ABSTRACT
The current treatment strategy for rectal cancer is a comprehensive treatment centered on surgery. The application of total mesorectal excision (TME) has significantly reduced the local recurrence rate and improved the survival prognosis, but a series of pelvic organ dysfunction caused by pelvic autonomic nerve injury during the operation will reduce the postoperative quality of life of patients. Pelvic autonomic nerve preserving (PANP) radical proctectomy has emerged, but the biggest challenge in the implementation process of this technology is the accurate identification of nerves. A series of studies have shown that pelvic intraoperative autonomic monitoring (pIONM) can effectively assist surgeons to identify nerves, The purpose of this article is to introduce the function of pelvic autonomic nerve, the clinical manifestation of postoperative pelvic dysfunction and its relationship with nerve injury, the key points of implementing PANP, and the current situation and research progress of pIONM technology application.
Subject(s)
Quality of Life , Rectal Neoplasms , Humans , Rectal Neoplasms/surgery , Autonomic Pathways/surgery , Pelvis/surgery , Pelvis/innervation , Autonomic Nervous System/surgery , Autonomic Nervous System/injuries , Rectum/surgeryABSTRACT
Despite the amazing progress in the treatment of gastric cancer (GC), it is still the third leading cause of cancer death in the world. This study explored the key genes that are related to the prognosis and pathogenesis of GC. Data from the cancer genome atlas (TCGA) and Oncomine were applied to evaluate the expression of cystatin 2 (CST2) in GC samples. Kaplan-Meier plotter was carried out to detect the overall survival of GC patients with different expression levels of CST2. Gene Set Enrichment Analysis (GSEA) was carried out to investigate the functions and pathways connected with CST2 expression. Quantitative real-time polymerase chain reaction (qPCR) and Western blot assays were used to assess CST2 expression. The biological properties of GC cells were assessed with the support of cell proliferation and Transwell assays. Important proteins involved in the regulation of CST2 in GC cell behaviors were evaluated by Western blot. Through analysis of the database, we found that CST2 expression was significantly upregulated in GC samples and actively related to GC patients' poor outcomes. Importantly, the analysis of GSEA showed that GST2 expression was closely connected with the proliferation and migration of cells, as well as the TGF-ß1 signaling pathway. In addition, biological assays illustrated that over-expression of CST2 strengthened the activity and metastasis of GC cells. After the upregulation of CST2, the expression of cyclin D1, N-cadherin, vimentin, TGF-ß1, and Smad4 increased, and E-cadherin expression decreased. Our findings revealed that over-expression of CST2 enhanced the growth, migration, and invasion of GC cells through modulating the epithelial-mesenchymal transition (EMT) and TGF-ß1 signaling pathway, affording a possible biomarker for the treatment of GC.
Subject(s)
Salivary Cystatins/genetics , Stomach Neoplasms , Cell Line, Tumor , Cell Movement , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Humans , Stomach Neoplasms/geneticsABSTRACT
OBJECTIVE: To provide biomarkers related to the radiation response of patients to avoid unnecessary side effects on those who were not sensitive to radiotherapy. PATIENTS AND METHODS: In the present study, we compared the different four proteins (PDIA3, Vimentin, Galectin3, Dhe3) patterns in rectal tumor tissue before and after radiation therapy by using 2-D PAGE, mass spectrometry, and bioinformatics analysis. RESULTS: The protein level of Galectin3 and PDIA3 were downregulated in rectal cancer patients before and after radiotherapy (1.42 folds); while Dhe3 protein and Vimentin were upregulated (1-2 folds), and we also revealed Vimentin as its role in the negative regulation of the well-known transcription factor ATF4. CONCLUSIONS: Our study showed that four candidate proteins, including PIDA3, Galectin3, Dhe3, and Vimentin, might be the potential biomarkers in the identification of radiation response in rectal cancer.
Subject(s)
Biomarkers, Tumor/metabolism , Proteomics/methods , Rectal Neoplasms/pathology , Activating Transcription Factor 4/metabolism , Adult , Down-Regulation , Female , Galectin 3/metabolism , Humans , Male , Middle Aged , Protein Disulfide-Isomerases/metabolism , Protein Interaction Maps , Rectal Neoplasms/metabolism , Rectal Neoplasms/radiotherapy , Up-Regulation , Vimentin/metabolismABSTRACT
The distribution of peripheral blood lymphocyte subsets were compared between patients with colorectal cancer and healthy controls. The number of natural killer(NK) cells and CD(8)(+)T cells and the percentage of naive CD(4)(+) T cells were all decreased significantly in patients. On the contrary, the percentages of memory CD(4)(+) T cells, HLA-DR(+) CD(8)(+) T cells and CD(38)(+) CD(8)(+) T cells were significantly increased. It suggests that the tumor killing effect of cytotoxic lymphocytes in peripheral blood is impaired in patients with colorectal cancer, whereas the immune response is over stimulated.
Subject(s)
Colorectal Neoplasms/immunology , Lymphocyte Subsets , T-Lymphocyte Subsets , Colorectal Neoplasms/surgery , Humans , Killer Cells, Natural/immunology , Lymphocyte CountABSTRACT
OBJECTIVE: Cell autophagy reduces the sensitivity of cancer cells to therapeutic reagents in various types of human cancer. Therefore, the aim of our study was to use human colorectal cancer HCT116 cells to explore whether inhibition of autophagy by 3-Methyladenine (3-MA, an autophagy inhibitor) is able to enhance hypoxia-induced apoptosis in vitro. MATERIALS AND METHODS: HCT116 cells were treated with 3-MA, hypoxia, or 3-MA plus hypoxia, and the autophagy, apoptosis and proliferation of the HCT116 cells were investigated. Western blot analysis was used to detect autophagy specificity protein microtubule-associated protein light chain 3 (LC3) expression. Effects on apoptosis were evaluated by using flow cytometry (JC-1 staining to measure mitochondrial membrane potential) and annexin V-propidium iodide (PI) staining. RESULTS: The results showed that the treatment of HCT116 cells in vitro with hypoxia alone increased autophagy as well as apoptosis, whereas combination treatment with 3-MA and hypoxia markedly inhibited hypoxia-induced autophagy, but increased hypoxia-induced cell apoptosis. CONCLUSIONS: Autophagy might play a role as a self-defense mechanism in hypoxia-treated colon cancer cells, and its inhibition could be a promising strategy for the adjuvant chemotherapy of colon cancer.
Subject(s)
Adenine/analogs & derivatives , Apoptosis/drug effects , Autophagy/drug effects , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Hypoxia/physiopathology , Adenine/pharmacology , Annexin A5/metabolism , Autophagy/physiology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Proliferation/physiology , Humans , Membrane Potential, Mitochondrial/drug effects , Microtubule-Associated Proteins/biosynthesisABSTRACT
The study aimed to investigate the bio-distribution and radio-immuno-imaging features of [(131)I]-herceptin in nude mice with BT-474 breast carcinoma. [(131)I]-Herceptin was administrated by tail intravenous injection to the nude mice with BT-474 breast carcinoma. Radiocounting was performed at 4, 12, 24, 48, and 96 h after administration. The activity ratio in the tumor tissue and non-tumor tissue (T/NT) and the radiocounting percentage per gram tissue to the injected dose (%ID/g) were calculated. The nude mice with BT-474 breast carcinoma were also visualized continuously by single photon emission computed tomography at 2, 4, 8, 12, 24, 48, and 96 h after the injection of [(131)I]-herceptin. Nude mice with MDA-MB-231 used as the control group were subjected to the same analyses. Clear tumor images were obtained after the injection of [(131)I]-herceptin in nude mice with BT-474 breast carcinoma. The images were the clearest at 24 h after the injection and remained clear even at 96 h. The T/NT ratio and %ID/g in the tumor tissues of nude mice with BT-474 were both significantly higher than those of the control group (P < 0.01). [(131)I]-Herceptin displays tumors clearly in the nude mice with BT-474 and accumulates well in the tumor tissues.