Efficacy and safety of lenvatinib combined with sintilimab as the second-line therapy for intrahepatic cholangiocarcinoma / 临床肝胆病杂志

Objective To investigate the efficacy and safety of lenvatinib combined with sintilimab as the second-line therapy for advanced intrahepatic cholangiocarcinoma (ICC). Methods A retrospective analysis was performed for the clinical data of the patients with advanced ICC who were admitted to Beijing Ditan Hospital from October 31, 2019 to October 31, 2021 and could not undergo surgery or experienced metastasis after surgery. All patients were treated with lenvatinib combined with sintilimab as the second-line therapy. The patients were followed up, and the RECIST1.1 criteria were used to assess treatment outcome. The primary endpoint was time to progression (TTP), and the secondary endpoints were tumor objective response rate (ORR), disease control rate (DCR), overall survival (OS) time, and safety. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison between groups. Results A total of 27 patients were enrolled, among whom there were15 male patients (55.6%) and 12 female patients (44.4%), with a median age of 58 years (range 33-73 years). The median TTP for these patients was 5.5 (95% confidence interval [ CI ]: 1.7-9.3) months, and 13 patients (48.1%) died of disease progression, with a median OS time of 11.2 (95% CI : 5.0-17.4) months. The overall ORR and DCR were 40.7% and 70.3%, respectively. Of all patients, 66.7% experienced varying degrees of adverse events, and among these patients, 44.4% had an increase in alanine aminotransferase, 44.4% had an increase in aspartate aminotransferase, 37.0% had hypertension, 29.6% had an increase in bilirubin, 29.6% experienced diarrhea, and 25.9% each experienced proteinuria, anorexia, and weakness. No treatment-related death was observed, and only 1 patient developed grade Ⅳ immune-related hepatotoxicity and was relieved without sequelae after corticosteroid therapy, resulting in permanent withdrawal of sintilimab. The patients with lymph node metastasis had a significantly shorter median TTP than those without lymph node metastasis (4.5 months vs 18.8 months, P =0.035), and the patients who achieved disease remission had a significantly longer median TTP [11.6 months (95% CI : 5.6-17.6) vs 2.8 months (95% CI : 1.8-3.8), P < 0.001]; the patients with lymph node metastasis had a shorter median OS time [9.6 months (95% CI: 7.9-11.3) vs 21.9 months (95% CI : 0-44.9), P =0.053], and the patients who achieved disease remission had a significantly longer median OS time [16.6 months (95% CI : 9.0-24.2) vs 6.9 months (95% CI : 3.6-10.2), P =0.011]. Conclusion Lenvatinib combined with sintilimab has a marked clinical effect and a low incidence rate of serious adverse events as the second-line therapy for advanced ICC, and therefore, it is a safe and effective treatment regimen.

Effect of IgG gene silencing by RNA interference on radiosensitivity of prostate cancer PC3 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of RNA interference of IgG gene on the radiosensitivity of the human prostate cancer PC3 cell line.</p><p><b>METHODS</b>PC3 cells were trasnfected via lipofectamine by the shRNA vector FCGR1AshRNA targeting the Fc segment of IgG, using NCshRNA as the negative control. Q-PCR and Western blotting were used to analyze the expression of IgG in the trasnfected cells. The cells were then exposed to ⁶⁰Co γ ray at 0, 2, 4, 6, 8, 10 Gy, and the cell proliferation was evaluated by MTS and the cells apoptosis estimated by flow cytometry at 12, 24 and 48 h.</p><p><b>RESULTS</b>MTS assay showed that ⁶⁰Co γ ray significantly inhibited the proliferation of PC3 cells transfected with FCGR1AshRNA as compared with NCshRNA-transfected and blank control cells (P<0.05). Flow cytometry showed that the cell apoptosis rate was significantly higher in FCGR1AshRNA group than in NCshRNA and blank control groups at 48 h after γ ray exposure (P<0.05). At 12, 24 and 48 h after 6 Gy radiation, the cells in FCGR1AshRNA group showed a significantly lowered proliferation rate and an increased apoptosis rate (P<0.05).</p><p><b>CONCLUSION</b>The shRNA targeting IgG gene can significantly enhance the sensitivity of PC3 cells to radiation. The combination of RNA interference targeting IgG gene with radiotherapy may be more effective in the treatment of prostate cancer.</p>

Effect of stable DNA methyltransferase 3bknockdown on proliferation and apoptosis in bladder cancer cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of stable knockdown of DNA methyltransferase 3b (DNMT3b) on the proliferation and apoptosis of bladder cancer cells.</p><p><b>METHODS</b>Lentivirus expressing DNMT3b siRNA or the negative control siRNA was infected in human bladder cancer BIU-87 cells. MTT assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. The inhibitory effect of DNMT3b knockdown on xenograft tumors in nude mice was observed. Real-time PCR and Western blotting were carried out to investigate the expression level of cell apoptosis related genes. Methylation specific PCR was used to examine the methylation in the promoter region of the cell apoptosis related genes.</p><p><b>RESULTS</b>The results of real-time PCR and Western blotting showed that DNMT3b mRNA and protein level were stably knocked down in BIU-87 cells. Stable DNMT3b knockdown suppressed BIU-87 cell growth and the tumor formation ability of the cells in nude mice. DNMT3b knockdown promoted the apoptosis of BIU-87 cells, increased the mRNA and protein expression of the cell growth and apoptosis related genes including DAPK, Bax and RASSF1A, and significantly decreased the methylation of these genes.</p><p><b>CONCLUSION</b>Stable DNMT3b knockdown can affect the methylation of the cell growth and apoptosis related genes to regulate their expression, which might be a possible mechanism for suppressed cell growth and enhanced apoptosis of BIU-87 cells.</p>

Effect of docetaxel on C-jun and androgen receptor interaction in prostate cancer LNCaP cells and its androgen-independence subtype LNCaP-bic cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of docetaxel on the interaction between C-jun and androgen receptor (AR) in prostate cancer LNCaP cells and its androgen-independence subtype LNCaP-bic cells.</p><p><b>METHODS</b>LNCaP and LNCaP-bic cells were treated with docetaxel and the changes in AR and AP-1 expression were evaluated using luciferase assay. Western blotting and immunoprecipitation assay were employed to analyze the effects of docetaxel on the expressions of C-jun and AR and their interaction.</p><p><b>RESULTS</b>Luciferase assay showed that LNCaP and LNCaP-bic cells expressed higher levels of AR and C-jun after docetaxel treatment. Docetaxel induced a higher level of p-c-jun expression in LNCaP-bic cells than in the parental LNCaP cells. Western blotting showed a strong PSA protein expression in LNCaP-bic cell after docetaxel treatment. Docetaxel caused a stronger interaction between AR and C-jun in LNCaP-bic cells.</p><p><b>CONCLUSION</b>Docetaxel activates ligand-independent AR transcription, and the interaction between AR and C-jun may affect the outcome of docetaxel chemotherapy.</p>

Expression of OCT4 protein in bladder cancer and its clinicopathological implications / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the expression of OCT4 protein in bladder cancer and its correlation to the clinicopathologic features and prognosis of bladder cancer.</p><p><b>METHODS</b>OCT4 mRNA and protein expression was detected in 5 bladder cancer cell lines (RT-4, Tcc-Sup, KK47, T24, and 5637) and 1 normal bladder cell lines by real-time PCR and Western blotting, respectively. Immunohistochemical analysis was used to detect the expression of OCT4 protein in 46 bladder cancer samples.</p><p><b>RESULTS</b>All the 5 bladder cancer cell lines expressed detectable levels of OCT4 mRNA and proteins, whereas the normal bladder cell line SV-HUC-1 was negative for OCT4 expression. The clinical bladder cancer tissues showed a high positivity rate of OCT4 expression (76.1%), which was not detected in normal bladder tissues. Specific OCT-4 signals were localized mainly in the nuclei of the cancer cells. The expression rate of OCT4 protein was significantly higher in bladder cancer tissue than in normal bladder epithelium (P<0.05), and showed a positive correlation to the grade of tumor differentiation and metastasis (P<0.05) but not to the patients' age, gender or TNM stage.</p><p><b>CONCLUSION</b>OCT4 protein expression is associated with tumor differentiation and metastasis in bladder cancer and may play an important role in the early diagnosis and prognostic evaluation of bladder cancer.</p>

Single-port laparoscopic surgery for radical nephrectomy: report of 22 cases / 南方医科大学学报

<p><b>OBJECTIVE</b>[corrected] To evaluate the method and technique of single-port laparoscopic radical nephrectomy.</p><p><b>METHODS</b>Form January 2009 to September 2011, 22 patients with renal carcinoma were treated with single-port laparoscopic radical nephrectomy. An incision about 5 cm in length was made through the umbilicus or in the postaxillary line under the 12th rib to establish the peritoneal or retroperitoneal working space. A single-port cannulation was deployed and the operation was carried out using standard and crooked laparoscopic equipment.</p><p><b>RESULTS</b>The operations were completed successfully in all the 22 cases without conversion to open surgery, but additional trocar was needed in 5 cases. The mean operative time of radical nephrectomy was 150 min (90-240 min). The mean postoperative hospital stay was 7.6 days (3-15 days). The operation left a roughly 5-cm-long scar in all the cases.</p><p><b>CONCLUSION</b>Single-port laparoscopic radical nephrectomy is safe and feasible with good cosmetic effect and shows much potential in radical resection of renal carcinoma.</p>

Pure laparoendoscopic single-site radical cystectomy: Initial experience with 10 cases report / 中华泌尿外科杂志

Objective To present our initial experience of pure laparoendoscopic single-site surgery (LESS) for radical cystectomy and bilateral pelvic lymph node dissections. Methods 10 patients with pathology confined bladder urothelial carcinoma underwent laparoendoscopic single-site radical cystectomy, including 9 males and 1 female. After a 3-4 cm lower median abdominal incision was made, quadport or homemade single multichannel port was inserted, and conventional and prebent laparoscopic instruments were utilized. The surgical procedure included bilateral pelvic lymphadenectomies, radical cystectomy and building with a sigmoid orthotopic neobladder by open surgery.Results No extra port needed, neither conversion to open or conventional laparoscopic surgery. The time of LESS procedure ranged from 130 to 330 min (mean 243 nin). Estimated blood loss ranged from 50 to 600 ml (mean 270 ml). 5 patients needed blood transfusion of 2 to 4 units. The pathologic evaluation revealed bladder urothelial carcinoma, negative margins and negative pelvic lymph node involvement. No mortality or severe complications were observed perioperatively. After followup of more than 6 months, all revealed controllable urination at daytime, while 4 revealed nocturnal incontinence and needed one or two pads during nighttime. No evidence of recurrent or metastatic disease was detected. Conclusions LESS radical cystectomy and bilateral lymphadenectomies was safe and feasible, and short-term follow-up showed good tumor control outcomes. Homemade single multichannel port made of two elastic ring and glove was simple and effective.

Construction of Detenial Sigmoid Neobladder after Laparoscopic Radical Cystectomy:Report of 71 Cases / 中国微创外科杂志

Objective To report our experience on construction of detenial sigmoid neobladder after laparoscopic radical cystectomy in 71 cases.Methods From August 2002 to May 2006,a total of 71 patients with invasive bladder carcinoma underwent construction of detenial sigmoid neobladder after laparoscopic radical cystectomy in our hospital.After the bladder was excised by laparoscopy,a 5-to 7-cm incision was made on the abdomen to remove the resected tissues,and then a 15-to 20-cm sigmoid colon was resected,the two colic bands opposite to the mesentery and the circular muscle and seromuscular layers between them were removed to construct a detenial sigmoid neobladder.Afterwards,the neobladder was anastomosed with the posterior urethra.Laparoscopic anastomosis was performed in 26 of the cases.Results The operation time was 240-390 min totally in the 71 cases.Laparoscopic radical cystectomy was finished in 80-270 min(mean,180 min),and the open surgery was completed in 160-240 min(mean 140 min).Oral intake was started at day 4-8 postoperation,ureteral stents were removed at week 3-4,and urethral catheter was removed at week 4.Three months after the operation,the mean intra-bladder pressure was 22.0 cm H2O(17-38 cm H2O),average bladder reservoir was 340 ml(200-410 ml),volume of residual urine was less than 25 ml in all the cases(