Cancer Research Center

Bladder cancer is one of the most common urological malignancies, with 5-year survival rates below 40% in advanced cases. Oncologic immunotherapy has become a popular approach to treating cancer and programmed death ligand 1 (PDL1), programmed death ligand 2 (PDL2), intercellular adhesion molecule 2 (ICAM2) and 4-1BB ligand (4-1BBL) are key costimulatory molecules in oncologic immunotherapy. Previous research has shown plant phytochemicals can act as immunomodulators by regulating costimulatory functions to increase T-cell activation and thus to inhibit malignant proliferation. However, the role of Aloe vera in the growth of bladder cancer and in the expression of these key costimulatory molecules has not been elucidated yet. This study is designed to investigate if Aloe vera could have a role in the growth of bladder cancer and if it has any effect on the expression of these key costimulatory molecules in bladder cancer. Clonogenic survival assay and immunohistochemistry (IHC) for PCNA staining were used to evaluate growth of a widely used bladder cancer cell line, T24, in the presence or absence of Aloe vera extract (AE). RT-PCR and IHC were performed to investigate the expression of important costimulatory molecules PDL1, PDL2, ICAM2, and 4-1BBL. Clonogenic survival assay showed a reduction in the percentage of bladder cancer cell colonies, and this result was supported by decreased PCNA staining intensity upon treatment with AE. RT-PCR revealed decreased expression levels of PDL1 and PDL2, which are pro-oncogenic costimulatory molecules and increased expression levels of ICAM2 and 4-1BBL, which are anti-oncogenic costimulatory molecules. Their expression levels were further supported by IHC staining. Aloe vera inhibits bladder cancer growth. Aloe vera upregulates the expression of ICAM2 and 4-1BBL and downregulates the expression of PDL1 and PDL2.

Resistance to systemic therapy is a major unmet challenge in pancreatic cancer. To identify potential mechanisms of resistance, we developed a novel 3D pipeline in clinical samples that uses deep learning to classify sensitive and persistent tumor cell populations based on morphological features, enabling subsequent molecular characterization of intratumoral heterogeneity. We applied this automated 3D pipeline to a cohort of human pancreatic cancer samples treated with neoadjuvant chemotherapy, identifying heterogeneity in response to therapy both between and within tumors. Application of spatial proteomics to these sensitive and persistent regions identified enhanced epithelial-to-mesenchymal transition and non-classical cell states in persistent cells, confirming our morphological classification. Integration of spatial transcriptomics in multiple pancreatic cancer cohorts associated fibroblast-cancer crosstalk via syndecans with resistance to cytotoxic therapy. Our validated 3D multi-omic pipeline is now poised for application to clinical trials, enabling discovery of resistance mechanisms and design of new therapeutic combinations to circumvent resistance.Statement of significanceWe developed a novel 3D multi-omic pipeline to identify mechanisms of resistance to chemotherapy in clinical samples. This approach associated fibroblast-cancer crosstalk via syndecans with resistance to cytotoxic therapy and is poised for broader application in neoadjuvant clinical trials.

The veracity of the findings in this article is in question due to apparent instances of western blot duplication and irregularities.Specifically, the first four panels of actin bands in Fig. 2A

BackgroundCirrhosis, particularly HBV-induced, poses a significant global health burden. This study compares immune cell landscapes in HBV and non-viral cirrhosis using single-cell RNA sequencing (scRNA-seq) to elucidate distinct immune mechanisms driving disease progression.MethodsLiver tissues from HBV cirrhosis patients and healthy controls were analyzed via scRNA-seq. Public single-cell and spatial transcriptomics data were integrated to map immune cell populations. Computational analyses included differential expression, pathway enrichment (KEGG/GO), and cell–cell communication (CellChat).ResultsHBV cirrhosis exhibited expanded Macrophage-PLCG2 (anti-inflammatory) and CD8 + T-FABP5 subsets, while Macrophage-CD5L, CD4 + T-ANXA1, CD4 + T-CCR6, and NK-FCER1G were reduced. Pathway analysis linked Macrophage-PLCG2 to Rap1 signaling, whereas Macrophage-CD5L associated with lysosomal pathways. Spatial analysis revealed myeloid-T cell colocalization in HBV cirrhosis. Enhanced HLA-E/KLRK1 signaling between myeloid and NK cells was identified in HBV cases (p < 0.05).ConclusionThis study delineates immune cell heterogeneity between HBV and non-viral cirrhosis, highlighting potential therapeutic targets like Macrophage-PLCG2 and CD8 + T-FABP5. Findings underscore the role of immune dysregulation in HBV cirrhosis progression.

With the increase of high-altitude sojourn population, more and more studies on hypoxia have been conducted, but the associated changes in gut bacteriome in different hypoxic environments need to be further investigated. Gut bacteriome plays an important role in host adaptation to high-altitude hypoxia, but the contribution of gut bacteriome in high-altitude hypoxia adaptation is still controversial and may be influenced by multiple factors. In this study, we reviewed the changes in diversity and composition of the gut bacteriome of different populations of animals in different highland hypoxic environments, clarified the dynamics of the gut bacteriome during exposure to high altitude, identified the core bacteriome that may contribute to host adaptation to hypoxic environments, and comprehensively considered the effects of multiple factors on the gut bacteriome.

Proteolysis-targeting chimeras (PROTACs) and degraders have been developed against the hRpn13 fragment hRpn13Pru that is present in various cancer types. Testing the performance of these hRpn13Pru-targeting compounds in pharmacokinetic and efficacy studies has been stymied, however, by their poor solubility. Here, we develop a rapid and cost-effective platform to Screen and Characterize small molecule Nanosuspensions (SCaN). We discovered that the hRpn13Pru degrader XL44 adopts a crystalline state, preventing its bioavailability. The first phase of SCaN screens vehicles to identify lead XL44 nanosuspension formulations based on particle size consistency, including in biorelevant media, while the second phase evaluates stability over time. The lead nanosuspensions are then advanced to the third phase of SCaN to assess their physical and colloidal stability. This pipeline allows the formulation of poorly soluble compounds for single-dose pharmacokinetic and pilot multidose tumor mouse studies. We additionally analyzed our XL44 formulation morphologically by atomic force microscopy to find that the XL44 nanoparticles are predominantly globular, with a small population of rod-like particles. Using the optimal nanosuspension determined by SCaN, XL44 slowed tumor growth in a myeloma xenograft model at 35% inhibition with a 48-72 mg/kg treatment regimen. This case study is the first in vivo demonstration that hRpn13Pru-targeting degraders can inhibit tumor growth, and the efficacy shown here motivates the development of more potent hRpn13Pru degraders. Broadly, our SCaN platform is designed for poorly soluble drug candidates to allow for pilot in vivo testing.

To examine the association between mild kidney disease and coronary plaque parameters using coronary computed tomography angiography in people living with HIV (PWH) compared with people without HIV in Uganda. Cross-sectional secondary analysis. We studied 165 participants aged >45 years with ≥1 cardiovascular risk factor (78 PWH on stable antiretroviral therapy, 87 HIV-negative). Kidney function was assessed using estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR). Coronary artery disease (CAD) was characterized by segment involvement score (SIS), segment stenosis score (SSS), and coronary artery calcium score. Multivariable Tobit regression assessed associations of kidney function measures with CAD parameters, testing for differences by HIV status. The median (interquartile range) age was 57.0 (53-62) years, 62.4% of subjects were female, and 87.3% had hypertension. Among PWH, mildly impaired eGFR (<90 mL/min/1.73 m2) was associated with higher SIS [β 3.31, 95% confidence interval (CI): 0.41 to 6.21, P = 0.03] and SSS (β 5.95, 95% CI: 0.54 to 11.36, P = 0.03). The association with SIS remained significant after adjusting for age, gender, and 10-year ASCVD score (β 2.58, 95% CI: 0.10 to 5.06, P = 0.04). Associations of ACR with coronary plaque were not statistically significant for participants with or without HIV (all P > 0.07). In PWH, mildly reduced eGFR was associated with greater coronary plaque burden (SIS, SSS) but not coronary artery calcium; ACR showed no associations with any CAD measures. Incorporating kidney function measures into cardiovascular risk assessment may be valuable in HIV care.