- Enhanced expression of lncRNA TP73-AS1 predicts unfavorable prognosis for gastric cancer and promotes cell migration and invasion by induction of EMT. [Journal Article]
- GENEGene 2018 Aug 14
- Gastric cancer (GC) is a deadly disease with high incidence worldwide in recent years. Long noncoding RNAs (lncRNAs) were found to play imperative roles in many biological processes, such as cancer d...
Gastric cancer (GC) is a deadly disease with high incidence worldwide in recent years. Long noncoding RNAs (lncRNAs) were found to play imperative roles in many biological processes, such as cancer development and progression. Specifically, TP73-AS1, a novel cancer-related lncRNA, was documented to be up-regulated in several malignancies, but the clinical significance and functional role of TP73-AS1 in GC is still unknown. RT-qPCR was performed to evaluate TP73-AS1 transcription in GC tissue specimens and cell lines. In addition, the correlation between TP73-AS1 transcription and clinicopathologic features was further evaluated. Moreover, the effects of TP73-AS1 on GC cell were measured in vitro and in vivo. The data documented that TP73-AS1 was enhanced in GC tissues and cells, and TP73-AS1 transcription level was tightly associated with tumor size, TNM stage, and overall survival in 76 GC patients. What's more, decreased TP73-AS1 could restrain cell growth and colony-forming capacity and promoted apoptosis partly by regulating Bcl-2/caspase-3 pathway. Importantly, TP73-AS1 could promote xenograft growth in vivo. Silencing of TP73-AS1 inhibited GC cell migratory and invasive properties partly by reversing snail-mediated epithelial-to-mesenchymal transition (EMT). Collectively, this study may help to develop the treatment strategy for GC.
- Next-generation sequencing reveals mutational accordance between cell-free DNA from plasma, malignant pleural effusion and ascites and directs targeted therapy in a gastric cancer patient. [Journal Article]
- CBCancer Biol Ther 2018 Aug 17; :1-6
- Cell-free DNA (cfDNA) has been a research hotspot in molecular tumor profiling. In advanced gastric cancer patients, malignant pleural effusion (MPE) and ascites provide a wealth of tumor cells that ...
Cell-free DNA (cfDNA) has been a research hotspot in molecular tumor profiling. In advanced gastric cancer patients, malignant pleural effusion (MPE) and ascites provide a wealth of tumor cells that can be investigated. Here we conducted next-generation sequencing (NGS) on matched cfDNA from plasma, MPE and ascites from a stage-IV gastric cancer patient to identify potential therapeutic targets. In all three samples, we detected an amplification in the cellular-mesenchymal to epithelial transition factor (MET) gene, a truncation mutation in SMAD3 (p.R368X), and four ataxia telangiectasia-mutated gene (ATM) variants, including a missense mutation (p.E2351A), an in-frame deletion (p.NPAVIM2353delinsK), a frame-shift deletion (p.D1758fs) and an ATM- BPI fold containing family B member 1 (BPIFB1) gene fusion. In contrast, we detected amplification of TEK only in malignant ascites. The patient was subjected to Crizotinib to counter MET amplification. Our study demonstrates high accordance in mutational spectra of matched cfDNA from plasma, MPE and ascites, and suggests that it is feasible to utilize these tumor sources in clinical decision-making.
- Long-term Outcome of Group D patients with negative test of serum anti-Helicobacter pylori antibody and positive test of serum pepsinogen in Health checkup Koreans. [Journal Article]
- JDJ Dig Dis 2018 Aug 17
- CONCLUSIONS: Family history of GC and low baseline pepsinogen I/II ratio were independently associated with the increased risk for progression of precursor lesions of GC. This article is protected by copyright. All rights reserved.
- Tumor Platinum Concentrations and Pathological Responses Following Cisplatin-Containing Chemotherapy in Gastric Cancer Patients. [Journal Article]
- JGJ Gastrointest Cancer 2018 Aug 16
- CONCLUSIONS: Platinum was detectable in surgical specimens up to 72 days after preoperative chemotherapy. Higher tumor platinum concentration correlated with improved pathological response. Collagen binding potentially explained the high interpatient variability in tumor platinum concentrations.
- Radiomics in esophageal and gastric cancer. [Review]
- ARAbdom Radiol (NY) 2018 Aug 16
- Esophageal, esophago-gastric, and gastric cancers are major causes of cancer morbidity and cancer death. For patients with potentially resectable disease, multi-modality treatment is recommended as i...
Esophageal, esophago-gastric, and gastric cancers are major causes of cancer morbidity and cancer death. For patients with potentially resectable disease, multi-modality treatment is recommended as it provides the best chance of survival. However, quality of life may be adversely affected by therapy, and with a wide variation in outcome despite multi-modality therapy, there is a clear need to improve patient stratification. Radiomic approaches provide an opportunity to improve tumor phenotyping. In this review we assess the evidence to date and discuss how these approaches could improve outcome in esophageal, esophago-gastric, and gastric cancer.
- Protective Effects of Miswak (Salvadora persica) against Experimentally Induced Gastric Ulcers in Rats. [Journal Article]
- OMOxid Med Cell Longev 2018; 2018:6703296
- Gastric ulcers are among the most broadly perceived illnesses affecting individuals. Alcohol consumption is the main cause of gastric ulceration. This study assessed the protective effects of Salvado...
Gastric ulcers are among the most broadly perceived illnesses affecting individuals. Alcohol consumption is the main cause of gastric ulceration. This study assessed the protective effects of Salvadora persica (SP) extract against ethanol-induced gastric ulcer and elucidated the conceivable underlying mechanisms involved. For this purpose, 40 rats were allotted into 4 equal groups (control, ethanol- (EtOH-) treated, and SP-treated "SP200 and SP400" groups). The control and EtOH-treated groups were given phosphate buffer saline (PBS), and both the SP200 and SP400 groups were given SP extract dissolved in PBS at doses of 200 and 400 mg/kg b.w., respectively. All treatments were given orally for 7 constitutive days. On the 8th day, all rats were fasted for 24 h followed by oral gavage of PBS in the control group and chilled absolute ethanol solution (5 ml/kg b.w.) in the EtOH- and SP-treated groups to induce gastric lesions. One hour later, the rats were sacrificed and the stomachs were harvested. Gross and microscopic examinations of the EtOH-treated group showed severe gastric hemorrhagic necrosis, submucosal edema, destruction of epithelial cells, and reduced glycoprotein content at the mucus surface. These pathological lesions were defeated by SP extract treatment. Administration of SP extract modulated the oxidative stress and augmented the antioxidant defenses. The elevated ethanol-expressed tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) genes, as well as bcl-2-like protein 4 (Bax) and inducible nitric oxide synthase (iNOS), were diminished in the SP-treated group. Curiously, SP extract upregulated endothelial nitric oxide synthase (eNOS) and transforming growth factor-β1 (TGF-β1) gene expression comparable to that of the EtOH-treated rats. Aggregately, SP exerted antiulcer activities in ethanol-induced gastric ulcer rat models via modulation of oxidant/antioxidant status, mitigation of proinflammatory cytokines, and apoptosis, as well as remodeling of both NOS isoforms.
- Anti-neuropilin-1 monoclonal antibody suppresses the migration and invasion of human gastric cancer cells via Akt dephosphorylation. [Journal Article]
- ETExp Ther Med 2018; 16(2):537-546
- Neuropilin-1 (NRP-1) is involved in a range of physiological and pathological processes, including neuronal cell guidance, cardiovascular development, immunity, angiogenesis and the pathogenesis of c...
Neuropilin-1 (NRP-1) is involved in a range of physiological and pathological processes, including neuronal cell guidance, cardiovascular development, immunity, angiogenesis and the pathogenesis of cancer. Targeting of NRP-1 is considered to be a potential cancer therapy and a number of approaches have been investigated, including the use of small interfering RNA, peptides, soluble NRP antagonists and monoclonal antibodies. The present study used a novel anti-neuropilin-1 monoclonal antibody (anti-NRP-1 mAb) to investigate its potential anti-tumor effects on human gastric cancer cells in vitro and in vivo, as well as its underlying mechanisms of action. Using an MTT assay, it was observed that anti-NRP-1 mAb (<150 µg/ml) had no effects on the viability of gastric cancer cell line BGC-823, while a Boyden chamber assay indicated that treatment with anti-NRP-1 mAb suppressed the migration and invasion of BGC-823 cells. Western blot analysis also demonstrated that phosphorylation of Akt was reduced in BGC-823 cells treated with anti-NRP-1 mAb. Furthermore, anti-NRP-1 mAb suppressed the growth of gastric cancer xenograft tumors and downregulated the expression of vascular endothelial growth factor proteins within tumors in nude mice. These data indicate the potential effects of anti-NRP-1 mAb on malignant tumors and suggest that inhibition of NRP-1 function with anti-NRP-1 mAb may be a novel therapeutic approach in the treatment of cancer.
- Significance of Preoperative Systemic Immune Score for Stage I Gastric Cancer Patients. [Journal Article]
- GRGastroenterol Res Pract 2018; 2018:3249436
- CONCLUSIONS: Patients with SIS = 2 may benefit from AC and thus may be considered candidates for adjuvant treatment. However, to confirm our findings, future prospective studies are warranted.
- Anti-tumor efficacy of Selinexor (KPT-330) in gastric cancer is dependent on nuclear accumulation of p53 tumor suppressor. [Journal Article]
- SRSci Rep 2018 Aug 16; 8(1):12248
- Exportin-1 (XPO1) controls the nucleo-cytoplasmic trafficking of several key growth regulatory and tumor suppressor proteins. Nuclear export blockade through XPO1 inhibition is a target for therapeut...
Exportin-1 (XPO1) controls the nucleo-cytoplasmic trafficking of several key growth regulatory and tumor suppressor proteins. Nuclear export blockade through XPO1 inhibition is a target for therapeutic inhibition in many cancers. Studies have suggested XPO1 upregulation as an indicator of poor prognosis in gastric cancer. In the current study, we investigated the anti-tumor efficacy of selective inhibitors of nuclear export (SINE) compounds KPT-185, KTP-276 and clinical stage selinexor (KPT-330) in gastric cancer. XPO1 was found to be overexpressed in gastric cancer as compared to adjacent normal tissues and was correlated with poor survival outcomes. Among the 3 SINE compounds, in vitro targeting of XPO1 with selinexor resulted in greatest potency with significant anti-proliferative effects at nano molar concentrations. XPO1 inhibition by selinexor resulted in nuclear accumulation of p53, causing cell cycle arrest and apoptosis. Also, inhibition of XPO1 lead to the cytoplasmic retention of p21 and suppression of survivin. Orally administered selienxor caused significant inhibition of tumor growth in xenograft models of gastric cancer. Furthermore, combination of selinexor with irinotecan exhibited greater anti-tumor effect compared to individual treatment. Taken together, our study underscores the therapeutic utility of XPO1 targeting in gastric cancer and suggests the potential benefits of XPO1 inhibition in-combination with chemotherapy.
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- Low serum gastrin associated with ER+ breast cancer development via inactivation of CCKBR/ERK/P65 signaling. [Journal Article]
- BCBMC Cancer 2018 Aug 16; 18(1):824
- CONCLUSIONS: We concluded that low serum gastrin is related to increased risk of ER+ BC development. The results also established that CCKBR/ERK/P65 signaling function is generally tumor suppressive in ER+ BC, indicating therapies should focus on restoring, not inhibiting, CCKBR/ERK/P65 pathway activity.