Arkana Laboratories

Abstract Pancreatic ductal adenocarcinoma (PDAC) is higly resistant to apoptosis and immunotherapy. Immunogenic cell death (ICD), characterized by the release of damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), offers a promising strategy to overcome this resistance by promoting dendritic cell activation and anti-tumor immunity. We developed VMG-apo, a synthetic oncolytic vesiculovirus engineered to enhance caspase-3 activity and ICD in PDAC. Here, we evaluated the immunomodulatory and cytotoxic effects of VMG-apo in vitro and in vivo. Human PDAC cell lines (HS766T, HPAFII, Panc1) were infected with VMG-apo and co-cultured with peripheral blood mononuclear cells (PBMCs). Real-time impedance analysis revealed that VMG-apo sensitized PDAC cells to PBMC-mediated cytotoxicity, with significant reductions in cell viability across all lines. Flow cytometry confirmed increased apoptosis and necrosis, particularly in semi-resistant and sensitive models. VMG-apo treatment elevated caspase-3, cytochrome c, and TNF-α levels in co-culture supernatants, indicating activation of intrinsic apoptotic and inflammatory pathways. In contrast, patient-derived PBMCs exhibited blunted responses, suggesting immune exhaustion or suppression. In an orthotopic Panc1 xenograft model, intratumoral VMG-apo administration increased TUNEL-positive cells and disrupted tumor architecture, with enhanced viral distribution and extracellular matrix remodeling. Despite modest effects on tumor volume, VMG-apo induced robust histological and molecular signatures of ICD. These findings demonstrate that VMG-apo effectively induces ICD and enhances immune-mediated cytotoxicity in PDAC, supporting its potential as a novel immunotherapeutic strategy for this treatment-refractory cancer. Citation Format: Aleksandra Cios, Khandoker Usran. Ferdous, Mulu Z. Tesfay, Bahaa Mustafa, Martin J. Cannon, Alexei Basnakian, Omeed Moaven, Bolni Marius. Nagalo. Reprogramming Apoptotic Resistance in PDAC Through Synthetic Oncolytic Immunotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B022.

Persistent left superior vena cava is a rare congenital condition, that is, commonly found to be asymptomatic in affected patients. Such pathology can lead to dilatation of the coronary arteries, creating a favorable environment for bacterial growth. We present a case of Granulicatella adiacens bacteremia ultimately leading to renal failure in the setting of an IgA-dominant infection-associated glomerulonephritis. Our case highlights the importance of multimodal imaging for the diagnosis of this unusual vascular anomaly, as well as the management of this atypical etiology of high-grade bacteremia.

Abstract The G1 and G2 variants of the gene encoding Apolipoprotein L1 (APOL1) increase risk for kidney disease and cardiometabolic traits. While previous studies have elucidated key mechanisms by which G1 and G2 APOL1 cause cellular inflammation and cytotoxicity, it remains unclear whether these mechanisms drive inflammation in G1 and G2 macrophages. In this study, we used mouse bone-marrow-derived macrophages and human induced pluripotent stem cell-derived macrophages to identify altered immune signaling and inflammatory activation caused by G1 and G2 APOL1. We demonstrated that G1 and G2 APOL1 increased lipid accumulation, pro-inflammatory cytokine expression, and inflammasome signaling; this inflammatory response was sustained when treated with anti-inflammatory cytokines IL-4 and IL-10. Additionally, in G1 and G2 macrophages we observed increased mitochondrial size and elongation, oxidative phosphorylation, and glycolysis. Finally, we used unbiased metabolite analysis to identify an accumulation of polyamine spermidine and the enrichment of the spermidine synthesis pathway in G1 and G2 macrophages. When treated with polyamine inhibitor α-difluoromethylornithine (DFMO), lipid accumulation and inflammasome gene expression decreased in G1 and G2 macrophages. Together, these findings establish the pro-inflammatory effects of G1 and G2 APOL1 in macrophages and identify a novel pathway which ameliorates G1 and G2 effects on cellular inflammation.

Currently, there are number of initiatives underway across the world to remove barriers and increase education about living donation and living donor transplantation, including among professionals. Widespread use of the internet and social media (SoMe) started a new era of online information sharing. Extensive studies have highlighted the significant role of visual abstracts (VAs) and infographics in disseminating medical information including related to donation and transplantation. SoMe can foster networking and collaboration between transplant professionals across the globe. The American Society of Transplantation Living Donor Community of Practice (LDCOP) Multimedia Workgroup (MMWG) was established to support the LDCOP's professional education mission by providing audiovisual support for various initiatives using visual abstracts, infographics, and professional community engagement. The MMWG employs rigorous multi-layered vetting by professionals with academic expertise to ensure the reliability and accuracy of the content, pioneering a model for creating visual educational content, collaborative learning and skill-building across experience levels. In this perspective review, we summarize the history of a professional society multimedia work group and our experience building a multimedia approach to living donation education for transplant professionals.

Diabetic kidney disease (DKD) is a chronic kidney disease characterized by massive proteinuria and decreased glomerular filtration rate. The main pathological feature of DKD is renal microangiopathy, and ~40% of diabetic patients will develop DKD. The podocyte-associated proteins CD2AP and WT-1 play a crucial role in maintaining the normal function of podocytes and the integrity of the glomerular filtration barrier. When podocyte structure or function is disrupted-due to inflammation, oxidative stress, or other pathological insults-the slit diaphragm and actin cytoskeleton are damaged, leading to increased permeability of the glomerular filtration barrier and resulting in proteinuria. Yinhuo Tang (YHT) is a traditional Chinese medicine prescription that has the function of reducing proteinuria and delaying the deterioration of renal function; however, the mechanism of YHT in treating DKD is not clear. In this paper, based on network pharmacology and animal experiments, we examined the blood glucose, liver function, renal function, blood lipids, renal pathology, expression levels of podocyte marker proteins CD2AP and WT-1, as well as the PI3K/AKT/NF-κB signaling pathway in db/db mice after the administration of YHT for 8 weeks. Our results show that YHT reduces the expression levels of inflammatory factors by inhibiting the PI3K/AKT/NF-κB signaling pathway, thus reducing podocyte damage to play a role in delaying the progression of DKD.

Case seriesPatients: Male, 72-year-old • Male, 68-year-oldFinal Diagnosis: Crystalline neprhopathySymptoms: Impaired kidney transplant functionClinical Procedure: —Specialty: NephrologyObjective: Unusual clinical courseBackgroundThe renal condition known as 2,8-dihydroxyadeninuria is an autosomal recessive disorder caused by adenine phosphoribosyl transferase (APRT) deficiency, which most commonly manifests as nephrolithiasis. APRT deficiency has also led to the development of chronic kidney disease and end-stage kidney disease in the absence of nephrolithiasis and has also been shown to recur following kidney transplantation.Case ReportsThis report aims to highlight the diagnostic and therapeutic challenges associated with APRT deficiency by presenting 2 patients with end-stage kidney disease who developed 2,8-dihydroxyadenine (DHA) crystalline nephropathy early in their post-transplant course. Neither patient had been diagnosed with APRT deficiency prior to transplantation, and one lacked a history of nephrolithiasis. Allograft biopsies revealed DHA crystal deposition with acute tubular injury, and genetic analysis confirmed APRT deficiency. Management included xanthine oxidase inhibitors, a low-purine diet, and modification of the immunosuppressive regimen with belatacept to reduce long-term tubulointerstitial injury. Both patients achieved stable long-term allograft function at 2 years, with follow-up biopsies at 1 year, showing a significant decrease in crystal deposition.ConclusionsThis case report underscores the importance of early recognition of APRT deficiency through timely biopsy, crystal identification, and genetic testing to guide effective treatment and prevent irreversible damage. It highlights the need for heightened clinical suspicion and tailored post-transplant management strategies in patients with recurrent DHA nephropathy.