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https://www.readbyqxmd.com/read/28210910/astrocyte-induced-reelin-expression-drives-proliferation-of-her2-breast-cancer-metastases
#1
Rahul Jandial, Cecilia Choy, Danielle M Levy, Mike Y Chen, Khairul I Ansari
Breast cancer metastasis to the brain develops after a clinical latency of years to even decades, suggesting that colonization of the brain is the most challenging step of the metastatic cascade. However, the underlying mechanisms used by breast cancer cells to successfully colonize the brain's microenvironment remain elusive. Reelin is an archetypal extracellular glycoprotein that regulates migration, proliferation, and lamination of neurons. It is epigenetically silenced in various cancers, and its expression in multiple myelomas is linked to poor patient survival...
February 17, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28178681/molecular-profiling-of-metastatic-colorectal-tumors-using-next-generation-sequencing-a-single-institution-experience
#2
Jun Gong, May Cho, Marvin Sy, Ravi Salgia, Marwan Fakih
BACKGROUND: Recent molecular characterization of colorectal tumors has identified several molecular alterations of interest that are considered targetable in metastatic colorectal cancer (mCRC). METHODS: We conducted a single-institution, retrospective study based on comprehensive genomic profiling of tumors from 138 patients with mCRC using next-generation sequencing (NGS) via FoundationOne. RESULTS: Overall, RAS mutations were present in 51...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28133217/-right-hemi-colectomy-for-a-metastatic-transverse-colon-tumor-from-breast-cancer-following-bilateral-breast-cancer-resection-a-case-report
#3
Shu Okamura, Tetsu Yanagisawa, Kazuhito Ohishi, Kohei Murata, Yoichiro Nushijima, Rie Hamano, Nariaki Fukuchi, Chikara Ebisui, Hideoki Yokouchi, Masakatsu Kinuta
We herein report the case of a 75-year-old female patient who underwent 4 surgeries for bilateral breast cancer and its recurrence. When she presented at a clinic with an irritable colon, a fist-sized tumor was palpated in the right upper abdomen at her first medical examination. Abdominal CT scan at the clinic revealed a tumor with a maximum diameter of 10 cm on the right side of the transverse colon and multiple swollen mesenteric lymph nodes. Therefore, the patient was referred to our hospital for surgery...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28067073/translating-genomic-profiling-to-gastrointestinal-cancer-treatment
#4
Kazuto Harada, Dilsa Mizrak Kaya, Yusuke Shimodaira, Shumei Song, Hideo Baba, Jaffer A Ajani
Next-generation sequencing enables faster, cheaper and more accurate whole-genome sequencing, allowing genome profiling and discovery of molecular features. As molecular targeted drugs are developed, treatment can be tailored according to molecular subtype. Gastric and colorectal cancers have each been divided into four subtypes according to molecular features. Profiling of the esophageal cancer genome is underway and its classification is anticipated. To date, identification of HER2 expression in gastric adenocarcinoma and KRAS, NRAS and BRAF mutations in colon cancer have proved essential for treatment decisions...
9, 2017: Future Oncology
https://www.readbyqxmd.com/read/28050146/personalized-oncogenomics-in-the-management-of-gastrointestinal-carcinomas-early-experiences-from-a-pilot-study
#5
B S Sheffield, B Tessier-Cloutier, H Li-Chang, Y Shen, E Pleasance, K Kasaian, Y Li, S J M Jones, H J Lim, D J Renouf, D G Huntsman, S Yip, J Laskin, M Marra, D F Schaeffer
BACKGROUND: Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. METHODS: We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma...
December 2016: Current Oncology
https://www.readbyqxmd.com/read/28040715/prolonged-response-to-her2-directed-therapy-in-a-patient-with-her2-amplified-rapidly-progressive-metastatic-colorectal-cancer
#6
Aparna Parikh, Chloe Atreya, W Michael Korn, Alan P Venook
HER2 gene amplifications and activating mutations in the HER2 receptor tyrosine kinase are present in 4% of metastatic colorectal cancers (mCRCs). HER2-targeted therapy is not standard of care, although preclinical and clinical data suggest that patients with HER2 amplifications and/or HER2-activating mutations may benefit from HER2-directed therapy. HER2 amplifications and activating mutations have also been implicated in resistance to anti-epidermal growth factor receptor-based therapy. This report describes a patient with KRAS, NRAS, and BRAF wild-type mCRC who experienced disease progression on first-line treatment with FOLFIRI and cetuximab after only 5 months, and subsequently experienced progression on second-line treatment with capecitabine and oxaliplatin plus bevacizumab after 2 months with significant functional decline...
January 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28032592/feedback-activation-of-her3-attenuates-response-to-egfr-inhibitors-in-colon-cancer-cells
#7
Albert Bosch-Vilaró, Bart Jacobs, Valentina Pomella, Layka Abbasi Asbagh, Richard Kirkland, Joe Michel, Sharat Singh, Xinjun Liu, Phillip Kim, Gregory Weitsman, Paul R Barber, Borivoj Vojnovic, Tony Ng, Sabine Tejpar
The EGFR inhibitor cetuximab is approved for the treatment of colorectal cancer. However, both innate and acquired resistance mechanisms, including compensatory feedback loops, limit its efficacy. Nevertheless, the emergence of these feedback loops has remained largely unexplored to date. Here, we showed feedback upregulation of HER3 and induction of HER3 phosphorylation after cetuximab treatment in colon cancer cells. We also showed that this upregulation occurs, at least partly, through AKT inhibition. Together with this, we observed increased HER2:HER3 dimerization upon cetuximab treatment...
December 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031408/predictive-outcomes-for-her2-enriched-cancer-using-growth-and-metastasis-signatures-driven-by-sparc
#8
Leandro N Guttlein, Lorena G Benedetti, Cristobal Fresno, Raul G Spallanzani, Sabrina F Mansilla, Cecilia Rotondaro, Ximena L Raffo Iraolagoitia, Edgardo Salvatierra, Alicia I Bravo, Elmer A Fernandez, Vanessa Gottifredi, Norberto W Zwirner, Andrea S Llera, Osvaldo L Podhajcer
: Understanding the mechanism of metastatic dissemination is crucial for the rational design of novel therapeutics. The secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein which has been extensively associated with human breast cancer aggressiveness although the underlying mechanisms are still unclear. Here, shRNA-mediated SPARC knockdown greatly reduced primary tumor growth and completely abolished lung colonization of murine 4T1 and LM3 breast malignant cells implanted in syngeneic BALB/c mice...
December 28, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27889782/molecular-pathology-a-requirement-for-precision-medicine-in-cancer
#9
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
https://www.readbyqxmd.com/read/27887848/simvastatin-inhibits-tumor-angiogenesis-in-her2-overexpressing-human-colorectal-cancer
#10
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...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27846453/a-case-report-of-chylous-ascites-after-gastric-bypass-for-morbid-obesity
#11
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...
2016: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/27737436/association-of-proton-pump-inhibitors-and-capecitabine-efficacy-in-advanced-gastroesophageal-cancer-secondary-analysis-of-the-trio-013-logic-randomized-clinical-trial
#12
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
https://www.readbyqxmd.com/read/27660891/the-increasingly-anti-tumor-effect-of-a-colonic-carcinoma-dna-vaccine-carrying-her2-by-the-adjuvanticity-of-il-12
#13
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
https://www.readbyqxmd.com/read/27598201/wnt-drug-discovery-weaving-through-the-screens-patents-and-clinical-trials
#14
REVIEW
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
https://www.readbyqxmd.com/read/27581375/a-new-mechanism-of-trastuzumab-resistance-in-gastric-cancer-macc1-promotes-the-warburg-effect-via-activation-of-the-pi3k-akt-signaling-pathway
#15
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
https://www.readbyqxmd.com/read/27556359/dual-targeting-of-her3-and-mek-may-overcome-her3-dependent-drug-resistance-of-colon-cancers
#16
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
https://www.readbyqxmd.com/read/27547057/tumor-markers-used-in-monitoring-the-tumor-recurrence-in-patients-with-colorectal-cancer
#17
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)
https://www.readbyqxmd.com/read/27416801/erbb2-and-p38%C3%AE-mapk-mediate-alcohol-induced-increase-in-breast-cancer-stem-cells-and-metastasis
#18
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
https://www.readbyqxmd.com/read/27340107/gene-expression-profiling-of-breast-cancer-brain-metastasis
#19
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
https://www.readbyqxmd.com/read/27332557/therapeutic-strategies-in-diseases-of-the-digestive-tract-2015-and-beyond-targeted-therapies-in-colon-cancer-today-and-tomorrow
#20
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
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