摘要:Background and purpose: The mutation of BRCA1 gene is widely acknowledged to be related to the incidence of triple-negative breast cancer (TNBC). The aim of this study was to investigate the association between TNBC and single nucleotide polymorphisms (SNPs) of BRCA1-associated genes. Methods: This study investigated the associations between the BRCA1-A complex genes and risk of developing TNBC in a case-control study of Chinese Han Women population including 414 patients with TNBC and 354 cancer-free controls diagnosed in the Fudan University Shanghai Cancer Center during 2008-2011. This study also detected 37 common variants in Abraxas, BRE, Rap80, NBA1 and BRCC36 genes encoding the BRCA1-A complex and evaluated their genetic susceptibility to the risk of TNBC. An additional cohort with 652 other types of breast cancer (non-TNBC) cases and 890 controls were used to investigate the associations between TNBC-specific SNPs genotype and non-TNBCs susceptibility. Results: This study found that rs7250266 in the promoter region of NBA1 confers a decreased risk to TNBC (P<0.01). Compared with CC genotype, women with the GC genotype (OR=0.70, 95%CI: 0.51-0.97) and GG genotype (OR=0.48, 95% CI: 0.21-1.07) had a lower risk of developing TNBC (P=0.03). In addition, the haplotypes containing two polymorphisms rs7250266 and rs2278256 were associated with a lower chance of TNBC development. In the second part of the study, the result showed that there was no difference in rs7250266 expression between non-TNBC and normal people (0.19 vs 0.18, P=0.85).Conclusion: Genetic variants in NBA1 may be an important genetic determinant of TNBC susceptibility in Chinese women.
关键词:Single nucleotide polymorphisms;Triple-negative breast cancer;BRCA1 gene;BRCA1-A complex
摘要:Background and purpose: miRNA plays important roles in tumorigenesis. It has been reported that many kinds of serum miRNA serve as markers for tumor diagnosis and screening. This study aimed to detect the expression of serum miRNA-31 (miR-31) in colorectal cancer patients and to explore the effect of miR-31 on cell proliferation, apoptosis and cell cycle distribution. Methods: The expressions of miR-31 in 40 cases of colorectal cancer serum and 35 cases of the healthy control were examined by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR). The correlation between miR-31 expression and clinicopathological features of colorectal cancer (including age, gender, depth of infiltration, lymph node metastasis, clinical stage) were further analyzed. The miR-31 mimics, inhibitor and miR-control (negative control) were transfected into HCT116 cells. The effect of miR-31 on cell proliferation was evaluated by CCK-8 method. Flow cytometry was used to examine the change of cell apoptosis and cell cycle. Results: Relative expression of serum miR-31 was significantly increased in cancer patients compared with healthy controls (P<0.01). Expression of serum miR-31 was higher in poorly differentiated carcinoma than that in well or moderately differentiated carcinoma (P<0.05). No correlation was found between serum miR-31 expression and other clinicopathological variables. CCK 8 assay showed that after transfection with miR-31 mimics, the cell proliferation was increased, compared with miR-31 inhibitor and negative control group. Meantime, the apoptotic cell number was significantly decreased, particularly in late apoptosis. The cell number of G1 stage was remarkably increased in miR-31 inhibitor group, compared with miR-31mimics and negative control group. Conclusion: The expression of serum miR-31 is higher in colorectal cancer. miR-31 can promote cell proliferation and inhibit the apoptosis of HCT116 cells. It might be a potential biomarker for colorectal cancer.
摘要:Background and purpose: The previous research has found that the prostate stromal cells derived from different prostate zones have distinct effect on prostate epithelial cells. We also revealed that LMO2 protein was highly expressed in PZ stromal cells (PZSCs) and prostate cancer associated fibroblasts (CAFs) compared with TZ stromal cells. This study investigated the effect of LMO2 protein in prostate stromal cells on proliferation and invasion of prostate cancer PC-3 cells and its mechanisms. Methods: Lentivirus overexpression vectors were used to establish LMO2-overexpressed prostate WPMY-1 stromal cell line. shRNA plasmids were used to suppress LMO2 in CAFs. LMO2 mRNA and protein level of both WPMY-1 and CAFs were evaluated by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) and Western blot. Then, PC-3 cells were co-cultured with different prostate stromal cells and the in vitro proliferation and invasion of PC-3 were measured by CCK-8 and matrigel invasion assays respectively. Results: When co-cultured with LMO2-overexpressed prostate stromal cells, both proliferation and invasion of PC-3 were improved. However, when co-cultured with CAFs which have inhibited expression of LMO2, the proliferation and invasion of PC-3 were reduced. The protein array profiling found that both interleukin-11 (IL-11) and fibroblast growth factor-9 (FGF-9) were enhanced extensively in the supernatant collected from LMO2-overexpressed WPMY-1 cells. Conclusion: The expression of LMO2 in prostate stromal cells could be responsible for development of prostate cancer. Paracrine of cytokines, such as IL-11 and FGF-9, from LMO2-overexpressed stromal cells had effects on the proliferation and invasion of prostate cancer cells.
摘要:Background and purpose: As a member of the catenin family, Delta-catenin protein could promote proliferation and invasion of tumor cells, but the accurate mechanism of Delta-catenin promoting cell proliferation is not clear. In the present study, we illustrated that Delta-catenin’s effect on cell apoptosis and their relationship with mitogen-activated protein kinase (MAPK) signaling pathway, and the possible mechanism was also explored for Deltacatenin promoting invasion and proliferation of tumor cells. Methods: The alterations of p38 and c-jun N-terminal rinasel JNK protein activity were detected in SPC and SK lung cancer cell lines with Delta-catenin overexpression or not, by Western blot method. At the same time, the apoptotic number of tumor cells was also examined by FCM method. Furthermore, the number of invasive tumor cells was examined by Matrigel invasive experiment. Results: Compared with untreated group and empty vector group, the activity of p38 protein was unchanged in lung cancer cell lines with Delta-catenin overexpressed (P>0.05), but the activity of JNK protein was decreased significantly (P<0.05), meanwhile, apoptotic proportion of tumor cells were also reduced (P<0.05), and invasive ability of tumor cells was enhanced significantly (P<0.05). Conclusion: Delta-catenin probably decreases apoptosis number of lung cancer cells via inhibiting the activity of JNK pathway, and then promotes invasive ability of tumor cells.
摘要:Background and purpose: AMP-activated protein kinase (AMPK) plays an important role in the regulation of cell metabolism and energy balance and is associated with cell proliferation, survival and multiple signaling pathways. Recent reports found that AMPK is involved in tumor suppression and drug resistance. The aim of this study was to explore the effect of AMPK on the anti-tumor effect of adriamycin and underlying mechanism in breast cancer MCF-7/adr cells. Methods: The anti-proliferative effects of adriamycin was detected by methyl thiazolyl tetrazolium (MTT) assay in MCF-7/adr, MCF-7/adr-vector and MCF-7/adr-AMPKα cells. The cell morphology in each group was stained with the fluorescent dye Hoechst 33528, and the effects on apoptosis induction were examined by flow cytometry (FCM). The intracellular concentration of adriamycin was detected by fluorescence assay. The resistance- and apoptosis-related proteins were analyzed by Western blot. Results: The growth of breast cancer MCF-7/adr cells was inhibited by adriamycin in a dose- and time-dependent manner. The IC50 values at 24 and 48 h were (36.8±2.1) and (28.8±1.3) μg/mL, respectively. AMPKα over-expression enhanced the cytotoxic effect of adriamycin in MCF-7/adr-AMPKα cells in a dose- and time-dependent manner. Its IC50 values at 24 and 48 h were (16.0±0.7) and (4.2±0.2) μg/mL, respectively. Fluorescent morphological assay showed that AMPKα overexpression contributed to adriamycin induced apoptosis in MCF-7/adr-AMPKα cells. After treatment with 1.0 μg/mL adriamycin for 48 h, the apoptosis rates of MCF-7/adr, MCF-7/adr-vector and MCF-7/adr-AMPKα cells were (12.0±1.4)%, (12.7±1.6)% and (32.0±4.2)%, respectively, indicating that overexpression of AMPKα enhanced the adriamycin-induced apoptosis in MCF-7/adr cells. Fluorescence microplate assay showed that over expression of AMPKα significantly increased the intracellular accumulation of adriamycin, in a concentration dependent manner. Western blot analysis showed that, compared with MCF-7/adr and MCF-7/adr-vector cells, the expressions of Bax, caspase-3 and cleaved PARP proteins were increased. Meanwhile, Bcl-2 and P-gp protein expressions were decreased in MCF-7/adr-AMPKα cells. Furthermore, the release of cytochrome c from mitochondria into the cytosol was also observed in MCF-7/adr-AMPKα cells. Conclusion: AMPKα overexpression can enhance the chemosensitivity of breast cancer MCF-7/adr cells to adriamycin through inhibiting the drug efflux transporter and regulating the expression of apoptosis-related proteins.
关键词:Breast cancer;Drug resistance;AMP-activated protein kinase;Apoptosis;Adriamycin
摘要:Background and purpose: Inflammatory bowel diseases (IBD) are a group of chronic intestinal diseases, including ulcerative colitis (UC) and Crohn’s disease (CD). This study identified differentially expressed miRNAs in UC, CD and colitis-associated colorectal cancers (CAC) to explore their potential as novel molecular biomarkers. Methods: Tissue samples were taken from 13 UC patients, 3 CD patients, 12 CAC patients, and 8 ageand gender-matched healthy controls. The miRNA expressions were detected by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) assay. Known targets of deregulated miRNAs were utilized using miRWalk 2.0 database, and subsequent bioinformatics analysis of these target genes was performed by DAVID software (GO-analysis, KEGG-analysis and BIOCARTA-analysis). Results: The data showed that miR-146a, miR-27a, miR-29a, miR-20a and miR-21 were upregulated in UC, CD and CAC tissues compared with normal control. Moreover, the target genes of these miRNAs were enriched in several key signal transduction pathways including cancer-related pathway and immunity-associated pathway. Conclusion: miR-146a, miR-27a, miR-29a, miR-20a and miR-21 may play important roles in the switching from IBD to CAC.
摘要:Background and purpose: This study aimed to estimate the spike-effect of domestic nanometer activated carbon on the radical operation for early stage low-lying rectal cancer. Methods: From Jan. 2013 to Dec. 2015, 66 patients with early stage low-lying rectal cancer were randomly divided into two groups: study group and control group. The patients of study group were treated with injection of carbon nanoparticles suspension in tumor vicinity before the operation. This study compared the total number of lymph node, the scale percentage of micro lymph node between two groups. SLNs of study group were obtained for pathological examination. Results: The differences in the total number of lymph node and the scale percentage of micro lymph node between two groups were statistically significant (P<0.05). The diagnostic sensitivity and false-negative rate were 90.9% and 3.8%, respectively. Conclusion: Local injection of nanometer activated carbon around the tumor is important to the metastasis lymph node resection, especially to SLN biopsy in the radical operation for rectal cancer.
摘要:Background and purpose: Concurrent radiochemotherapy is the standard modality for locally advanced esophageal squamous cell carcinoma (ESCC) patients. This clinical trial aimed to assess the effectiveness and toxicity of continuous infusion of 5-fluorouracil (5-FU) and weekly paclitaxel combined with radiotherapy in ESCC patients. Methods: Patients with locally advanced (T2-4N0-1M0-1a) esophageal squamous cell carcinoma were enrolled in a prospective, single-institutional, single-arm study of definitive chemoradiotherapy. Patients received 61.2 Gy with IMRT in 34 fractions. Patients had a Karnofsky performance status of 70 or greater, and normal liver, renal, and bone marrow functions. Patients were recommended to receive concurrent 5-FU (300 mg/m2 civ 96 h) for 5 days a week for 5 weeks, plus paclitaxel (50 mg/m2) given during 3 hours every week for 5 weeks. Patients were recommended to receive 2 courses of consolidation chemotherapy after concurrent radio (chemo) therapy (5-FU 1 800 mg/m2 civ 72 h, plus paclitaxel 175 mg/m2 every 28 days). The primary endpoints of the study were 5 year overall survival and acute toxicity. Results: Fifty patients were enrolled in this study, including 38 male patients and 12 female patients; median age: 58 years (ranged 26 to 75 years). 72% patients completed all the chemotherapy and 98% patients received the full dose of radiotherapy. 1-, 2-, 3-, and 5- year survival were 75%, 56%, 42% and 28% respectively. Among haematological toxicities, grade 3 leukopenia (16%) was recorded, and no patients experienced any ≥ grade 2 thrombocytopenia or anaemia. Among non-haematological toxicities, the rates of grade 2 peripheral neurotoxicity, arthralgias and myalgias, nausea, vomiting, and fatigue were 8%, 4%, 4%, 2% and 6% respectively. The rates of ≥ grade 2 acute radiationinduced esophageal toxicity, radiation pneumonitis and skin toxicity were 32%, 44% and 14% respectively. No treatment-related deaths occurred and no patients experienced any ≥ grade 4 toxicities. Conclusion: Continuous infusion of 5-FU plus paclitaxel given concurrently with radiotherapy may be an effective and tolerable treatment option for ESCC patients.
摘要:Background and purpose: Postoperative sore throat (POST) is one of the common complaints of patients after radical thyroidectomy. Tracheal intubation is the main cause of POST. This study compared the effect of intubation with visual endoscopy and general laryngoscope on POST in patients undergoing radical thyroidectomy. Methods: One hundred patients (18-60 years, ASAⅠ-Ⅱ) undergoing elective radical thyroidectomy were randomized into two groups: patients in group A (n=50) were intubated with visual endoscope while patients in group B (n=50) were intubated with general laryngoscope. Endotracheal tube cuffs pressure was maintained at 20mmHg in all patients. Visual analogue scale (VAS) and Bruggrmann comfort scale (BCS) were recorded at the time points of 1, 6 and 24 h after extubation. Results: Compared with group B, the incidence of POST in group A was signifcantly reduced (42% vs 64%, P=0.027). The VAS of group A was lower than that of group B (3.05±1.56 vs 4.25±1.30, 3.05±1.56 vs 4.01±1.98, 2.72±1.77 vs 3.31±1.12) (P<0.05). The BCS of group A was higher than that of group B (0.99±0.46 vs 0.69±0.30, 1.95±0.47 vs 1.51±0.58, 2.82±0.87 vs 2.31±0.72) (P<0.05). Conclusion: Using visual endoscopic intubation can reduce the incidence of the POST in patients undergoing radical thyroidectomy.
摘要:Background and purpose: Since the number and tumor size of localized liver metastases can be controlled, local minimally invasive treatment can improve the survival of patients. Hence, microwave ablation has become an important treatment method for liver metastases. This study was to investigate the value of percutaneous microwave ablation in the treatment of tumor metastases. Methods: From Sep. 2011 to Oct. 2014, 26 advanced nasopharyngeal carcinoma patients with post-chemotherapy consolidation, liver metastases were collected. All the patients with the number of tumor lesions less than 3, diameter less than 5 cm, no other distant metastases was excluded. The ultrasound-guided percutaneous microwave ablation was used for 26 patients. Finally, 43 ablations were completed followed by liver function test, enhanced CT and MRI diagnosis 1 month later. mRECIST criteria was used to evaluate the efficacy of cancer treatment. Progression-free survival (PFS) and overall survival (OS) were calculated. Results: Twenty-six cases of a total of 53 lesions, including complete ablation (CA) 20 patients (20/26, 77.0%), partial ablation (PA) 3 patients (3/26,11.5%). The overall efficiency was 88.5% (CA + PA) with no serious complications. 6 months, 1-, 2-year survival rates of 26 patients were 96.1%, 65.3% and 23.0%. PFS was 11.4 months. The median survival time (MST) was 11.9 months, while OS was 23.7 months. Conclusion: Percutaneous microwave ablation for limited liver metastases of nasopharyngeal carcinoma is a minimally invasive, safe and effective treatment method.
摘要:With the development of the next generation sequencing technology, considerable attention has been paid to the utility of circulating tumor DNA (ctDNA) detection in breast cancer. There are many clinical trials showed the ctDNA detection is a potential biomarker for the diagnosis, management and prognosis of breast cancer. ctDNA detection can provide a more accurate diagnosis for patients to guide clinical treatment in precision medicine era.
摘要:Schwannomas of the vagus nerve (SVN) and schwannomas of the cervical sympathetic nerve (SSN) are the two most common schwannomas in the carotid space. Because schwannomas are asymptomatic, moreover, the vagus nerve and the cervical sympathetic nerve have adjacent anatomical location, it is difficult to differentiate SVN or SSN. In addition, the current surgical treatment of schwannomas still remains controversial. This article summarized the studies on SVN and SSN, and meanwhile discussed the advances in the diagnosis and management of the disease.