Efficacy and safety evaluation of PSOX, DOF and SOX regimens as neoadjuvant chemotherapy for advanced gastric cancer.

Aim: To explore the efficacy and safety of paclitaxel+oxaliplatin+S-1 (PSOX), docetaxel+oxaliplatin+fluorouracil (DOF) and oxaliplatin+S-1 (SOX) regimens as neoadjuvant chemotherapy for advanced gastric cancer (GC). Methods: A retrospective analysis was used in 306 patients with GC who underwent neoadjuvant chemotherapy, consisting of 102 from the PSOX group, 100 from the DOF group and 104 from the SOX group. Results: The total effective rates and disease control rates for the PSOX, DOF and SOX groups were 31.4, 18 and 16.3% and 96.1, 94 and 92.3%, respectively. The highest total effective rate and disease control rate were found in the PSOX groups. Moreover, no difference among the PSOX, DOF and SOX groups on the incidence of adverse events was observed (p > 0.05). Conclusion: The PSOX regimen is an alternative neoadjuvant chemotherapy regimen for GC patients.

Bioinformatics identification of potentially involved microRNAs in Tibetan with gastric cancer based on microRNA profiling.

OBJECTIVE: The incidence of gastric cancer is high in Chinese Tibetan. This study aimed to identify the differentially expressed microRNAs (miRNAs) and further explore their potential roles in Tibetan with gastric cancer so as to predict potential therapeutic targets. METHODS: A total of 10 Tibetan patients (male:female = 6:4) with gastric cancer were enrolled for isolation of matched gastric cancer and adjacent non-cancerous tissue samples. Affymetrix GeneChip microRNA 3.0 Array was employed for detection of miRNA expression in samples. Differential expression analysis between two sample groups was analyzed using Limma package. Then, MultiMiR package was used to predict targets for miRNAs. Following, the target genes were put into DAVID (Database for Annotation, Visualization and Integrated Discovery) to identify the significant pathways of miRNAs. RESULTS: Using Limma package in R, a total of 27 differentially expressed miRNAs were screened out in gastric cancer, including 25 down-regulated (e.g. hsa-miR-148a-3p, hsa-miR-148b-3p and hsa-miR-363-3p) and 2 up-regulated miRNAs. According to multiMiR package, a number of 1445 target genes (e.g. Wnt1, KLF4 and S1PR1) of 13 differentially expressed miRNAs were screened out. Among those miRNAs, hsa-miR-148a-3p, hsa-miR-148b-3p and hsa-miR-363-3p were identified with the most target genes. Furthermore, three miRNAs were significantly enriched in numerous common cancer-related pathways, including "Wnt signaling pathway", "MAPK signaling pathway" and "Jak-STAT signaling pathway". CONCLUSIONS: The present study identified a downregulation and enrichment in cancer-related pathways of hsa-miR-148a-3p, hsa-miR-148b-3p and hsa-miR-363-3p in Tibetan with gastric cancer, which can be suggested as therapeutic targets.

Application of Circulating Tumor Cells and Circulating Free DNA from Peripheral Blood in the Prognosis of Advanced Gastric Cancer.

OBJECTIVE: To explore the application value of circulating tumor cells (CTCs) and circulating free DNA (cfDNA) from peripheral blood in the prognosis of advanced gastric cancer (AGC). Here, we measured CTCs and cfDNA quantity for predicting the outcome of patients. Patients and Methods. Forty-five patients with advanced gastric cancer who underwent neoadjuvant chemotherapy and surgical treatment were enrolled in this study. All patients received neoadjuvant chemotherapy with paclitaxel + S-1 + oxaliplatin (PSOX) regimen, and CTCs and cfDNA of the peripheral blood were detected before and after neoadjuvant therapy. Relationships between the number/type of CTC or cfDNA and the efficacy of neoadjuvant chemotherapy were analyzed. RESULTS: Among 45 patients, 43 (95.6%) were positive, and the positive rate of mesenchymal CTC was increased with the increase in the T stage. The proportion of mesenchymal CTC was positively correlated with the N stage (P < 0.05), and the larger N stage will have the higher proportion of mesenchymal CTC. Patients with a small number of mesenchymal CTC before neoadjuvant chemotherapy were more likely to achieve partial response (PR) with neoadjuvant therapy. Patients with positive CA-199 were more likely to achieve PR with neoadjuvant therapy (P < 0.05). Patients in the PR group were more likely to have decreased/unchanged cfDNA concentration after neoadjuvant therapy (P=0.119). After neoadjuvant therapy (before surgery), the cfDNA concentration was higher and the efficacy of neoadjuvant therapy (SD or PD) was lower (P=0.045). CONCLUSIONS: Peripheral blood CTC, especially interstitial CTC and cfDNA, has a certain value in predicting the efficacy and prognosis of neoadjuvant chemotherapy in advanced gastric cancer.

Comparison of incidence and prognosis between young and old gastric cancer patient in North-Western China: A retrospective cohort study.

Gastric cancer (GC) is the fourth most common cancer in the world and the second most common cancer in China. In this study, we compared the clinicopathological features and prognosis of GC between young and old patients after curative resection. Six hundred and eighty-six patients with GC resected were divided two groups according to patient age: Younger GC patients ≤40 years of age (YGC, n = 52) and older GC patients >40 years of age (OGC, n = 634). The YGC group had 52 (7.6%) patients in total 686 GC patients. YGC patients was predominant in women (53.8% vs 26.5%) compared with OGC patients. 5-year overall survival exhibited differences in tumor sites, tumor sizes, macroscopic types, T staging, N staging, rate of N staging (rN), tumor node metastasis staging, scope of gastrectomy, radical degree, and lymphatic vascular invasion within each of YGC and OGC group. Univariate analysis of the clinical factors affecting overall survival in YGC group revealed the significant differences in tumor size, macroscopic types (except Borrmann), T staging (except T2), N staging (N3a and N3b), rN, tumor node metastasis staging (III), scope of gastrectomy, radical degree, and lymphatic vascular invasion. Gender, N staging, rN, radical degrees were the independent prognostic factors of younger patients with GC. Similar results were found in the OGC groups. The significant differences in radical degree and lymphatic vascular invasion were found between male and female patients in YGC group. Similar results were found in the OGC groups. Our results showed that YGC patients differ from OGC patients in predominance of women. Gender, N staging, rN, radical degrees were independent risk factors for the prognosis in YGC patients.

Inhibitory Effect of Crocin Against Gastric Carcinoma via Regulating TPM4 Gene.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors and the second most frequent cause of cancer death worldwide. Crocin is a kind of bioactive constituent found in the stigmas of saffron, which has shown various pharmacological activities. METHODS: In this study, we investigated the inhibitory effect of crocin on gastric cancer AGS cells proliferation and explored the underlying mechanism. A series of methods were used including cell counting kit assay, gene microarray analysis, qRT-PCR, Celigo image cytometry, cell clone formation assay, Western blot, and cell xenograft growth in vivo. RESULTS: The results indicated that crocin inhibited AGS cells proliferation and promoted cell apoptosis. Further studies suggested that crocin decreased a series of genes expression, among which TPM4 gene downregulation inhibited the tumor cells proliferation and tumor growth in mice, and overexpression of TPM4 gene abolishes the inhibitory effect of crocin. Further study using microarray analysis suggested that knocking down of TPM4 altered genes related to the proliferation and apoptosis of cells. DISCUSSION: Crocin could inhibit the gastric cancer cells AGS cells proliferation by regulating TPM4 gene expression, and TPM4 may be a promising therapeutic target for GC treatment.

Malignant acanthosis nigricans with Leser-Trélat sign and tripe palms: A case report.

BACKGROUND: Acanthosis nigricans (AN), Leser-Trélat sign, and tripe palm are all skin diseases. To date, reports of these appearing as a paraneoplastic syndrome in a gastric cancer patient are quite rare. CASE SUMMARY: We report the case of a 61-year-old man with darkened skin color in the face and torso with no obvious inducement after 1 year of treatment for Riehl's melanosis. He had 40 brown maculopapular eruptions on his face and the top of his head with obvious itching. Papillary wart-like hyperkeratosis with dark brown pigmentation was also observed on both sides of the areola. He had papilloma-like lesions on the face, around the orbit, and on the neck. His bilateral palms had small, smooth, papillary projections with millet-like appearance. Histopathological examination of the skin showed that the patient was suffering from AN, tripe palms, and Leser-Trélat sign. Gastroscopy showed the patient's cardia was affected, and pathological biopsy revealed that he had moderate-to-poorly differentiated adenocarcinoma. Computed tomography test results showed that his cardia wall had thickened. Based on these histological and skin characteristics, the patient was diagnosed with gastric cancer with AN, tripe palms, and Leser-Trélat sign. CONCLUSION: Researchers should follow up on patients with malignant AN, Leser-Trélat sign, and tripe palms.

Methylation of WWOX gene promotes proliferation of osteosarcoma cells.

PURPOSE: To explore the effects of WW domain-containing oxidoreductase (WWOX) gene methylation on proliferation and apoptosis of osteosarcoma cells. METHODS: A total of 51 patients with osteosarcoma confirmed by pathological examinations were enrolled as the observation group, while 49 cases with non-osteosarcoma diagnosed and treated in our hospital were randomly selected as the control group. Osteosarcoma cell lines MG63 and HOS were selected as observation group, while those added with methylation inhibitor were set as control group, of which genomic methylation level was determined via HPLC. Proliferation of the two cell lines was compared via cell counting kit-8 (CCK-8) assay at 12 h, 24 h, 36 h and 48 h. Invasion rate of cells in each group was tested via Transwell assay at 24 h. RESULTS: The average methylation rate of WWOX gene was remarkably higher in osteosarcoma tissues in comparison with normal adjacent tissues and control group (p<0.05). A higher methylation rate was found in MG63 cell line compared with in HOS cell line (p<0.05). More cells were observed in MG63 cell line than in HOS cell line and control group from 24h (p<0.05). Besides, 24-h invasion rate was higher in MG63 cell line than in HOS cell line and control group (p<0.05). Moreover, MG63 cell line prompted a lower 24-h apoptotic rate in comparison with HOS cell line and control group (p<0.05). CONCLUSIONS: Methylation level of WWOX gene is intimately associated with the occurrence and progression of osteosarcoma, which is able to promote the proliferation of cancer cells to a certain extent, thus accelerating the development of disease.

Comparison of clinicopathologic profiles and prognosis of gastric cancer in the upper, middle and lower third of the stomach: A retrospective cohort study.

Gastric cancer (GC) is the fourth most common cancer in the world and the second most common cancer in China. The aim of this study was to investigate the clinicopathologic profiles and prognosis of GC in the upper third (UT), middle third (MT) and low third (LT) of the stomach.Five hundred and forty-two patients with GC resected between January 2010 and January 2014 were retrospectively studied and divided in 3 groups according to cancer location: upper third gastric cancer (UTGC) (n = 62); MTGC (n = 131) and LTGC (n = 349). Clinical and pathological parameters including gender, age, tumor size, macroscopic types, histological types, depth of invasion, lymph node metastasis, venous infiltration and lymph embolism were compared among groups. Overall survival (OS) was calculated based on the aforementioned parameters. Univariate and multivariate survival was analyzed and Cox regression was conducted for each location. The prognostic accuracy was determined using receiver operating characteristic curve analysis.Patients with UTGC was similar to those with MTGC and both were distinct from those with LTGC based on the tumor size, macroscopic types, depth of invasion and 5-year OS. Patients with MTGC were similar to those with LTGC and distinct from UTGC patients based on gender. 5-year OS were lower for patients with UTGC than those with LTGC (P = .001) and were comparable between MTGC and LTGC. No significant differences in 5-year OS were observed between UTGC and MTGC. Cox regression revealed that macroscopic types, depth of invasion and lymph node metastasis were the independent prognostic factors for GC patients regardless of locations. Receiver operating characteristic curve analysis revealed that macroscopic types, depth of invasion and lymph node metastasis were the significantly effective prognosis for the 5-year OS in GC patients regardless of locations.Our results showed that UTGC is distinct from LTGC whereas MTGC shares some characteristics from both UTGC and LTGC.

Pathogenesis and anti-proliferation mechanisms of Crocin in human gastric carcinoma cells.

Gastric cancer is the fourth most common cause of cancer death globally and the second most common in Asia. Many studies suggest that Crocin has the potential for gastric cancer antineoplastic combined chemotherapy protocols. Here we investigated genomic changes related to the inhibitory effect of Crocin, and elucidated the molecular mechanism of this inhibition in gastric carcinoma cells. We found that, compared with the control group, 216 significantly upregulated and 301 significantly downregulated genes were identified in Crocin-treated AGS cells. Many of these differentially expressed genes in AGS cells are involved in Nrf2-mediated oxidative stress response, p53 signaling, and integrin signaling, which suggested the mechanism of Crocin functions in therapy of gastric cancer. In summary, our study indicates that Crocin has the potential for gastric cancer adjuvant treatment through reducing cell oxidative stress levels.

Melanotic Xp11-associated tumor of the sigmoid colon: A case report.

BACKGROUND: Melanotic Xp11-associated tumors are rare mesenchymal-derived tumors. So far, most primary melanotic Xp11-associated tumors have been reported in the kidney, and reports of this tumor in the gastrointestinal tract are rare. CASE SUMMARY: Here we describe the case of a 25-year-old woman who presented with a melanotic Xp11-associated tumor in the sigmoid colon. Colonoscopy revealed a large mucosal bulge in the sigmoid colon, approximately 32 cm inside the anus. The surface was rough with local erosion. The tumor was brittle on biopsy and bled easily. Computed tomography revealed thickening of the rectal wall with edema. Postoperative pathology indicated the likelihood of a perivascular epithelioid cell tumor. Histologically, the tumor comprised plump epithelioid cells with abundant clear to lightly eosinophilic cytoplasm and round nuclei arranged in an alveolar or trabecular pattern. The tumor cells were strongly positive for HMB-45, Melan-A, Cathepsin K, and TFE3 but negative for vimentin, smooth muscle actin, S100 protein, CD10, CK20, and desmin. The tumor cells had a low Ki-67 labeling index (approximately 2%). Fluorescence in situ hybridization revealed TFE3 fracture. Based on these histologic and immunohistochemical features, a diagnosis of melanotic Xp11-associated tumor of the sigmoid colon was made. CONCLUSION: In summary, we report the clinicopathological features of a primary tumor that is extremely rare in the sigmoid colon and review the clinicopathological characteristics of melanotic Xp11-associated tumors, compatible with the very rare tumor termed "melanotic Xp11 translocation renal cancer" in all aspects.