Carcinoma, Squamous Cell ; genetics ; Head and Neck Neoplasms ; genetics ; Humans ; MicroRNAs ; genetics

Objective: To investigate the short-term efficacy and adverse events of chemotherapy combined with androgen-deprivation therapy in high-volume metastatic hormone sensitive prostate cancer. Methods: From March 2015 to August 2017, 55 patients with high-volume metastatic hormone sensitive prostate cancer were enrolled at Department of Urology, Fudan University Shanghai Cancer Center receiving chemotherapy combined with androgen-deprivation therapy. The age was 65(8) years (M(Q_R)) (range: 46 to 79 years). Patients were enrolled in the study for continuous androgen-deprivation therapy (medical or surgical castration), combined with docetaxel 75 mg/m² intravenous injection on the first day, repeated every 21 days (6 cycles). Endpoints included overall survival, progression-free survival of prostate cancer, prostate specific antigen (PSA) response rate, and adverse events. Results: The follow-up time was 21.2(11.7) months. The PSA value before chemotherapy was 144.9(415.3) μg/L. The days in patients undergoing androgen deprivation therapy before chemotherapy was 14(23) days. Four patients (7.3%) presented 0 in Eastern Cooperative Oncology Group scoring system and 51 patients(92.7%) presented 1. Thirty-nine patients (70.9%) completed more than 6 cycles of combined chemotherapy, 17 patients (30.9%) showed PSA<0.2 μg/L at 6 months after treatment, and 14 patients (25.5%) showed PSA<0.2 μg/L at 12 months after treatment. Twenty-eight patients (50.9%) had grade 3 to 4 neutropenia and 1 patient (1.8%) developed infectious neutropenia and died. Nausea and vomit occurred in 16 patients (29.1%). Twelve patients (21.8%) underwent dose adjustment due to adverse events in blood system. Conclusions The short-term effect was confirmed in high-volume metastatic hormone sensitive prostate cancer using chemotherapy combined androgen-deprivation therapy, and the long-term effect remains to be seen. Myelosuppression during chemotherapy requires close attention, and taking timely examination is recommended.

OBJECTIVETo investigate the expression of miR-140-5p and ADAM10 in hypopharyngeal carcinoma tissues and their effects on the migration and invasion of FaDu cells and underlying mechanism.

METHODSThe miR-140-5p and ADAM10 mRNA levels in 33 cases of hypopharyngeal carcinoma tissues and adjacent normal tissues were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Transwell migration assay and transwell invasion assay were used to test the metastasis ability of FaDu cells after upregulation or downregulation of miR-140-5p and downregulation of ADAM10. The protein expression levels of ADAM10 in hypopharyngeal carcinoma tissues and the FaDu cells after transfection were determined by Western blot assays.

RESULTSThe expression level of miR-140-5p was significantly downregulated in hypopharyngeal carcinoma tissues compared with adjacent tissues (t=-4.016, P<0.01), which was significantly correlated with tumor classification and lymph node metastasis (P<0.05). Conversely, mRNA and protein expressions of ADAM10 were significantly upregulated in tumor tissues (t=3.960, P<0.01; t=12.089, P<0.01), and were significantly downregulated in the FaDu cells after tranfected with si-ADAM10 (t=8.653, P<0.05; t=5.191, P<0.05). Transwell assay showed that compare with control group, the migration and invasive cells decreased significantly in hsa-mir-140-5p group (t=3.255, P<0.05; t=2.942, P<0.05), while increased significantly in anti-hsa-mir-140-5p group, (t=-13.521, P<0.05; t=-6.223, P<0.05). The migration and invasive cells in si-ADAM10 group were less than those in control group (t=4.759, P<0.05; t=3.663, P<0.05). The downregulation of ADAM10 attenuated the effect of anti-mir-140-5p in FaDu cells. Western blot assay showed that ADAM10 expression was apparently decreased in hsa-mir-140-5p group and increased in anti-mir-140-5p group compared with control group.

CONCLUSIONSThe expression of miR-140-5p was significantly downregulated in hypopharyngeal carcinoma tissues and correlated with tumor classification and lymph node metastasis. ADAM10 was upregulated in tumor tissues. MiR-140-5p suppresses the migration and invasion abilities of FaDu cells, possibly through downregulation of ADAM10.

ADAM Proteins ; metabolism ; ADAM10 Protein ; Amyloid Precursor Protein Secretases ; metabolism ; Cell Line, Tumor ; Cell Movement ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; Hypopharyngeal Neoplasms ; pathology ; Lymphatic Metastasis ; Membrane Proteins ; metabolism ; MicroRNAs ; metabolism ; RNA, Messenger ; metabolism ; Transfection

Objective To investigate the short-term efficacy,safety and factors affecting the efficacy of BCG intravesical therapy in high risk non-muscle-invasive bladder cancer (NMIBC) patients.Methods A total of 161 high-risk non-muscle invasive bladder cancer (NMIBC) patients were reviewed in our hospital from March 2014 to December 2017.They were all treated with BCG instillation after transurethral resection of bladder tumor (TURBT).There were 121 males (75.2％) and 40 females (24.8％).Median age was 65 years old,including 17 cases (10.6％) ＜50 years old,23 cases (14.3％) within 50-59 years old,72 cases (44.7％) within 60-69 years old,49 cases ≥70 years old (30.4％).There were 112 patients (69.6％) with primary bladder cancer and 49 (30.4％) patients with recurrent bladder cancer.56 cases (34.8％) had single tumor and 105 cases (65.2％) had multiple tumors.The tumors size in 106 cases (65.8％) was less than 3 cm,and tumor size in 55 cases (34.2％) was more than 3 cm.43 patients (26.7％) suffered carcinoma in situ.10 patients (6.2％) suffered urothelial carcinoma with variant types.According to the American Joint Commission for Cancer (AJCC) version 7 TNM staging system,25 cases (15.5％) were classified into Ta stage,129 cases (80.1％) were classified into T1 stage,and 7 cases (4.3％) were classified into Tis stage.There were 8 cases (5％) with low-grade cancer and 153 cases (95％) with high-grade cancer.69 patients (42.9％) received chemo-instillation before.43 cases were directly perfused without re-TURBT and 118 cases were perfused after re-TURBT.They were all treated with BCG instillation after transurethral resection of bladder tumor (TURBT).The 120 mg BCG were dissolved into 50 ml saline for instillation and were kept for 2 hours.Induction scheme of six-weekly and three fortnightly instillations started two weeks after the initial TUR or re-TUR.Maintenance instillations were then be offered in a scheme of ten monthly instillations.During treatment,patients were offered cystoscopy and cytology every three months,while CT and chest radiographs were reviewed every 6-12 months.Recurrence status and adverse effects were recorded.Univariate and multivariate regression analyses were performed to predict risk factors for failure of BCG instillation in bladder cancer.Results A total of 161 patients were followed up.The median follow-up time was 13 months,ranging 7-22 months.The overall recurrence rate was 26.1％ (42/161) and the 1-year recurrence-free survival rate was 79.0％.On univariate analysis,recurrence history,history of instillation chemotherapy application and history of re-staging transurethral resection influenced recurrence.Multivariate regression analysis showed recurrence status was an independent prognostic factor regarding recurrence-free survival.The incidence of adverse events in all 161 instillation patients was 40.4％ (26/65).Grade 1,grade 2 and grade 3 adverse events accounted for 53.8％ (35/65),40.0％ (26/65) and 6.2％ (4/65) respectively.6 cases (3.7％) reduced the dose of BGC and 1 case stop the instillation due to the intolerance of BCG.Conclusion Short-term efficiency and safety were confirmed in BCG-treated high-risk NMIBC patients.And recurrence status was an independent prognostic factor for recurrence-free survival.

Progressive multifocal leukoencephalopathy (PML) is a rare and yet serious central nervous system disorder due to JC viral infection.PML occurs predominantly in immunocompromised individuals, including solid organ transplant (SOT) recipients.Clinically, SOT-related PML commonly presents as cognitive and behavioral impairments. Pathologically, PML is characterized by multifocal demyelinating lesions, with neuroimaging technique typically revealing white matter damage in the temporoparietal regions. Clinical diagnosis usually involves integrating clinical manifestations, cranial magnetic resonance imaging, and detection of JC virus in cerebrospinal fluid. Currently, specific medications for PML are lacking, and the treatment mainly relies on supportive care and immunomodulatory strategies. The prognosis of PML remains unfavorable, early diagnosis and enhanced adaptive immune responses are crucial for PML management in SOT recipients.