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Her2 colon

Manfred Dietel
The increasing importance of targeting drugs and check-point inhibitors in the treatment of several tumor entities (breast, colon, lung, malignant melanoma, lymphoma, etc.) and the necessity of a companion diagnostic (HER2, (pan)RAS, EGFR, ALK, BRAF, ROS1, MET, PD-L1, etc.) is leading to new challenges for surgical pathology. Since almost all the biomarkers to be specifically detected are tissue based, a precise and reliable diagnostic is absolutely crucial. To meet this challenge surgical pathology has adapted a number of molecular methods (semi-quantitative immunohistochemistry, fluorescence in situ hybridization, PCR and its multiple variants, (pyro/Sanger) sequencing, next generation sequencing (amplicon, whole exome, whole genome), DNA arrays, methylation analyses, etc...
2016: Oncology Research and Treatment
Gang Li, Junhua Zheng, Bin Xu, Jie Ling, Wei Qiu, Yongbing Wang
Overexpression of the HER2 oncogene contributes to tumor angiogenesis, which is an essential hallmark of cancer. Simvastatin has been reported to exhibit antitumor activities in several cancers; however, its roles and molecular mechanismsin the regulation of colorectal angiogenesis remain to be clarified. Here, we show that colon cancer cells express high levels of VEGF, total HER2 and phosphorylated HER2, and simvastatin apparently decreased their expression in HER2-overexpressing colon cancer cells. Simvastatin pretreatment reduced endothelial tube formation in vitro and microvessel density in vivo...
November 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Esmeralda Capristo, Valerio Spuntarelli, Giorgio Treglia, Vincenzo Arena, Alessandro Giordano, Geltrude Mingrone
INTRODUCTION: We described the case of a highly aggressive antral gastric carcinoma with a scarce symptomatology, in a patient undergone Roux-en-Y Gastric Bypass (RYGB) for obesity. PRESENTATION OF CASE: A 61 year-old white man in apparent good health, who underwent laparoscopic RYGB for obesity 18 months earlier, with a loss of 30kg, reported a sudden abdominal distension and breath shortness with a weight gain of 5kg in few days. Endoscopy of both upper gastro-intestinal tract and the colon were performed along with CT-scan and positron-emission tomography (PET) CT- scan...
November 5, 2016: International Journal of Surgery Case Reports
Michael P Chu, J Randolph Hecht, Dennis Slamon, Zev A Wainberg, Yung-Jue Bang, Paulo M Hoff, Alberto Sobrero, Shukui Qin, Karen Afenjar, Vincent Houe, Karen King, Sheryl Koski, Karen Mulder, Julie Price Hiller, Andrew Scarfe, Jennifer Spratlin, Yingjie J Huang, Saba Khan-Wasti, Neil Chua, Michael B Sawyer
Importance: Capecitabine is an oral cytotoxic chemotherapeutic commonly used across cancer subtypes. As with other oral medications though, it may suffer from drug interactions that could impair its absorption. Objective: To determine if gastric acid suppressants such as proton pump inhibitors (PPIs) may impair capecitabine efficacy. Design, Setting, and Participants: This secondary analysis of TRIO-013, a phase III randomized trial, compares capecitabine and oxaliplatin (CapeOx) with or without lapatinib in 545 patients with ERBB2/HER2-positive metastatic gastroesophageal cancer (GEC); patients were randomized 1:1 between CapeOx with or without lapatinib...
October 13, 2016: JAMA Oncology
Ping Gao, Chunhua Zhang, Xiaoxia Bian, Yanjun Guo, Yueguang Wei, Li Zhang, Zhaoyang Liu, Xiuying Wang, Shumin Huang
The present study aimed to determine the effect of recombinant DNA vaccine-based human epidermal growth factor receptor-2 (HER2) and Interleukin 12 (IL-12) on the development of colonic carcinoma in mice and the potential immune mechanisms involved. Recombinant plasmids pVAX1-HER2, pVAX1-IL-12 and pVAX1-HER2-IL-12 were constructed, and injected into female mice intramuscularly (i.m.) followed by an electric pulse. The humoral and cellular immune responses after immunization were examined by enzyme linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT), respectively...
September 23, 2016: Immunopharmacology and Immunotoxicology
Benjamin Lu, Brooke A Green, Jacqueline M Farr, Flávia C M Lopes, Terence J Van Raay
The Wnt signaling pathway is intricately involved in many aspects of development and is the root cause of an increasing number of diseases. For example, colorectal cancer is the second leading cause of death in the industrialized world and aberration of Wnt signaling within the colonic stem cell is the cause of more than 90% of these cancers. Despite our advances in successfully targeting other pathways, such as Human Epidermal Growth Factor Receptor 2 (HER2), there are no clinically relevant therapies available for Wnt-related diseases...
September 1, 2016: Cancers
Jing Liu, Changqie Pan, Lihong Guo, Mengwan Wu, Jing Guo, Sheng Peng, Qianying Wu, Qiang Zuo
BACKGROUND: Trastuzumab, a humanized antibody targeting HER2, exhibits remarkable therapeutic efficacy against HER2-positive gastric cancer. However, recurrent therapeutic resistance presents revolutionary claims. Warburg effect and AKT signaling pathway was involved in the resistance to trastuzumab. Our previous studies have demonstrated that overexpression of metastasis associated with the colon cancer 1 (MACC1) predicted poor prognosis of GC and promoted tumor cells proliferation and invasion...
2016: Journal of Hematology & Oncology
Giulia Bon, Rossella Loria, Carla Azzurra Amoreo, Alessandra Verdina, Isabella Sperduti, Arianna Mastrofrancesco, Silvia Soddu, Maria Grazia Diodoro, Marcella Mottolese, Matilde Todaro, Giorgio Stassi, Michele Milella, Ruggero De Maria, Rita Falcioni
Although the medical treatment of colorectal cancer has evolved greatly in the last years, a significant portion of early-stage patients develops recurrence after therapies. The current clinical trials are directed to evaluate new drug combinations and treatment schedules. By the use of patient-derived or established colon cancer cell lines, we found that the tyrosine kinase receptor HER3 is involved in the mechanisms of resistance to therapies. In agreement, the immunohistochemical analysis of total and phospho-HER3 expression in 185 colorectal cancer specimens revealed a significant correlation with lower disease-free survival...
August 19, 2016: Oncotarget
Claudia Burz, Ben Youssef Mohamed Aziz, Loredana Bălăcescu, Luminiţa Leluţiu, Rareş Buiga, Gabriel Samasca, Alexandru Irimie, Cosmin Lisencu
BACKGROUND AND AIMS: The aim of this study was to investigate the value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) correlated with some tissue molecules as predictive markers for recurrence in colon cancer. METHODS: A total of 30 patients diagnosed with colon cancer stage II or III who underwent optimal surgery were enrolled in study. Tumor markers CEA and CA 19-9 were determined before surgery. Tumor samples were prepared using tissue microarray kit (TMA) then stained for different cellular markers (Ki 67, HER2, BCL2, CD56, CD4, CD8) and analyzed using Inforatio programme for quantitative determination...
2016: Clujul Medical (1957)
Mei Xu, Zhenhua Ren, Xin Wang, Ashley Comer, Jacqueline A Frank, Zun-Ji Ke, Yi Huang, Zhuo Zhang, Xianglin Shi, Siying Wang, Jia Luo
BACKGROUND: Both epidemiological and experimental studies suggest that excessive alcohol exposure increases the risk for breast cancer and enhances metastasis/recurrence. We have previously demonstrated that alcohol enhanced the migration/invasion of breast cancer cells and cancer cells overexpressing ErbB2/HER2 were more sensitive to alcohol exposure. However, the underlying mechanisms remain unclear. This study was designed to investigate the mechanisms underlying alcohol-enhanced aggressiveness of breast cancer...
2016: Molecular Cancer
Ji Yun Lee, Kyunghee Park, Eunjin Lee, TaeJin Ahn, Hae Hyun Jung, Sung Hee Lim, Mineui Hong, In-Gu Do, Eun Yoon Cho, Duk-Hwan Kim, Ji-Yeon Kim, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
The biology of breast cancer brain metastasis (BCBM) is poorly understood. We aimed to explore genes that are implicated in the process of brain metastasis of primary breast cancer (BC). NanoString nCounter Analysis covering 252 target genes was used for comparison of gene expression levels between 20 primary BCs that relapsed to brain and 41 BCBM samples. PAM50-based intrinsic subtypes such as HER2-enriched and basal-like were clearly over-represented in BCBM. A panel of 22 genes was found to be significantly differentially expressed between primary BC and BCBM...
2016: Scientific Reports
Michael Pohl, Wolff Schmiegel
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer type in Western countries. Significant progress has been made in the last decade in the therapy of metastatic CRC (mCRC) with a median overall survival (OS) of patients exceeding 30 months. The integration of biologic targeted therapies and anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MABs) in the treatment of patients with genomically selected all-RAS wild-type mCRC leads to a significant progress in advanced incurable disease state...
2016: Digestive Diseases
Camilla Natasha Cederbye, Jesper Andreas Palshof, Tine Plato Hansen, Anne Katrine Duun-Henriksen, Dorte Linnemann, Jan Stenvang, Dorte Lisbet Nielsen, Nils Brünner, Birgitte Martine Viuff
Overexpression of the ATP-dependent drug efflux pump ABCG2 is a major molecular mechanism of multidrug resistance in cancer and might be a predictive biomarker for drug response. Contradictory results have been reported for immunohistochemical studies of ABCG2 protein expression in colorectal cancer (CRC), probably because of the use of different antibodies and scoring approaches. In this study, we systematically studied six commercially available anti-ABCG2 antibodies, using cell lines with up-regulation of ABCG2, and selected one antibody for validation in CRC tissue...
2016: Scientific Reports
Jahanshah Ashkani, Kevin J Naidoo
Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung...
2016: Scientific Reports
Sishir K Kamalapuram, Rupinder K Kanwar, Kislay Roy, Rajneesh Chaudhary, Rakesh Sehgal, Jagat R Kanwar
The present study successfully developed orally deliverable multimodular zinc (Zn) iron oxide (Fe3O4)-saturated bovine lactoferrin (bLf)-loaded polymeric nanocapsules (NCs), and evaluated their theranostic potential (antitumor efficacy, magnetophotothermal efficacy and imaging capability) in an in vivo human xenograft CpG-island methylator phenotype (CIMP)-1(+)/CIMP2(-)/chromosome instability-positive colonic adenocarcinoma (Caco2) and claudin-low, triple-negative (ER(-)/PR(-)/HER2(-); MDA-MB-231) breast cancer model...
2016: International Journal of Nanomedicine
Bisrat G Debeb, Lara Lacerda, Simone Anfossi, Parmeswaran Diagaradjane, Khoi Chu, Arvind Bambhroliya, Lei Huo, Caimiao Wei, Richard A Larson, Adam R Wolfe, Wei Xu, Daniel L Smith, Li Li, Cristina Ivan, Pamela K Allen, Wenhui Wu, George A Calin, Savitri Krishnamurthy, Xiang H Zhang, Thomas A Buchholz, Naoto T Ueno, James M Reuben, Wendy A Woodward
BACKGROUND: Brain metastasis poses a major treatment challenge and remains an unmet clinical need. Finding novel therapies to prevent and treat brain metastases requires an understanding of the biology and molecular basis of the process, which currently is constrained by a dearth of experimental models and specific therapeutic targets. METHODS: Green Fluorescent Protein (GFP)-labeled breast cancer cells were injected via tail vein into SCID/Beige mice (n = 10-15 per group), and metastatic colonization to the brain and lung was evaluated eight weeks later...
August 2016: Journal of the National Cancer Institute
Nier Cha, Xiuhua Han, Baoqing Jia, Yanheng Liu, Xiaoli Wang, Yanwei Gao, Jun Ren
In this study, we found that four novel peptides designed by molecular modeling techniques were successfully applicated with cytotoxicity on colon cancer cells sw620. First, the interactions between the Herstatin and the HER2 were explored by ational-designed approaches, which were combined with homology modeling, protein/protein docking, and structural superimposition analysis. Then, based on the results derived from theoretical analysis, four novel peptides were designed, synthesized, and experimentally evaluated for biological function; it was found that they showed a remarkable enhancement on Herceptin to inhibit the genesis and development of colon cancers, and no significant side effects on normal colon cells NCM460 were observed but Doxorubicin had...
April 11, 2016: Artificial Cells, Nanomedicine, and Biotechnology
Marina Frimer, Kelly S Levano, Alicia Rodriguez-Gabin, Yanhua Wang, Gary L Goldberg, Susan Band Horwitz, June Y Hou
OBJECTIVE: Treatment options are limited for patients with uterine serous carcinoma (USC). Knowledge of USC's somatic mutation landscape is rapidly increasing, but its role in hereditary cancers remains unclear. We aim to evaluate the frequency and characteristics of germline mutations in genes commonly implicated in carcinogenesis, including those within homologous recombination (HR) and mismatch repair (MMR) pathways in patients with pure USC. METHODS: By using targeted capture exome sequencing, 43 genes were analyzed in a cohort of 7 consecutive patients with paired tumor and non-tumor USC samples in our institutional tumor repository...
April 2016: Gynecologic Oncology
Takaaki Masuda, Naoki Hayashi, Tomohiro Iguchi, Shuhei Ito, Hidetoshi Eguchi, Koshi Mimori
During the process of metastasis, which is the leading cause of cancer-related death, cancer cells dissociate from primary tumors, migrate to distal sites, and finally colonize, eventually leading to the formation of metastatic tumors. The migrating tumor cells in circulation, e.g., those found in peripheral blood (PB) or bone marrow (BM), are called circulating tumor cells (CTCs). CTCs in the BM are generally called disseminated tumor cells (DTCs). Many studies have reported the detection and characterization of CTCs to facilitate early diagnosis of relapse or metastasis and improve early detection and appropriate treatment decisions...
March 2016: Molecular Oncology
Frida Lédel, Kristina Stenstedt, Marja Hallström, Peter Ragnhammar, David Edler
UNLABELLED: Background HER3 is a member of the human epidermal growth factor receptor complex (EGFR, HER2, HER3 and HER4). It has been investigated as a prognostic biomarker in colorectal cancer but is sparingly studied in colon cancer. HER3 can affect cellular proliferation, differentiation and migration in oncogenesis through ligand binding and activation of intracellular signal pathways. Recently, we found that expression of cell surface HER3 can be detected at a high extent in primary colorectal tumors, lymph node and liver metastases and that it correlated with poor prognosis...
July 2016: Acta Oncologica
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