Background and purpose:Melanoma is a highly invasive malignant tumor originating from melanocytes,which poses a great threat to human life and health around the world,and its morbidity and mortality have been rising continuously in recent years.Telomerase and autophagy play crucial roles in cell proliferation,survival and stress response.Telomerase maintains the replication ability of cells by prolonging telomeres at the ends of chromosomes,and autophagy,as a self-degradation mechanism of cells,can not only help cells remove damaged components to promote survival,but also induce cell death under certain conditions.In the tumor environment,they are often abnormally activated or out of balance,and participate in the occurrence and development of many cancers,including melanoma.This study investigated the roles of telomerase and autophagy in melanoma progression and evaluated the potential synergistic therapeutic effects of combined application of telomerase inhibitor BIBR1532 and autophagy inhibitor chloroquine(CQ)in melanoma treatment.Methods:Malignant melanoma cells A375 were treated with telomerase inhibitor BIBR1532.The cell viability was assessed using the cell counting kit-8(CCK-8)assay,and the cell apoptosis was detected using the Annexin Ⅴ/propidium iodide(PI)double staining method.Additionally,the expressions of autophagy-related proteins LC3-Ⅱand p62 were detected by Western blot,and the changes in autophagy flux were observed using dual-tagged adenovirus transfection technology.Based on these studies,BIBR1532 and the autophagy inhibitor CQ were further applied in combination to analyze cell proliferation,apoptotic rate,changes in mitochondrial membrane potential,and cell cycle distribution,and the cloning formation experiment was used to verify the cell's proliferative capacity,thereby comprehensively evaluating the efficacy of this combined treatment strategy.Results:Telomerase inhibitor BIBR1532 at a concentration of 50 μmol/L significantly inhibited the growth of malignant melanoma cells A375 and induced apoptosis.At the same concentration,BIBR1532 upregulated the expression of the autophagy-related protein LC3-Ⅱ in A375 cells,while downregulating the expression of p62 protein.By transducing A375 cells with a dual-tagged adenovirus,it was observed that autophagy flux was significantly enhanced after treatment with BIBR1532.Furthermore,the combined application of BIBR1532(50 μmol/L)and the autophagy inhibitor CQ(20 μmol/L)significantly promoted the death of A375 cells,induced apoptosis and destruction of mitochondrial membrane potential,caused cell cycle arrest at the G2/M phase,and significantly inhibited the cell's clonogenic ability.Conclusion:Telomerase inhibitor BIBR1532 not only inhibits the proliferation of malignant melanoma cells but also activates the autophagy process in these cells,and inhibition of the autophagy response by autophagy inhibitor CQ can enhance the sensitivity of malignant melanoma cells to telomerase inhibitor BIBR1532.

Background and purpose:Melanoma is a highly invasive malignant tumor originating from melanocytes,which poses a great threat to human life and health around the world,and its morbidity and mortality have been rising continuously in recent years.Telomerase and autophagy play crucial roles in cell proliferation,survival and stress response.Telomerase maintains the replication ability of cells by prolonging telomeres at the ends of chromosomes,and autophagy,as a self-degradation mechanism of cells,can not only help cells remove damaged components to promote survival,but also induce cell death under certain conditions.In the tumor environment,they are often abnormally activated or out of balance,and participate in the occurrence and development of many cancers,including melanoma.This study investigated the roles of telomerase and autophagy in melanoma progression and evaluated the potential synergistic therapeutic effects of combined application of telomerase inhibitor BIBR1532 and autophagy inhibitor chloroquine(CQ)in melanoma treatment.Methods:Malignant melanoma cells A375 were treated with telomerase inhibitor BIBR1532.The cell viability was assessed using the cell counting kit-8(CCK-8)assay,and the cell apoptosis was detected using the Annexin Ⅴ/propidium iodide(PI)double staining method.Additionally,the expressions of autophagy-related proteins LC3-Ⅱand p62 were detected by Western blot,and the changes in autophagy flux were observed using dual-tagged adenovirus transfection technology.Based on these studies,BIBR1532 and the autophagy inhibitor CQ were further applied in combination to analyze cell proliferation,apoptotic rate,changes in mitochondrial membrane potential,and cell cycle distribution,and the cloning formation experiment was used to verify the cell's proliferative capacity,thereby comprehensively evaluating the efficacy of this combined treatment strategy.Results:Telomerase inhibitor BIBR1532 at a concentration of 50 μmol/L significantly inhibited the growth of malignant melanoma cells A375 and induced apoptosis.At the same concentration,BIBR1532 upregulated the expression of the autophagy-related protein LC3-Ⅱ in A375 cells,while downregulating the expression of p62 protein.By transducing A375 cells with a dual-tagged adenovirus,it was observed that autophagy flux was significantly enhanced after treatment with BIBR1532.Furthermore,the combined application of BIBR1532(50 μmol/L)and the autophagy inhibitor CQ(20 μmol/L)significantly promoted the death of A375 cells,induced apoptosis and destruction of mitochondrial membrane potential,caused cell cycle arrest at the G2/M phase,and significantly inhibited the cell's clonogenic ability.Conclusion:Telomerase inhibitor BIBR1532 not only inhibits the proliferation of malignant melanoma cells but also activates the autophagy process in these cells,and inhibition of the autophagy response by autophagy inhibitor CQ can enhance the sensitivity of malignant melanoma cells to telomerase inhibitor BIBR1532.

Background and purpose:Lobaplatin,as a traditional chemotherapeutic drug,is widely used in the treatment of malignant tumor.In recent years,its application in the field of hyperthermic intraperitoneal chemotherapy(HIPEC)has garnered increasing attention.This study evaluated the efficacy and safety of lobaplatin-based HIPEC in advanced abdominal metastatic cancer.Methods:This study collected data of patients with advanced cancers and malignant ascites who treated in the Cancer Center of Shanghai Tenth People's Hospital,Tongji University School of Medicine,from January 2019 to January 2023.We excluded patients who did not meet the inclusion criteria.Short-term efficacy was assessed by changes in ascitic fluid volume,and long-term survival was analyzed using the Kaplan-Meier method.The correlation between CA12-5 levels before and after treatment was evaluated using Pearson correlation analysis.Baseline characteristics and treatment outcomes were described using descriptive statistics,and the changes in CA12-5 levels before and after treatment were compared using significance tests(P＜0.01).Data entry and statistical analyses were conducted using SPSS version 26.0,and survival curves and efficacy plots were generated with GraphPad Prism(10.4.0 version).The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital(Ethics approval number:SHSY-IEC-5.0/24K134/P01).This prospective single-arm study strictly adhered to the guideline of Consolidated Standards of Reporting Trials(CONSORT)checklist.Results:A total of 21 patients were enrolled in this study.The median age of the patients was 61 years(ranging from 31 to 71 years).Among the 21 patients,5(23.8%)achieved complete remission(CR),5(23.8%)achieved partial remission(PR),8(38.1%)had stable disease(SD),and 3(14.3%)experienced disease progression(PD).The overall response rate(ORR)was 47.6%,and the disease control rate(DCR)was 85.7%.Survival analysis revealed a median progression-free survival(PFS)of 12.33 months and a median overall survival(OS)of 16.37 months.Analysis of tumor markers showed a significant negative correlation between efficacy and CA12-5 levels(P＜0.01).Adverse reactions primarily included myelosuppression,hepatic and renal impairment,and nausea and vomiting,with most adverse events being mild to moderate.Conclusion:Lobaplatin-based HIPEC is effective in the treatment of advanced gastrointestinal malignancies with malignant ascites,providing survival benefits and demonstrating good safety.CA12-5 may serve as a valuable predictor of poor prognosis.

Background and purpose:Lobaplatin,as a traditional chemotherapeutic drug,is widely used in the treatment of malignant tumor.In recent years,its application in the field of hyperthermic intraperitoneal chemotherapy(HIPEC)has garnered increasing attention.This study evaluated the efficacy and safety of lobaplatin-based HIPEC in advanced abdominal metastatic cancer.Methods:This study collected data of patients with advanced cancers and malignant ascites who treated in the Cancer Center of Shanghai Tenth People's Hospital,Tongji University School of Medicine,from January 2019 to January 2023.We excluded patients who did not meet the inclusion criteria.Short-term efficacy was assessed by changes in ascitic fluid volume,and long-term survival was analyzed using the Kaplan-Meier method.The correlation between CA12-5 levels before and after treatment was evaluated using Pearson correlation analysis.Baseline characteristics and treatment outcomes were described using descriptive statistics,and the changes in CA12-5 levels before and after treatment were compared using significance tests(P＜0.01).Data entry and statistical analyses were conducted using SPSS version 26.0,and survival curves and efficacy plots were generated with GraphPad Prism(10.4.0 version).The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital(Ethics approval number:SHSY-IEC-5.0/24K134/P01).This prospective single-arm study strictly adhered to the guideline of Consolidated Standards of Reporting Trials(CONSORT)checklist.Results:A total of 21 patients were enrolled in this study.The median age of the patients was 61 years(ranging from 31 to 71 years).Among the 21 patients,5(23.8%)achieved complete remission(CR),5(23.8%)achieved partial remission(PR),8(38.1%)had stable disease(SD),and 3(14.3%)experienced disease progression(PD).The overall response rate(ORR)was 47.6%,and the disease control rate(DCR)was 85.7%.Survival analysis revealed a median progression-free survival(PFS)of 12.33 months and a median overall survival(OS)of 16.37 months.Analysis of tumor markers showed a significant negative correlation between efficacy and CA12-5 levels(P＜0.01).Adverse reactions primarily included myelosuppression,hepatic and renal impairment,and nausea and vomiting,with most adverse events being mild to moderate.Conclusion:Lobaplatin-based HIPEC is effective in the treatment of advanced gastrointestinal malignancies with malignant ascites,providing survival benefits and demonstrating good safety.CA12-5 may serve as a valuable predictor of poor prognosis.

OBJECTIVE: To evaluate the safety and efficacy of the seven-step two-lobe holmium laser enucleation of the prostate (HoLEP) technique with low power laser device, and to introduce the detailed operating procedures, key points, short-term outcomes of this modified HoLEP technique. METHODS: From March 2016 to November 2017, 90 patients underwent HoLEP in Peking University Third Hospital. The patients were divided into two groups: high-power group (32 patients) were performed with traditional Gilling's three-lobe enucleation using high power (90 W) laser; Low-power group (58 patients) were performed with seven-step two-lobe enucleation using low power (40 W) laser. The main steps of the low power seven-step two-lobe HoLEP phase included: (1) The identification of the correct plane between adenoma and capsule at 5 and 7 o'clock laterally to the veru montanum; (2) The connection of the bilateral plane by making a adenoma incision at the proximal point of veru montanum; (3) The extension of the dorsal plane under the whole three lobes between adenoma and capsule towards the bladder neck; (4) The separation of the middle lobe from two lateral lobes by making two retrograde incisions separately from apex 5 and 7 o'clock towards the bladder neck; (5) The enucleation of the middle lobe adenoma by extending the dorsal plane through into the bladder; (6) The prevention of the apex mucosa by making a circle incision at the apex of the prostate; (7) The en-bloc enucleation of the two lateral lobe adenomas by extending the lateral and ventral plane between adenoma and capsule from 5 and 7 o'clock to 12 o'clock conjunction and through into the bladder. RESULTS: The mean patient age was (66.25±5.37) years vs. (68.00±5.18) years; The mean body mass indexes were (24.13±4.06) kg/m² vs. (24.57±3.50) kg/m²; The mean prostate specific antigen values were (3.23±2.47) μg/L vs. (6.00±6.09) μg/L; The average prostatic volumes evaluated by ultrasound was (49.03±20.63) mL vs. (67.55±36.97) mL. There was no significant difference between the two groups. Furthermore, there were no significant differences in terms of perioperative and follow up data, including operative time; enucleation efficiencies; hemoglobin decrease; blood sodium and potassiumthe change postoperatively; catheterization duration and hospital stay; the international prostate symptom scores and quality of life scores pre- and post-operatively. There was 1 transurethral resection of the prostate (TURP) conversion in high-power group and 1 transfusion in low-power group during the operations. The follow-up one month after operation showed no severe stress incontinence in both the groups, whereas 3 cases ejaculatory dysfunctions in high-power group versus 1 case in low-power group were observed; Other surgeryrelated complications included: 2 cases postoperative hemorrhage (Clavien II and Clavien IIIb) in high-power group, 2 cases postoperative temperature more than 38 °C (Clavien I) and 1 case dysuria following catheter removal (Clavien I) in low-power group. CONCLUSION Low power laser device can be applied safe and effectively for HoLEP procedure using the seven-step two-lobe HoLEP technique. The outcomes comparable with high power laser HoLEP can be achieved.
Holmium ; Humans ; Laser Therapy ; Lasers, Solid-State ; Male ; Prostatic Hyperplasia/surgery* ; Quality of Life ; Transurethral Resection of Prostate ; Treatment Outcome