bioRxiv Science⌕ Search

bioRxiv · 10.1101/2022.07.30.502136

Surgical techniques and tips for a reliable murine model of primary and metastatic pancreatic cancer

Abstract

For patients with pancreatic cancer, survival rates lag behind other common cancers. This is in part due to the relative resistance to conventional chemotherapeutics and novel immune- or targeted-therapies. Ongoing research efforts are needed to identify and validate effective therapies. It is the unfortunate reality that a significant proportion of pre-clinical success does not translate into improved patient outcomes, likely due to a multitude of factors. In the current research landscape, flank xenograft models are commonly utilized to study pancreatic cancer, as this technique is fast, fairly non-invasive, and reliable. However, this model is not anatomically or physiologically accurate, does not impact other intra-abdominal organs, and experiments are often ended based on tumor size rather than systemic illness. Orthotopic injections of cancer cells directly into the pancreas for study of localized disease or into the spleen for study of hepatic metastases can be performed via a quick, reliable, minimally invasive surgical procedure with minimal morbidity and mortality. Existing methodologic reports are often sparse. Thus, there are significant knowledge and technical gaps for researchers attempting these techniques for the first time. In the current report, details of orthotopic pancreatic injections and splenic injections for metastatic disease are provided. Details of commonly encountered operative issues and mistakes are presented with suggestions to improve performance are described. A summary of expected outcomes is also provided herein.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Hue, J. J., Zarei, M., Graor, H. J., Hajihassani, O., Katayama, E. S., Loftus, A. W., Vaziri-Gohar, A., Winter, J. M.. 2022-08-02. Surgical techniques and tips for a reliable murine model of primary and metastatic pancreatic cancer. https://doi.org/10.1101/2022.07.30.502136

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Glycolysis and interferon transcription in melanoma immunotherapy

Glycolysis and interferon signalling have both been associated with responses to PD-1 blockade, but their joint transcriptional relationship with treatment outcome remains uncertain. We examined whether a state with high glycolysis and low interferon- response was associated with reduced disease control in melanoma. Fixed Hallmark gene sets were scored by single-sample gene set enrichment analysis in GSE91061, GSE78220 and an additional Liu cohort. Disease control analyses included 47, 26 and 100 patients. Conditional odds ratios for the joint state were 6.06 (exact 95% confidence interval, 1.04 to 65.61), 0.35 (0.026 to 3.11) and 1.03 (0.39 to 2.73), respectively. Holm-adjusted P values for the two initial comparisons were 0.073 and 0.365. The additional exploratory P value was 1.000. Continuous models and analyses that omitted each patient in turn did not provide consistent evidence of an adverse association. IFN scores were negatively correlated with DNA-derived tumour purity in 102 patients (Spearman {rho} = -0.671). Among 40 patients with paired biopsies, disease control was associated with higher on-treatment IFN scores after baseline adjustment, although the paired subset had lower baseline glycolysis than patients without paired profiles. In patient-level single-cell analyses, the baseline CD8 T cell correlation weakened when an alternative rank score used a common gene background. The defined joint state was not consistently associated with poorer disease control across cohorts. Bulk IFN scores were related to tumour purity, and cellular correlations were sensitive to scoring choices. These transcriptomic results do not measure pyruvate concentration, glycolytic flux or STAT1 pyruvylation.

cancer biology↗

Psychoneuroimmunology of Viral Hepatitis and Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Hepatocellular carcinoma (HCC) and viral hepatitis (VH) are recognized primarily as hepatic diseases, yet they impose a substantial neuropsychiatric disorders (NPDs) encompassing depression, anxiety, cognitive impairment, and fatigue. Whether these manifestations reflect psychological reactions or biologically grounded psychoneuroimmune dysfunction remains poorly understood. Here, we present a pre-registered systematic review and meta-analysis (PROSPERO 2026 CRD420251081757) synthesizing evidence from 24 studies combining psychosocial outcomes with immune dysregulation markers across HCC and VH populations. Bibliometric and network analyses identified a growing psychoneuroimmunology research hub linking cytokine signaling, microglial activation, blood-brain barrier (BBB) disruption, and gut-liver-brain axis dysregulation to the neuropsychiatric phenotype of these diseases. Meta-analysis revealed a pooled hazard ratio (HR) of 1.92 (95% CI: 1.09-3.39) for adverse outcomes in HCC and a pooled HR of 2.28 (95% CI: 1.48-3.52) for depression associated to genetic variants in VH. TNF-a, but not IL-6, showed a tendency toward lower levels in VH patients with versus without NPDs, suggesting differential inflammatory roles. The literature, however, remains fragmented by heterogeneous designs and a paucity of longitudinal data. A psychoneuroimmunological approach, integrating immune, endocrine, neural, and psychosocial dimensions, is essential for capturing the full systemic impact of HCC and VH and should inform future mechanistic research and multidisciplinary clinical strategies.

cancer biology↗

Nutrient Availability as a Driver of Transcriptome Reprogramming in Osteosarcoma

Background: Gene expression in mammalian cells is intricately regulated by environmental and metabolic cues. Among these, nutrient availability represents a key feature of the tumor microenvironment and has recently emerged as a potent modulator of oncogenic signaling networks. In this study, we employed a cell-line model of osteosarcoma, a rare but highly aggressive bone malignancy affecting both humans and dogs. We demonstrate that altering the concentration of a single nutrient can profoundly reprogram gene expression in osteosarcoma cells, revealing a previously underexplored phenomenon: nutrient-dependent gene regulation. This finding highlights potential opportunities for therapeutic intervention and underscores the broader implications of metabolic regulation for personalized medicine and nutrition. Methods/Results: We performed bulk RNA sequencing of an established osteosarcoma cell line cultured under varying concentrations of two key nutrients, glucose and glutamine. Differential gene expression analysis revealed a pronounced nutrient-dependent transcriptional response. The identified genes were functionally associated with pathways involved in cancer, development, nervous system regulation, metabolism, cellular signaling, and immune responses. We identified seven distinct expression patterns, one of which exhibited a striking correlation with cell growth rate and resembled a FOS-like transcriptional signature. Notably, the proto-oncogene FOS was among the identified genes and displayed a strong growth-rate-dependent expression pattern. Conclusion/Impact: Our findings demonstrate that modulation of nutrient availability profoundly reshapes the gene expression landscape of osteosarcoma cells, revealing nutrient-responsive targets with potential therapeutic relevance. This work expands our understanding of metabolic regulation in cancer and suggests that nutrient-based interventions may provide a controllable means of influencing tumor progression. Beyond oncology, such approaches may also have broader implications for developmental biology, autoimmune disorders, and nervous system function. More broadly, this study highlights the potential of metabolic interventions as a strategy for targeted modulation of gene expression programs.

cancer biology↗