Louisiana Cancer Research Center

Palliative care improves quality of life for patients and families. More research is needed to understand how care delivery and patient and family experiences have changed in the 5 years since the COVID-19 pandemic onset. To systematically review the delivery of palliative care and patient and family experiences in palliative care since the COVID-19 pandemic onset. The search examined articles indexed in Medline, Science Direct, and Scopus, published between January 2020 and April 2025. Articles were included if they were peer-reviewed and included hospital and home-based palliative care for pediatric and adult patients and their families and examined changes in (a) patient experiences, (b) family experiences, or (c) aspects of service delivery regarding palliative care since the COVID-19 pandemic onset. Of 529 abstracts screened, 10 met the inclusion criteria for review. The most common patient and family experiences among the studies included caregiver social isolation (80%) and increased distress (70%). Among the studies, delivery changes included precautions on infection control (100%) and telehealth (90%). Most studies focused on adults (70.0%), typically cancer or COVID-19 populations (20% and 30%, respectively), and heterogeneous, seriously ill populations (50%). No study commented on the impact of COVID-19 using data collected after 2022, 10% were prospective, and 20% of studies reported on participants' race or ethnicity. This systematic review shows that since the COVID-19 pandemic onset, studies of palliative care programs have found that caregivers experience more distress and isolation, and programs have modified infection control precautions and increased the availability of telehealth. Implications for the future of family-centered palliative care are discussed.

More effective treatments for metastatic prostate cancer (mPC) are needed as disease progression remains universal. 177Lu-PSMA-617 radiopharmaceutical therapy (RPT)—Pluvicto (Novartis)—was first approved for the treatment of castration-resistant prostate cancer (PC) based on the landmark VISION

Kaposi sarcoma (KS) remains a global health concern. In sub-Saharan Africa, where there is a high burden of HIV-1 infection, there is also a high prevalence of infection by the etiologic agent of KS, the KS-associated herpesvirus (KSHV). Despite the successes of antiretroviral treatment (ART), the burden of KS and other KSHV-associated malignancies among people living with HIV under ART remained high, stressing the need for a greater understanding of the immune response against KSHV infection. Here, we review the current information on KSHV-specific humoral response in infected individuals in detail. We discuss the significance of anti-KSHV responses, mechanisms used by KSHV to subvert and modulate humoral immunity, and implications for pathogenesis and therapy. We highlight cutting-edge serological assays and bioinformatics tools that aid the development of effective vaccines against KSHV, underscoring the complexity of the humoral response and its critical role within the context of infection and vaccine design.

Despite extensive efforts to develop strategies to inhibit cancer metastasis-the leading cause of cancer-related deaths-progress has been limited in recent decades. Epithelial-to-mesenchymal transition (EMT) initiates metastasis by enhancing the migratory capacity and plasticity of cancer cells, enabling them to escape the primary tumor site. Identifying vulnerabilities unique to mesenchymal cancer cells is, therefore, critical for developing effective antimetastatic therapies. Our prior research has highlighted the crucial role of the Golgi apparatus in EMT-driven cancer cell motility and metastasis. In this study, we investigated the antimigratory effects of various Golgi-disrupting compounds and identified Monensin, a polyether ionophore antibiotic, as a potent migration suppressor in mesenchymal non-small cell lung cancer (NSCLC) cells. Monensin treatment increases the pH within the Golgi lumen, inducing rapid exocytosis of the promigratory Golgi scaffold protein Golgi Integral Membrane Protein 4 (GOLIM4). GOLIM4 plays a key role in regulating cell motility and adhesion by modulating the post-Golgi trafficking of Talin 1 (TLN1), an essential focal adhesion component. Furthermore, we found that both GOLIM4 and TLN1 are highly expressed in mesenchymal cancer cells and are direct targets of microRNA-200b, a microRNA that is suppressed during EMT. Treatment with Monensin or depletion of GOLIM4 or TLN1 significantly impaired the migratory activity of mesenchymal NSCLC cells. In summary, this study demonstrates that Monensin exhibits potential antimetastatic activity by disrupting the promigratory GOLIM4-TLN1 axis in mesenchymal NSCLC cells.

The full extent of interactions between human immunodeficiency virus (HIV) infection, injection drug use, and the human microbiome is unclear. In this study, we examined the microbiomes of HIV-positive and HIV-negative individuals, both drug-injecting and non-injecting, to identify bacterial community changes in response to HIV and drug use. We utilized a well-established cohort of people who inject drugs in Puerto Rico, a region with historically high levels of injection drug use and an HIV incidence rate disproportionately associated with drug use. Using amplicon-based 16S rDNA sequencing, we identified amplicon sequence variants (ASVs) that demonstrated significant variations in the composition of microbial communities based on HIV status and drug use. Our findings indicate that the HIV-positive group exhibited a higher abundance of ASVs belonging to the genera Prevotella, Alloprevotella, Sutterella, Megasphaera, Fusobacterium, and Mitsuokella. However, Bifidobacteria and Lactobacillus ASVs were more abundant in injectors than in non-injectors. We examined the effect of drug use on the gut microbiome in both HIV-infected and non-infected patients, and found that multiple drug use significantly affected the microbial community composition. Analysis of differential of bacterial taxa revealed an enrichment of Bifidobacterium spp., Faecalibacterium spp., and Lactobacillus spp. in the multiple drug-injecting group. However, in the non-injecting group, Parabacteroides spp., Prevotella spp., Paraprevotella spp., Sutterella spp., and Lachnoclostridium spp. The presence of multiple drug-injecting groups was observed to be more prevalent. Our findings provide detailed insight into ASV-level changes in the microbiome in response to HIV and drug use, suggesting that the effect of HIV status and drug injection may have different effects on microbiome composition and in modulating gut bacterial populations.

Abstract Background: Standard therapies provide marginal benefits in overall survival and leading immunologic agents have proven ineffective in the immunologically cold environment of pancreatic ductal adenocarcinoma (PDAC). Current standard of care chemotherapies experience demonstrable resistance in the clinical setting with primary and secondary resistance frequently leading to poor outcomes. Oncolytic virus (OV) therapies are emerging as an avenue of therapeutic potential with vesicular stomatitis virus (VSV) providing an onco- selective platform with potential for rapid replication and minimal outside virulence. The aim of this project is to determine if the addition of OV to the standard systemic treatments would result in a synergistic improvement of the therapeutic efficacy, and investigate the potential mechanisms involved. Methods: A VSV variant containing the Morreton G protein inserted into a wild-type VSV backbone (VMG)was propagated and purified for in vitro and in vivo studies. In vitro studies investigating oncolytic potential and viral kinetics of VSV in combination with FOLFIRINOX (FFX) and Gemcitabine Paclitaxel (GP) therapies were compared to monotherapy in multiple cell culture formats including 2D Monolayer, 3D Spheroid, and ongoing investigation into patient derived organoids. Proteomics analysis of monotherapies along with combination therapy was performed on in vitro cultures. Ongoing in vivo studies are investigating the therapeutic potential of concurrent treatments. Results: Cytotoxicity assay studies of equivalent multiplicities of infection (MOI) demonstrated increased cytotoxicity of combination therapy (Percent viable 10.2% ± 1.3%) compared to virus alone (30.7% ± 1.9%) or FFX alone (84.4% ± 6.6%) in Hs766T PDAC cell lineAsPC-1 cell line demonstrated similar effects with minimal cytotoxicity from FFX alone (100% ± 5%) with comparable resistance to virus alone (69.9% ± 1.8%) in comparison to combination therapy (40.3% ± 1.0%). Additional cell lines including Panc-01 and MiaPaCa2 provided similar results. Treatment of formed spheroids with combination therapy resulted in reduction in overall size of spheroid along with increased Viral GFP marker fluorescence, in combination group, compared to monotherapy with each treatment. Proteomic analysis investigating concomitant treatment with both standards of care produced unique expression profiles. Multiple pathways including cell cycle regulation, apoptosis, MAPK signaling, PI3K-Akt signaling, ErbB signaling showed significant regulatory changes in protein expression across all treatment groups. Conclusion: VSV oncolytic virus in conjunction with standard of care therapy demonstrates a potentially effective approach for synergistic enhancement of the therapeutic efficacy against PDAC. Ongoing research is investigating the immunomodulatory and metabolic effects of both monotherapies in conjunction with combination therapy to further determine the synergistic mechanisms involved and how they can be further utilized to overcome treatment resistance in PDAC. Citation Format: Conner Hartupee, Amirsalar Mansouri, Joycelynn Coleman-Barnett, Dana Adamcova, Dorota Wyczechowska, Bolni Marius Nagalo, Mulu Tesfay, Jovanny Zabaleta, Luis Del Valle, John West, Jiri Adamec, Omeed Moaven. Oncolytic virotherapy as an effective tool to synergistically enhance therapeutic efficacy of standard systemic treatments for pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B049.

Macrophages have important roles in mammary gland development and tissue homeostasis, but the specific mechanisms that regulate macrophage function need further elucidation. We have identified C/EBPβ as an important transcription factor expressed by multiple macrophage populations in the normal mammary gland. Mammary glands from mice with C/EBPβ-deficient macrophages (Cebpb ΔM) show a significant decrease in alveolar budding during the diestrus stage of the reproductive cycle, whereas branching morphogenesis remains unchanged. Defects in alveolar budding were found to be the result of both systemic hormones and local macrophage-directed signals. RNA sequencing shows significant changes in PR-responsive genes and alterations in the Wnt landscape of mammary epithelial cells of Cebpb ΔM mice, which regulate stem cell expansion during diestrus. Cebpb ΔM macrophages demonstrate a shift from a pro-inflammatory to a tissue-reparative phenotype, and exhibit increased phagocytic capacity as compared to WT. Finally, Cebpb ΔM macrophages down-regulate Notch2 and Notch3, which normally promote stem cell expansion during alveolar budding. These results suggest that C/EBPβ is an important macrophage factor that facilitates macrophage-epithelial crosstalk during a key stage of mammary gland tissue homeostasis.