Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF- κ B and PI3K/AKT Signaling In Vitro and In Vivo / 中国结合医学杂志

OBJECTIVE@#To explore the influences of andrographolide (Andro) on bladder cancer cell lines and a tumor xenograft mouse model bearing 5637 cells.@*METHODS@#For in vitro experiments, T24 cells were stimulated with Andro (0-40 µmol/L) and 5637 cells were stimulated with Andro (0 to 80 µmol/L). Cell growth, migration, and infiltration were assessed using cell counting kit-8, colony formation, wound healing, and transwell assays. Apoptosis rate was examined using flow cytometry. In in vivo study, the antitumor effect of Andro (10 mg/kg) was evaluated by 5637 tumor-bearing mice, and levels of nuclear factor κ B (NF- κ B) and phosphoinositide 3-kinase/AKT related-proteins were determined by immunoblotting.@*RESULTS@#Andro suppressed growth, migration, and infiltraion of bladder cancer cells (P⩽0.05 or P⩽0.01). Additionally, Andro induced intrinsic mitochondria-dependent apoptosis in bladder cancer cell lines. Furthermore, Andro inhibited bladder cancer growth in mice (P⩽0.01). The expression of p65, p-AKT were suppressed by Andro treatment in vitro and in vivo (P⩽0.05 or P⩽0.01).@*CONCLUSIONS@#Andrographolide inhibits proliferation and promotes apoptosis in bladder cancer cells by interfering with NF- κ B and PI3K/AKT signaling in vitro and in vivo.

Treatment of actinic keratoses and cancerization field of the face and scalp with 0 015% ingenol mebutate gel in Brazilian individuals: safety, tolerability and patients' perspectives

Abstract: Background: Actinic keratosis (AK) represents a risk of progression to squamous cell carcinoma. Ingenol mebutate gel is a novel therapeutic option for field-directed treatment. Objectives: To evaluate the safety, tolerability and patients' perspectives, related to the therapeutic success of managing AKs on the face and scalp with ingenol mebutate gel in Brazilian individuals. Methods: This was an observational, retrospective and descriptive study of 68 areas of actinic keratosis on the face and scalp treated with Ingenol mebutate gel involving a total of 37 patients. The drug was applied for three consecutive days on an area of of 25 cm2 and documentation was performed on baseline and days 4, 8, 15, 60 and 180. On day 4, the composite local skin reaction score was calculated. At the end, a questionnaire was applied to evaluate patients' perspectives about the treatment. Results: Adherence was 100%, no serious adverse events were recorded and the mean composite local skin reaction score (standard deviation) was 8.61±4.22. The treatment was considered optimum by 75.68% of the patients. Study limitations: Calculation of composite local skin reaction score performed only on the fourth day. Conclusions: Treatment with ingenol mebutate gel was considered safe and tolerable in Brazilian subjects. Patients had a maximum adherence rate and a great improvement in self-esteem. The results of this research reproduce the findings of the literature.

Interstitial cystitis - intravesical treatment

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Ingenol mebutate in the treatment of actinic keratoses: clearance rate and adverse effects

Abstract: Background: Actinic keratoses are benign intraepithelial skin neoplasms that develop in photoexposed areas and can progress to invasive carcinoma. They are seen frequently in dermatological practice, occurring in 5.1% of consultations. Ingenol mebutate (IM) was recently approved in Brazil as a topical therapy for field cancerization in actinic keratosis. Objective: To evaluate the clearance rate and adverse events in the treatment of actinic keratoses with ingenol mebutate. Methods: A longitudinal, prospective, non-randomized, interventional, open, single-center study was conducted. Patients with actinic keratoses applied ingenol mebutate on a 25cm2 area of the face and/or scalp for three consecutive days (0.015%) or on the forearm for two days (0.05%). Results: 27 patients completed the protocol, of whom 13 on the face and/or scalp and 14 on the forearm. Complete clearance occurred in 53.8% in the first group and 42.8% in the second. Partial response was observed in 15.4% and 35.7%, respectively. The most common side effects were erythema, edema, desquamation, pruritus, and local erosion. Study limitations: The study had a small sample and was not randomized, double-blind, placebo-controlled, or vehicle-controlled. Conclusion: Ingenol mebutate is well-tolerated for the treatment of actinic keratosis, with good patient adherence thanks to the short treatment period.

Pseudolaric Acid B Inhibits Proliferation, Invasion and Epithelial-to-Mesenchymal Transition in Human Pancreatic Cancer Cell

PURPOSE: This study was aimed to investigate the effect of pseudolaric acid B (PAB) on proliferation, invasion and epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cells and to explore the possible mechanism. MATERIALS AND METHODS: The pancreatic cancer cell line SW1990 was cultured and treated with PAB dose- and time-dependent manners. Cell proliferation and invasion ability were measured by MTT assay and Matrigel/Transwell test, respectively. Semi-quantitative real-time polymerase chain reaction and Western blotting were conducted to detect the expression of EMT markers and the key molecules. Finally, nude mice subcutaneous transplantation tumor model was used to confirm the therapy efficacy of PAB. RESULTS: PAB could inhibit SW1990 cell proliferation and invasion in time- and dose-dependent manners. Vimentin, fibronectin, N-cadherin, Snail, Slug, YAP, TEAD1, and Survivin were down-regulated (p < 0.01), while E-cadherin, caspase-9, MST1, and pYAP were up-regulated (p < 0.05). Combined PAB and gemcitabine treatment markedly restricted the tumor growth compared with gencitabin or PAB alone groups. CONCLUSION: PAB could inhibit the proliferation and invasion ability of pancreatic cancer cells through activating Hippo-YAP pathway and inhibiting the process of EMT.

Resiniferatoxin for detrusor instability refractory to anticholinergics

PURPOSE: We have evaluated the clinical and urodynamic effects of intravesical instillation of resiniferatoxin in patients with idiopathic detrusor instability refractory to anticholinergics. MATERIALS AND METHODS: There were 30 women, median age 56 years old with detrusor instability for over 6 months and a history of anticholinergic use with no response or intolerable collateral effects. A 50 nM solution of resiniferatoxin was prepared for intravesical instillation. All patients were evaluated for urinary symptoms, as well as for urodynamic assessments before and 30 days after instillation. Tolerability was analyzed during the instillation. RESULTS: A clinical improvement was observed in 30 percent of the patients with urinary urgency and in 33 percent of the patients with urge-incontinence. The mean maximum cystometric capacity before application was 303.9 ± 78.9 and after application 341 ± 84.6. No significant difference was observed (p = 0.585). The mean maximum amplitude of the contractions diminished from 47.86 ± 29.64 to 38.72 ± 30.77 (p = 0.002). CONCLUSIONS: Resiniferatoxin, in this concentration, proved to be useful in a small percentage of patients regarding clinical detrusor instability. Maximum amplitude of the involuntary contractions was significantly reduced and in 33 percent patients the involuntary contractions disappeared. Further studies with different concentrations are recommended.