Approach For Gastric Cancer Research Articles

Identified VCAM1 as prognostic gene in gastric cancer by co-expression network analysis

The diffuse gastric cancer (DGC) is a malignant tumor distinct from intestinal gastric cancer (IGC). This study aims to identify genetic variances and potential diagnostic and therapeutic approaches for diverse types of gastric cancer utilizing an extensive dataset. Data from RNA sequencing and clinical pathological details were acquired from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) dataset. Co‐expression gene modules were constructed via Weighted Gene Co‐Expression Network Analysis (WGCNA), followed by deciphering gene functions and protein–protein interaction networks within significantly associated modules. In total, analysis was conducted on 56,753 genes from 247 individuals with gastric cancer. Particularly, 621 genes from the green module exhibited strong associations with the Lauren type of gastric cancer. The prominent genes in the green module showed enrichment in processes such as signal transduction, immune response, and the positive regulation of GTPase activity. Noteworthy among these, VCAM1 was identified as the central gene linked to patients’ prognosis. Moreover, 72 gastric cancer specimens were collected from The First Affiliated Hospital of University of Science and Technology of China. Immunohistochemical analysis demonstrated a significantly higher expression of VCAM1 in DGC compared to IGC (p = 0.019). Furthermore, it was confirmed that VCAM1 expression serves as a prognostic indicator for patients with DGC (p = 0.002), a correlation not observed in IGC (p = 0.760). In conclusion, this study identifies VCAM1 as a promising diagnostic and prognostic factor, suggesting novel avenues for diagnostic and therapeutic approaches in gastric cancer.

Novel immunotherapeutic approaches in gastric cancer.

Gastric cancer is a malignant tumor that ranks third in cancer-related deaths worldwide. Early-stage gastric cancer can often be effectively managed through surgical resection. However, the majority of cases are diagnosed in advanced stages, where outcomes with conventional radiotherapy and chemotherapy remain unsatisfactory. Immunotherapy offers a novel approach to treating molecularly heterogeneous gastric cancer by modifying the immunosuppressive tumor microenvironment. Immune checkpoint inhibitors and adoptive cell therapy are regarded as promising modalities in cancer immunotherapy. Food and Drug Administration-approved programmed death-receptor inhibitors, such as pembrolizumab, in combination with chemotherapy, have significantly extended overall survival in gastric cancer patients and is recommended as a first-line treatment. Despite challenges in solid tumor applications, adoptive cell therapy has demonstrated efficacy against various targets in gastric cancer treatment. Among these approaches, chimeric antigen receptor-T cell therapy research is the most widely explored and chimeric antigen receptor-T cell therapy targeting claudin18.2 has shown acceptable safety and robust anti-tumor capabilities. However, these advancements primarily remain in preclinical stages and further investigation should be made to promote their clinical application. This review summarizes the latest research on immune checkpoint inhibitors and adoptive cell therapy and their limitations, as well as the role of nanoparticles in enhancing immunotherapy.

Role of AT-rich interaction domain 1A in gastric cancer immunotherapy: Preclinical and clinical perspectives.

The application of immune checkpoint inhibitor (ICI) using monoclonal antibodies has brought about a profound transformation in the clinical outcomes for patients grappling with advanced gastric cancer (GC). Nonetheless, despite these achievements, the quest for effective functional biomarkers for ICI therapy remains constrained. Recent research endeavours have shed light on the critical involvement of modified epigenetic regulators in the pathogenesis of gastric tumorigenesis, thus providing a glimpse into potential biomarkers. Among these regulatory factors, AT-rich interaction domain 1A (ARID1A), a pivotal constituent of the switch/sucrose non-fermentable (SWI/SNF) complex, has emerged as a promising candidate. Investigations have unveiled the pivotal role of ARID1A in bridging the gap between genome instability and the reconfiguration of the tumour immune microenvironment, culminating in an enhanced response to ICI within the landscape of gastric cancer treatment. This all-encompassing review aims to dissect the potential of ARID1A as a valuable biomarker for immunotherapeutic approaches in gastric cancer, drawing from insights garnered from both preclinical experimentation and clinical observations.

Sensitivity and specificity of folate receptor α-positive circulating tumour cells in gastric cancer.

We aimed to investigate whether folate receptor α (FRα)-positive circulating tumour cells (CTCs) could be used as a noninvasive liquid biopsy approach in gastric cancer (GC). Tissue microarray and bioinformatic analyses were used to evaluate FRα expression in GC. Patients with FRα-positive CTC examinations at our institute between July 2021 and May 2022 were retrospectively evaluated. Receiver operating characteristic curves were used to evaluate the diagnostic performance of FRα-positive CTCs in GC. FRα was highly expressed and associated with poor prognosis in GC based on public database. Data for 163 patients (20 with benign disease and 143 with GC) were retrospectively collected. FRα-positive CTC levels were significantly higher in the GC group than in the benign disease group (12.15 ± 1.47 FU/3ml vs. 10.47 ± 1.63 FU/3ml, P < 0.01). FRα-positive CTC levels were also elevated in GC patients with vessel/neuron invasion or extra-nodal tumour deposits (12.31 ± 1.47 FU/3ml vs. 11.77 ± 1.38 FU/3ml, P = 0.037). Areas under the curve of FRα-positive CTC levels for GC and early GC were 0.774 (P < 0.001) and 0.736 (P = 0.005). With a cut-off value of 10.95 FU/3ml, the Youden indexes for GC and early GC were 0.502 (sensitivity = 85.2% and specificity = 65.0%) and 0.450 (sensitivity = 80.0% and specificity = 65.0%), respectively. FRα-positive CTC detection by noninvasive liquid biopsy is a useful and effective approach for screening of patients with GC.

Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer: S Pyrhönen, T Kuitunen, P Nyandoto & M Kouri.

We discuss Pyrhönen's paper as a catalyst for defining systemic therapy approaches in gastric cancer and how the field has evolved in the last two decades in sequential, targeted and more recently immune-directed therapies and how it may develop to transform survival in this cancer of high unmet need.

Surgeon’s Neoadjuvan Therapy Approach in Gastric Cancer

Surgeon’s Neoadjuvan Therapy Approach in Gastric Cancer

DNA Damage Repair and Current Therapeutic Approaches in Gastric Cancer: A Comprehensive Review.

DNA in cells is frequently damaged by endogenous and exogenous agents. However, comprehensive mechanisms to combat and repair DNA damage have evolved to ensure genomic stability and integrity. Improper DNA damage repair may result in various diseases, including some types of tumors and autoimmune diseases. Therefore, DNA damage repair mechanisms have been proposed as novel antitumor drug targets. To date, numerous drugs targeting DNA damage mechanisms have been developed. For example, PARP inhibitors that elicit synthetic lethality are widely used in individualized cancer therapies. In this review, we describe the latent DNA damage repair mechanisms in gastric cancer, the types of DNA damage that can contribute to the development of gastric cancer, and new therapeutic approaches for gastric cancer that target DNA damage repair pathways.

Abstract 5832: Utilizing small noncoding RNAs as biomarkers for selinexor treatment in gastric cancer

Abstract Gastric cancer is a deadly disease with a low 5-year survival rate of 32%. This disease is characterized by high rates of chemo resistance and late initial detection. We have previously reported that inhibition of nuclear exporter protein Exportin 1 (XPO1/CRM1) with the small molecule inhibitor selinexor (KPT-330) is a viable therapeutic approach in gastric cancer. Inhibition of XPO1 blocks proliferation and suppresses tumor growth through nuclear retention of tumor suppressor proteins such as TP53. Besides nuclear retention, we also demonstrated that XPO1 inhibition leads to a perturbation of cancer specific microRNAs including microRNA-7974 downregulation (miR-7974) and microRNA-129-1-3p upregulation (miR-129-1-3p) within a small RNA sequencing study. In this study we evaluated the role of these microRNAs in gastric cancer perpetuation in respect to their naive functions in five distinct subtypes of gastric cancer. Our results show over-expression of miR-7974 and loss of miR-129-1-3p promotes gastric cancer growth and progression, based on specific subtype of disease. We have further found that the differential expression of these microRNAs leads to gastric cancer cellular changes including cell cycle alterations, upregulation of autophagy processes, chemoresistance and alterations in the cellular framework leading to more invasive phenotypes. Validation with normal gastric epithelial cells revealed these microRNAs are relevant as they are perturbed in gastric cancer as well as the proteins in which they modulate. Finally, we have validated treatment of gastric cancer cells with the XPO1 inhibitor selinexor altered the expression of miR-7974 and miR-129-1-3p differently, based on subtype, as we have previously observed in small RNA sequencing screen, leading to a reversal of the pro-cancerous phenotypes previously observed. In vivo investigation is currently ongoing to identify whether we can capture either miR-7974 or miR-129-1-3p within the serum as further evidence of microRNA perturbation as a predictive biomarker for selinexor efficacy. Citation Format: Rachel E. Sexton, Amro Aboukameel, Yiwei Li, Husain Y. Khan, Md Hafiz Uddin, Trishyan Kashyap, Yosef Landesman, Anteneh Tesfaye, Asfar S. Azmi. Utilizing small noncoding RNAs as biomarkers for selinexor treatment in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5832.

Glucose starvation suppresses gastric cancer through targeting miR-216a-5p/Farnesyl-Diphosphate Farnesyltransferase 1 axis

BackgroundFasting mimic diet is an effect approach for gastric cancer (GC) treatment. Exploring mechanisms of glucose deprivation-mediated GC suppression is required to develop novel therapeutic regimens. Farnesyltransferase 1 (FDFT1), as a novel target in basic research, has been reported to regulate malignant progression in some types of cancer. However, biological functions of FDFT1 in GC are still unclear. This study focused on biological functions of FDFT1 in GC and the association between glucose starvation (GS) and FDFT1.MethodsThe data derived from the Kaplan–Meier Plotter database were collected to identify the relationship between survival time and FDFT1 expression levels of GC patients. Bioinformatic analysis was performed to explore the biological functions of FDFT1. The expression levels of targeted genes and microRNAs (miRNAs) were detected with immunohistochemistry, quantitative real-time PCR and western blot. Malignant behaviors were measured using cell counting, cell counting kit-8, 5-ethynyl-2-deoxyuridine, wound healing, invasion transwell assays in vitro and constructions of subcutaneous and lung-metastatic tumors in vivo. The glycolysis of GC cells was determined by a series of metabolites, including lactate acid, pyruvic acid, ATP production, rates of glucose uptake, extracellular acidification rate and oxygen consumption rate.ResultsFDFT1 was downregulated in GC and negatively correlated with pathological T stage, pathological TNM stage and cancer differentiation. High expression of FDFT1 also indicated better prognosis of GC patients. FDFT1 upregulation attenuated proliferation, migration and invasion of GC. miR-216a-5p was identified as a critical suppressor of FDFT1 expression and miR-216a-5p/FDFT1 axis regulated malignant behaviors and glycolysis of GC cells. GS suppressed malignant behaviors of GC by targeting miR-216a-5p/FDFT1 axis both in vitro and in vivo.ConclusionThis study illustrated novel mechanisms by which GS effectively suppresses GC. FDFT1 may become a potential prognostic indicator and novel target of GC therapy.

Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer.

Background: Osteopontin (OPN) splice variants are identified as predictors of tumour progression and therapeutic resistance in certain types of solid tumours. However, their roles in gastric cancer (GC) remain poorly characterized. The current study sought to assess the prognostic value of the three OPN splice variants (namely OPN-a, OPN-b, and OPN-c) in gastric cancer and their potential functions within gastric cancer cells. Methods: RNA extraction and reverse transcription were performed using our clinical cohort of gastric carcinomas and matched normal tissues (n = 324 matched pairs). Transcript levels were determined using real-time quantitative PCR. Three OPN splice variants overexpressed cell lines were created from the gastric cancer cell line HGC-27. Subsequently, biological functions, including cell growth, adhesion, migration, and invasion, were studied. The potential effects of OPN isoforms on cisplatin and 5-Fu were evaluated by detecting cellular reactive oxygen species (ROS) levels in the HGC-27-derived cell lines. Results: Compared with normal tissues, the expression levels of three splice variants were all elevated in gastric cancer tissues in an order of OPN-a > OPN-b > OPN-c. The OPN-a level significantly increased with increasing TNM staging and worse clinical outcome. There appeared to be a downregulation for OPN-c in increasing lymph node status (p < 0.05), increasing TNM staging, and poor differentiation. High levels of OPN-a and OPN-b were correlated with short overall survival and disease-free survival of gastric cancer patients. However, the low expression of OPN-c was significantly associated with a poor prognosis. Functional analyses further showed that ectopic expression of OPN-c suppressed in vitro proliferation, adhesiveness, migration, and invasion properties of HGC-27 cells, while the opposite role was seen for OPN-a. Cellular ROS detection indicated that OPN-a and OPN-c significantly promoted ROS production after treatment with 5-Fu comparing to OPN-vector, while only OPN-a markedly induced ROS production after treatment with cisplatin. Conclusion: Our results suggest that OPN splice variants have distinguished potential to predict the prognosis of gastric cancer. Three OPN variants exert distinctive functions in gastric cancer cells. Focusing on specific OPN isoforms could be a novel direction for developing diagnostic and therapeutic approaches in gastric cancer.

Novel Immunotherapeutic Approach in Gastric Cancer

Abstract Gastric cancer (GC) is suitable for immunotherapy because 80% of it display microsatellite and chromosomal instability, some mutations and DNA hypermethylation. Therefore, GC is more immunogenic. The immunotherapy with monoclonal antibodies, adoptive cell therapy and checkpoint inhibition are discussed. The commonly used monoclonal antibodies are Trastuzumab targeting HER2 and Bevacizumab suppressing VEGF and tumor angiogenesis. Treatment with tumor-specific T cells is called adoptive cell therapy. There is experience with the application of tumor infiltrating lymphocytes (TILs), cytotoxic T lymphocytes (CTLs) and cytokine-induced killer cells (CIK). This review discusses the therapy with innate immune cells with anti-tumor activity such as dendritic cells and NK cells. The checkpoint inhibition was also reviewed. In conclusion, it could be stated that the immunotherapy of GC has the potential to provide a more favorable outcome to patients with GC, but it also have some limitations which need to be considered.

Poor Clinical Outcomes and Immunoevasive Contexture in Intratumoral IL-10-Producing Macrophages Enriched Gastric Cancer Patients.

To investigate the clinical significance of IL-10+ tumor-associated macrophages (TAMs) in gastric cancer. Due to the plasticity and diversity of TAMs, it is necessary to phenotypically and functionally classify subsets of TAMs to better understand the critical role of TAMs in cancer progression. TAMs expressing interleukin-10 (IL-10) have been found to facilitate immune evasion in many malignancies, but the role of IL-10+ TAMs in gastric cancer remains obscure. Four hundred and sixty-eight tumor tissue microarray specimens, 52 fresh tumor tissue samples of gastric cancer patients from Zhongshan Hospital, and data of 298 gastric cancer patients from the Cancer Genome Atlas (TCGA) were analyzed. IL-10+ TAM level and immune contexture were examined by CIBERSORT, immunohistochemistry, and flow cytometry. Clinical outcomes were analyzed by Kaplan-Meier curves and Cox model. Gastric cancer patients with high IL-10+ TAM infiltration exhibited poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy. IL-10+ TAM infiltration yielded an immunoevasive tumor microenvironment featured by regulatory T cell infiltration and CD8+ T cell dysfunction. The combinational analysis of IL-10+ TAM and CD8+ T cell infiltration stratified patients into distinct risk groups with different clinical outcomes. Moreover, IL-10+ TAM infiltration was correlated with tumor-intrinsic characteristics including EBV status, PD-L1 expression, and genome stability in gastric cancer. This study revealed that IL-10+ TAMs might drive an immunoevasive microenvironment and determine poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy, indicating IL-10+ TAMs could be applied as a potential target for immunotherapeutic approach in gastric cancer.

Radiomics approaches in gastric cancer: a frontier in clinical decision making.

Objective:To review the application of radiomics in gastric cancer and its challenges as well as future prospects.Data sources:A research for relevant studies were performed in PubMed with the terms of “radiomics,” “texture analysis,” and “gastric cancer.” The search was updated until February 28th, 2019.Study selection:All original articles regarding the investigation of texture analysis or radiomics in gastric cancer were retrieved. Only papers written in English were included.Results:A total of 17 original articles were selected in final. It is shown that radiomics has yielded moderate to excellent performance in a spectrum of respects including differential diagnosis, assessment of histological differential degree, evaluation of tumor stage, prediction of response to therapy, and prognosis in gastric cancer. Yet, a number of challenges are facing both radiomics itself and its application in gastric cancer.Conclusions:Radiomics holds great potential in facilitating decision-making in gastric cancer. With the standardization of work-flow and advancement of machine learning methods, radiomics is expected to make great breakthroughs in precision medicine of gastric cancer.

The necessity of adjuvant radiotherapy for locally advanced gastric cancer in China

Nearly 50% of the new gastric cancer cases and gastric cancer-related deaths worldwide occur in China. Although the Guidelines for the Diagnosis and Treatment of Gastric Cancer from the National Health Commission of the People’s Republic of China have explicitly emphasized the necessity of adjuvant chemoradiation for gastric cancer, few clinical institutions in China routinely administer postoperative adjuvant radiation therapy in patients with gastric cancer. At present, radical resection combined with postoperative chemotherapy alone is the most common treatment for locally advanced gastric cancer in China. However, several phase III prospective randomized controlled trials in Europe have shown that adjuvant chemotherapy alone after a radical resection does not improve the disease-free survival (DFS) or overall survival (OS) of patients with gastric cancer. As in Japan and South Korea, D2 radical resection is the recommended surgical approach for gastric cancer in China. However, several studies have shown that the rate of D2 resection in the treatment of gastric cancer patients in China is low. Nearly 50% of patients undergo a D0-1 radical resection, even at the leading gastric cancer centers in China. The results of the INT-0116 study in the US suggest that gastric cancer patients who undergo a D0-1 radical resection and have stage T3-4 or N+ disease should receive concurrent postoperative radiation therapy and chemotherapy. In conclusion, many patients with gastric cancer do not receive a standard D2 resection in China. As a result, it is important to consider postoperative adjuvant chemoradiation especially in those patients who undergo a D0-1 radical resection.

Neoadjuvant treatment in patients with locally advanced gastric cancer.

127 Background: Although neoadjuvant treatment has been standart approach in gastric cancer with the positive results of randomized controlled studies in recent years, neoadjuvant treatment approach rates are far below the expectations in our country. We aimed to evaluate neoadjuvant treatment approaches and results of gastric cancer patients in this retrospective study. Methods: We evaluated characteristics and survival outcomes of 54 patients that were operated after neoadjuvant systemic treatment out of 1,143 gastric cancer patients recorded in our database. Results: The median follow-up was 12 months in this study. 38% of the patients was female and the median age was 61 (24-78). While 46 % of the tumors were located in gastro-esophagial junction and cardia, others were located distally. All of the patients treated with neoadjuvant treatment had positive lymph nodes. While lymphatic and perineural invasion were detected in 67% of the patients, vascular invasion was detected in 39 % of the patients after the operation. While 43 % of the patients had grade 3 tumors, others had grade 1-2 tumors. R0 resection was achieved in 91% of the patients and D2 dissection was done in 82% of the patients. FOLFOX/XELOX, DCF/DCX, EOX/ECF and FLOT were applied as neoadjuvant treatment regimes in 19%, 50%, 21% and 11% of the patients respectively. The median chemotherapy cycle number was 3 applied pre and postoperatively. The disease control rate (response or stable disease) was achieved in 75,9 % of the patients after the neoadjuvant chemotherapy. In 13 patients progressive disease was detected and these patients were not operated. We found the median disease free survival was 25 months and overall survival was 41 months in survival analysis. Three year DFS was 29 % and 3 year OS was 52 %. Conclusions: Neoadjuvant treatment approach is important both to facilitate operation procedure and to evaluate efficacy of systemic treatment. As the survival advantage was shown in a study last year, FLOT regime is expected to be used more commonly. The patients have to be evaluated and the treatment decisions should be made in a multidisiplinary tumor board including surgeon, radiologist, medical oncologist to provide optimal treatment benefit.

Evaluation of altered expression of miR-9 and miR-106a as an early diagnostic approach in gastric cancer.

The role of microRNAs (miRNAs) in cellular processes such as growth, apoptosis, differentiation and proliferation verifies the importance of miRNAs in carcinogenesis. Moreover, levels of miRNAs are dysregulated in cancer cells, so they could be used as novel classes of biomarkers for diagnosing cancer. The oncogenic role of miR-106a and its increased expression have been demonstrated in some cancers. In contrast, there is no consensus for miR-9 expression rate in different cancers. Therefore, this study was done to investigate the role of miR-106a and miR-9 in gastric cancer (GC). The current study was performed on 31 GC tissues as case, and 31 healthy adjacent tissues as a control group. Quantitative reverse transcriptase (q-RT) PCR was used for studying the expression rate of both miR-106a and miR-9. The expression rate of both miRNAs in cancerous tissues was significantly higher than healthy adjacent tissues (≈10 folds) (P<0.05). The results showed that the expression rate of both markers was significantly increased in cancerous tissues. Therefore, they can be suggested as potential biomarkers for cancer diagnosis and prognosis as well as targets for therapy.

Staging and surgical approaches in gastric cancer: a clinical practice guideline.

Resection is the cornerstone of cure for gastric adenocarcinoma; however, several aspects of surgical intervention remain controversial or are suboptimally applied at a population level, including staging, extent of lymphadenectomy (lnd), minimum number of lymph nodes that have to be assessed, gross resection margins, use of minimally invasive surgery, and relationship of surgical volumes with patient outcomes and resection in stage iv gastric cancer. Literature searches were conducted in databases including medline (up to 10 June 2016), embase (up to week 24 of 2016), the Cochrane Library and various other practice guideline sites and guideline developer Web sites. A practice guideline was developed. One guideline, seven systematic reviews, and forty-eight primary studies were included in the evidence base for this guidance document. Seven recommendations are presented. All patients should be discussed at a multidisciplinary team meeting, and computed tomography (ct) imaging of chest and abdomen should always be performed when staging patients. Diagnostic laparoscopy is useful in the determination of M1 disease not visible on ct images. A D2 lnd is preferred for curative-intent resection of gastric cancer. At least 16 lymph nodes should be assessed for adequate staging of curative-resected gastric cancer. Gastric cancer surgery should aim to achieve an R0 resection margin. In the metastatic setting, surgery should be considered only for palliation of symptoms. Patients should be referred to higher-volume centres and those that have adequate support to manage potential complications. Laparoscopic resections should be performed to the same standards as those for open resections, by surgeons who are experienced in both advanced laparoscopic surgery and gastric cancer management.

Abstract 5069: Inhibition of BET bromodomain, epigenetic regulator, as an effective therapeutic approach for gastric cancer

Abstract Epigenetic dysregulation is a common characteristic of cancer, including gastric cancer(GC), which ultimately contributes to the development and progression of GC. Sequencing of cancer genomes has revealed frequent mutations in epigenetic regulators, particularly chromatin remodelers and histone modifiers, and disordered chromatin regulation has emerged as a distinct mechanism contributing to tumor development. As a highly conserved class of epigenome readers, BRD4 is a member of the BET (bromodomain and extra-terminal domain) family that recognizes and binds acetylated histones H3 and H4 and influences gene regulation. Small molecule BET inhibitors prevent binding of BET proteins to acetylated histones and inhibit transcriptional activation of BET target genes. BET inhibitors attenuate cell growth and survival in several hematologic cancer models, partially through the down-regulation of the critical oncogene, c-Myc. We would like to elucidate the sensitivity to I-BET151 and its relationship with genetic/epigenetic alterations to identify predictive biomarkers in 49 gastric cancer cell lines. Anticancer effect of small molecular inhibitor of the BET family, GSK1210151A (I-BET151, GSK, PA, USA), was treated for 6 days and assessed using CCK-8 assay. For exploring predictive biomarkers, we analyzed genetic and molecular characterization of BRD4-related genes using whole exome sequencing (WES), RNA sequencing and western blots. As a result, ARID1A deletion (SNU-5 and YCC-6) and single nucleotide variant (14/49, 28.5%) were correlated with decreased protein expression (p&amp;lt;0.0001). However, these ARID1A variants were not related to sensitivity of I-BET151. While, BRD4 was expressed in almost cell lines with no mutations. When we screened 49 cell lines for growth inhibition by I-BET151 and 73%(36) of cells showed modest activity to I-BET-151. We divided into two groups according to the sensitivity: extremely sensitive (IC50 &amp;lt; 1 uM: 13 cell lines) and extremely resistant (IC50 &amp;gt; 5 uM: 13 cell lines). Then, we analyzed Differentially Expressed Gene (DEG) in each group and selected about 600 genes (FDR &amp;lt; 0.05, p &amp;lt; 0.001 and 1.5 fold) including CXCL5, HRK, BMPER and IGDCC4. BRD4 mRNA expression was lower in extremely sensitive group compared to extremely resistant group (p = 0.0163), but BRD4 protein expression was not. In addition, no association has been observed between other genes expression, such as MYC, BCL2, HEXIM1/2, SRC, TXNIP, CCND1 and MLKL, and sensitivity to I-BET151. Our data indicates that I-BET151 is a potent inhibitor of GC and showed the possibility of development a predictive biomarker based on genetic and molecular profiling. Citation Format: Sun Kyoung Kang, Tae Soo Kim, Woo Sun Kwon, Jae Kyung Roh, Ho-Yeong Lim, Hyun Cheol Chun, Sun Young Rha. Inhibition of BET bromodomain, epigenetic regulator, as an effective therapeutic approach for gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5069. doi:10.1158/1538-7445.AM2017-5069

Crocodile choline from Crocodylus siamensis induces apoptosis of human gastric cancer.

Crocodile choline, an active compound isolated from Crocodylus siamensis, was found to exert potent anti-cancer activities against human gastric cancer cells in vitro and in vivo. Our study revealed that crocodile choline led to cell cycle arrest at the G2/M phase through attenuating the expressions of cyclins, Cyclin B1, and CDK-1. Furthermore, crocodile choline accelerated apoptosis through the mitochondrial apoptotic pathway with the decrease in mitochondrial membrane potential, the increase in reactive oxygen species production and Bax/Bcl-2 ratio, and the activation of caspase-3 along with the release of cytochrome c. In addition, this study, for the first time, shows that Notch pathway is remarkably deregulated by crocodile choline. The combination of crocodile choline and Notch1 short interfering RNA led to dramatically increased cytotoxicity than observed with either agent alone. Notch1 short interfering RNA sensitized and potentiated the capability of crocodile choline to suppress the cell progression and invasion of gastric cancer. Taken together, these data suggested that crocodile choline was a potent progression inhibitor of gastric cancer cells, which was correlated with mitochondrial apoptotic pathway and Notch pathway. Combining Notch1 inhibitors with crocodile choline might represent a novel approach for gastric cancer.

Robotic, laparoscopic and open surgery for gastric cancer compared on surgical, clinical and oncological outcomes: a multi-institutional chart review. A study protocol of the International study group on Minimally Invasive surgery for GASTRIc Cancer—IMIGASTRIC

IntroductionGastric cancer represents a great challenge for healthcare providers and requires a multidisciplinary treatment approach in which surgery plays a major role. Minimally invasive surgery has been progressively developed, first...