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Shadi Chamseddine,1,* Michael LaPelusa,2,* Lianchun Xiao,3 Yehia I Mohamed,1 Sunyoung S Lee,1 Zishuo Ian Hu,1 Rikita I Hatia,4 Manal Hassan,4 James C Yao,1 Dan G Duda,5 Saumil Datar,6 Hesham M Amin,7,8 Ahmed O Kaseb1 1Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 4Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 5Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; 6Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA; 7Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 8MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA*These authors contributed equally to this workCorrespondence: Hesham M Amin, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Houston, TX, 77030, USA, Tel +1 713 794-1769, Fax +1 713 792-7273, Email hamin@mdanderson.org Ahmed O Kaseb, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA, Tel +1-713-792-2828, Fax +1 713-745-1163, Email akaseb@mdanderson.orgIntroduction: In this study, we explored the potential of plasma growth hormone (GH) as a prognostic biomarker in patients with advanced HCC treated with durvalumab plus tremelimumab (D+T).Methods: In this study, we included 16 patients with advanced HCC who received D+T at MD Anderson Cancer Center between 2022 and 2023 and had plasma GH measurements recorded before treatment. Plasma GH levels were measured from prospectively collected blood samples and were correlated with progression-free survival (PFS) and overall survival (OS). The cutoff for normal GH levels in women and men was defined as ≤ 3.7 μg/L and ≤ 0.9 μg/L, respectively. The Kaplan–Meier method was employed to compute the median OS and PFS, while the Log rank test was applied to compare the survival outcomes between the GH-high and GH-low groups.Results: Sixteen patients were included in this analysis, two female and fourteen male, with a median age of 65.5 years. At the time of the analysis, the 6-month OS rate was 100% among GH-low patients (6 patients) and 30% among GH-high patients (10 patients). OS was significantly longer in GH-low patients (not evaluable) compared to GH-high patients (3.94 months) (p = 0.030). PFS was also significantly longer in GH-low patients (not evaluable) compared to the GH-high patients (1.87 months) (p = 0.036).Conclusion: Plasma GH is a prognostic biomarker in patients with advanced HCC treated with D+T. Given the relatively small patient cohort size, this finding should be further validated in larger randomized clinical trials in advanced HCC patients.Keywords: hepatocellular carcinoma, growth hormone, durvalumab, tremelimumab, overall survival, progression-free survival

Background: Pulmonary interstitial glycogenosis (PIG) arises from a developmental disorder of the pulmonary mesenchyme and presents clinically with reversible neonatal respiratory distress and/or persistent pulmonary hypertension of the newborn (PPHN). Obj

Pulmonary arteriovenous malformations (PAVMs) are a common source of morbidity after bidirectional superior cavopulmonary anastomosis (Glenn). The diversion of hepatic venous effluent away from the pulmonary circulation after Glenn appears to play a signif

Overexpression of the Drosophila homologue of cyclin D (in combination with its catalytic partner CDK4) in the developing wing and eye leads to an increase in cell growth which can coordinate with increases in cell division. In mouse and human cells, cyclin D/CDK4 is well established for its ability to phosphorylate the tumor suppressor retinoblastoma (Rb). This modification of Rb results in the release of the transcription factor, E2F, which promotes progression into S-phase by transactivating a number of genes required for DNA replication. In Drosophila, overexpression of E2F stimulates cell division without promoting cell growth. Similarly, loss of RbF (a Drosophila Rb homologue) does not stimulate cell growth. These results suggest that cyclin D/CDK4 has effectors in addition to Rb through which it modulates cell growth. To further examine the role of cyclin D, the gene search (GS) P-element is being used to screen for modifiers of an overgrowth phenotype resulting from cyclin D/CDK4 overexpression in the eye. To date, 60 lines that alter the cyclin D/CDK4-directed phenotype have been established and the affected genes are now being identified. This approach is likely to detect downstream effectors of cyclin D function which are limiting as well as negative regulators of cyclin D/CDK4 activity. This genetic screen will allow us to investigate the role of cyclin D and its effectors in growth control and may help establish whether cyclin D may mediate growth in response to developmental cues.

The therapeutic potential of stem cells has led to renewed interest in regenerative biology. Pancreatic stellate cells have been reported in the mammalian pancreas; however, there are very few reports on stellate cells in the chicken pancreas. The intercalated duct epithelial cells observed in the A and B islets of the chicken pancreas have been claimed to be stellate cells from their morphological appearance. While isolating islets and acinar cells from the chick pancreas, we have found a population of stellate-like cells, which has been successfully propagated in a defined nutrient medium. These cells were immunopositive for vimentin, desmin, and fibronectin and also expressed alkaline phosphatase, indicating their undifferentiated state. On exposure to serum-free medium containing specific nutrients and differentiating agents, these stellate-like-cells gave rise to islet-like cell clusters. Islet-like clusters stained positive for the islet specific stain diphenyl thiocarbazone and were immunopositive for C-peptide indicating de novo insulin synthesis. These clusters secreted insulin in response to glucose challenge, thus suggesting their similarity to islets. Thus stellate cells found in chick pancreatic islets exhibit potential to differentiate into islet-like clusters. Taken together, our study documents for the first time the presence of a stellate-like cell population in chick pancreatic islets providing a source for islet neogenesis. [ABSTRACT FROM AUTHOR]

Previously, we reported a simple technique to isolate functional B islets from chick pancreata with retention of their insulin secretory ability in response to glucose challenge. To test the hypothesis that chick B islets are equally good candidates as mammalian islets for screening hypoglycemics and insulin secretagogues, we compared the structural and functional status of chick B islets with those of normal and diabetic mouse islets. Pancreata from chick, normal (nondiabetic) mice, and diabetic mice were collected, fixed, and processed for histological analysis using Gomori stain to distinguish A and B cells from islets. Similarly isolated islets from these animals were treated with different concentrations of tolbutamide, a known insulin secretagogue, and glucose to study insulin release. Histological analysis of pancreata from chicks and normal mice revealed intact B cells, whereas those from diabetic mice were destroyed. The insulin secretory response of chick B islets against the tolbutamide and glucose challenge was comparable to that of normal mouse islets. However, diabetic mouse islets did not respond to glucose challenge, indicating impaired functionality. We have identified a critical window that lies within 5 to 6 d posthatching for isolating chick B islets showing maximum glucose responsiveness and insulin secretion. The previous reports on chicken pancreatic islets involve the use of 4- to 6-wk-old chicks in which islets were found to be nonresponsive to glucose and, hence, could not be used for testing insulin secretory activity. However, our data on B islets from 5- to 6-d-old chick pancreata is highly promising, as islets are responsive to insulin secretagogues. The present data thus indicates that chick B islets can be used as an alternative in vitro model for screening insulin secretagogue and hypoglycemics. [ABSTRACT FROM AUTHOR]