Y06014 is a selective BET inhibitor for the treatment of prostate cancer.

Bromodomain and extra-terminal proteins (BETs) are potential targets for the therapeutic treatment of prostate cancer (PC). Herein, we report the design, the synthesis, and a structure-activity relationship study of 6-(3,5-dimethylisoxazol-4-yl)benzo[cd]indol-2(1H)-one derivative as novel selective BET inhibitors. One representative compound, 19 (Y06014), bound to BRD4(1) in the low micromolar range and demonstrated high selectivity for BRD4(1) over other non-BET bromodomain-containing proteins. This molecule also potently inhibited cell growth, colony formation, and mRNA expression of AR-regulated genes in PC cell lines. Y06014 also shows stronger activity than the second-generation antiandrogen enzalutamide. Y06014 may serve as a new small molecule probe for further validation of BET as a molecular target for PC drug development.

Analysis of internal spermatic vein embolization through catheter versus laparoscopic high ligation in treatment of left varicocele.

OBJECTIVE: Varicocele is a common disease in young and middle-aged men. This study aims to compare the efficacy of internal spermatic vein embolization of left varicocele versus laparoscopic high ligation. METHODS: From January 2017 to September 2018, a total of 69 varicocele patients were admitted and given the opportunity to choose the treatment option. Among these, 26 patients were treated with sclerosing agent injection, while 43 patients underwent laparoscopic surgery. They were followed up for 12 months after surgery, and the technical success rate, recurrence rate, complication rate, cost, operative time, and hospitalization time with regard to these two methods were analyzed. RESULTS: All patients completed the medical procedures. There was no recurrence in patients in the sclerotherapy group during the follow-up period; however, the complication rate was 19.2%. Furthermore, the operative time, hospitalization time, and cost of treatment were 31.1 ± 11.1 min, 1.2 ± 0.49 days, and 9613.11 ± 895.97 Yuan, respectively. In the laparoscopic group, 9 patients underwent laparoscopic bilateral high ligation, while 34 patients received treatment on the left side alone. The recurrence rate of left varicocele was 4.7% and the complication rate was 44.2%. Furthermore, the operative time, hospitalization time, and treatment cost were 50.4 ± 14.48 min, 4.0 ± 2.02 days, and 10,948.29 ± 2547.00 Yuan, respectively. Moreover, there were statistically significant differences (P < 0.05) in operative time, hospitalization time, and treatment cost. Patients in the sclerotherapy group had an advantage with respect to the overall complication rate when compared with patients from the laparoscopic group (X2 = 4.448, P < 0.05), and there was a statistically significant difference in hydrocele (X2 = 4.555, P < 0.05). However, there was no significant difference in the recurrence rate between these two groups (X2 = 1.245, P > 0.05). CONCLUSION: Patients who underwent sclerotherapy showed a higher technical success rate, a lower recurrence rate, fewer complications, and shorter hospitalization time compared to those treated with laparoscopic ligation. Transcatheter sclerosing agent injection may be a preferable treatment option for patients with unilateral varicocele.

Efficacy of Endovenous Laser Treatment Combined with Sclerosing Foam in Treating Varicose Veins of the Lower Extremities.

INTRODUCTION: This study aims to investigate the efficacy of incision-free endovenous laser treatment (EVLT) combined with sclerosing foam in treating varicose veins of the lower extremities. METHODS: A total of 140 patients (186 limbs) who underwent laser closure of the great saphenous vein + injection sclerotherapy were included in the present study. Preoperative information, intraoperative conditions, duration of the operation, and length of hospital stay were recorded in detail. During the 6-month follow-up, the closure of the trunk and branches of the great saphenous vein, postoperative pain, the recovery of ulcer and dermatitis, and postoperative complications were traced. RESULTS: All patients were treated with laser closure of the great saphenous vein and lauromacrogol injection. Twenty-six stage C6 limbs (lower extremity with ulcer) healed within 6 months, and the postoperative subjective pain disappeared after 1 month. In six patients, pigmentation in the surgical site did not completely disappear at 6 months after the operation. Saphenous nerve injury was found in five patients within 3 months after the operation, and all healed at 6 months after the operation. CONCLUSION: EVLT combined with sclerosing foam is effective for treating varicose great saphenous veins. TRIAL REGISTRATION: This study was registered at http://www.chictr.org.cn (registration number: ChiCTR1900021409).

Nanoliposome-mediated FL/TRAIL double-gene therapy for colon cancer: in vitro and in vivo evaluation.

OBJECTIVE: To investigate the therapeutic effects of cationic nanoliposome-mediated gene therapy combined with immunotherapy for colon cancer treatment. METHODS: Recombinant plasmids containing green and red fluorescent protein reporter genes were constructed using gene cloning methods. Gene-carrying cationic nanoliposomes were prepared based on the electrostatic adherence principle and then transfected into dendritic cells (DC), which were transplanted into colon cancer cells. RESULTS: Recombinant plasmids containing green or red fluorescent protein reporter genes were successfully constructed by gene cloning and confirmed by restriction enzyme digestion and sequencing. Gene-carrying cationic nanoliposomes were transfected into colon cancer cells, and good gene expression was detected. A better level of apoptosis was observed in the combined group of tyrosine kinase receptor 3 ligand (FL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), while the lowest level was detected in the control group. The parameters in the FL and TRAIL groups were between the above-mentioned combined group. CONCLUSION: Cationic nanoliposomes have the advantage of being gene carriers. The joint therapeutic effects of the two genes are superior to those of a single gene. Gene therapy combined with immunotherapy has significant implications for cancer treatment.

Endovascular treatment of Budd-Chiari syndrome.

BACKGROUND: Budd-Chiari syndrome (BCS) is a posthepatic portal hypertension caused by the obstruction of the lumen of the hepatic veins or the proximal inferior vena cava (IVC). This study aimed to evaluate the clinical experience of interventional therapy for Budd-Chiari syndrome. METHODS: IVC venography was carried out first, the obliteration or stenosis in the IVC was opened or dilated with the hard guided wire or Rups100 puncture needle and balloon, then a stent was routinely implanted for the type of obliteration or stenosis. RESULTS: The procedure was successful in 821 out of 903 cases including IVC intervention in 760 cases, and hepatic vein intervention in 61 cases. An IVC stent was used in 517 cases and hepatic vein stent in 19 cases. There were no pulmonary embolisms, but acute renal failure occurred in eight cases, hepatic coma in two cases and acute heart failure in 43 cases. Two patients died in this group and five cases were complicated with acute IVC thrombosis. Follow up of 7 to 124 months was made in 679 cases with recurrence found in 59 cases. CONCLUSIONS: Interventional therapy is safe and effective with a fast recovery for most types of BCS. It is gradually becoming the first therapeutic choice.

Correlation between the expression of the BAG-1 gene and clinicopathologic factors in colorectal cancer.

OBJECTIVE: The present study aims to investigate the expression and significance of the anti-apoptotic gene Bag-1 in colorectal cancer and to evaluate the relationship between the gene and the disease. METHODS: Bag-1 expression was examined in 320 colorectal cancer and 30 normal colorectal tissue samples using reverse transcriptase polymerase chain reaction (RT-PCR) and the immunohistochemical staining (streptavidin-biotin-peroxidase complex method. RESULTS: Using RT-PCR, Bag-1 was observed to be expressed in colorectal cancer tissues, but not in normal colorectal tissues. The expression of Bag-1 in colorectal cancer was closely correlated with pathologic grade, distant metastasis, Dukes stage, and prognosis, but it was not correlated with the pathologic type, tumor diameter, depth of invasion, and lymph node metastasis. CONCLUSION: Bag-1 protein was found to be overexpressed in colorectal cancer. They might be regarded as a biomarker for the diagnosis of the early stages of colorectal cancer. In addition, they have particular significance for the prognosis of colorectal cancer.