Heterocyclic organobismuth(III) compound induces nonapoptotic cell death via lipid peroxidation
Heterocyclic organobismuth compounds, such as N-tert-butyl-bi-chlorodibenzo[c,f][1,5]azabismocine (compound 1) and bi-chlorodibenzo[c,f ][1,5]thiabismocine (compound 3), exert potent antiproliferative activities in vitro in human cancer cell lines. We showed that compound 3 induced both apoptotic and nonapoptotic cell death via reactive oxygen species production and mitotic arrest in a dose-dependent manner. The mechanisms underlying the dose-dependent effect of these organobismuth compounds were not clear. In the present study, we examined the dose-dependent mechanism underlying cell death induced by compound 1 in a human pancreatic cancer cell line, SUIT-2, and a human colorectal cancer cell line, DLD-1. Compound 1 inhibited cell growth in a dose-dependent manner and induced cell death. Treatment with the pan-caspase inhibitor zVAD-fmk reduced cell death induced by compound 1, whereas the inhibitory effect of zVAD-fmk was limited. Moreover, compound 1 significantly induced lipid peroxidation with concomitant induction of caspase-independent cell death. Our results suggested that eight-membered ring organobismuth compounds induce nonapoptotic cell death via lipid peroxidation.
We present a case of LGI1 encephalitis only partially responsive to immunotherapy with eventual complete resolution after resection of a squamous cell lung carcinoma.
Authors: Ebelt ND, Zamloot V, Manuel ER Abstract Pancreatic cancer is considered one of the most lethal cancers in the US. It contributes to an estimated 47,000 deaths annually and is predicted to surpass prostate, breast and colorectal cancers as the leading cause of cancer-related death. Although major advancements in cancer treatment have improved outcomes for many cancer types, survival rate for pancreatic cancer has not improved in nearly four decades despite tremendous effort. One attribute of pancreatic cancer that is considered a major barrier to effective treatment is the formation of fibrotic tissue aroun...
In this SEER ‐Medicare study of GI cancers, the 21% of patients with a pre‐existing mental disorder had inferior overall survival outcomes (52 months vs 43 months,p
n Vered Padler-Karavani Glycosylation patterns commonly change in cancer, resulting in expression of tumor-associated carbohydrate antigens (TACA). While promising, currently available anti-glycan antibodies are not useful for clinical cancer therapy. Here, we show that potent anti-glycan antibodies can be engineered to acquire cancer therapeutic efficacy. We designed yeast surface display to generate and select for therapeutic antibodies against the TACA SLea (CA19−9) in colon and pancreatic cancers. Elite clones showed increased affinity, better specificity, improved binding of human pancreatic and colon ...
Conditions: Neoplasm, Colorectal; Neoplasm of Lung; Neoplasm, Bladder; Neoplasms Pancreatic; Biliary Tract Neoplasms; Gastro Intestinal Stromal Tumour Intervention: Other: ctDNA blood sampling Sponsor: Royal Marsden NHS Foundation Trust Recruiting
Conditions: Resectable Colorectal Carcinoma; Resectable Digestive System Carcinoma; Resectable Pancreatic Carcinoma Interventions: Procedure: Acupuncture Therapy; Other: Best Practice; Other: Questionnaire Administration Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI) Recruiting