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Current and novel approaches in the pharmacological treatment of hepatocellular carcinoma

World Journal of Gastroenterology 2023年第17期29卷 2571-2599页

作者： Fernanda Villarruel-Melquiades María Eugenia Mendoza-Garrido Claudia M García-Cuellar yesennia sánchez-pérez Julio Isael pérez-Carreón Javier Camacho Departamento de Farmacología Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional(CINVESTAV-IPN)Mexico City 07360Mexico Departamento de Fisiología Biofísica y NeurocienciasCentro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional(CINVESTAVIPN)Mexico City 07360Mexico subdirección de Investigación Básica Instituto Nacional de Cancerología(INCan)Mexico City 14080Mexico Instituto Nacional de Medicina Genómica Instituto Nacional de Medicina Genómica(INMEGEN)Mexico City 14610Mexico

Hepatocellular carcinoma(HCC)is one of the most lethal malignant tumours *** mortality-to-incidence ratio is up to 91.6%in many countries,representing the third leading cause of cancer-related *** drugs,including the multikinase inhibitors sorafenib and lenvatinib,are first-line drugs used in HCC ***,these therapies are ineffective in most cases due to late diagnosis and the development of tumour ***,novel pharmacological alternatives are urgently *** instance,immune checkpoint inhibitors have provided new approaches targeting cells of the immune ***,monoclonal antibodies against programmed cell death-1 have shown benefits in HCC *** addition,drug combinations,including first-line treatment and immunotherapy,as well as drug repurposing,are promising novel therapeutic ***,we review the current and novel pharmacological approaches to fight *** studies,as well as approved and ongoing clinical trials for liver cancer treatment,are *** pharmacological opportunities analysed here should lead to significant improvement in HCC therapy.

关键词： Liver cancer systemic therapy Immunotherapy Drug repurposing Drug combinations Hepatocellular carcinoma

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Mutational landscape of gastric adenocarcinoma in Latin America: A genetic approach for precision medicine

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Genes & Diseases 2022年第4期9卷 928-940页

作者： Dennis Cerrato-Izaguirre Yolanda I.Chirino Claudia M.García-Cuellar Miguel santibáñez-Andrade Diddier prada Angélica Hernández-Guerrero Octavio Alonso Larraga Javier Camacho yesennia sánchez-pérez subdirección de Investigación Básica Instituto Nacional de Cancerología(INCan)TlalpanCiudad de MéxicoCP 14080Mexico Departamento de Farmacología Centro de Investigación y de Estudios Avanzados del I.P.N.(CINVESTAV)Ciudad de MéxicoCP 07360Mexico Unidad de Biomedicina Facultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoLos Reyes IztacalaTlalnepantla de BazEstado de MéxicoCP 54090Mexico Departamento de Informática Biomédica Facultad de MedicinaUniversidad Nacional Autónoma de MéxicoCoyoacánCiudad de MéxicoCP 04510Mexico Department of Environmental Health science Mailman School of Public HealthColumbia UniversityNew YorkNY 10027USA servicio de Endoscopía Instituto Nacional de Cancerología(INCan)TlalpanCiudad de MéxicoCP 14080Mexico

Latin-America (LATAM) is the second region in gastric cancer incidence;gastric adenocarcinoma (GA) represents 95% of all cases. We provide a mutational landscape of GA highlighting a) germline pathogenic variants associated with hereditary GA, b) germline risk variants associated with sporadic GA, and c) somatic variants present in sporadic GA in LATAM, and analyze how this landscape can be applied for precision medicine. We found that Brazil, Chile, Colombia, Mexico, peru, and Venezuela are the countries with more published studies from LATAM explicitly related to GA. Our analysis displayed that different germline pathogenic variants for the CDH1 gene have been identified for hereditary GA in Brazilian, Chilean, Colombian, and Mexican populations. An increased risk of developing somatic GA is associated with the following germline risk variants: IL-4, IL-8, TNF-α, pTGs2, NFKB1, RAF1, KRAs and MApK1 in Brazilian;IL-10 in Chilean;IL-10 in Colombian;EGFR and ERRB2 in Mexican, TCF7L2 and Chr8q24 in Venezuelan population. The path from mutational landscape to precision medicine requires four development levels: 1) Data compilation, 2) Data analysis and integration, 3) Development and approval of clinical approaches, and 4) population benefits. Generating local genomic information is the initial padlock to overcome to generate and apply precision medicine.

关键词： Ethnicities Genome Latin America Mutati on precisi on medicine stomach neoplasms

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A single dose of caffeic acid phenethyl ester prevents initiation in a medium-term rat hepatocarcinogenesis model

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World Journal of Gastroenterology 2006年第42期12卷 6779-6785页

作者： Claudia Esther Carrasco-Legleu yesennia sánchez-pérez Lucrecia Márquez-Rosado samia Fattel-Fazenda Evelia Arce-popoca sergio Hernández-García saúl Villa-Trevio Departamento de Biología Celular Centro de Investigación y de Estudios Avanzados del IPN (Cinvestav). Ave. IPN #2508. Col. San Pedro Zacatenco C.P. 07360 México D.F. México Instituto Nacional de Cancerología San Fernando No. 22 C.P.14080 México D.F. México

AIM： To study of the effect of caffeic acid phenethyl ester （CApE） on the initiation period in a medium-term assay of hepatocarcinogenesis. METHODs： Male Wistar rats were subjected to a carcinogenic treatment （CT） and sacrificed at 25^th d; altered hepatic foci （AHF） were generated efficiently. To a second group of rats a single 20 mg/kg doses of CApE was given 12 h before initiation with CT and were sacrificed at 25^th d. We evaluated the expression of preneoplastic markers as Y-glutamyltranspeptidase （GGT） and glutathione s-transferase type pi protein （GsTp） by histochemistry, RT-pCR and Western blot analyses, respectively. We measured thiobarbituric acid reactive substances （TBARs） in homogenates of liver and used Unscheduled DNA synthesis （UDs） assay by incorporation of [^3H] thymidine （^3HdT） in primary hepatocyte cultures （pHC）. REsULTs： At 25^th d after CT CApE reduced the observed increase of GGT^＋AHF by 84% and liver expression ofggt mRNA by 100%. In case of the GsTp protein, the level was reduced by 90%. As indicative of oxidative stress generated by diethylnitrosamine （DEN） 12 h after its administration, we detected a 68% increase of TBARs. When CApE was administered before DEN, it completely protected from liver TBARs induction. To have an indication of the sole effect of CApE on initiation, two carcinogens were tested in a UDs assay in pHC, we used methyl-n-nitrosoguanidine as a direct carcinogen and DEN, as indirect carcinogen. In this assay, genotoxic damage caused by carcinogens was abolished at 5μM CApE concentration. CONCLUsION： Our results demonstrated that CApE possesses anti-genotoxic and antineoplastic capabilities, by an anti-oxidative and free-radical scavenging mechanism.

关键词： Caffeic acid phenethyl ester Antioxidant Hepatocarcinogenesis Initiation

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