Pancreatic cancer remains one of the most lethal cancers, primarily due to its late diagnosis and limited treatment options. This review examines the challenges and potential of using immunotherapy to treat pancreatic cancer, highlighting the role of artificial intelligence (AI) as a promising tool to enhance early detection and monitor the effectiveness of these therapies. By synthesizing recent advancements and identifying gaps in the current research, this review aims to provide a comprehensive overview of how AI and immunotherapy can be integrated to develop more personalized and effective treatment strategies. The insights from this review may guide future research efforts and contribute to improving patient outcomes in pancreatic cancer management.

Autosomal dominant polycystic kidney disease (PKD) is a hereditary disorder affecting multiple organs, including the heart. PKD has been associated with many cardiac abnormalities including the arrhythmogenic remodeling in clinical evaluations. In our current study, we hypothesized that Pkd2 gene mutation results in structural and functional defects in the myocardium. The structural and functional changes of Pkd2 mutant hearts were analyzed in the myocardial-specific Pkd2 knockout (KO) mouse. We further assessed a potential role of TGF-b₁ signaling in the pathology of Pkd2-KO hearts. Hearts from age-matched 6-month-old MyH6•Pkd2^wt/wt (control or wild-type) and MyH6•Pkd2^flox/flox (mutant or Pkd2-KO) mice were used to study differential heart structure and function. Cardiac histology was used to study structure, and the “isolated working heart” system was adapted to mount and perfuse mouse heart to measure different cardiac parameters. We found that macrophage1 (M1) and macrophage 2 (M2) infiltration, transforming growth factor (TGF-b₁) and TGF-b₁ receptor expressions were significantly higher in Pkd2-KO, compared to wild-type hearts. The increase in the extracellular matrix in Pkd2-KO myocardium led to cardiac hypertrophy, interstitial and conduction system fibrosis, causing cardiac dysfunction with a predisposition to arrhythmia. Left ventricular (LV) expansion or compliance and LV filling were impaired in fibrotic Pkd2-KO hearts, resulted in diastolic dysfunction. LV systolic contractility and elastance decreased in fibrotic Pkd2-KO hearts, resulted in systolic dysfunction. Compared to wild-type hearts, Pkd2-KO hearts were less responsive to the pharmacological stress-test and changes in preload. In conclusion, Pkd2-KO mice had systolic and diastolic dysfunction with arrhythmogenic hearts.

Colorectal liver metastasis (CRLM) poses a significant challenge in oncology due to its high incidence and poor prognosis in unresectable cases. Current treatments, including surgical resection, systemic chemotherapy, and liver-directed therapies, often fail to effectively target hypoxic tumor regions, which are inherently more resistant to these interventions. This review examines the potential of a novel therapeutic strategy combining irreversible electroporation (IRE) ablation and Clostridium novyi-nontoxic (C. novyi-NT) bacterial therapy. IRE is a non-thermal tumor ablation technique that uses high-voltage electric pulses to create permanent nanopores in cell membranes, leading to cell death while preserving surrounding structures, and is often associated with temporary tumor hypoxia due to disrupted perfusion. C. novyi-NT is an attenuated, anaerobic bacterium engineered to selectively germinate and proliferate in hypoxic tumor regions, resulting in localized tumor cell lysis while sparing healthy, oxygenated tissue. The synergy between IRE-induced hypoxia and hypoxia-sensitive C. novyi-NT may enhance tumor destruction and stimulate systemic antitumor immunity. Furthermore, the integration of advanced imaging and artificial intelligence can support precise treatment planning and real-time monitoring. This integrated approach holds promise for improving outcomes in patients with CRLM, though further preclinical and clinical validation is needed.

Progesterone receptors are classified into nuclear and membrane-bound receptor families. Previous unbiased proteomic studies indicate a potential association between cardiac diseases and the progesterone receptor membrane-bound component-2 (PGRMC2); however, the role of PGRMC2 in the heart remains unknown. In this study, we use a heart-specific knockout (KO) mouse model (MyH6•Pgrmc2^flox/flox) in which the Pgrmc2 gene was selectively deleted in cardiomyocytes. Here we show that PGRMC2 serves as a mediator of steroid hormones for rapid calcium signaling in cardiomyocytes to maintain cardiac contraction, sufficient stroke volume, and adequate cardiac output by regulating the cardiac pressure-volume relationship. The KO hearts from male and female mice exhibit an impairment in pressure-volume relationship. Under hypoxic conditions, this pressure-volume dysregulation progresses to congestive left and right ventricular failure in the KO hearts. Overall, we propose that PGRMC2 is a cardiac pressure-volume regulator to maintain normal cardiac physiology, especially during hypoxic stress.

Background/Objectives: Hepatocellular carcinoma (HCC) remains a significant global health issue due to its high mortality rate and resistance to standard treatments. Sorafenib, the first-line systemic therapy for unresectable HCC, shows limited effectiveness due to resistance and severe side effects. Recent studies suggest that combining sorafenib with immunotherapy, particularly natural killer (NK) cells, may improve treatment outcomes. Methods: This study examined the effectiveness of sorafenib combined with NK cells pretreated with interleukin-12 (IL-12) and interleukin-18 (IL-18) in a rat HCC model. Tumor progression and treatment outcomes were assessed using MRI and histological analysis. Results: The results show that combination therapy significantly reduced tumor growth, increased tumor cell density, and inhibited angiogenesis and fibrosis in the tumor microenvironment. The sorafenib- and IL-12/IL-18-pretreated NK cell combination enhanced tumor inhibition by overcoming drug resistance and modulating the immune response. Conclusions: This study suggests that this combination therapy could be a promising strategy for treating HCC, offering both direct antitumor effects and modification of the tumor microenvironment for better clinical outcomes.