ABSTRACT
Gastric cancer is one of the most common malignancies worldwide; however, the molecular mechanism in tumorigenesis still needs exploration. BCL2L11 belongs to the BCL-2 family, and acts as a central regulator of the intrinsic apoptotic cascade and mediates cell apoptosis. Although miRNAs have been reported to be involved in each stage of cancer development, the role of miR-24 in GC has not been reported yet. In the present study, miR-24 was found to be up-regulated while the expression of BCL2L11 was inhibited in tumor tissues of GC. Studies from both in vitro and in vivo shown that miR-24 regulates BCL2L11 expression by directly binding with 3'UTR of mRNA, thus promoting cell growth, migration while inhibiting cell apoptosis. Therefore, miR-24 is a novel onco-miRNA that can be potential drug targets for future clinical use.
Subject(s)
Animals , Male , Mice , Rats , Apoptosis , Genetics , Apoptosis Regulatory Proteins , Genetics , Base Sequence , Bcl-2-Like Protein 11 , Cell Line, Tumor , Cell Movement , Genetics , Cell Proliferation , Genetics , Down-Regulation , Genetics , Gene Silencing , Membrane Proteins , Genetics , MicroRNAs , Genetics , Proto-Oncogene Proteins , Genetics , Stomach Neoplasms , Genetics , PathologyABSTRACT
Objective: To investigate the survival and individualized therapy of metastatic colorectal cancer (mCRC) patients who achieved a stable disease state after induction chemotherapy. Methods:Data were reviewed from 204 metastatic colorectal cancer pa-tients, who presented a stable disease state after first-line and second-line chemotherapy at Tianjin Medical University Cancer Insti-tute and Hospital. The clinical and pathological characteristics were analyzed. Moreover, we analyzed the significance of maintenance treatment in patients with certain mCRC characteristics. Results:Univariate analysis indicated that the line of chemotherapy, levels of CA724, CEA, and CA19-9, and platelet-to-lymphocyte ratio (PLR) were considered prognostic factors of treatment after induction che-motherapy. According to the multivariate analysis, first-line chemotherapy, as well as low levels of CA19-9 and PLR, with maintenance treatment after the induction chemotherapy was significantly associated with better survival. Among the patients with high levels of PLR, those who underwent maintenance treatment achieved a progression-free survival of 13.43 months (versus 10.63 months in pa-tients from the observation group, P=0.003). Conclusion:The levels of CA19-9 and PLR, and treatment after chemotherapy were signif-icant prognostic factors for mCRC patients who achieved a stable disease state after induction chemotherapy. These patients, especial-ly those with high PLR, could benefit from the maintenance treatment.
ABSTRACT
MTH1 protein can mitigate DNA damage which caused by reactive oxygen species through hydrolyzing oxidized deoxy-ribonucleoside triphosphate.MTH1 is highly expressed in various cancers, so as to maintain the viability of cancer cells.MTH1 is closely related to tumor associated genes such as microRNA,RAS gene and p53 gene.Moreover, MTH1 inhibitors can selectively suppress the proliferation of cancers,which is a potential new target in tumor therapy.
ABSTRACT
Objective:To investigate the influence of chemotherapy on the phenotype of secreted protein, acidic and rich in cysteine (SPARC) in gastric cancer (GC). Methods:Immunohistochemistry was used to analyze SPARC expression in 132 GC patients. Among these patients, 54 with preoperative chemotherapy and 78 without preoperative chemotherapy were selected to analyze the effect of chemotherapy on SPARC phenotype by comparing the postoperative specimens of the two cohorts. Results:SPARC expression was higher in GC lesions than in the desmoplastic stroma surrounding the tumor cells and noncancerous tissues. High SPARC expression was related to invasion depth, lymph node metastasis, and TNM staging. SPARC expression was lower in patients with preoperative chemotherapy than in controls ( P<0.05). Gross type, histology, depth of invasion, lymph node metastasis, TNM staging, and SPARC phenotype correlated with the overall survival of the patients with preoperative chemotherapy. Further multivariate analysis suggested that lymph node metastasis, histology, and SPARC phenotype after chemotherapy were independent prognostic indicators of GC. Conclusion:SPARC expression was associated with invasion depth, lymph node metastasis, TNM staging and GC prognosis. Preoperative chemotherapy may change the phenotype of SPARC in GC patients.
ABSTRACT
The efficacy of conventional chemotherapy for gastric cancer is extremely limited because of its relatively low chemo-sensitivity and obvious heterogeneity. Molecular phenotype-directed target therapy is important for the improvement of the effi-cacy of conventional chemotherapy in treating advanced gastric cancer. Trastuzumab has been confirmed to have a survival benefit when added to chemotherapy for HER-2 positive gastric cancer. Ramucirumab can increase the survival of gastric cancer patients as second line treatment compared with a placebo. The anti-c-MET monoclonal antibody Rilotumumab indicates promising results in phaseⅡtrial. However, most of the targeting drugs in gastric cancer clinical trials have failed. Therefore, further efforts are required to explore critical targeted genes and effective agents.
ABSTRACT
Malignant pheochromocytomas are rare tumors that arise from chromaffin tissue, and the diagnostic criterion of malig-nancy is based on the development of metastases. In the case a patient suffers the tumor with liver, lung and bone metastases. However, the test results of tumor markers, gastroscopy, chest and abdominal CT, and PET-CT examination are hard to make a definite diagnosis. The patient was finally diagnosed with malignant pheochromocytoma with liver, lung and bone metastases following the needle biopsy of liver and underwent the excision of a right adrenal pheochromocytoma. Therapeutic standard for the malignant pheochromocytomas is not available so far. It is reported that chemotherapeutic CVD regimen (cyclophosphamide, vincristine, and daecarbazine) and suni-tinib may be effectual in the alike cases. The patient received two cycles of CVD and one cycle of sunitinib, nevertheless, slow progres-sion of the disease remained after the treatment. The results of multi-disciplinary treatment have suggested that 131I-MIBG may just be a choice for this patient.
ABSTRACT
Objective: To analyze the association of thrombocytosis with the prognosis of patients with gastric cancer.Methods: The clinical materials of 782 patients with gastric cancer who underwent initial surgery in our hospital between January 1995 and December 1999 were retrospectively analyzed.Kaplan- Meier and Log-Rank test were used to analyze the data.Prognostic factors were analyzed by multivariate Cox proportional hazards model.Results: Thrombocytosis oc-curred in 11.4% (87/782) patients.The platelet level was not significantly different among patients of different gender, tumor stage, and histological differentiation (P>0.05).However, a significant difference was observed in the platelet level among patients with different age and surgical approach (P<0.05).The 1-, 3-, and 5-year survival rates were 75.0%, 40.1% and 28.9% in patients without thrombocytosis and 52.8%, 16.9%, and 13.5% in patients with thrombocytosis (P=0.002).Univari-ate analysis showed that histological differentiation, pathological stage, surgical approach and thrombocytosis significantly affected the survival of patients.While age and gender had no significant impact on patient survival.Multivariate analysis showed that pathological stage, surgical approach, and thrombocytosis were independent prognostic factors for gastric can-cer.The relative risk of death of patients with thrombocytosis was elevated by 1.454 times (RR=1.454, 95% CI: 1.135~1.861, P=0.005).Conclusion: Thrombocytosis is an independent prognostic indicator for the survival of initially treated pa-tients with gastric cancer.