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Biomedical subjects

Francisco G Cigarroa

Publications and source records attributed to Francisco G Cigarroa.

5 recordsLinked to original sources
PubMed2026

p21-senescent cells drive pancreatic islet dysfunction through targetable paracrine signaling in type 2 diabetes.

Cellular senescence is an irreversible stress response, which leads to loss of cellular function and remodeling of the cellular secretory profile. In humans, pancreatic β cells undergo cellular senescence during the progression to type 2 diabetes (T2D). However, the mechanism linking β cell senescence to islet dysfunction remains unknown, and thus the therapeutic potential of targeting senescent cells in T2D is not established. Herein, we identified a subpopulation of senescent β cells expressing p21, which emerged early in the progression of T2D in humans and mice. Spatial transcriptomics and proteomics analyses confirmed senescence and loss of cellular identity in this subpopulation in humans. Functional analysis revealed lack of glucose responsiveness, high basal insulin secretion, and transcription of senescence-associated secretory phenotype (SASP) factors. SASP factors from p21+ β cells induced secondary senescence in neighboring cells, characterized by dysfunction and loss of identity. JAK inhibitors counteracted the induction of secondary senescence and restored β cell function in islets from humans with T2D and in mice fed a high-fat diet. These findings reveal the critical role of p21+ β cells in T2D pathogenesis and the therapeutic potential of targeting this pathophysiological process.

Animals↗
PubMed2003

Radiofrequency tissue ablation: effect of hepatic blood flow occlusion on thermal injuries produced in cirrhotic livers.

BACKGROUND: Radiofrequency thermal ablation has been used as a treatment for several types of hepatic malignancies. Many of these lesions exist in the presence of cirrhosis. Limitations exist to the size of the ablations and, subsequently, the efficacy of treatment. Hepatic vascular inflow occlusion has been advocated as an adjunctive measure to increase the efficacy of the ablation. We present a model in the human cirrhotic liver that demonstrates the advantage of blood flow occlusion during radiofrequency ablation. METHODS: Five patients with advanced endstage liver disease scheduled to have orthotopic liver transplantation were enrolled in this study. After laparotomy and before hepatectomy, radiofrequency ablation was performed without and with hepatic blood flow occlusion. After hepatectomy, the liver was sectioned, the area of ablation was measured in three dimensions, and the volume of ablation calculated. RESULTS: Three of the patients had had previously placed transjugular intrahepatic portosystemic shunt. The mean volume of the ablation without blood flow occlusion was 22.5 +/- 7.4 cm(3) and that with blood flow occlusion was 48.4 +/- 24.0 cm(3) (P =.05). CONCLUSIONS: Ablation area is increased significantly with hepatic blood flow occlusion in the human cirrhotic liver. This result may have application in the treatment of larger (>3 cm) hepatic malignancies.

Carcinoma, Hepatocellular↗
PubMed2002

Sonographically observed echogenic response during intraoperative radiofrequency ablation of cirrhotic livers: pathologic correlation.

OBJECTIVE: We performed a study to determine the correlation between the diameter of the echogenic response observed with intraoperative sonography during radiofrequency ablation of the cirrhotic liver and the mean diameter of tissue necrosis. SUBJECTS AND METHODS: A total of 22 intraoperative radiofrequency ablations were created in 11 cirrhotic livers. The largest diameter of the sonographically observed echogenic response surrounding and perpendicular to the radiofrequency probe was measured. The subsequent zone of necrosis observed at pathology in the hepatectomy specimens after liver transplantation was measured in three planes and compared with the measured diameter of the echogenic response. RESULTS: During all except three ablations, a hyperechoic region was visualized surrounding the radiofrequency probe. The diameter of the echogenic response correlated significantly with the mean diameter of necrosis (correlation coefficient, 0.84). However, the echogenic response overestimated the minimal diameter of necrosis (mean difference, 0.8 +/- 0.4 cm) in 18 of 22 ablations and underestimated the maximum diameter of necrosis (mean difference, 0.9 +/- 0.8 cm) in 16 of 22 ablations. CONCLUSION: The diameter of the echogenic response observed with intraoperative sonography during radiofrequency ablation of the cirrhotic liver correlates closely with the mean diameter of the subsequent area of tissue necrosis. However, the solitary diameter of the echogenic response as measured in our study was often greater than the smallest diameter and less than the largest diameter of the area of tissue necrosis. Therefore, the echogenic response associated with radiofrequency ablation of the cirrhotic liver should be viewed only as a rough approximation of the area of induced tissue necrosis; the final assessment of the adequacy of ablation should be deferred to an alternative imaging technique.

Adult↗