ABSTRACT
[This corrects the article DOI: 10.7759/cureus.39335.].
ABSTRACT
Backgorund: Fruits and seed extracts of Annona montana have significant cytotoxic potential in several cancer cells. This study evaluates the effect of A. montana leaves hexane extract on several signaling cascades and gene expression in metastatic breast cancer cells upon insulin-like growth factor-1 (IGF-1) stimulation. Methods: MTT assay was performed to determine the proliferation of cancer cells. Propidium iodide staining and flow cytometry analysis of Annexin V binding was utilized to measure the progression of the cell cycle and the induction of apoptosis. Protein expression and phosphorylation were determined by western blotting analysis to examine the underlying cellular mechanism triggered upon treatment with A. montana leaves hexane extract. Results: A. montana leaves hexane (sub-fraction V) blocked the constitutive stimulation of the PI3K/mTOR signaling pathways. This inhibitory effect was associated with apoptosis induction as evidenced by the positivity with Annexin V and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNNEL) staining, activation of caspase-3, and cleavage of PPAR. It also limited the expression of various downstream genes that regulate proliferation, survival, metastasis, and angiogenesis (i.e., cyclin D1, survivin, COX-2, and VEGF). It increased the expression of p53 and p21. Interestingly, we also observed that this extract blocked the activation of AKT and ERK without affecting the phosphorylation of the IGF-1 receptor and activation of Ras upon IGF-1 stimulation. Conclusion: Our study indicates that A. montana leaves (sub-fraction V) extract exhibits a selective anti-proliferative and proapoptotic effect on the metastatic MDA-MB-231 breast cancer cells through the involvement of PI3K/AKT/mTOR/S6K1 pathways.
ABSTRACT
INTRODUCTION AND OBJECTIVE: The United States (US) currently faces a medical malpractice crisis, and a survey done in 2006 informed that 63% of urologists faced an average of 2.1 medical malpractice lawsuits. Surgery for benign prostatic hyperplasia (BPH) is performed by 95% of US urologists. Hence, we postulated that these procedures might be responsible for a substantial number of medical malpractice lawsuits. We examined claims related to BPH surgery in various US courts. MATERIALS AND METHODS: Data were collected from Westlaw and LexisNexis databases using the keywords "benign prostatic hyperplasia," "enlarged prostate," "surgery," and "malpractice" to search for cases from the entire US from January 2000 to December 2021. We extracted details such as the type of procedure, the plaintiff and defendant, the nature of the allegation, the alleged complications, the verdict, and the compensation amount. RESULTS: We found 30 cases in which the most common procedure was transurethral resection of the prostate (37%), with inadequate postoperative care as the most frequent reason for claims (33%). Urologists were the most frequently processed professionals (57%). The postsurgical outcomes that resulted in lawsuits were urinary incontinence (23%), erectile dysfunction (13%), and urinary retention (13%). Interestingly, 43% of the patients were inmates. Plaintiffs won only two (7%) cases: colon perforation after interstitial laser coagulation with Indigo laser and recto-urethral fistula after transurethral microwave therapy. CONCLUSION: Most lawsuits were related to postoperative incontinence and erectile dysfunction, with the verdict favoring the defendant in most cases. Inmates were the plaintiffs in a relatively high percentage of cases. Only two cases resulted in a plaintiff victory, wherein both cases presented unexpected and serious postsurgical complications.