Selective cytotoxicity of epidithiodiketopiperazine DC1149B, produced by marine-derived Trichoderma lixii on the cancer cells adapted to glucose starvation

AbstractThe core of solid tumors is characterized by hypoxia and a nutrient-starved microenvironment and has gained much attention as targets of anti-cancer drugs. In the course of search for selective growth inhibitors against the cancer cells adapted to nutrient starvation, epidithiodiketopiperazine DC1149B (1) together with structurally related compounds, trichodermamide A (2) and aspergillazine A (3), were isolated from culture extract of marine-derivedTrichoderma lixii. Compounds1 exhibited potent selective cytotoxic activity against human pancreatic carcinoma PANC-1 cells cultured under glucose-starved conditions with IC50 values of 0.02  µM. The selective index of the compound1 was found to be 35,500-fold higher for cells cultured under glucose-starved conditions than those under the general culture conditions. The mechanistic analysis indicated that compound1 inhibited the response of the ER stress signaling. In addition, these effects of compound1 could be mediated by inhibiting complex II in the mitochondrial electron transport chain.
Source: Journal of Natural Medicines - Category: Drugs & Pharmacology Source Type: research

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Publication date: Available online 13 October 2019Source: Seminars in Cancer BiologyAuthor(s): Vikram Shaw, Suyash Srivastava, Sanjay K. SrivastavaAbstractThe recent development of high throughput compound screening has allowed drug repurposing to emerge as an effective avenue for discovering novel treatments for cancer. FDA-approved antipsychotic drugs fluspirilene, penfluridol, and pimozide are clinically used for the treatment of psychotic disorders, primarily schizophrenia. These compounds, belong to diphenylbutylpiperidine class of antipsychotic drugs, are the potent inhibitors of dopamine D2 receptor and calcium chan...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 11 October 2019Source: The American Journal of SurgeryAuthor(s): Dhruv J. Patel, Waseem Lutfi, Patrick Sweigert, Emanuel Eguia, Gerard Abood, Lawrence Knab, Paul C. Kuo, Marshall S. BakerAbstractBackgroundPrior studies of adjuvant systemic therapy in pancreatic acinar cell carcinoma have been underpowered.MethodsWe queried the National Cancer Data Base to identify patients presenting with resectable (clinical stage I and II) acinar cell carcinoma between 2004 and 2015. Multivariable Cox Regression was used to evaluate the association between overall survival and systemic therapy.Results29...
Source: The American Journal of Surgery - Category: Surgery Source Type: research
Conclusion: The EUS and FNA are good tools to confirm malignancy and rule out benign treatable conditions like TB for any patient with a pancreatic mass suspicious for carcinoma. PMID: 31588486 [PubMed - in process]
Source: Saudi Medical Journal - Category: Middle East Health Tags: Saudi Med J Source Type: research
Source: Cancer Management and Research - Category: Cancer & Oncology Tags: Cancer Management and Research Source Type: research
This report describes a patient whose presenting complaints were “Physical examination showed that the pancreas was occupied for one month.” He initially was diagnosed with stage IV PC based on conventional imaging and pathologic assessment. He had a known germline BRCA 2 mutation, which exhibited a good response to PARP inhibitor therapy. Diagnosis: Through the biopsy histopathological examination, imaging examination, and genetic testing, the patient was diagnosed as metastatic PC with BRCA2 mutation. Interventions: He received gemcitabine and albumin-bound paclitaxel chemotherapy from March 15, 2017 to...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
This study investigated the prevalence and the distribution of FGFR aberrations in Chinese cancer patients.MethodsWe screened genomic profiling results of plasma or tissue samples from 10,582 patients spanning 16 cancer types: lung, breast, gastric, hepatobiliary, pancreatic, soft tissue sarcoma, esophageal, ovarian, colorectal, head and neck, renal, endometrial, osteogenic sarcoma, cervical, melanoma and lymphoma.ResultsOf the 10,582 patients screened, we observed 745 patients with FGFR aberrations, revealing an overall prevalence of 7.03%. Approximately, 3.78% harbored FGFR amplification, 2.73% had other mutations and 0....
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsThe combination of LUR and IRI is well tolerated, with no unexpected toxicities. Myelosuppression was dose-limiting, but predictable and manageable. The RD is LUR 2.0  mg/m2 on D1 + IRI 75  mg/m2 on D1 and D8 q3w with GCSF. Notable antitumor activity was observed, especially in SCLC, EC, GB and STS. Expansion in these indications is warranted.Clinical trial identificationNCT02611024.Legal entity responsible for the studyPharmaMar SA.FundingPharmaMar.DisclosureS. Ponce Aix: Advisory / Consultancy: Roche; Speaker Bureau / Expert testimony: Roche, BMS, MSD. G. Cot é: Advisory / Consultancy: Agi...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsAnalysis of cfDNA identified a unique subset of pts with germline BRCA1/2 mutations in advanced GI cancers. Given the association of these findings with efficacy of PARP inhibitor and immune-based therapies, these findings suggest that the identification of BRCA1/2 mutations and their germline-somatic origin may have future implications for therapy selection.Clinical trial identificationUMIN000029315.Legal entity responsible for the studySCRUM-Japan GI-SCREEN.FundingGuardant Health, Ono Pharmaceutical.DisclosureY. Kawamoto: Honoraria (self): Taiho Pharmaceutical Co., Ltd.; Honoraria (self): Daiichi Sankyo Co., L...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
AbstractBackgroundKRAS GA are common oncogenic drivers. Effective systemic treatment of KRAS altered cancers has been largely elusive; however covalent inhibitors of G12C (AMG510, MRTX849) and SHP2 inhibitors (TNO155, RMC-4630) have recently entered the clinic in multiple tumor types.MethodsHybrid capture-based comprehensive genomic profiling (CGP) was performed on tumor samples from 213,312 unique patients with solid or hematological malignancies. Tumor mutational burden (TMB) was determined on 0.8-1.1 Mbp of sequenced DNA. PD-L1 expression was determined by IHC (22C3 or SP142 antibodies) for 17% of cases.ResultsKRAS GA w...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
AbstractBackgroundTumor Treating Fields (TTFields) are a non-invasive, antimitotic therapy delivered to the tumor via transducer arrays applied to the skin at tumor site. The only TTFields-related adverse event (AE) reported in clinical trials was localized dermatitis beneath the arrays. The safety of TTFields has also been investigated in glioblastoma, non-small-cell lung cancer (NSCLC), mesothelioma, pancreatic and ovarian cancer. This meta-analysis reported AEs in clinical studies with TTFields torso delivery.Methods192 patients from 4 pilot studies were included in the analysis: EF-15 (n  = 41, advanced N...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
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