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Cancer of gastric

Yoshikane Nonagase, Kimio Yonesaka, Hisato Kawakami, Satomi Watanabe, Koji Haratani, Takayuki Takahama, Naoki Takegawa, Hiroto Ueda, Junko Tanizaki, Hidetoshi Hayashi, Takeshi Yoshida, Masayuki Takeda, Yasutaka Chiba, Takao Tamura, Kazuhiko Nakagawa, Junji Tsurutani
BACKGROUND: Overexpression of heregulin, a HER3 ligand, is one mechanism that confers resistance to the anti-HER2 agents trastuzumab and lapatinib. We investigated the impact of heregulin expression on the efficacy of HER2-targeted therapeutic agents, including trastuzumab, trastuzumab emtansine (T-DM1) and lapatinib, in vitro and in vivo and evaluated the heregulin messenger RNA (mRNA) levels in specimens from patients with HER2-positive breast or gastric cancer. RESULTS: Cell proliferation and apoptosis assays demonstrated that heregulin conferred robust resistance to lapatinib and trastuzumab via HER3-Akt pathway activation followed by survivin overexpression; however, heregulin conferred minimal or no resistance to T-DM1 and paclitaxel...
October 19, 2016: Oncotarget
E Faghihloo, Y Araei, M Mohammadi, H Mirzaei, H R Mohammadi, T Mokhtari-Azad
Gastric cancer is among the leading causes of cancer-related death, and the symptoms are commonly characterized in advanced stages. Histone acetylation is among the most important epigenetic alterations occurring during cancer development. In addition, reduced E-cadherin expression is a major contributor in the process of tumor cell invasion and metastasis. Oxamflatin is a histone deacetylase inhibitor that has been suggested as a promising anti-tumor agent; yet its effect on the viability and invasion of gastric tumor cells is unclear...
October 21, 2016: Cancer Gene Therapy
Fehmida Bibi, Muhammad I Naseer, Sana Akhtar Alvi, Muhammad Yasir, Asif A Jiman-Fatani, Ali Sawan, Adel M Abuzenadah, Mohammed H Al-Qahtani, Esam I Azhar
BACKGROUND: The role of small non-coding microRNAs (miRNAs) in several types of cancer has been evident. However, its expression studies have never been performed in gastric cancer (GC) patients from Saudi population. First time this study was conducted to identify miRNAs that are differentially expressed in GC patients compared with normal controls. METHODS: We investigated the role of miRNAs in GC patients using formalin-fixed paraffin-embedded (FFPE) tissues of 34 samples from GC patients (early stage = 7 and late-stage = 26) and 15 from normal control...
October 17, 2016: BMC Genomics
Keisuke Kubota, Akihiro Suzuki, Aoi Fujikawa, Takayuki Watanabe, Yuki Sekido, Hironori Shiozaki, Takashi Taketa, Gen Shimada, Seiji Ohigashi, Shintaro Sakurai, Akihiro Kishida
INTRODUCTION: The aim of this study was to introduce and examine a modified mechanical end-to-side esophagogastrostomy method ("reverse-Tornado" anastomosis) in laparoscopy-assisted proximal gastrectomy. METHODS: Five patients with gastric cancer who underwent laparoscopy-assisted proximal gastrectomy were analyzed retrospectively. Esophagogastrostomy in the anterior wall was performed in three patients, and esophagogastrostomy in the posterior wall was performed in two patients...
October 21, 2016: Asian Journal of Endoscopic Surgery
Gustav Linder, Jakob Hedberg, Martin Björck, Magnus Sundbom
In esophageal cancer surgery, perfusion of the gastric conduit is a critical issue. Measurement of gastric intramucosal pH (pHi ) is a method to identify anaerobic metabolism as a sign of impaired perfusion. In this study we aimed to monitor changes in the perfusion of the gastric conduit at key steps during and after esophagectomy. pHi was measured per- and postoperatively using intermittent gastric tonometry in 32 patients undergoing open, 65%, or video-assisted thoracoscopic esophagectomy for esophageal cancer...
October 21, 2016: Diseases of the Esophagus: Official Journal of the International Society for Diseases of the Esophagus
Hanlu Zhang, Longqi Chen, Yingcai Geng, Yu Zheng, Yun Wang
Thoracoscopic intrathoracic esophagogastrostomy is a technically demanding operation; these technical requirements restrict the extensive application of minimally invasive Ivor Lewis esophagectomy. In an attempt to reduce the difficulty of this surgical procedure, we developed a modified anastomotic technique for thoracolaparoscopic Ivor Lewis esophagectomy. During the entirety of this modified approach, neither technically challenging operations such as intrathoracic suturing, or knotting, nor special instruments such as an OrVil system or a reverse-puncture head are required...
October 21, 2016: Diseases of the Esophagus: Official Journal of the International Society for Diseases of the Esophagus
Koji Kono, Wei-Peng Yong, Hirokazu Okayama, Asim Shabbir, Tomoyuki Momma, Shinji Ohki, Seiichi Takenoshita, Jimmy So
Among advanced gastric cancer cases, peritoneal dissemination is a life-threatening mode of metastasis, and any strategy to control peritoneal metastasis will significantly improve treatment outcomes. Since intraperitoneal administration of anticancer drugs can induce an extremely high concentration of drugs in the peritoneal cavity, intraperitoneal chemotherapy would appear to be a reasonable and promising strategy to control the peritoneal dissemination. However, it has been reported in the past that intraperitoneal administration of mitomycin C or cisplatin resulted in no significant clinical effects against peritoneal metastasis of gastric cancer...
October 20, 2016: Gastric Cancer
L-C Horn, C E Brambs, R Handzel, S Lax, I Sändig, D Schmidt, K Schierle
The World Health Organization (WHO) classification from 2014 differentiates between different subtypes of mucinous adenocarcinoma of the uterine cervix. A gastric subtype was recently described that showed no association with high-risk human papillomavirus (HPV) infections, has a poor prognosis, is mainly diagnosed in women of Asian origin and can occur in patients with Peutz-Jeghers syndrome. Although no clear grading system has been recommended in the WHO classification, it is likely that grading of adenocarcinomas of the uterine cervix will partly be based on the different patterns of invasion...
October 20, 2016: Der Pathologe
Nadia F Nocera, M Catherine Lee, Lucy M De La Cruz, Cinthia Rosemblit, Brian J Czerniecki
The ErbB/B2 (HER-2/neu) oncogene family plays a critical role in the development and metastatic spread of several tumor types including breast, ovarian and gastric cancer. In breast cancer, HER-2/neu is expressed in early disease development in a large percentage of DCIS lesions and its expression is associated with an increased risk of invasion and recurrence. Targeting HER-2 with antibodies such as trastuzumab or pertuzumab has improved survival, but patients with more extensive disease may develop resistance to therapy...
2016: Frontiers in Pharmacology
Cheol Keun Park, Ji Soo Park, Hyo Song Kim, Sun Young Rha, Woo Jin Hyung, Jae-Ho Cheong, Sung Hoon Noh, Sang Kil Lee, Yong Chan Lee, Yong-Min Huh, Hyunki Kim
Although targeted therapy for receptor tyrosine kinases (RTKs) of advanced gastric cancers (AGCs) has been in the spotlight, guidelines for the identification of RTK-amplified gastric cancers (RA-GCs) have not been established. In this study, we investigate clinicopathologic characteristics of RA-GCs and propose a screening algorithm for their identification. We performed immunohistochemistry (IHC) for MLH1, MSH2, PMS2, MSH6, key RTKs (EGFR, HER2, MET), and p53, in situ hybridization for Epstein-Barr virus encoding RNA, and silver in situ hybridization (SISH) for EGFR, HER2, and MET using tissue microarrays of 993 AGCs...
September 27, 2016: Oncotarget
H H Yoon, J C Bendell, F S Braiteh, I Firdaus, P A Philip, A L Cohn, N Lewis, D M Anderson, E Arrowsmith, J D Schwartz, L Gao, Y Hsu, Y Xu, D Ferry, S R Alberts, Z A Wainberg
BACKGROUND: We report the first randomized, Phase II trial of ramucirumab, an anti-vascular endothelial growth factor receptor-2 monoclonal antibody, as front-line therapy in patients with advanced adenocarcinoma of the esophagus or gastric/gastroesophageal junction (GEJ). PATIENTS AND METHODS: Patients from the USA with advanced esophageal, gastric, or GEJ adenocarcinoma randomly received (1:1) mFOLFOX6 plus ramucirumab (8 mg/kg) or mFOLFOX6 plus placebo every 2 weeks...
October 20, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Kathryn F Flack, Jay Desai, Jennifer M Kolb, Prapti Chatterjee, Lars C Wallentin, Michael Ezekowitz, Salim Yusuf, Stuart Connolly, Paul Reilly, Martina Brueckmann, John Ilgenfritz, James Aisenberg
BACKGROUND & AIMS: Gastrointestinal (GI) bleeding in patients receiving anticoagulation agents can be caused by occult malignancies. We investigated the proportions and features of major GI bleeding (MGIB) events related to occult GI cancers in patients receiving anticoagulation therapy. METHODS: We analyzed data from the Randomized Evaluation of Long Term Anticoagulant Therapy study (conducted between December 2005 and March 2009 in 951 clinical centers in 44 countries worldwide), which compared the abilities of dabigatran vs warfarin to prevent stroke and systemic embolism in 18,113 patients with atrial fibrillation...
October 17, 2016: Clinical Gastroenterology and Hepatology
Khaldoun Almhanna, Gopi K Prithviraj, Petter Veiby, Thea Kalebic
Antibody-directed cancer chemotherapy in the form of antibody-drug conjugates (ADCs) may improve the therapeutic index with the potential to enhance efficacy and decrease systemic toxicity. ADCs consist of three key components including an antibody that specifically binds to the target, a toxic agent and a linker which releases the toxic agent inside tumor cells. A novel ADC, MLN0264 (TAK-264) was recently investigated in patients with gastrointestinal (GI) malignancies. TAK-264 is an anti- guanylyl cyclase C (GCC) antibody conjugated via a protease-cleavable linker to the potent anti-microtubule agent monomethyl auristatin E (MMAE) (linker and toxin licensed from Seattle Genetics)...
October 17, 2016: Pharmacology & Therapeutics
Lucas Goense, Peter S N van Rossum, Jelle P Ruurda, Marco van Vulpen, Stella Mook, Gert J Meijer, Richard van Hillegersberg
BACKGROUND: Concerns have been raised regarding the toxicity of neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer that could contribute to an increased risk of postoperative complications. The aim of this study was to determine the influence of the radiation dose to the gastric fundus on the risk of postoperative anastomotic leakage in patients undergoing nCRT followed by transthoracic esophagectomy. METHODS: Between January 2012 and July 2015, 97 consecutive patients who underwent nCRT followed by transthoracic esophagectomy were included in this single-center cohort study...
October 17, 2016: Annals of Thoracic Surgery
Keun-Wook Lee, Bum Jun Kim, Mi-Jung Kim, Hye Sook Han, Jin Won Kim, Young Iee Park, Sook Ryun Park
Purpose: This study evaluated the re-challenge of S-1 or cisplatin in combination with docetaxel in metastatic gastric cancer (MGC) that had progressed on a cisplatin plus either S-1 or capecitabine regimen. Materials and Methods: Patients with progressive disease after first-line cisplatin plus S-1 or capecitabine were randomized to receive 3-week cycles of docetaxel 75 mg/m² intravenously (IV) on D1 (D), docetaxel 60 mg/m² IV plus cisplatin 60 mg/m² IV on D1 (DC), or docetaxel 60 mg/m² IV D1 plus oral S-1 30 mg/m² b...
October 18, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Yanfen Fang, Yannan Kong, Jianbei Xi, Mengli Zhu, Tong Zhu, Tongtong Jiang, Wenhao Hu, Mingliang Ma, Xiongwen Zhang
NEK2 is a conserved mitotic regulator critical for cell cycle progression. Aberrant expression of NEK2 has been found in a variety of human cancers, making it an attractive molecular target for the design of novel anticancer therapeutics. In the present study, we have identified a novel compound MBM-5, which was found to bind to NEK2 with high affinity by docking simulations study. MBM-5 potently inhibited NEK2 kinase activity in vitro in a concentration-dependent manner. MBM-5 also suppressed cellular NEK2 kinase activity, as evidenced by the decreased phosphorylation of its substrate Hec1 on S165 in a concentration- and time-dependent manner...
October 15, 2016: Oncotarget
Dong Jin Kim, Wook Kim, Jun Hyun Lee
PURPOSE: Intra-corporeal esophagojejunostomy (EJ) using a linear stapler creates a stapler entry hole that requires secure closure during the totally laparoscopic total gastrectomy (TLTG) procedure for gastric cancer. Since a standard method has not been established yet, the feasibility of using V-loc 180 (Covidien, Mansfield, MA, USA) suture material was evaluated in this study. MATERIALS AND METHODS: During January 2012 to March 2015, 25 patients who underwent linear stapling EJ and V-loc 180 closure of remaining enterotomy were included in this study...
October 20, 2016: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
Lingxiang Wu, Xiujie Chen, Denan Zhang, Wubing Zhang, Lei Liu, Hongzhe Ma, Jingbo Yang, Hongbo Xie, Bo Liu, Qing Jin
Analysis of gene sets has been widely applied in various high-throughput biological studies. One weakness in the traditional methods is that they neglect the heterogeneity of genes expressions in samples which may lead to the omission of some specific and important gene sets. It is also difficult for them to reflect the severities of disease and provide expression profiles of gene sets for individuals. We developed an application software called IGSA that leverages a powerful analytical capacity in gene sets enrichment and samples clustering...
2016: PloS One
Heng Zhang, Hao Liu, Zhenbin Shen, Chao Lin, Xuefei Wang, Jing Qin, Xinyu Qin, Jiejie Xu, Yihong Sun
OBJECTIVE: This study was aimed to investigate the prognostic value of tumor-infiltrating neutrophils (TINs) and to generate a predictive model to refine postoperative risk stratification system for patients with gastric cancer. BACKGROUND: TIN presents in various malignant tumors, but its clinical significance in gastric cancer remains obscure. METHODS: The study enrolled 3 independent sets of patients with gastric cancer from 2 institutional medical centers of China...
October 14, 2016: Annals of Surgery
David Altree-Tacha, Jillian Tyrrell, Thomas Haas
CONTEXT: -CDH17, which is expressed in the intestinal epithelium, is a novel oncogene involved in tumor invasion and metastasis. A panel consisting of cytokeratin (CK) 7, CD20, and CDX2 antibodies is typically used to diagnose gastrointestinal adenocarcinomas. However, studies have shown that CDH17 is a highly specific marker for gastrointestinal adenocarcinoma and may be important in clinical diagnosis. OBJECTIVE: -To evaluate the sensitivity and specificity of CDH17, CK20, and CDX2 antibodies in neoplastic tissues, with emphasis on colon, stomach, and esophageal gastrointestinal lineage...
October 20, 2016: Archives of Pathology & Laboratory Medicine
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