic and proteomic approaches. To procure high quality and quantity of RNA after LCM, we optimized the procedures on tissue preparations and applied the approach for cell type-specific miRNA expression profiling in colorectal tumors. Results: We found that the ethanol fixation of tissue sections for 2 hours had the maximum improvement of RNA quality (1.8 fold, p=0.0014) and quantity (1.5 fold, p=0.066). Overall, the quality (RNA in...

Dpp Signaling Directs Cell Motility and Invasiveness during Epithelial Morphogenesis.

Current Biology — Wed, 10 Mar 2010 00:00:00 +0100

Authors: Ninov N, Menezes-Cabral S, Prat-Rojo C, Manjón C, Weiss A, Pyrowolakis G, Affolter M, Martín-Blanco E Tissue remodeling in development and disease [1, 2] involves the coordinated invasion of neighboring territories and/or the replacement of entire cell populations. Cell guidance, cell matching, transitions from passive to migratory epithelia, cell growth and death, and extracellular matrix remodeling all impinge on epithelial spreading. Significantly, the extracellular signals that direct these activities and the specific cellular elements and mechanisms regulated by these signals remain in most cases to be identified. To address these issues, we performed an analysis of histoblasts (Drosophila abdominal epithelial founder cells [3, 4]) on their transition from a dor...

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The evaluation of metallothionein expression in nasal polyps with respect to immune cell presence and activity

BMC Immunology — Tue, 09 Mar 2010 00:00:00 +0100

Conclusion: MT expression seems to favor the survival of nasal polyp epithelial cells in the adjacent increasing cytotoxic immune activity. RCAS1 expressing macrophages seem to participate in the creation of the immune suppressive microenvironment, thus helping to sustain the local inflammation. (Source: BMC Immunology)

A High Proportion of DNA Variants of BRCA1 and BRCA2 Is Associated with Aberrant Splicing in Breast/Ovarian Cancer Patients.

Clinical Cancer Research — Tue, 09 Mar 2010 00:00:00 +0100

CONCLUSIONS: An important fraction of DNA variants of BRCA1/2 presents splicing aberrations that may represent a relevant disease-causing mechanism in HBOC. The identification of splicing disruptions by functional assays is a valuable tool to discriminate between benign polymorphisms and pathogenic mutations. Clin Cancer Res; 16(6); 1957-67. PMID: 20215541 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Glycoprotein Nonmetastatic B Is an Independent Prognostic Indicator of Recurrence and a Novel Therapeutic Target in Breast Cancer.

Clinical Cancer Research — Tue, 09 Mar 2010 00:00:00 +0100

CONCLUSIONS: GPNMB expression is associated with the basal/triple-negative subtype and is a prognostic marker of poor outcome in patients with breast cancer. CDX-011 (glembatumumab vedotin) is a promising new targeted therapy for patients with metastatic triple-negative breast cancers, a patient population that currently lacks targeted-therapy options. Clin Cancer Res; 16(7); OF1-10. PMID: 20215530 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Prospective external validation of the "ovarian crescent sign" as a single ultrasound parameter to distinguish between benign and malignant adnexal pathology.

The Ultrasound Review of Obstetrics and Gynecology — Tue, 09 Mar 2010 00:00:00 +0100

CONCLUSION:: This study confirms previous reports that the presence of the OCS decreases the likelihood of invasive malignancy in adnexal masses. However it is a poor discriminator between benign and malignant adnexal masses. Copyright (c) 2010 ISUOG. Published by John Wiley & Sons, Ltd. PMID: 20217895 [PubMed - as supplied by publisher] (Source: The Ultrasound Review of Obstetrics and Gynecology)

Enhanced antiproliferative and apoptotic response to combined treatment of gamma-tocotrienol with erlotinib or gefitinib in mammary tumor cells

BMC Cancer — Mon, 08 Mar 2010 00:00:00 +0100

Conclusion: Combination treatment of gamma-tocotrienol with specific ErbB receptor inhibitors is more effective in reducing mammary tumor cell growth and viability than high dose monotherapy, suggesting that targeting multiple ErbB receptors with combination therapy may significantly improve the therapeutic response in breast cancer patients. (Source: BMC Cancer)

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Promotion of hepatocellular carcinoma metastasis through matrix metalloproteinase activation by epithelial-mesenchymal transition regulator twist1.

J Cell Mol Med — Mon, 08 Mar 2010 00:00:00 +0100

Authors: Zhao XL, Sun T, Che N, Sun D, Zhao N, Dong XY, Gu Q, Yao Z, Sun BC E-cadherin loss is a key biological mechanism in tumor invasion. As a main regulator of Epithelial-Mesenchymal Transition (EMT) mechanism-mediated invasion and metastasis, Twist1 plays an important role through its regulation of E-cadherin expression. However, whether or not Twist2 has the same function in tumor metastasis remains unclear. The purpose of this study is to investigate the expressions and different roles of Twist1 and Twist2 in human hepatocellular carcinoma (HCC). The expressions of Twist1 and Twist2 in HCC tissue were evaluated by immunohistochemical staining. The role of Twist1 and Twist2 in invasiveness was also evaluated in vitro by using HCC cell lines. Twist1 nuclear over-expression is foun...

Effect of tumour-cell-derived or recombinant keratinocyte growth factor (KGF) on proliferation and radioresponse of human epithelial tumour cells (HNSCC) and normal keratinocytes in vitro.

Radiation and Environmental Biophysics — Sun, 07 Mar 2010 00:00:00 +0100

Authors: Hille A, Grüger S, Christiansen H, Wolff HA, Volkmer B, Lehmann J, Dörr W, Rave-Fränk M Purpose of this work was to test the effect of tumour-cell-derived keratinocyte growth factor (KGF) or recombinant KGF (palifermin) on cell proliferation and radiation response of human HNSCC cells and normal keratinocytes in vitro. Four tumour cell cultures derived from head and neck squamous cell carcinomas, primary keratinocytes, and immortalized keratinocytes were analysed. Fibroblasts, the natural source of KGF protein, served as controls. KGF expression was observed in primary and immortalized keratinocytes, fibroblasts, and in tumour cells, while significant KGF receptor expression was only found in keratinocytes. Recombinant KGF as well as tumour-cell-derived KGF caus...

Copper binds the carboxy-terminus of trefoil protein 1 (TFF1), favoring its homodimerization and motogenic activity.

Cellular and Molecular Life Sciences : CMLS — Sun, 07 Mar 2010 00:00:00 +0100

Authors: Tosco A, Monti MC, Fontanella B, Montefusco S, D'Andrea L, Ziaco B, Baldantoni D, Rio MC, Marzullo L Trefoil protein 1 (TFF1) is a small secreted protein belonging to the trefoil factor family of proteins, that are present mainly in the gastrointestinal (GI) tract and play pivotal roles as motogenic factors in epithelial restitution, cell motility, and other incompletely characterized biological processes. We previously reported the up-regulation of TFF1 gene in copper deficient rats and the unexpected property of the peptide to selectively bind copper. Following the previous evidence, here we report the characterization of the copper binding site by fluorescence quenching spectroscopy and mass spectrometric analyses. We demonstrate that Cys58 and at least three Glu surroundin...

Identification of long stress-responsive non-coding transcripts that have altered expression in cancer.

Genomics — Sat, 06 Mar 2010 00:00:00 +0100

Authors: Silva JM, Perez DS, Pritchett JR, Halling ML, Tang H, Smith DI It has recently become clear that the transcriptional output of the human genome is far more abundant than previously anticipated, with the vast majority of transcripts not coding for protein. Utilizing whole-genome tiling arrays, we analyzed the transcription across the entire genome in both normal human bronchial epithelial cells (NHBE) and NHBE cells exposed to the tobacco carcinogen NNK. Our efforts focused on the characterization of non-coding transcripts that were greater than 300 nucleotides in length and whose expression was increased in response to NNK. We identified 12 long NNK-induced non-coding transcripts that we term NiTs. Northern blot analysis revealed that these transcripts were larger than predict...

Common alleles of predisposition in endocrine neoplasia.

Current Opinion in Genetics and Development — Sat, 06 Mar 2010 00:00:00 +0100

Authors: Eng C The identification of germline high penetrance gain-of-function mutations in the RET proto-oncogene as causative of multiple endocrine neoplasia led to accurate molecular diagnosis, predictive testing and gene-informed preventative medicine. Many syndromic endocrine neoplasias fell under this clinically utile model, although not all endocrine neoplasias were accounted for by these high penetrance predisposition genes associated with the validated practice of clinical cancer genetics. The past decade has seen the identification of low penetrance alleles for various endocrine neoplasias, including medullary and epithelial thyroid carcinomas and isolated pituitary adenomas. Functional characterisation of these effects, which range from subtle expressional or micro-RNA regul...

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c-Jun Induces Mammary Epithelial Cellular Invasion and Breast Cancer Stem Cell Expansion [Cell Biology]

Journal of Biological Chemistry — Fri, 05 Mar 2010 14:37:14 +0100

The molecular mechanisms governing breast tumor cellular self-renewal contribute to breast cancer progression and therapeutic resistance. The ErbB2 oncogene is overexpressed in ~30% of human breast cancers. c-Jun, the first cellular proto-oncogene, is overexpressed in human breast cancer. However, the role of endogenous c-Jun in mammary tumor progression is unknown. Herein, transgenic mice expressing the mammary gland-targeted ErbB2 oncogene were crossed with c-junf/f transgenic mice to determine the role of endogenous c-Jun in mammary tumor invasion and stem cell function. The excision of c-jun by Cre recombinase reduced cellular migration, invasion, and mammosphere formation of ErbB2-induced mammary tumors. Proteomic analysis identified a subset of secreted proteins (stem cell factor (SC...

Racial Differences in Treatment Modalities Among Female Residents of Florida Diagnosed with Epithelial Ovarian Cancer

Journal of Gynecologic Surgery — Fri, 05 Mar 2010 12:51:42 +0100

Journal of Gynecologic Surgery Jan 2010, Vol. 26, No. 1: 15-22. (Source: Journal of Gynecologic Surgery)

New Study Introduces The Prospect For Concurrent Antiangiogenic/Antitumorigenic Therapy

Cancer / Oncology News From Medical News Today — Fri, 05 Mar 2010 10:00:00 +0100

During the 39th Annual Meeting of the American Association for Dental Research, convening at the Walter E. Washington Convention Center in Washington, DC, lead researcher M. Tong, The Ohio State University, will present a poster of a study titled "Epithelial-to-Endothelial Transition: An Epithelial Phenotypic Modulation Facilitating Oral-Squamous-Cell Carcinoma Progression... (Source: Cancer / Oncology News From Medical News Today)

New Study Introduces The Prospect For Concurrent Antiangiogenic/Antitumorigenic Therapy

Health News from Medical News Today — Fri, 05 Mar 2010 10:00:00 +0100

During the 39th Annual Meeting of the American Association for Dental Research, convening at the Walter E. Washington Convention Center in Washington, DC, lead researcher M. Tong, The Ohio State University, will present a poster of a study titled "Epithelial-to-Endothelial Transition: An Epithelial Phenotypic Modulation Facilitating Oral-Squamous-Cell Carcinoma Progression." Tong and a team of researchers have reported that oral squamous cell carcinoma (OSCC) cells endogenously produce exceptionally high levels of vascular endothelial growth factor (VEGF)... (Source: Health News from Medical News Today)

New study introduces the prospect for concurrent antiangiogenic/antitumorigenic therapy

EurekAlert! - Medicine and Health — Fri, 05 Mar 2010 05:00:00 +0100

(International & American Association for Dental Research) Today, during the 39th Annual Meeting of the American Association for Dental Research, lead researcher M. Tong, the Ohio State University, will present a poster of a study titled "Epithelial-to-Endothelial Transition: An Epithelial Phenotypic Modulation Facilitating Oral-Squamous-Cell Carcinoma Progression." Tong and a team of researchers have reported that oral squamous cell carcinoma cells endogenously produce exceptionally high levels of vascular endothelial growth factor. (Source: EurekAlert! - Medicine and Health)

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Identification of 5 novel genes methylated in breast and other epithelial cancers

Molecular Cancer — Fri, 05 Mar 2010 00:00:00 +0100

Conclusion: The combination of the MIRA assay with CpG island arrays is a very useful technique for identifying epigenetically inactivated genes in cancer genomes and can provide molecular markers for early cancer diagnosis, prognosis and epigenetic therapy. (Source: Molecular Cancer)

Arachidonic acid promotes epithelial-to-mesenchymal-like transition in mammary epithelial cells MCF10A.

European Journal of Cell Biology — Fri, 05 Mar 2010 00:00:00 +0100

In conclusion, our results demonstrate, for the first time, that AA promotes an epithelial-to-mesenchymal-like transition in MCF10A human mammary non-tumorigenic epithelial cells. PMID: 20207443 [PubMed - as supplied by publisher] (Source: European Journal of Cell Biology)

Exposure to chrysotile asbestos causes carbonylation of glucose 6-phosphate dehydrogenase through a reaction with lipid peroxidation products in human lung epithelial cells.

Toxicology Letters — Fri, 05 Mar 2010 00:00:00 +0100

Authors: Ogasawara Y, Ishii K Exposure to asbestos is known to lead to a reduction in glucose 6-phosphate dehydrogenase (G6PDH) activity and to cause oxidative damage to cells. In the present study, we exposed the human lung carcinoma cell line A549 to chrysotile. We observed an increase in the production of thiobarbituric acid-reactive substances (TBARS, the breakdown products of lipid peroxide) along with a significant decrease in G6PDH activity. Alternatively, when chrysotile was added directly to the cell extract obtained by removing the cell membrane, no loss of G6PDH activity was observed. To elucidate the mechanism of G6PDH inactivation due to exposure to chrysotile, we focused on the TBARS responsible for protein modification via carbonylation. When malondialdehyde or 4-hydroxy...

Development of an oral cancer recurrence mouse model after surgical resection.

International Journal of Oncology — Thu, 04 Mar 2010 22:59:21 +0100

Authors: Behren A, Kamenisch Y, Muehlen S, Flechtenmacher C, Haberkorn U, Hilber H, Myers JN, Bergmann Z, Plinkert PK, Simon C Oral squamous cell carcinomas (OSCC) are frequent epithelial malignancies and afflicted with a poor prognosis. The majority of these cancers are treated with surgical resection and local recurrences are predominantly responsible for a fatal outcome. In order to provide a better understanding of the development of these local recurrences after surgical ablation, we developed an orthotopic floor-of-mouth squamous cell carcinoma murine model, in which local recurrences occur at a high frequency (55%, 8 out of 15 mice) within 6-21 days after microsurgical removal of the primary. Expression of the enhanced green fluorescent protein (eGFP) in the cancer cells allows ...

Effects of an EGFR-binding affibody molecule on intracellular signaling pathways.

International Journal of Oncology — Thu, 04 Mar 2010 22:58:33 +0100

Authors: Nordberg E, Ekerljung L, Sahlberg SH, Carlsson J, Lennartsson J, Glimelius B Effects on intracellular signaling were studied in cells treated with the affibody molecule (ZEGFR:955)2 that targets the epithelial growth factor receptor (EGFR). EGFR is overexpressed in many types of cancers and plays a fundamental role in cell signaling and it is of interest to find targeting agents capable of blocking the receptor. The clinically approved antibody cetuximab (Erbitux(R)) and the natural ligand EGF were included as reference molecules. Two EGFR-rich cell lines, A-431 and U-343, were exposed to the three targeting agents and lysed. The cell lysates were immunoprecipitated with the receptors, or directly separated by SDS-Page. Autophosphorylation of the receptors and phosphorylation ...

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Novel epitheliomesenchymal biphasic stomach tumour (gastroblastoma) in a 9-year-old: morphological, usltrastructural and immunohistochemical findings

Journal of Clinical Pathology — Thu, 04 Mar 2010 15:42:50 +0100

This report describes a probable fourth case of this unique type of neoplasm. The present case arose in the gastric antrum of a 9-year-old boy. While similarities were evident with the other cases, there were some differences. The epithelial component was more predominant and showed more mature morphology. Immunohistochemically, the epithelial component showed immunolabelling for c-KIT and CD56. The mesenchymal component was only focally positive for CD10. Ultrastructually, desmosomes and microvilli were found supporting a truly epithelial lesion. (Source: Journal of Clinical Pathology)

The clinicopathological characteristics of 'triple-negative' epithelial ovarian cancer

Journal of Clinical Pathology — Thu, 04 Mar 2010 15:42:49 +0100

Conclusions A novel subtype of ovarian carcinoma, which is negative for ER, PR and HER2 expression, has been identified; this specific ovarian subtype tends to have aggressive characteristics and a poor prognosis, which is similar to triple-negative breast cancer in most respects. TNEOC should be considered in future investigations of informative classification of ovarian cancer. (Source: Journal of Clinical Pathology)

Human papillomavirus type 16 E5 protein inhibits hydrogen peroxide-induced apoptosis by stimulating ubiquitin-proteasome-mediated degradation of Bax in human cervical cancer cells

Carcinogenesis — Thu, 04 Mar 2010 15:26:26 +0100

To investigate the mechanism by which the human papillomavirus (HPV) E5 protein contributes to the carcinogenesis of uterine cervical cancer, we studied the effect of HPV E5 on apoptosis of cervical cancer cells and its underlying mechanism. Expression of HPV16 E5 protein inhibited hydrogen peroxide-induced apoptosis in C-33A cervical cancer cells. E5 decreased the expression of Bax protein, and exogenous expression of Bax abolished the anti-apoptotic effect of E5. Knockdown of E5 by small interfering RNA sensitized CaSki cervical cancer cells to hydrogen peroxide-induced apoptosis with concurrent increase in Bax expression. Transient expression of E5 significantly increased the degradation rate of Bax protein by inducing the ubiquitination. The E5-induced decrease in Bax expression was in...

Hypoxia activates the cyclooxygenase-2-prostaglandin E synthase axis

Carcinogenesis — Thu, 04 Mar 2010 15:26:26 +0100

Hypoxia-inducible factors (HIFs), in particular HIF-1, have been implicated in tumor biology. However, HIF target genes in the esophageal tumor microenvironment remain elusive. Gene expression profiling was performed upon hypoxia-exposed non-transformed immortalized human esophageal epithelial cells, EPC2-hTERT, and comparing with a gene signature of esophageal squamous cell carcinoma (ESCC). In addition to known HIF-1 target genes such as carbonic anhydrase 9, insulin-like growth factor binding protein-3 (IGFBP3) and cyclooxygenase (COX)-2, prostaglandin E synthase (PTGES) was identified as a novel target gene among the commonly upregulated genes in ESCC as well as the cells exposed to hypoxia. The PTGES induction was augmented upon stabilization of HIF-1 by hypoxia or cobalt chloride und...

The making of hemidesmosome structures in vivo

Developmental Dynamics — Thu, 04 Mar 2010 00:00:00 +0100

Hemidesmosomes are evolutionarily conserved attachment complexes linked to intermediate filaments that connect epithelial cells to the extracellular matrix. They provide tissue integrity and resistance to mechanical forces. Alterations in hemidesmosome structures are responsible for skin blistering, carcinoma invasion, and wound-healing defects. Valuable information about hemidesmosome assembly and disassembly has been obtained from in vitro cell culture studies. However, how these processes take place in vivo still remains elusive. Here, we discuss recent data about the formation and reorganization of hemidesmosomes in several in vivo model systems, particularly zebrafish and Caenorhabditis elegans, focusing on various factors affecting their dynamics. Mechanisms found in different organi...

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Anti-GD2 Antibody Therapy for GD2-Expressing Tumors.

Current Cancer Drug Targets — Thu, 04 Mar 2010 00:00:00 +0100

Authors: Navid F, Santana VM, Barfield RC In the development of novel immune therapies for high-risk cancers, one goal is to find tumor targets that are not widely shared by normal cells. One such target is the surface disialoganglioside GD2. This antigen is expressed on the surface of a variety of tumors for which no curative therapies exist for patients with advanced disease. In childhood, the most common GD2-expressing tumor is neuroblastoma. GD2 is also expressed on several other high-risk tumors, including those of neuroectodermal or epithelial origin, virtually all melanomas, and approximately 50% of tumor samples from osteosarcoma and soft-tissue sarcomas. Because of the tumor-selective expression of this molecule, it is an attractive target for tumor-specific therapies such as ...

Similarities and differences between smoking-related gene expression in nasal and bronchial epithelium

Physiological Genomics — Wed, 03 Mar 2010 22:09:11 +0100

In this study, we sought to determine the similarity of the effects of tobacco smoke throughout the respiratory tract by determining patterns of smoking-related gene expression in paired nasal and bronchial epithelial brushings collected from 14 healthy nonsmokers and 13 healthy current smokers. Using whole genome expression arrays, we identified 119 genes whose expression was affected by smoking similarly in both bronchial and nasal epithelium, including genes related to detoxification, oxidative stress, and wound healing. While the vast majority of smoking-related gene expression changes occur in both bronchial and nasal epithelium, we also identified 27 genes whose expression was affected by smoking more dramatically in bronchial epithelium than nasal epithelium. Both common and site-sp...

A primary sclerosing epithelioid fibrosarcoma of the pubic bone, with evidence of divergent epithelial differentiation.

Ultrastructural Pathology — Wed, 03 Mar 2010 18:16:25 +0100

Authors: Wang G, Eyden B Sclerosing epithelioid fibrosarcoma (SEF) is a rare variant of fibrosarcoma, described initially by Meis-Kindblom et al. in 1995 (Meis-Kindblom JM, Kindblom L-G, Enzinger FM. Sclerosing epithelioid fibrosarcoma: a variant of fibrosarcoma simulating carcinoma. Am J Surg Pathol. 1995;19:979-993): more than 80 cases have been documented clinicopathologically since. Bone is a rare primary site for SEF, with only 2 cases so far reported. This paper documents the detailed clinical, histological, immunohistochemical, and ultrastructural features of a case occurring in the pubic bone of a 57-year-old diabetic woman presenting with a history of pain and compromised mobility involving her hip. Radiology revealed a destructive lesion in the right pubic bone. The lesion wa...

Significance of Interleukin-6 Signaling in the Resistance of Pharyngeal Cancer to Irradiation and the Epidermal Growth Factor Receptor Inhibitor

International Journal of Radiation Oncology * Biology * Physics — Wed, 03 Mar 2010 15:35:16 +0100

Conclusions: IL-6 and p-STAT3 may be significant predictors of pharyngeal carcinoma, and regulating IL-6 signaling can be considered a promising therapeutic approach. (Source: International Journal of Radiation Oncology * Biology * Physics)

Poverty and childhood cancer incidence in the United States

Cancer Causes and Control — Wed, 03 Mar 2010 08:03:45 +0100

This study examined socioeconomic differentials in cancer incidence rates during 2000–2005 among children aged 0–19 in the United States. The data on childhood cancers, which were classified by the International Classification of Childhood Cancer, Third Edition (ICCC-3), were obtained from the Surveillance, Epidemiology, and End Results program. The socioeconomic status of residential area at diagnosis was estimated by county-level poverty rate in Census 2000, i.e., percentage of persons in the county living below the national poverty thresholds. Counties were categorized as low-, medium-, and high-poverty areas when the poverty rates were <10, 10–19.99, and 20% or higher, respectively. The results showed that medium- and high-poverty counties had lower age-adjusted incidenc...

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Helicobacter hepaticus Cytolethal Distending Toxin Causes Cell Death in Intestinal Epithelial Cells via Mitochondrial Apoptotic Pathway

Helicobacter — Wed, 03 Mar 2010 00:00:00 +0100

Conclusion: These findings show, for the first time, the ability of HhCDT to induce apoptosis via the mitochondrial pathway. (Source: Helicobacter)

Non-receptor tyrosine kinase Etk is involved in the apoptosis of small cell lung cancer cells.

Experimental and Molecular Pathology — Wed, 03 Mar 2010 00:00:00 +0100

Authors: Guo L, Chen P, Zhou Y, Sun Y Epithelial and endothelial tyrosine kinase (Etk), also known as Bmx (bone marrow X kinase) plays an important role in apoptosis of epithelial cells. The goal of this study was to investigate whether Etk is involved in apoptosis of small cell lung cancer (SCLC) cells and correlated with the expression levels of apoptosis-associated proteins such as Bcl-2, Bcl-X(L) and p53. One hundred and seventy-one cases of lung cancer specimens including seventy-one SCLCs and one hundred NSCLCs were immunostained for Etk, Bcl-2, Bcl-X(L) and p53. Parental SCLC H446 cell line, and its subline (H446-Etk) that overexpresses Etk, were used to study the role of Etk in apoptosis induced by doxorubicin. It was found that high expression of Etk occurs in 74.6% of SCLC ca...

Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells

BioMed Central — Tue, 02 Mar 2010 00:00:00 +0100

Conclusions: : SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB) phosphorylation and reducing the levels of free E2F-1 appears to play an important role in EOC growth arrest. (Source: BioMed Central)

Simultaneous Visualization of Protumorigenic Src and MT1-MMP Activities with Fluorescence Resonance Energy Transfer.

Cell Research — Tue, 02 Mar 2010 00:00:00 +0100

Authors: Ouyang M, Huang H, Shaner NC, Remacle AG, Shiryaev SA, Strongin AY, Tsien RY, Wang Y Both Src kinase and membrane type 1 matrix metalloproteinase (MT1-MMP) play critical roles in cancer invasion and metastasis. It is not clear, however, how the spatiotemporal activation of these two critical enzymes is coordinated in response to an oncogenic epithelial growth factor (EGF) stimulation. Here, we have visualized the activities of Src and MT1-MMP concurrently in a single live cell by combining two fluorescence resonance energy transfer (FRET) pairs with distinct spectra: (a) cyan fluorescent protein (CFP) and yellow FP (YFP), and (b) orange FP (mOrange2) and red FP (mCherry). The new FRET pair, mOrange2 and mCherry, was first characterized in vitro and in cultured mammalian cells....

PAX5{alpha} Enhances the Epithelial Behavior of Human Mammary Carcinoma Cells.

Cell Research — Tue, 02 Mar 2010 00:00:00 +0100

Authors: Vidal LJ, Perry JK, Vouyovitch CM, Pandey V, Brunet-Dunand SE, Mertani HC, Liu DX, Lobie PE Deregulated PAX5 expression has been associated with metastatic mammary carcinoma, although the precise role of PAX5 in cancer progression is unclear. Stable forced expression of PAX5alpha in the mammary carcinoma cell lines MCF-7 and MDA-MB-231 reduced cell cycle progression, cell survival, and anchorage-independent cell growth. In xenograft studies, forced expression of PAX5alpha was associated with a significant reduction in tumor volume. Furthermore, forced expression of PAX5alpha in mammary carcinoma cells resulted in altered cell morphology with resultant enhancement of epithelial cell characteristics. Morphologic changes were associated with localization of beta-CATENIN at cell-c...

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Autotaxin Signaling via Lysophosphatidic Acid Receptors Contributes to Vascular Endothelial Growth Factor-Induced Endothelial Cell Migration.

Cell Research — Tue, 02 Mar 2010 00:00:00 +0100

We examined whether these two angiogenic factors cooperate in regulation of endothelial cell migratory responses. VEGF stimulated expression of ATX and LPA1, a receptor for the ATX enzymatic product lysophosphatidic acid (LPA), in human umbilical vein endothelial cells. Knockdown of ATX expression significantly decreased mRNA levels for the receptors LPA1, LPA2, S1P1, S1P2, S1P3, and VEGFR2 and abolished cell migration to lysophosphatidylcholine, LPA, recombinant ATX, and VEGF. Migration to sphingosylphosphorylcholine and sphinogosine-1-phosphate was also reduced in ATX knockdown cells, whereas migration to serum remained unchanged. Furthermore, ATX knockdown decreased Akt2 mRNA levels, whereas LPA treatment strongly stimulated Akt2 expression. We propose that VEGF stimulates LPA productio...

PAI-1 Regulates the Invasive Phenotype in Human Cutaneous Squamous Cell Carcinoma

Journal of Oncology — Mon, 01 Mar 2010 13:54:58 +0100

The emergence of highly aggressive subtypes of human cutaneous squamous cell carcinoma (SCC) often reflects increased autocrine/paracrine TGF-β synthesis and epidermal growth factor receptor (EGFR) amplification. Cooperative TGF-β/EGFR signaling promotes cell migration and induces expression of both proteases and protease inhibitors that regulate stromal remodeling resulting in the acquisition of an invasive phenotype. In one physiologically relevant model of human cutaneous SCC progression, TGF-β1+EGF stimulation increases the production of several matrix metalloproteinases (MMPs), among the most prominent of which is MMP-10—an MMP known to be elevated in SCC in situ. Activation of stromal plasminogen appears to be critical in triggering downstream MMP activit...

Activation of Phosphatidylcholine Cycle Enzymes in Human Epithelial Ovarian Cancer Cells

Cancer Research — Mon, 01 Mar 2010 05:07:49 +0100

Ovarian cancers exhibit elevated choline kinase and phosphatidylcholine-specific phospholipase C resulting in increased phosphocholine, providing novel targets for imaging-based diagnosis and treatment. (Source: Cancer Research)

Loss of FOXA1/2 Is Essential for the Epithelial-to-Mesenchymal Transition in Pancreatic Cancer

Cancer Research — Mon, 01 Mar 2010 05:07:48 +0100

FoxA transcription factors suppress the epithelial-mesenchymal transition, preventing the acquisition of invasive and metastatic properties. (Source: Cancer Research)

Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1

Cancer Research — Mon, 01 Mar 2010 05:07:46 +0100

Two pathways downstream of the Jak2 kinase are revealed that have opposing effects on EMT, with possible implications for understanding EMT as well as the clinical application of Jak2 inhibitors. (Source: Cancer Research)

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Molecular blockade of VEGFR2 in human epithelial ovarian carcinoma cells

Laboratory Investigation AOP — Mon, 01 Mar 2010 00:00:00 +0100

Authors: Sirin A I Adham, Ifat Sher & Brenda L Coomber (Source: Laboratory Investigation AOP)

Interplay between Helicobacter pylori and immune cells in immune pathogenesis of gastric inflammation and mucosal pathology.

Cellular and Molecular Immunology — Mon, 01 Mar 2010 00:00:00 +0100

This article will review the recent novel findings on the interactions of H. pylori with diverse host epithelial signaling pathways and events involved in the initiation of gastric pathology, including gastric inflammation, mucosal damage and development of MALT lymphomas. PMID: 20190789 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Immunology)

Pseudoneoplastic mimics of prostate and bladder carcinomas.

Archives of Pathology and Laboratory Medicine — Mon, 01 Mar 2010 00:00:00 +0100

Conclusions.-Pseudoneoplastic lesions in the prostate include those of prostatic epithelial origin, the most common being atrophy, adenosis (atypical adenomatous hyperplasia), basal cell hyperplasia, and crowded benign glands, as well as those of nonprostatic origin, such as seminal vesicle epithelium. Such lesions often mimic lower-grade prostatic adenocarcinoma, whereas others, such as clear cell cribriform hyperplasia and granulomatous prostatitis, for example, are in the differential diagnosis of Gleason adenocarcinoma, Gleason grade 4 or 5. Pseudoneoplastic lesions of the urinary bladder include lesions that could potentially be confused with urothelial carcinoma in situ, such as reactive urothelial atypia, and others, such as polypoid/papillary cystitis, where papillary urothelial ne...

Pseudoneoplastic lesions of the female genital tract.

Archives of Pathology and Laboratory Medicine — Mon, 01 Mar 2010 00:00:00 +0100

Conclusions.-Many benign hyperplastic or reactive processes that occur in the female genital tract may be mistaken for neoplasms both clinically and pathologically. Awareness of the features of such lesions will aid in their correct diagnosis and prevent overtreatment of benign processes. PMID: 20196667 [PubMed - in process] (Source: Archives of Pathology and Laboratory Medicine)

Narrow Band Imaging in Borderline Ovarian Tumor

The Journal of Minimally Invasive Gynecology — Mon, 01 Mar 2010 00:00:00 +0100

Borderline ovarian tumors (BOT) comprise 15% of all epithelial ovarian neoplasms, and the outcome is much better than for women with invasive ovarian cancer . The histologic study of peritoneal implants represents a crucial factor in the clinical management of patients with BOT because it identifies patients suitable for systemic chemotherapy . (Source: The Journal of Minimally Invasive Gynecology)

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Prognostic significance of epithelial-mesenchymal transition in malignant pleural mesothelioma [Original articles]

European Journal of Cardio-Thoracic Surgery — Fri, 26 Feb 2010 22:01:57 +0100

Conclusion: Activation of periostin-triggered EMT is associated with the sarcomatoid histotype and has an impact on shorter survival of MPM patients. Finally, only the high expression of PTEN and the low expression of cytosolic periostin could be shown to be independent prognostic factors for longer OS. (Source: European Journal of Cardio-Thoracic Surgery)

Diacylglycerol Kinase {delta} and Protein Kinase C{alpha} Modulate Epidermal Growth Factor Receptor Abundance and Degradation through Ubiquitin-specific Protease 8 [Signal Transduction]

Journal of Biological Chemistry — Fri, 26 Feb 2010 14:42:00 +0100

Many human epithelial cancers are characterized by abnormal activation of the epidermal growth factor receptor (EGFR), which is often caused by its excessive expression in tumor cells. The abundance of EGFR is modulated, in part, by its ubiquitination, which targets it for degradation. The components responsible for adding ubiquitin to EGFR are well characterized, but this is a reversible process, and the mechanisms that modulate the removal of ubiquitin from the EGFR are not well known. We found that de-ubiquitination of EGFR was regulated by diacylglycerol kinase (DGK), a lipid kinase that terminates diacylglycerol signaling. In DGK-deficient cells, ubiquitination of EGFR was enhanced, which attenuated the steady-state levels of EGFR and promoted its ligand-induced degradation. These eff...

Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion

Journal of Ovarian Research — Fri, 26 Feb 2010 00:00:00 +0100

Conclusions: We propose that the key steps of ovarian cancer metastasis, specifically cell cohesion of multicellular aggregates in ascites and cell adhesion for reattachment to secondary sites, may be inhibited by overactive BMP signalling, thereby decreasing the ultimate malignant potential of ovarian cancer in this model system. (Source: Journal of Ovarian Research)

A novel method for sample preparation of fresh lung cancer tissue for proteomics analysis by tumor cell enrichment and removal of blood contaminants

Proteome Science — Fri, 26 Feb 2010 00:00:00 +0100

Conclusion: The method is feasible and reproducible. We could obtain a fair enrichment of cells but the major benefit of the method was an effective removal of contaminants from red blood cells and plasma proteins resulting in larger proteome coverage compared to the direct lysis of frozen samples. This sample preparation method may be successfully implemented for the discovery of lung cancer biomarkers on tissue samples using mass spectrometry-based proteomics. (Source: Proteome Science)

Increased paclitaxel resistance in recurrent epithelial ovarian cancer: analysis of metachronous tumors

International Journal of Clinical Oncology — Thu, 25 Feb 2010 06:54:49 +0100

Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s10147-010-0032-2Authors Koji Matsuo, University of Texas Department of Gynecologic Oncology, Unit 1362, M. D. Anderson Cancer Center 1151 Herman Pressler Street P.O. Box 301439 Houston TX 77230-1439 USADwight D. Im, University of Maryland School of Medicine Department of Obstetrics, Gynecology, and Reproductive Sciences Baltimore MD USANeil B. Rosenshein, University of Maryland School of Medicine Department of Obstetrics, Gynecology, and Reproductive Sciences Baltimore MD USA Journal International Journal of Clinical OncologyOnline ISSN 1437-7772Print ISSN 1341-9625 (Source: International Journal of Clinical Oncology)

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The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptide

Cancer Chemotherapy and Pharmacology — Thu, 25 Feb 2010 06:49:32 +0100

Conclusions PNC-27 induces cancer cell membrane lysis by acting as the whole peptide, not fragments. The punctate yellow fluorescence is due to interaction of PNC-27 with intramembrane targets of MCF-7 cells that do not exist in the membrane of the untransformed cell line. This interaction increases the lifetime of PNC-27. Absence of these targets in the membranes of the untransformed MCF-10-2A cells results in initial uniform fluorescence of the double-labeled peptide in their membranes after which the peptide is degraded. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00280-009-1166-7Authors Kelley A. Sookraj, SUNY Downstate Medical Center Department of Surgery 450 Clarkson Avenue Brooklyn NY 11203 USAWilbur B. Bowne, SUNY Downstate Medical Ce...

Cytokines levels, Severity of acute mucositis and the need of PEG tube installation during chemo-radiation for head and neck cancer - a prospective pilot study

Radiation Oncology — Thu, 25 Feb 2010 00:00:00 +0100

Conclusion: These preliminary results, indicating a correlation between IL-6 and IL-8 serum levels and severity of mucositis and a need for a PEG tube installation, justify a large scale study. (Source: Radiation Oncology)

A Genome-wide screen identifies frequently methylated genes in haematological and epithelial cancers

BioMed Central — Thu, 25 Feb 2010 00:00:00 +0100

Background: Genetic as well as epigenetic alterations are a hallmark of both epithelial and haematological malignancies. High throughput screens are required to identify epigenetic markers that can be useful for diagnostic and prognostic purposes across malignancies. Results: Here we report for the first time the use of the MIRA assay (methylated CpG island recovery assay) in combination with genome-wide CpG island arrays to identify epigenetic molecular markers in childhood acute lymphoblastic leukemia (ALL) on a genome-wide scale. We identified 30 genes demonstrating methylation frequencies of greater than or equal to 25% in childhood ALL, nine genes showed significantly different methylation frequencies in B vs T-ALL. For majority of the genes expression could be restored in methylated ...

Genome-wide analysis of aberrant methylation in human breast cancer cells using methyl-DNA immunoprecipitation combined with high-throughput sequencing

BMC Genomics - Latest articles — Thu, 25 Feb 2010 00:00:00 +0100

Conclusions: This study provides the most comprehensive analysis to date of the methylome of human mammary cell lines and has produced novel insights into the mechanisms of methylome alteration during tumorigenesis and the interdependence between DNA methylome alterations and morphological changes. (Source: BMC Genomics - Latest articles)

SplicerAV: A tool for mining microarray expression data for changes in RNA processing

BMC Bioinformatics - Latest articles — Thu, 25 Feb 2010 00:00:00 +0100

Conclusions: Using SplicerAV, we identified several hundred previously uncharacterized isoform changes induced by in vitro oncogene over-expression and revealed a previously unknown mechanism of EGFR activation in human mammary epithelial cells. We analyzed Affymetrix GeneChip data from over 400 human breast tumors in three independent studies, making this the largest clinical dataset analyzed for en masse changes in alternative mRNA processing. The capacity to detect RNA isoform changes in archival microarray data using SplicerAV allowed us to carry out the first analysis of isoform specific mRNA changes directly associated with cancer survival. (Source: BMC Bioinformatics - Latest articles)

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Inhibitor of differentiation 1 (Id1) promotes cell survival and proliferation of prostate epithelial cells.

Cellular and Molecular Biology Letters — Thu, 25 Feb 2010 00:00:00 +0100

Authors: Schmidt M, Asirvatham AJ, Chaudhary J Id1 (inhibitor of differentiation 1) is a member of the bHLH protein family. Consistent with its role in promoting proliferation and inhibiting differentiation, Id1 expression is low or negligible in normal prostate epithelial cells but is high in prostate cancer. Ectopic expression of Id1 in normal prostate epithelial cells could therefore provide a model for understanding early events involved in initiation of prostate cancer. Over-expression of Id1 immortalized but did not transform ventral prostate epithelial cells (Id1-RPE). Immortalization was associated with decreased Cdkn2a, Cdkn1a, androgen receptor and increased Tert expression. Gene expression profiling over successive doublings was used to identify transcriptomic changes involv...

Large cell neuroendocrine carcinoma with sarcomatous changes of the endometrium: A case report with immunohistochemical studies and molecular genetic study of KIT and PDGFRA.

Pathology, Research and Practice — Thu, 25 Feb 2010 00:00:00 +0100

Authors: Terada T The author herein reports a very rare case of large cell neuroendocrine carcinoma (LCNEC) with sarcomatous changes of the endometrium. A 40-year-old woman was admitted to our hospital because of abnormal uterine bleeding. Gynecologic examination and imaging modalities revealed a polypoid tumor of the uterine corpus. Uterine curettage biopsy revealed a sarcomatous undifferentiated carcinoma. Simple hysterectomy, salpingo-oophorectomy, extensive lymph node dissection, and omentectomy were performed. The patient was diagnosed as having FIGO stage Ib (T1N0M0) carcinoma, and adjuvant chemotherapy was performed. The patient is now alive 16 months after the operation. Pathologically, a polypoid tumor measuring 3x2x2cm(3) was found in the uterine corpus. Histologically, the t...

Clinical Activity of Gemcitabine Plus Pertuzumab in Platinum-Resistant Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer [Gynecologic Cancer]

Journal of Clinical Oncology — Wed, 24 Feb 2010 23:01:03 +0100

Conclusion Pertuzumab may add activity to gemcitabine for the treatment of platinum-resistant ovarian cancer. Low HER3 mRNA expression may predict pertuzumab clinical benefit and be a valuable prognostic marker. (Source: Journal of Clinical Oncology)

Loss of clusterin expression worsens renal ischemia-reperfusion injury

AJP: Renal Physiology — Wed, 24 Feb 2010 22:28:41 +0100

Prevention of ischemia-reperfusion injury (IRI) is a challenge in clinical care of the patients with kidney transplants or acute kidney injury, and understanding of the intrinsic mechanisms of resistance to injury in the kidney will lead to a novel therapy. Clusterin, a secreted glycoprotein, is an antiapoptotic protein in cancer cells. Our study is to investigate the role of clusterin in renal IRI. Renal IRI in mice was induced by clamping renal vein and artery for 45 or 50 min at 32°C. Apoptosis of renal tubular epithelial cells (TECs) was determined by FACS analysis. Clusterin expression was examined by Western blot or immunohistochemistry. Here, we showed that clusterin protein was induced in TECs following IRI, and more tubules expressed clusterin in the kidneys following ischemia...

Diet and Survival after Ovarian Cancer: Where Are We and What's Next?

Journal of the American Dietetic Association — Wed, 24 Feb 2010 15:15:40 +0100

The prognosis after epithelial ovarian cancer treatment remains dismal. It is estimated that 21,500 women will be diagnosed with ovarian cancer in 2009; 14,600 will die of their disease, making ovarian cancer among the most lethal of cancer diagnoses (). Whereas ovarian cancer accounts for only 3% of new cancer cases, it represents 5% of total cancer deaths in the United States with a reported 5-year overall survival rate for all stages of disease of 45.5%. Early detection continues to be a major challenge and explains much of the mortality because women diagnosed with local disease demonstrate a 92% survival rate. There are no strong risk factors for ovarian cancer; however, age, nulliparity, family history, previous diagnosis of breast cancer, estrogen therapy, and genetic variants in BR...

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Prediagnosis Food Patterns Are Associated with Length of Survival from Epithelial Ovarian Cancer

Journal of the American Dietetic Association — Wed, 24 Feb 2010 15:15:40 +0100

Abstract: Background: Dietary factors have been the focus of many studies on the etiology of ovarian cancer and may potentially affect survival. Indeed, three recent studies outside the United States have suggested that diet plays a role in ovarian cancer survival.Objective: The study purpose was to evaluate the hypothesis that women diagnosed with ovarian cancer whose reported prediagnosis food patterns more closely reflect recommendations for optimal health experience a survival advantage compared with those reporting poorer diets.Design: A longitudinal follow-up study design was used to examine prediagnosis usual diet effects on survival among 341 Cook County, Illinois, residents diagnosed with epithelial ovarian cancer during 1994-1998. These women participated in a previous case-contr...

E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer

BMC Cancer — Wed, 24 Feb 2010 00:00:00 +0100

Conclusions: Overall, our findings, in addition to opening a realistic possibility for improved OEC diagnosis, provide an indirect evidence that a cell-cycle regulatory protein E2F5 might play a significant role in OEC pathogenesis. (Source: BMC Cancer)

Protein kinase Cgamma in colon cancer cells: Expression, Thr(514) phophorylation and sensitivity to butyrate-mediated upregulation as related to the degree of differentiation.

Chemico-Biological Interactions — Wed, 24 Feb 2010 00:00:00 +0100

Authors: Garczarczyk D, Szeker K, Galfi P, Csordas A, Hofmann J Protein kinase C (PKC) isoenzymes are expressed and activated in a cell type-specific manner, and play an essential role in tissue-specific signal transduction. The presence of butyrate at millimolar concentrations in the colon raises the question of whether it affects the expression of PKC isoenzymes in the different cell types of the colonic epithelium. We investigated the protein expression levels of PKCgamma, Thr(514)-phosphorylated PKCgamma (pPKCgamma-Thr(514)), and their subcellular distribution as affected by butyrate in a set of colon cancer cell lines. Thr(514)-phosphorylation of de novo synthesized PKCgamma is the first step in priming of the inactive PKCgamma before its release into the cytoplasm. For immunoblot...

SPARC (Osteonectin) in Breast Tumors of Different Histologic Types and Its Role in the Outcome of Invasive Ductal Carcinoma

The Breast Journal — Tue, 23 Feb 2010 00:00:00 +0100

Abstract: The purpose of this study was to characterize the immunohistochemical distribution of secreted protein acidic and rich in cystein (SPARC) in benign and malignant breast tumors of different histologic types and define its association with the outcome of invasive ductal carcinoma (IDC) patients. A total of 286 samples of benign and malignant breast lesions between 1994 and 2005 were retrieved from National Taiwan University Hospital. Up to 11 years clinical follow-up data were available for 185 patients with IDC. Immunohistochemistry staining with SPARC was performed in tissue microarray or whole section. The association of expression of SPARC and cumulative overall survival of IDC patients were analyzed using Kaplan[ndash]Meier survival analysis and Cox regression analysis. Secret...

Columnar cell lesions of the canine mammary gland: pathological features and immunophenotypic analysis

BMC Cancer — Tue, 23 Feb 2010 00:00:00 +0100

Conclusions: Columnar cell lesions in canine mammary gland are pathologically and immunophenotypically similar to those in human breast. This may suggest that dogs are a suitable model for the comparative study of noninvasive breast lesions. (Source: BMC Cancer)

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Cyclooxygenase-2 Inhibition Does Not Improve the Reduction in Ductal Carcinoma In situ Proliferation with Aromatase Inhibitor Therapy: Results of the ERISAC Randomized Placebo-Controlled Trial.

Clinical Breast Cancer — Tue, 23 Feb 2010 00:00:00 +0100

CONCLUSIONS: Exemestane reduces proliferation in ER-positive DCIS. Aromatase inhibition is a potential alternative to tamoxifen in patients who have undergone breast conservation for ER-positive DCIS. Clin Cancer Res; 16(5); 1605-12. PMID: 20179229 [PubMed - as supplied by publisher] (Source: Clinical Breast Cancer)

Predictive Value of Symptoms for Early Detection of Ovarian Cancer

JNCI — Mon, 22 Feb 2010 16:06:23 +0100

Conclusion Use of symptoms to trigger medical evaluation for ovarian cancer is likely to result in diagnosis of the disease in only one of 100 women in the general population with such symptoms. (Source: JNCI)

BRCA1 as a Therapeutic Target in Sporadic Epithelial Ovarian Cancer

Journal of Oncology — Mon, 22 Feb 2010 13:50:28 +0100

In sporadic epithelial ovarian cancer (EOC), the inactivation of BRCA1 through various mechanisms is a relatively common event. BRCA1 protein dysfunction results in the breakdown of various critical pathways in the cell, notably, the DNA damage response and repair pathway. Tumors from patients with BRCA1 germline mutations have an increased sensitivity to DNA damaging chemotherapeutic agents, such as cisplatin, due to defective DNA repair. Thus, inhibiting BRCA1 in sporadic EOC using novel targeted therapies is an attractive strategy for the treatment of advanced or recurrent EOC. Several classes of small molecule inhibitors that affect BRCA1 have now been tested in preclinical and clinical studies suggesting that this is a rational therapeutic approach. The aim of this paper is to provide...

Disease-related expression of the IL6/STAT3/SOCS3 signalling pathway in ulcerative colitis and ulcerative colitis-related carcinogenesis

Gut — Mon, 22 Feb 2010 10:58:24 +0100

Conclusion The importance of IL6/p-STAT3 in patients with inflammation-induced CRC was demonstrated. Moreover, SOCS3 may be involved in UC pathogenesis and the absence of SOCS3 seems critical for CRC progression. (Source: Gut)

Long-term proton pump induced hypergastrinaemia does induce lineage-specific restitution but not clonal expansion in benign Barrett's oesophagus in vivo

Gut — Mon, 22 Feb 2010 10:58:23 +0100

Conclusion While the short-term effects of gastrin enhance epithelial restitution in Barrett's oesophagus (but not squamous mucosa) there is no clinical evidence that Barrett's oesophagus length expands over time. This study, which is the largest and longest term randomised controlled trial of gastrin biology in Barrett's oesophagus, is further proof of the clinical safety of PPI therapy. (Source: Gut)

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Two members of the SIBLING family of proteins, DSPP and BSP, may predict the transition of oral epithelial dysplasia to oral squamous cell carcinoma

Cancer — Mon, 22 Feb 2010 00:00:00 +0100

Patients with oral premalignant lesions (OPL) present with oral squamous cell carcinomas (OSCC) at a much higher rate than the general population. There are currently no useful markers that indicate specifically which OPLs are most likely to progress. Three small integrin binding ligands N-linked glycoprotein (SIBLING) family proteins, bone sialoprotein (BSP), osteopontin (OPN), and dentin sialophosphoprotein (DSPP), have been shown to be up-regulated in many cancers, including OSCC. The status of SIBLING expression in OPLs and their correlation to transition to oral cancer are unknown.Sixty archival surgical biopsies of dysplastic OPLs were evaluated by immunohistochemistry for expression of BSP, DSPP, and OPN and correlated with local transformation to OSCC at sites adjacent to surgicall...

Immunoglobulin G is present in a wide variety of soft tissue tumors and correlates well with proliferation markers and tumor grades

Cancer — Mon, 22 Feb 2010 00:00:00 +0100

The traditional view that immunoglobulin (Ig) is produced only by B lymphocytes has been challenged, because it has been demonstrated that Ig genes and proteins are expressed in epithelial cancer cells. However, whether Ig expression in nonlymphoid cells is limited to epithelial cells is unclear. Because sarcomas differ distinctly from carcinomas in their biologic and clinical features, the authors investigated the question of nonlymphoid IgG expression in soft tissue lesions.Immunohistochemistry, in situ hybridization, and polymerase chain reaction (PCR) were used to demonstrate IgG expression in 80 soft tissue lesions. The correlation between Ig expression and proliferation markers (proliferating cell nuclear antigen [PCNA], Ki-67, and cyclin D1) in sarcomas was investigated by immunohis...

Rosiglitazone Inhibits Cell Proliferation by Inducing G1 Cell Cycle Arrest and Apoptosis in ADPKD Cyst-Lining Epithelia Cells

Basic and Clinical Pharmacology and Toxicology — Mon, 22 Feb 2010 00:00:00 +0100

Abstract: Abnormal proliferation is an important pathological feature of autosomal dominant polycystic kidney disease (ADPKD). Many drugs inhibiting cell proliferation have been proved to be effective in slowing the disease progression in ADPKD. Recent evidence has suggested that peroxisome proliferator-activated receptor [gamma] (PPAR[gamma]) ligands have anti-neoplasm effects through inhibiting cell growth and inducing cell apoptosis in various cancer cells. In the present study, we examined the expression of PPAR[gamma] in human ADPKD kidney tissues and cyst-lining epithelial cell line, and found that the expression of PPAR[gamma] was greater in ADPKD kidney tissues and cyst-lining epithelial cell line than in normal kidney tissues and human kidney cortex (HKC) cell line. Rosiglitazone ...

Activities of E7 promoters in the Human papillomavirus type 16 genome during cell differentiation.

Virus Research — Mon, 22 Feb 2010 00:00:00 +0100

Authors: Hansen CN, Nielsen L, Norrild B Worldwide, one of the most common cancer forms diagnosed in women is cervical cancer induced by infections with high-risk human papillomaviruses (HPVs) with HPV type 16 (HPV-16) being the most frequently identified. The oncogenicity is caused mainly by expression of the oncogenes E6 and E7 leading to deregulation of the cell cycle control. HPV-16 preferably infects the proliferating cells that will differentiate when they move upwards in the epithelium. The viral gene expression is tightly coupled to the cellular differentiation program with early gene-expression being initiated in non- or low differentiated cells and late gene-expression in more differentiated cells. We induced epithelial cells to differentiate by growth in medium with a high c...

Resistance to platinum-based chemotherapy in lung cancer cell lines

Cancer Chemotherapy and Pharmacology — Sun, 21 Feb 2010 06:54:11 +0100

Conclusion Thus, sensitivity to cisplatin appeared to be associated with DDH levels in epithelial lung cancer cell lines with the DDH-1 isoform producing the greatest effect. Results in keeping with transfection experiments with ovarian and other cell lines. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00280-010-1268-2Authors Jianli Chen, The Feinstein Institute for Medical Research North Shore-Long Island Jewish Health System 350 Community Drive Manhasset NY 11030 USANashwa Emara, Temple University School of Medicine Department of Pathology and Laboratory Medicine Philadelphia PA USACharalambos Solomides, Temple University School of Medicine Department of Pathology and Laboratory Medicine Philadelphia PA USAHemant Parekh, Temple University School...

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Myc-modulated miR-9 makes more metastases

Nature Cell Biology — Sun, 21 Feb 2010 00:00:00 +0100

Authors: Yeesim Khew-Goodall & Gregory J. Goodall The microRNA miR-9 is induced by Myc in breast cancer cells where it targets the major epithelial adherens junction protein, E-cadherin. This primes the cancer cells for epithelial–mesenchymal transition (EMT) and also stimulates angiogenesis in tumours. (Source: Nature Cell Biology)

MAGE-A antigens in lesions of the oral mucosa

Clinical Oral Investigations — Sat, 20 Feb 2010 06:51:50 +0100

Abstract Oral squamous cell carcinoma develops continuously out of predamaged oral mucosa. For the physician and pathologist, difficulties arise in distinguishing precancerous from cancerous lesions. MAGE-A antigens are tumor antigens that are found solely in malignant transformed cells. These antigens might be useful in distinguishing precancerous from cancerous lesions. The aim of this study was to verify this assumption by comparing MAGE-A expression in benign, precancerous, and cancerous lesions of the oral mucosa. Retrospectively, biopsies of different oral lesions were randomly selected. The lesions that were included are 64 benign oral lesions (25 traumatic lesions (oral ulcers), 13 dental follicles, and 26 epulis), 26 oral lichen planus, 123 epithelial precursor le...

Tumor initiation via loss of cell contact inhibition versus Ras mutation: Do all roads lead to EMT?

Cell Cycle — Fri, 19 Feb 2010 15:31:36 +0100

Authors: Liu Y, Dean DC Many tumors have been found to contain a subset of cells referred to as cancer stem cells. As opposed to the remainder of the tumor, these cells are undifferentiated-they do not express markers of differentiation and they can re-express stem cell specification genes. The cells can divide asymmetrically to yield differentiated cells as well as cells comprising the original heterogeneous population of the tumor while maintaining their number. Because cancer stem cells display some properties of stem cells, it has been presumed that the presence of such cells in tumors reflects a stem cell origin for cancer. However, recent studies suggest that cancer can originate with outgrowth of differentiated somatic cells, and that cells with properties of cancer stem cells c...

ZEB proteins link cell motility with cell cycle control and cell survival in cancer.

Cell Cycle — Fri, 19 Feb 2010 15:31:04 +0100

Authors: Browne G, Sayan AE, Tulchinsky E Epithelial mesenchymal transitions (EMT), the generation of motile mesenchymal cells from epithelial sheets, are differentiation programs which take place at several critical steps of embryonic development and in metastatic cancer. Recent data have shown that the transcription factors which are master regulators of EMT also regulate cell cycle progression, apoptosis and senescence. In light of these new observations, the role of these factors in human cancer may be broader than previously anticipated. Here we review recent literature on non-EMT functions of EMT-controlling transcription factors. We will mainly focus on transcription factors belonging to the ZEB family, but some important results obtained by investigators studying other key EMT ...

The Lysyl Oxidases LOX and LOXL2 Are Necessary and Sufficient to Repress E-cadherin in Hypoxia: INSIGHTS INTO CELLULAR TRANSFORMATION PROCESSES MEDIATED BY HIF-1 [Cell Biology]

Journal of Biological Chemistry — Fri, 19 Feb 2010 14:39:20 +0100

Hypoxia has been shown to promote tumor metastasis and lead to therapy resistance. Recent work has demonstrated that hypoxia represses E-cadherin expression, a hallmark of epithelial to mesenchymal transition, which is believed to amplify tumor aggressiveness. The molecular mechanism of E-cadherin repression is unknown, yet lysyl oxidases have been implicated to be involved. Gene expression of lysyl oxidase (LOX) and the related LOX-like 2 (LOXL2) is strongly induced by hypoxia. In addition to the previously demonstrated LOX, we characterize LOXL2 as a direct transcriptional target of HIF-1. We demonstrate that activation of lysyl oxidases is required and sufficient for hypoxic repression of E-cadherin, which mediates cellular transformation and takes effect in cellular invasion assays. Ou...

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New Findings Reported From National Institutes Of Health Describe Advances In Ovarian Cancer Therapy

Cancercompass News: Gynecological Cancer — Fri, 19 Feb 2010 00:00:00 +0100

A new study, 'MicroRNAs in ovarian carcinomas,' is now available. "The molecular mechanisms involved in epithelial ovarian cancer initiation and progression are just beginning to be elucidated. In particular, it has become evident that microRNAs (miRNAs or miRs), a class of molecules that post-transcriptionally regulate gene expression, play a major role in ovarian tumorigenesis, scientists in the United States report. (Source: Cancercompass News: Gynecological Cancer)

Abbott Submits New Automated Ovarian Cancer Test For U.S. Approval

Cancercompass News: Gynecological Cancer — Fri, 19 Feb 2010 00:00:00 +0100

A new diagnostic tool physicians can use to monitor patients for the most common form of ovarian cancer may soon be available in the United States. Abbott's ARCHITECT HE4 assay uses a simple blood test to help in monitoring for the recurrence or progression of epithelial ovarian cancer. If approved, this important immunoassay would be the first automated HE4 test available in the United States. (Source: Cancercompass News: Gynecological Cancer)

Can primary optimal cytoreduction be predicted in advanced epithelial ovarian cancer preoperatively?

World Journal of Surgical Oncology — Fri, 19 Feb 2010 00:00:00 +0100

Conclusions: Because of small populations in our study the results are not reproducible in alternate populations. Only the patient who is most unlikely to undergo optimal cytoreduction should be offered neoadjuvant chemotherapy, unless her medical condition renders her unsuitable for primary surgery. (Source: World Journal of Surgical Oncology)

Eicosanoids and cancer

Nature Reviews Cancer — Fri, 19 Feb 2010 00:00:00 +0100

Authors: Dingzhi Wang & Raymond N. DuBois Eicosanoids, including prostaglandins and leukotrienes, are biologically active lipids that have been implicated in various pathological processes, such as inflammation and cancer. This Review highlights our understanding of the intricate roles of eicosanoids in epithelial-derived tumours and their microenvironment. The knowledge of how these lipids (Source: Nature Reviews Cancer)

The p53 orchestra: Mdm2 and Mdmx set the tone.

Trends in Cell Biology — Fri, 19 Feb 2010 00:00:00 +0100

Authors: Wade M, Wang YV, Wahl GM The activities of p53 cover diverse aspects of cell biology, including cell cycle control, apoptosis, metabolism, fertility, differentiation and cellular reprogramming. Although loss of p53 function engenders tumor susceptibility, hyperactivation of p53 is lethal. Therefore, p53 activity must be strictly regulated to maintain normal tissue homeostasis. Critical for the control of p53 function are its two main negative regulators: Mdm2 and Mdmx. Recent reports have provided insight into the complex mechanisms that regulate these two proteins and have revealed novel functions for each. Here, we review and evaluate models of Mdm2- and Mdmx-dependent regulation of p53 activity. Both Mdm2 and Mdmx receive input from numerous signaling pathways and interact ...

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Plasma cell-free DNA in ovarian cancer

Cancer — Thu, 18 Feb 2010 00:00:00 +0100

Cell-free DNA reflects both normal and tumor-derived DNA released into the circulation through cellular necrosis and apoptosis. The authors sought to determine the role of preoperative total plasma cell-free DNA levels in predicting clinical outcome in patients with ovarian cancer.After institutional review board consent, DNA was extracted from plasma of 164 women with invasive epithelial ovarian carcinoma (EOC), 49 with benign ovarian neoplasms, and 75 age-matched controls. The samples were randomly divided into training (n = 144) and validation (n = 144) sets. Quantification of cell-free DNA was performed using real-time polymerase chain reaction for [beta]-globin, and the number of genome equivalents (GE) per milliliter of plasma was determined. Cell-free DNA was correlated with clinico...

Snail transcription factor regulates neuroendocrine differentiation in LNCaP prostate cancer cells

The Prostate — Thu, 18 Feb 2010 00:00:00 +0100

Snail transcription factor induces epithelial-mesenchymal transition (EMT) via decreased cell adhesion-associated molecules like E-cadherin, and increased mesenchymal markers like vimentin. We previously established Snail-mediated EMT model utilizing androgen-dependent LNCaP cells. These cells express increased vimentin protein and relocalization of E-cadherin from the cell membrane to the cytosol. Interestingly, Snail transfection in LNCaP cells resulted in cells acquiring a neuroendocrine (NE)-like morphology with long neurite-like processes.We tested for expression of NE markers neuron-specific enolase (NSE) and chromogranin A (CgA) by Western blot analysis, and performed proliferation assays to test for paracrine cell proliferation.LNCaP cells transfected with Snail displayed increase ...

TGF-beta Pathway as a Therapeutic Target in Bone Metastases.

Current Pharmaceutical Design — Thu, 18 Feb 2010 00:00:00 +0100

Authors: Juárez P, Guise TA Breast and prostate cancer frequently metastasizes to the skeleton and causes bone destruction. In skeletal tissue, transforming growth factor-beta (TGF-beta) is a major bone-derived factor responsible for driving a feed-forward vicious cycle of breast cancer growth in bone. TGF-beta is released from bone in active form by osteoclastic resorption and increases the tumor secretion of factors, which stimulate osteolytic destruction of the bone adjacent to the tumor. Moreover it activates epithelial-mesenchymal transition and tumor cell invasion, increases angiogenesis and induces immunosuppression. Blocking the TGF-beta signaling pathway to interrupt this vicious cycle between tumor and bone offers a target for therapeutic intervention to decrease skeleta...

Epithelial–mesenchymal transition gene signature to predict clinical outcome of hepatocellular carcinoma

Cancer Science — Thu, 18 Feb 2010 00:00:00 +0100

In conclusion, we suggest that the proposed gene signature may improve the prediction accuracy for survival of hepatocellular carcinoma patients, and complement prognostic assessment based on important clinicopathologic parameters such as tumor stage. (Cancer Sci 2010) (Source: Cancer Science)

The Role of Dysregulated Glucose Metabolism in Epithelial Ovarian Cancer

Journal of Oncology — Wed, 17 Feb 2010 13:48:56 +0100

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer and also one of the most poorly understood. Other health issues that are affecting women with increasing frequency are obesity and diabetes, which are associated with dysglycemia and increased blood glucose. The Warburg Effect describes the ability of fast-growing cancer cells to preferentially metabolize glucose via anaerobic glycolysis rather than oxidative phosphorylation. Recent epidemiological studies have suggested a role for hyperglycemia in the pathogenesis of a number of cancers. If hyperglycemia contributes to tumour growth and progression, then it is intuitive that antihyperglycemic drugs may also have an important antitumour role. Preliminary reports suggest that these drugs not only reduce available plasma g...

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Ungual seborrheic keratosis

Journal of the European Academy of Dermatology and Venereology — Wed, 17 Feb 2010 00:00:00 +0100

Conclusion To our knowledge, this is the first report of a typical, histologically documented seborrheic keratosis of the nail bed. Therefore, this condition should be added to the differential diagnosis of acquired longitudinal leukoxanthonychia. However, surgical treatment remains necessary to rule out other causes, including squamous cell carcinoma. (Source: Journal of the European Academy of Dermatology and Venereology)

Chromosomal imbalances are uncommon in chagasic megaesophagus

BMC Gastroenterology — Wed, 17 Feb 2010 00:00:00 +0100

Conclusions: Genomic imbalances common in esophageal carcinomas are not present in chagasic megaesophagus suggesting that these features will not be effective markers for risk assessment of ESCC in patients with chagasic megaesophagus. (Source: BMC Gastroenterology)

Differential regulation of steroid nuclear receptor coregulator expression between normal and neoplastic prostate epithelial cells

The Prostate — Wed, 17 Feb 2010 00:00:00 +0100

Deregulated androgen receptor (AR) action is critical for prostate cancer (PCa) progression. Aberrant expression of AR-associated coregulators contributes to AR activity in PCa. The mechanisms underlying coregulator expression in PCa are under intense investigation as they may lead to alternative means of targeting AR activity in PCa cells. We have recently shown that over 30% of coregulator expression in the PCa cell line LNCaP is subject to androgen regulation.Using multiple PCa cell lines as well as xenograft models, non-malignant prostate epithelial cell lines and androgen-responsive tissues derived from a male Wistar rat model system, we explored the effect of androgen stimulation and androgen deprivation on the expression of the core coactivators SRC1, SRC2, SRC3, CBP, and p300.Andro...

Inhibition of DHCR24/Seladin-1 impairs cellular homeostasis in prostate cancer

The Prostate — Wed, 17 Feb 2010 00:00:00 +0100

Seladin-1 belongs to a subgroup of androgen-dependent genes associated with anti-proliferative, pro-differentiation, and pro-apoptotic functions and plays a protective role against oncogenic stress. The present study aims to investigate the localization and expression of Seladin-1 protein in normal and tumoral human prostatic tissues as well as to explore its role in proliferation and steroid secretion in androgen-dependent (LnCaP) and androgen-independent (DU145) cell lines and in human prostate primary cell culture.Seladin-1 protein localization and expression were assessed on whole tissue sections by tissue array/immunohistochemistry and following immunofluorescence and Western blotting. Proliferation (Ki67 fluorescence labeling and cell counts) and steroid secretion (ELISA) were assess...

Association of distinctive Epstein-Barr virus variants with gastric carcinoma in Guangzhou, southern China

Journal of Medical Virology — Wed, 17 Feb 2010 00:00:00 +0100

To investigate the clinicopathologic features, Epstein-Barr virus (EBV) latency pattern and genome polymorphism of EBV-associated gastric carcinoma (EBVaGC) in Guangzhou, an endemic area of nasopharyngeal carcinoma (NPC), an in situ hybridization assay of EBV-encoded small RNA-1 (EBER-1) was used to identify the presence of EBV in 676 consecutive gastric carcinoma cases. EBV-encoded proteins EBNA1, EBNA2, LMP1, and ZEBRA were detected by immunohistochemistry. EBV genome polymorphism was also analyzed by PCR and DNA sequencing. Of the 676 cases, 45 EBV-positive cases (6.7%) were identified, including 37 (8.5%) male and 8 (3.3%) female cases. EBNA1 was detected in 42 cases (93.3%), while EBNA2, LMP1, and ZEBRA were all negative. In the EBV genome polymorphism analysis, type A strain, prototy...

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Expression of cancer testis antigen CT45 in classical Hodgkin lymphoma and other B-cell lymphomas [Medical_Sciences]

Proceedings of the National Academy of Sciences — Tue, 16 Feb 2010 18:56:48 +0100

We have shown previously that cancer/testis (CT) antigen, CT45, is expressed in various epithelial cancers at a frequency of <5%... (Source: Proceedings of the National Academy of Sciences)

The Relationship Between Vitamin D and Breast Cancer Incidence and Natural History

Current Oncology Reports — Tue, 16 Feb 2010 18:10:53 +0100

Abstract Endocrine action of vitamin D and its role in calcium homeostasis and bone health are well known. The discovery that breast epithelial cells possess the same enzyme system as the kidney, permitting local manufacture of active vitamin D (1,25 dihydroxyvitamin D, or 1,25[(OH)2D]) from circulating precursors 25 hydroxyvitamin D [25(OH)D], has suggested an autocrine role for vitamin D, as well. Preclinical and ecologic studies support a role of vitamin D in prevention of breast cancer. Correlative study results of vitamin D intake or measurement of 25(OH)D, the long-lived precursor, are mixed but suggest a protective effect in premenopausal women. The large Women’s Health Initiative failed to show any reduction in breast cancer incidence in postmenopausal women with ...

Epidermotropic Merkel cell carcinoma: A case series with histopathologic examination

Journal of the American Academy of Dermatology — Tue, 16 Feb 2010 14:09:30 +0100

Conclusion: The data presented reinforce the differential diagnosis of tumors with an epidermotropic growth pattern and the importance of immunohistochemical staining in the histologic workup of such tumors: squamous cell carcinoma in situ, melanoma, mycosis fungoides, eccrine porocarcinoma, sebaceous carcinoma of the eyelid, mammary and extramammary Paget disease, MCC, and epidermotropic metastases. It is notable that 3 of 6 identified tumors were located on the eyelid; further study of epidermotropic MCC may shed more light on this finding, either as an unusual coincidence or a finding with unexplained significance. (Source: Journal of the American Academy of Dermatology)

Mesothelioma Researchers Study the Effect of Induction Chemotherapy on Pleural Mesothelioma Patients

Asbestos and Mesothelioma News — Mon, 15 Feb 2010 19:27:47 +0100

Because it has yet to be largely studied, Italian researchers examined the effect of induction chemotherapy on lung function and exercise capacity in patients with pleural mesothelioma. Malignant mesothelioma is an aggressive form of cancer caused almost exclusively by asbestos exposure. Pleural mesothelioma is the most common form of the cancer, affecting the pleural lining of the lungs. Other forms of mesothelioma include peritoneal mesothelioma (abdominal lining), pericardial mesothelioma (heart lining), and testicular mesothelioma (testicular lining). Patients with pleural mesothelioma often experience compromised lung function and exercise capacity, but the effects of chemotherapy can also play a role in the cancer’s side effects. Since there has been little research on chemotherape...

Overexpression of Galectin-1 is negatively correlated with pathologic differentiation grade in oral squamous cell carcinoma

Journal of Cancer Research and Clinical Oncology — Mon, 15 Feb 2010 17:59:45 +0100

Conclusions Galectin-1 protein expression level increases in OSCC, it may serve as a candidate marker for pathologic differentiation grade of OSCC. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00432-010-0810-2Authors Lai-ping Zhong, Ninth People’s Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology Department of Oral and Maxillofacial Surgery Shanghai People’s Republic of ChinaKui-jie Wei, Ninth People’s Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology Department of Oral and Maxillofacial Surgery Shanghai People’s Republic of ChinaXiao Yang, Ninth People’s Hospital, School of Stomatology, Shanghai Ji...

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68Ga-labelled recombinant antibody variants for immuno-PET imaging of solid tumours

European Journal of Nuclear Medicine and Molecular Imaging — Mon, 15 Feb 2010 17:58:46 +0100

Conclusion The antibody variants differed considerably in normal organ uptake, clearance from circulation and tumour accumulation. The data demonstrate the feasibility of imaging solid tumours with the 68Ga-labelled diabody format. This type of recombinant protein might be a promising carrier even for the short-lived radiometal 68Ga to support e.g. the management of immunotherapy which may provide important information regarding receptor expression of solid tumours. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00259-010-1392-6Authors Matthias Eder, German Cancer Research Center Radiopharmaceutical Chemistry Im Neuenheimer Feld 280 69120 Heidelberg GermanyStefan Knackmuss, Affimed Therapeutics AG Heidelberg GermanyFabrice Le Gall, Affimed Therapeu...

Discovery Of Switch That Turns On The Spread Of Cancer

Health News from Medical News Today — Mon, 15 Feb 2010 10:00:00 +0100

Reporting in Nature Cell Biology, researchers describe the discovery of a specific protein called disabled-2 (Dab2) that switches on the process that releases cancer cells from the original tumor and allows the cells to spread and develop into new tumors in other parts of the body. The process called epithelial-mesenchymal transdifferientiation (EMT) has been known to play a role in releasing cells (epithelial cells) on the surface of the solid tumor and transforming them into transient mesenchymal cell: cells with the ability to start to grow a new tumor... (Source: Health News from Medical News Today)

Tumor Detection by Imaging Proteolytic Activity

Cancer Research — Mon, 15 Feb 2010 05:08:32 +0100

A generalizable method to non-invasively visualize epithelial tumors in vivo using fluorescently labeled antibodies to a commonly amplified cell surface protease is described. (Source: Cancer Research)

Inflammatory Processes Triggered by Helicobacter pylori Infection Cause Aberrant DNA Methylation in Gastric Epithelial Cells

Cancer Research — Mon, 15 Feb 2010 05:08:31 +0100

Cancer-associated inflammation is increasingly seen as a root drivers of disease risk and malignant progression, and induction of aberrant DNA methylation is one of the key mechanisms. (Source: Cancer Research)