Clinical relevance and druggability of sole reciprocal kinase fusions: A large-scale study.

BACKGROUND: Building on our prior work that RNA alternative splicing modulates the druggability of kinase fusions, this study probes the clinical significance of sole reciprocal fusions. These rare genomic arrangements, despite lacking kinase domains at the DNA level, demonstrated potential RNA-level druggability in sporadic cases from our prior research. METHODS: Utilizing the large-scale multicenter approach, we performed RNA sequencing and clinical follow-up to evaluate a broad spectrum of kinase fusions, including ALK, ROS1, RET, BRAF, NTRK, MET, NRG1, and EGFR, in 1943 patients. RESULTS: Our findings revealed 51 instances (2.57%) of sole reciprocal fusions, predominantly in lung (57%), colorectal (14%), and glioma (10%) cancers. Comparative analysis with an MSKCC cohort confirmed the prevalence in diverse cancer types and identified unique fusion partners and chromosomal locales. Cross-validation through RNA-NGS and FISH authenticated the existence of functional kinase domains in subsets including ALK, ROS1, RET, and BRAF, which correlated with positive clinical responses to targeted kinase inhibitors (KIs). Conversely, fusions involving EGFR, NRG1, and NTRK1/2/3 generated nonfunctional transcripts, suggesting the need for alternative therapeutic interventions. CONCLUSION: This inaugural multicenter study introduces a novel algorithm for detecting and treating sole reciprocal fusions in advanced cancers, expanding the patient population potentially amenable to KIs.

WYC-209 suppresses gastric cancer by down-regulating FGF18 via inactivating the STAT3 signaling pathway.

BACKGROUND: Gastric cancer (GC) is regarded as a major health burden all over the world. WYC-209 inhibits the growth and metastasis of tumor-repopulating cells (TRCs). However, its effectiveness on GC was unexplored. Herein, this study aims to investigate the effect of WYC-209 on GC and elucidate its underlying mechanism. METHODS: We examined the effects of WYC-209 on cell survival, migration, invasion, and colony-forming capacities of two GC cell lines (AGS and HGC-27). Subsequently, RNA-seq and enrichment analyses were performed to screen the differentially expressed genes (DEGs) and the enriched signaling pathways. To further explore the underlying mechanism, loss- and gain-function experiments, Chromatin immunoprecipitation, and luciferase reporter were conducted. Finally, xenograft models were constructed to examine the effects of WYC-209 in vivo. RESULTS: WYC-209 significantly inhibited cell motility in vitro and tumor growth in vivo. RNA-seq performed in AGS cells after WYC-209 treatment revealed that the inhibition effect of WYC-209 on GCs may be associated with the down-regulation of fibroblast growth factor-18 (FGF18), and pleasantly, FGF18 overexpression abrogated the suppression effect of the drug. In addition, we found that WYC-209 attenuated the activation of the Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway, and impeded the FGF18 levels expressed in GCs. Importantly, the WYC-209 treatment circumvented the binding of STAT3 to the FGF18 promoter, suggested that WYC-209 down-regulated FGF18 expression via the STAT3 signaling pathway. CONCLUSION: Together, our findings presented the promise of WYC-209 in suppressing GC by down-regulating FGF18 expression through inactivating the STAT3 signaling pathway.

A prognostic risk model based on lactate metabolism and transport-related lncRNAs for gastric adenocarcinoma.

BACKGROUND: Increased lactate levels and metastasis in tumours are strongly associated with dismal outcomes. But prognostic value of lactate metabolism and transport-related lncRNAs in gastric adenocarcinoma (GA) patients remains unaddressed. METHODS: Gene expression data of GA were provided by The Cancer Genome Atlas. Lactate metabolism and transport-related gene data were accessed from GSEA. LncRNAs related to lactate metabolism and transport were identified by correlation analysis. A prognostic model was built by regression analysis. Validity of prognostic model was confirmed through survival analysis and receiver operating characteristic (ROC) curve. Immunity of each risk group was evaluated by immune correlation analysis .LncRNA-mRNA network was built by correlation analysis using Cytoscape software. RESULTS: A 12-gene prognostic model based on lactate metabolism and transport-related lncRNAs was built in GA. Median riskscore was utilized to classify GA samples into high- and low-risk groups. Survival analysis and ROC curves demonstrated validity of prognostic model. Most immune checkpoint molecules and TIDE scores were lower in the low-risk group. LINC01303 and LINC01545 may be the key prognostic factors in patients with GA. CONCLUSION: This study successfully built a prognostic model of lactate metabolism and transport-related lncRNAs in GA. The findings guide prognostic management of GA patients.

WYC-209 inhibited GC malignant progression by down-regulating WNT4 through RARα.

Gastric cancer (GC) has been a major health burden all over the world but there are fewer promising chemotherapeutic drugs due to its multidrug resistance. It has been reported that WYC-209 suppresses the growth and metastasis of tumor-repopulating cells but the effect on GC was not explored. MTT, colony formation, and transwell assays were performed to examine the effects of WYC-209 on the proliferation, colony growth, and mobility of GC cells. Western blotting and qRT-PCR were used to detect the expression of proteins and mRNA. RNA-seq and enrichment analyses were conducted for the differentially expressed genes and enriched biological processes and pathways. The rescue experiments were carried out for further validation. Besides, we constructed xenograft model to confirm the effect of WYC-209 in vivo. The dual-luciferase reporter and Chromatin immunoprecipitation were implemented to confirm the underlying mechanism. WYC-209 exerted excellent anti-cancer effects both in vitro and in vivo. Based on RNA-seq and enrichment analyses, we found that Wnt family member 4 (WNT4) was significantly down-regulated. More importantly, WNT4 overexpression breached the inhibitory effect of WYC-209 on GC progression. Mechanically, WYC-209 significantly promoted the binding between retinoic acid receptor α (RARα) and WNT4 promoter. WYC-209 exerts anti-tumor effects in GC by down-regulating the expression of WNT4 via RARα.

Oridonin Suppresses Human Gastric Cancer Growth in Vitro and in Vivo via Inhibition of VEGF, Integrin ß3, and PCNA.

The diterpenoid oridonin is an extract from the herb Rabdosia rubescens, commonly used in Traditional Chinese medicine. Oridonin has putative inhibitory activity in many human cancers. This study continued investigations into the therapeutic potential of oridonin against gastric carcinoma, and the underlying mechanism. An in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with BGC823 cells was used to examine the cytotoxicity and apoptosis associated with oridonin treatment. RT-PCR and immunocytochemistry results showed evaluated levels of vascular endothelial growth factor (VEGF), cluster of differentiation 31 (CD31), integrin ß3, and proliferating cell nuclear antigen (PCNA) in BGC823 cells, or BGC823 xenografts nude mice. The inhibitory effect of oridonin was determined in vivo using the xenograft model, comparing tumor weight and volume, and calculating the tumor inhibition rate. The oridonin treatment and control groups were compared for associations between microvessel density and tumor inhibition rate, VEGF mRNA, integrin ß3 mRNA, and PCNA protein. The IC50s of oridonin at 12 and 72 h were 17.08 ± 2.38 and 8.76 ± 0.90 µg/mL, respectively. VEGF protein levels dramatically decreased in a time- and dose-dependent manner with oridonin treatment. BGC823 xenograft growth was notably less in the oridonin treatment groups, responding in a dose-dependent manner. After 14 d of treatment, VEGF, integrin ß3, and PCNA levels were dramatically lower, and positively correlated with CD31 levels. Oridonin was associated with inhibition of BGC823 cell growth and tumor angiogenesis, in vitro and in vivo, in a dose-and-time dependent manner with lower levels of VEGF, integrin ß3, and PCNA. Oridonin is a potential candidate agent for chemotherapy of gastric carcinoma.

miR-618 Suppresses Metastasis in Gastric Cancer by Downregulating the Expression of TGF-ß2.

Recent studies have demonstrated that microRNAs regulate gene expression and are related to cancer progression. Increasing evidence shows that miR-618 plays an important role in a variety of tumors, including thyroid carcinomas, breast cancer and lymphoma cancer. However, no studies have examined the expression or function of miR-618 in gastric cancer (GC). In this study, we examined the effects and molecular mechanisms of miR-618 in GC. We compared the expression levels of miR-618 in 90 paired GC tissues and adjacent noncancerous tissues. Cell cycle, apoptosis and transwell assays were performed in GC cells with miR-618 mimic or inhibitor in vitro. We first used quantitative PCR(qPCR) to show that miR-618 expression levels were downregulated in GC tissues, which showed statistical significance. Next we used transwell assays to prove that miR-618 suppressed the invasion and migration capacity of GC cells. Furthermore, screening of the miRDB and Target Scan Human databases indicated TGF-ß2 as a downstream target of miR-618. In further research, we identified TGF-ß2 as a target gene of miR-618 by the luciferase reporter assay. Western blot analysis confirmed that TGF-ß2 expression was inversely correlated with miR-618 expression. In situ hybridization showed that miR-618 expression level was downregulated in GC tissues. In conclusion, our findings suggest that miR-618 may function as a tumor suppressor in GC and suppresses metastasis in GC by negatively regulating the transcriptional level of TGF-ß2. Anat Rec, 302:931-940, 2019. © 2019 Wiley Periodicals, Inc.

Up-regulation of long noncoding RNA M26317 correlates with tumor progression and poor prognosis in gastric cancer.

To investigate the expression and clinical significance of long noncoding RNA (lncRNA) in gastric cancer, we applied microarray analysis to obtain expression profiles of protein-coding genes and lncRNAs in tumor and paired adjacent nontumor tissues. We found that 41 lncRNAs were up-regulated and 31 lncRNAs were down-regulated more than 2-fold in gastric cancer versus noncancerous tissues (ratio >2.0, P < .01). We established a coexpression network of the differentially expressed lncRNAs and targeted coding genes that included 17 lncRNAs and 16 coding genes. Because the results of microarray analysis showed that lncRNA M26317 was up-regulated in gastric cancer tissues, we examined the expression level of M26317 in 103 gastric cancer tissues by reverse-transcription polymerase chain reaction and 436 gastric cancer tissues by in situ hybridization. Our data confirmed that M26317 was up-regulated in gastric cancer tissues. Moreover, expression of M26317 correlated with patient age, size of tumor, Lauren's classification, depth of invasion, lymph node and distant metastasis, TNM stage, and poor prognosis (P < .05), but was not associated with sex, location of tumor, and differentiation (P > .05). M26317 may have an important role in malignant transformation and metastasis of gastric cancer.

Overexpression of MYC binding protein promotes invasion and migration in gastric cancer.

Gastric cancer (GC) is the second leading cause of cancer-associated mortality worldwide. Although the mortality rate of patients with GC has improved, it remains a significant health issue. The MYC proto-oncogene protein serves key roles in cellular proliferation, differentiation, transformation and apoptosis. Previous studies have identified the abnormal expression of MYC-binding protein (MYCBP) during tumorigenesis in multiple types of cancer. Furthermore, evidence demonstrates that the abnormal expression of MYCBP contributes to the invasion and migration of human cancer types, including colon cancer and glioma; however, its influence on GC remains unclear. In the present study, the expression of MYCBP in GC cells and tissues was analyzed by reverse transcription-quantitative polymerase chain reaction. Additionally, GC cell lines were transfected with small interfering RNAs against MYCBP or lymphoid enhancer-binding factor 1 (LEF-1) and assessed by in vitro transwell migration and invasion assays. The results indicated that the expression of MYCBP in GC cells and tissues was markedly increased compared with a normal gastric epithelial cell line and adjacent normal gastric mucosal tissues, respectively. Furthermore, MYCBP downregulation notably inhibited the metastatic capacity of GC cells, and LEF-1 knockdown was found to downregulate the expression of MYCBP. On the basis of the findings of the present study, MYCBP may be a direct target of the ß-catenin/LEF-1 pathway via binding LEF-1, and could potentially be used as a biomarker for the diagnosis and prognosis of GC.

Metastasis-associated protein 1 (MTA1) in gastric cancer tissues is positively associated with poorer prognosis.

BACKGROUND: The present study examined the clinical significance of metastasis-associated protein 1 (MTA1) in the progression and patient survival of gastric cancer. METHODS: Paraffin-embedded resected tissues of gastric cancer mucosa (n = 436) and adjacent normal mucosa (n = 92) were assessed immunohistochemically for MTA1 protein, and scored according to the percentage of cells positively stained for MTA1 combined with stain intensity. Associations between MTA1 staining scores and clinicopathological factors, including survival time, were evaluated. RESULTS: The staining scores for MTA1 were significantly higher in gastric cancer tissues than in matched normal tissues. MTA1 scores positively correlated with tumor size, depth of invasion, presence of lymph node metastasis, lymphatic involvement, venous invasion, distal metastasis, and advanced clinical staging. Patients with high MTA1 scores in gastric cancer tissues had a significantly lower five-year survival rate compared with patients with low MTA1 scores. The multivariate analysis indicated that MTA1 protein levels in resected gastric cancer tissues, as reflected by immunohistochemical staining, are an independent prognostic index of gastric carcinoma (P < 0.01). CONCLUSION: MTA1 immunopositivity was significantly associated with progression of gastric cancer, and may be helpful in gastric cancer prognosis.

Lentiviral delivery of CTLA-4 shRNA improves the expansion of cytokine-induced killer cells and enhances cytotoxic activity in vitro.

Cytokine-induced killer (CIK) cells are in vitro-expanded cells harboring potent toxicity against tumor cells. Recently, it was identified that the cytotoxicity and proliferation of CIK cells are restricted by a prolonged CIK cell culture period. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) serves a negative role in T cell activation and proliferation. This study aims to determine whether CTLA-4 expression is associated with the inhibition of CIK cells. CIK cells were generated from peripheral blood mononuclear cells (PBMCs), and CTLA-4 shRNA (shCTLA-4) lentivirus was applied to knockdown CTLA-4 expression in CIK cells. The proliferation of CIK cells was evaluated following shCTLA-4 lentiviral transduction, and the cytotoxicity of CIK cells was investigated using the CytoTox 96 Non-Radioactive Cytotoxicity assay. The expression of CTLA-4 in CIK cells was significantly increased, compared with that in PBMCs. The shCTLA-4 lentivirus efficiently knocked down the expression of CTLA-4 in CIK cells. The shCTLA-4 lentivirus transduction of CIK cells promoted the proliferation of CIK cells in vitro (3.18±0.19-fold vs. 2.42±0.29-fold). Furthermore, the cytotoxicity of shCTLA-4 lentivirus-transduced CIK cells was significantly improved when compared with that of control shRNA lentivirus-transduced CIK cells (54.5±2.13% vs. 30.5±1.67%). Thus, the suppression of CTLA-4 expression increases cytotoxicity and ex vivo expansion of CIK cells, which indicates a clinical significance for CTLA-4 blockade in CIK cell therapy.

miR-551b regulates epithelial-mesenchymal transition and metastasis of gastric cancer by inhibiting ERBB4 expression.

Epithelial-mesenchymal transition (EMT) is an important biological process that is characteristic of malignant tumor cells with metastatic potential. We investigated the role of miR-551b in EMT and metastasis in gastric cancer (GC). We found that low miR-551b levels were associated with EMT, metastasis and a poor prognosis in GC patients. Further, two GC cell lines, MNK45 and SGC7901, exhibited lower miR-551b levels than the GES normal stomach cell line. Exposing MNK45 and SGC7901 cells to TGF-ß1 resulted in cell morphology changes characteristic of EMT, which was confirmed by Western blot analysis demonstrating low E-Cadherin and high N-Cadherin and Vimentin levels. Treatment with miR-551b mimics inhibited these EMT changes as well as Transwell migration and invasiveness. We identified ERBB4 as a potential target of miR-551b based on patient data from the TCGA. ERBB4 was upregulated in GC specimens, and its high expression correlated with a poor prognosis of GC patients. Dual luciferase assays revealed that miR-551b directly inhibited ERBB4 by binding to its 3'UTR. Moreover, treatment with miR-551b mimics or the ERBB4 inhibitor AST-1306 inhibited EMT in the GC cell lines. Finally, nude mice xenografted with GC cancer cell lines expressing miR-551b mimics exhibited smaller tumors and longer survival than mice engrafted with control GC cancer cells. These data indicate that miR-551b inhibits EMT and metastasis in GC by inhibiting ERBB4. miR-551b and ERBB4 are thus potential therapeutic targets for the treatment of GC.

Expression of eukaryotic translation initiation factor 5A-2 (eIF5A-2) associated with poor survival in gastric cancer.

Altered expression of eukaryotic translation initiation factor 5A-2 (eIF5A-2) was associated with human carcinogenesis and progression. This study assessed eIF5A-2 expression in gastric cancer tissues for association with clinicopathological parameters and survival of patients. A total of 436 gastric cancer tissues and 92 normal mucosal blocks were collected for construction of tissue microarrays and immunohistochemical assessment of eIF5A-2 expression. The data were statistically analyzed for association with clinicopathological factors and survival of patients. Immunohistochemical data showed that eIF5A-2 protein was highly expressed in gastric cancer tissues (p < 0.001). Upregulated expression of eIF5A-2 protein was associated with tumor Lauren classification, size, location, invasion, TNM stages, and lymph node and distant metastases. The 3- and 5-year cumulative survival rates of these 436 patients were 88.5 and 58.1 %, respectively. In contrast, the mean survival time of patients with increased tumor eIF5A-2 was 30.22 ± 1.23 vs. 51.29 ± 0.86 months for those with low tumor eIF5A-2 (p < 0.001). Multivariate analysis showed that eIF5A-2 expression and related tumor parameters were independent indicators of overall survival in gastric cancer patients. In conclusion, the current study indicates that overexpression of eIF5A-2 protein was associated with poor overall survival of gastric cancer patients.

[Expression of NEK-6 in gastric cancer and its clinical significance].

OBJECTIVE: To explore the NEK-6 expression in gastric cancer tissue and its relationship with clinicopathological features. METHODS: Fluorescent quantification PCR and Western blotting were used to examine the NEK-6 expression in 36 samples of fresh gastric cancer tissues and para-cancer gastric mucosal tissues, human gastric cancer cell lines(BGC-823, MKN-28, SGC-7901, MGC-803, HGC-27, AGS), and human normal gastric epithelial cell line (GES-1). Gastric cancer cell lines with the highest expression level were selected to perform the invasion and migration tests, and the effect of down-regulated NEK-6 expression by siRNA transfection on above invasion and migration tests were observed. Meanwhile NEK-6 expression in 94 paraffin samples of gastric cancer tissues was examined by immunohistochemistry and its positivity was compared among different clinicopathologic features. RESULTS: Fluorescent quantification PCR revealed gastric cancer tissues had significantly higher NEK-6 expression than para-cancer tissues(0.002 80±0.001 36 vs. 0.001 91±0.001 48, P<0.05), NEK-6 expression was up-regulated in 31 gastric cancer tissues (86.1%), and human gastric cancer cell lines had significantly higher NEK-6 expression than GES-1 cells, among whom BGC-823 and AGS cell lines were the highest. Invasion and migration tests showed that as compared to negative siRNA control group, ability of invasion and migration in BGC-823 and AGS cells after siRNA transfection was obviously decreased. In 94 paraffin samples, positive expression rate of NEK-6 was 60.6%(57/94), and NEK-6 expression was significantly associated with gastric cancer distant metastasis, lymph nodes metastasis and TNM staging(all P<0.05). CONCLUSIONS: NEK-6 expression is up-regulated in gastric cancer tissues, which is significantly associated with distant metastasis, lymph nodes metastasis and TNM staging. Down-regulation of NEK-6 expression can inhibit the ability of invasion and migration in gastric cancer cells.

MicroRNA-10b promotes migration and invasion through Hoxd10 in human gastric cancer.

BACKGROUND: This study aims to investigate the effect of miR-10b overexpression on cancer cell proliferation, migration, invasion, and Hoxd10 expression. METHODS: The effect of miR-10b on proliferation, migration, and invasion of MKN-28, BGC-823, and SGC-7901 cells and the expression of Hoxd10 protein in SGC-7901 and BGC-823 cells were detected following transfection of miR-10b inhibitor or Negative Control B. Expression of Hoxd10 protein in 436 paraffin-embedded cancer tissues was also investigated. RESULTS: miR-10b was significantly upregulated in AGS, MKN-28, BGC-823, HCG-27, SGC-7901, and MKN-45 cell lines, miR-10b inhibitor significantly inhibited proliferation and migration of MKN-45, BGC-823 and SGC-7901 cells 48 h after transfection, while Hoxd10 protein in these cells lines had increased 72 h after transfection. Hoxd10 was highly expressed in gastric cancer and correlated with size of tumor, Lauren classification, depth of invasion, lymph node and distant metastasis, Tumor-Node-Metastasis (TNM) stage, and prognosis. CONCLUSIONS: miR-10b promotes migration and invasion through Hoxd10 in human gastric cancer cell lines and may play an important role in tumorigenesis, progression, and prognosis.

Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation.

BACKGROUND: Several somatic mutation hotspots were recently identified in the telomerase reverse transcriptase (TERT) promoter region in human cancers. Large scale studies of these mutations in multiple tumour types are limited, in particular in Asian populations. This study aimed to: analyse TERT promoter mutations in multiple tumour types in a large Chinese patient cohort, investigate novel tumour types and assess the functional significance of the mutations. METHODS: TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumour types and 799 tumour tissues from Chinese cancer patients. Thymic epithelial tumours, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), telomerase activity by the telomeric repeat amplification protocol (TRAP) assay and promoter activity by the luciferase reporter assay. RESULTS: TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%) and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in gastrointestinal stromal tumour (GIST), thymic epithelial tumours, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. CONCLUSIONS: TERT promoter mutations are frequent in multiple tumour types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumourigenesis, making them potential therapeutic targets.

Analysis of exfoliated gastric carcinoma cells attached on surgical supplies.

Surgery is considered to have a leading role in the treatment of gastric carcinoma. Surgical supplies are used to cut, divide, and ligate during surgery, and are not only in close contact with normal tissues, but may also be contaminated by pathological tissues and cells. This study sought to determine the presence of exfoliated tumor cells on surgical supplies at different stages during the surgical procedure. We collected five types of surgical supplies from 90 patients who underwent D2 radical gastrectomy to find out if there was any cancer cells attached to them. Highest numbers of cancer cells were found on gauze used to clean the surgical instruments and on the gloves of scrub nurses. The likelihood of finding cancer cells increased with advancing clinical stage of disease, lower differentiation of cancer cells, increasing frequency of use of supplies and extent of contact, and was also associated with the characteristic of surgical supplies. Dissemination of tumor cells could be prevented by using a number of methods, depending on the type of surgical supply items.

Involvement of c-KIT mutation in the development of gastrointestinal stromal tumors through proliferation promotion and apoptosis inhibition.

The aim of this study was to discuss the role of c-KIT mutation in the pathogenesis of gastrointestinal stromal tumors (GISTs) and analyze its correlation with proliferation and apoptosis. c-KIT and PDGFRA genotypes were examined by deoxyribonucleic acid sequencing. Immunohistochemistry was performed to determine the expression levels of Kit, Ki-67 (proliferation marker), and apoptotic protease-activating factor (APAF)-1 (apoptosis marker) and the relationship between their three genes. In the 68 cases examined, 44 cases (64.7%) showed mutations in one of the four exons of c-KIT. The mutations were most frequently found in exon 11 (30 cases [44.1%]), followed by exon 9 (ten cases [14.7%]) and exon 13 (four cases [5.9%]). c-KIT mutation showed no association with prognostic factors using the classification of risk of aggressive behavior in GIST proposed by Fletcher et al. No cases had mutated exon 17 of c-KIT, and neither did exon 12, 14, or 18 of PDGFRA in our present study. There was a positive correlation between the expression level of Kit and Ki-67 (R=0.282, P=0.020). Conversely, a negative correlation was found between the expression levels of Kit and APAF1 (R=-0.243, P=0.046). In conclusion, most GISTs with Kit expression showed c-KIT mutation. Kit expression has a positive correlation with Ki-67 and a negative correlation with APAF1, showing that c-KIT is involved in GIST occurrence and development through proliferation promotion and apoptosis inhibition.

[Efficacies of neoadjuvant chemotherapy plus nutritional support in advanced gastric cancer complicated with pylori obstruction].

OBJECTIVE: To explore the efficacies of neoadjuvant chemotherapy plus nutritional supports for gastric cancer complicated with pyloric obstruction. METHODS: Retrospective analyses were performed for a total of 116 patients of gastric cancer complicated with pyloric obstruction undergoing exploratory laparotomy from January 2004 to June 2013. RESULTS: Sixty-two patients (group A) received neoadjuvant chemotherapy (regimen of FOLFOX) plus preoperative nutritional support. And parenteral (PN, n = 30) and enteral (EN, n = 32) nutritional supports were provided. Another 54 patients (group B) underwent exploratory laparotomy alone. The serum level of albumin and score of quality of life in group A at the last preoperative day improved significantly. And EN was better than PN. The rate of excision/radical excision of group A (85.5%, 45.2%) was much higher than group B (64.8%, 18.5%) (both P < 0.05). CONCLUSION: Nutritional support, especially EN, can improve the nutritional status and quality of life in patients with gastric cancer complicated with pyloric obstruction. And nutritional support plus neoadjuvant chemotherapy increase the rate of tumor excision.

[Application of home enteral nutrition and its impact on the quality of life in patients with advanced gastric cancer].

OBJECTIVE: To investigate the application of home enteral nutrition (HEN) in patients with advanced gastric cancer and its impact on the quality of life. METHODS: Data of 60 consecutive patients with advanced gastric cancer, who could not underwent operation and had relapse metastasis, from June 2010 to June 2012 were retrospectively analyzed. According to familial nutritional pattern, these 60 patients were divided into HEN group (25 cases) receiving home enteral nutritional support and control group (35 cases). HEN patients were supported through jejunostomy tube or nasal gastric tube. Control patients were supported through total parental nutrition or purely eating respectively. All the patients received intravenous chemotherapy and evaluated by Karnofsky index and Spitzer system in the first, third, sixth and twelfth month. In the sixth month, patients were also examined by EORTC QLQ-C30. RESULTS: No significant differences were found between the two groups according to 8 elements containing age, sex, BMI, etc. A total of 53 patients died within one year, including 21 in HEN group and 32 in control group. The Karnofsky scales showed that HEN group scored meanly 57.4, 39.6 and 28.2 in the third, sixth and twelfth month respectively, which were significantly higher than those of control group (45.3, 29.2 and 20.1, P=0.041, P=0.012 and P=0.015 respectively). The Spitzer scales showed that HEN group scored meanly 5.12, 4.04 and 2.54 on average in the third, sixth and twelfth month respectively, which were significantly higher than those of control group (4.32, 3.01 and 1.97, P=0.048, 0.035 and P=0.024 respectively). The EROTC QLQ-C30 scales showed that HEN group scored higher than control group in functional scales (P<0.05), and lower in the symptom scales of short breathing, pain and tired (P=0.025, P=0.044, P=0.036 respectively), while higher in diarrhea (P=0.047). CONCLUSIONS: The quality of life of patients with advanced gastric cancer declines gradually with the nutritional status deteriorating. HEN can be applied to improve the nutritional status and quality of life.