Journal of Buon最新文献

Purpose: Platin-based chemotherapies are first-line treatment methods after surgery in bladder cancer. Recently, novel immunotherapies emerged after platin-based regimens. The purpose of this study was to evaluate the prognostic significance of microsatellite instability (MSI), tumor infiltrating lymphocytes (TILs) and programmed cell death ligand-1 (PD-L1) expression which are used as predictive biomarkers in immunotherapy.

Methods: Clinical and pathological features of bladder cancer patients who underwent radical cystectomy were retrospectively analyzed from their records in this single-center study. PD-L1, PD-L1 on TIL, PMS2, MSH2, MSH6 and MLH1 immunohistochemistry staining were carried out to archieve resected tumor specimens of the eligible patients. MSI was evaluated according to existing of PMS2, MSH2, MSH6 and MLH1.

Results: MSI was high in 24.6% of 61 patients. PD-L1 expression on tumor cells and PD-L1 expression on TIL were positive in 14.8% and 16.4% of the patients, respectively. Intratumoral TIL rate was >10% in 12 patients (19.7%). There was no statistically significant relationship between PD-L1, PD-L1 on TIL, MSI and TIL rate and patients' characteristics including sex, stage, pathologic grade and lymph node status. There was a positive trend between MSI-high patients and overall survival (OS) (p=0.089). Univariate analysis did not reveal any significant difference at 3-years OS with PD-L1 tumor expression and PD-L1 expression on TIL and TIL rate >10% (p=0.822, p=0.638, p=0.318, respectively) Conclusion: This study revealed that there is a positive trend between OS and MSI but no prognostic significance of PD-L1 and TIL which are proven predictive biomarkers of immunotherapy in patients with bladder cancer.

Purpose: To explore the role and molecular mechanism of circRNA protein arginine methyltransferase-5 (circ-PRMT5) in regulating cisplatin (DDP) resistance and immune response of non-small cell lung cancer (NSCLC).

Methods: The expression of circ-PRMT5, miR-138-5p and myosin heavy chain 9 (MYH9) was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, transwell assay, and western blot assay were utilized to evaluate DDP sensitivity. Interleukin 2 (IL-2), tumor necrosis factor alpha (TNF-α) and transforming growth factor β (TGF-β) production were measured by enzyme-linked immunosorbent assay (ELISA) to assess immune system's ability. A xenograft tumor model was established to explore the role of circ-PRMT5 in DDP resistance in vivo. The interaction between miR-138-5p and circ-PRMT5 or MYH9 was predicted by starBase and verified by dual-luciferase reporter assay.

Results: Circ-PRMT5 and MYH9 were upregulated and miR-138-5p was downregulated in DDP-resistant NSCLC tissues and cells. Circ-PRMT5 knockdown enhanced DDP sensitivity of NSCLC cells by inhibiting cell viability, migration and invasion and inducing apoptosis. Circ-PRMT5 knockdown also increased immune response by promoting the levels of IL-2 and TNF-a and decreasing the production of TGF-β. Moreover, circ-PRMT5 interference improved DDP sensitivity of NSCLC in vivo. MiR-138-5p was a direct target of circ-PRMT5 and its knockdown abated the effects of circ-PRMT5 downregulation on DDP resistance and immune response.

Conclusion: Circ-PRMT5 knockdown increased DDP sensitivity and immune response of NSCLC cells by regulating miR-138-5p/MYH9 axis, hinting potential value of circ-PRMT5 in the diagnosis and treatment for NSCLC.

Purpose: Wide surgical margins are needed in order to treat locally the in situ ductal carcinoma of the breast. Breast conserving surgery using oncoplastic techniques in treating in situ ductal carcinoma can be a good option improving cosmetic and pathological outcome.

Methods: Between January 2019 and July 2019, 76 patients with invasive carcinoma associated with in situ ductal carcinoma were eligible for breast conserving surgery and were admitted to Cluj-Napoca First Surgical Clinic. Patients were divided into two groups, one group with simple lumpectomy and the other group with oncoplastic procedure.

Results: 26 patients had oncoplastic surgery while 47 patients underwent simple lumpectomy. Lateral mammoplasty was the most frequent oncoplastic procedure (41.3%). Mean tumor size was 3.19 cm (SD 0.76) in the oncoplastic cohort while in the simple lumpectomy cohort the mean tumor size was 1.20 cm (SD 0.89). Regarding tumor size, better surgical resection margins were obtained using oncoplastic procedure (p=0.051). No difference between groups in terms of perioperative complications was observed (p=0.32).

Conclusions: Breast conserving surgery with oncoplastic techniques are oncologically safe, obtaining better surgical margins in ductal carcinoma in situ.

Purpose: To study the treatment effect of concurrent chemoradiotherapy (CCRT) after surgery and its effect on postoperative swallowing function of patients with locally advanced hypopharyngeal carcinoma.

Methods: The clinical data of 84 patients with advanced hypopharyngeal carcinoma treated in our hospital were retrospectively analyzed. The patients were randomly divided into experimental group and control group, with 42 cases in each group. After both groups of patients were treated with radical neck dissection, the control group received adjuvant radiotherapy while the experimental group received CCRT.

Results: The Burke score in the experimental group after treatment was significantly lower than that in the control group (p<0.001). The objective remission rate in the experimental group was significantly higher than that in the control group (p<0.05). The jitter and shimmer in the experimental group after treatment were significantly lower than those in the control group (p<0.05). The quality of life scores of patients in the two groups after treatment were significantly higher than those before treatment (p<0.001), and the quality of life score in the experimental group was significantly higher than that in the control group (p<0.001). And the incidence of gastrointestinal reactions and neutropenia in the experimental group after treatment was significantly lower than that in the control group (p<0.05). The 3-year cumulative survival rate after surgery in the experimental group was significantly higher than in the control group (p<0.05).

Conclusions: CCRT after surgery can effectively improve the swallowing function of patients with locally advanced hypopharyngeal carcinoma, which is worthy of promotion and application.

Purpose: Long non-coding RNA (lncRNA) TP73-AS1 is abnormally expressed in multiple types of tumors, which is able to mediate tumor cell signals. This study aims to explore the role of TP73-AS1 in affecting biological functions of NK/T-cell lymphoma (NKTCL) and DKK1 methylation.

Methods: TP73-AS1 levels in peripheral blood of NKTCL patients and healthy volunteers was detected by quantitative real-time polymerase chain reaction (qRT-PCR). After knockdown of TP73-AS1, proliferative and migratory abilities in SNK-6 and HANK-1 cells were assessed by cell counting kit-8 (CCK-8) and Transwell assay, respectively. Regulatory effect of TP73-AS1 on DKK1 methylation in NKTCL cells was evaluated through methylation-specific PCR (MSP), dual-luciferase reporter assay and RNA Binding Protein Immunoprecipitation (RIP). Rescue experiments were conducted to further validate the interaction between TP73-AS1 and DKK1.

Results: TP73-AS1 level was higher in peripheral blood of NKTCL patients than that of healthy volunteers. Knockdown of TP73-AS1 in vitro weakened proliferative and migratory functions of NKTCL cells. TP73-AS1 induced methylation of DKK1 promoter through DNMT1/DNMT3, thus regulating NKTCL cell functions.

Conclusions: TP73-AS1 level was higher in peripheral blood of NKTCL patients. Through inducing methylation of DKK1 promoter, TP73-AS1 aggravates the malignant progression of NKTCL.

Purpose: Metformin has been widely used for the treatment of Type 2 Diabetes Mellitus (T2DM), hyperglycemia and polycystic ovarian syndrome. Recent studies have suggested the potential of this substance as a cancer chemopreventive agent. We evaluated the antitumoral effect of iRNA-PFK-1 and the combined therapy iRNA-PFK-1 + metformin in RKO p53-positive cells.

Methods: mRNA levels of tumor suppressor genes AMPK, APC, and c-MYC, KRAS oncogenes were measured by qRT-PCR in RKO cells treated with 25 µM metformin alone or combined with iRNA-PFK-1, to evaluate the effect of both treatments.

Results: At 72 h after treatment with either 25 µM metformin, 150 nM iRNA-PFK-1, or the combined treatment, the transcriptional levels of these biomarkers were decreased by ~73% (p˂0.05), ~99.9%, (p˂0.01), and ~76% (p˂0.05), respectively.

Conclusion: These in vitro results support the potential therapeutic role of metformin and PFK-1 in the treatment of colon cancer via down-modulation of the expression of several important cancer biomarkers.

Purpose: To explore the effects of atorvastatin (ATST) on the proliferation and apoptosis of colon cancer cells through the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2)/β-catenin pathway.

Methods: HCT116 cells were cultured and transfected, and they were treated with ATST at different concentrations for different time. The association between the expressions of COX-2 and PGE2 and the survival time of patients with colon cancer was analyzed via Kaplan-Meier survival analysis. Then the protein expressions of COX-2, β-catenin and apoptosis-related molecules in HCT116 cells were determined using Western blotting, and the proliferation of HCT116 cells was detected via cell counting kit-8 (CCK-8) assay.

Results: There was a significant difference in the survival rate between HCT116 cells treated with 30 μM ATST and those treated with 0 μM ATST. The survival time was obviously longer in patients with low expressions of COX-2 and PGE2 than that those with high expressions of COX-2 and PGE2. Low expressions of COX-2 and PGE2 in colon cancer tissues indicate a longer survival time. Moreover, a positive correlation was found between HCT116 cell density and COX-2 level, HCT116 cell density and PGE2 level, and COX-2 and PGE2 levels. ATST could down-regulate COX-2 and β-catenin, and knocking down COX-2 could lower β-catenin. After treatment with ATST and ATST + anti-COX-2, the activity of cleaved caspase-9, caspase-3 and PARP was remarkably enhanced, suggesting that ATST and ATST + anti-COX-2 can promote apoptosis of HCT116 cells. It was found that ATST and ATST + anti-COX-2 could also inhibit the proliferation of HCT116 cells.