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Tumor tissue collections are used to uncover pathways associated with disease outcomes that can also serve as targets for cancer treatment, ideally by comparing the molecular properties of cancer tissues to matching normal tissues. The quality of such collections determines the value of the data and information generated from their analyses including expression and modifications of nucleic acids and proteins. These biomolecules are dysregulated upon ischemia and decompose once the living cells start to decay into inanimate matter. Therefore, ischemia time before final tissue preservation is the most important determinant of the quality of a tissue collection. Here we show the impact of ischemia time on tumor and matching adjacent normal tissue samples for mRNAs in 1664, proteins in 1818, and phosphosites in 1800 cases (tumor and matching normal samples) of four solid tumor types (CRC, HCC, LUAD, and LUSC NSCLC subtypes). In CRC, ischemia times exceeding 15 min impacted 12.5% (mRNA), 25% (protein), and 50% (phosphosites) of differentially expressed molecules in tumor versus normal tissues. This hypoxia- and decay-induced dysregulation increased with longer ischemia times and was observed across tumor types. Interestingly, the proteomics analysis revealed that specimen ischemia time above 15 min is mostly associated with a dysregulation of proteins in the immune-response pathway and less so with metabolic processes. We conclude that ischemia time is a crucial quality parameter for tissue collections used for target discovery and validation in cancer research., (© 2024. The Author(s).)

Purpose: Despite the wide adoption of tumor molecular profiling, there is a dearth of evidence linking molecular biomarkers for treatment selection to prediction of treatment outcomes in patients with metastatic pancreatic cancer. We initiated a pilot study to test the feasibility of designing a larger phase II trial of molecularly tailored treatment for metastatic pancreatic cancer. Methods: Our study aimed to assess the feasibility of following a treatment algorithm based on the expression of three published predictive markers of response to chemotherapy: ribonucleotide reductase catalytic subunit M1 (for gemcitabine); excision repair cross-complementation group 1 (for platinum agents); and thymidylate synthase (for 5-fluorouracil) in patients with untreated, metastatic pancreatic cancer. Results of the tumor biopsy analysis were used to assign patients to one of seven doublet regimens. Key secondary objectives included response rate (RR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Between December 2012 and March 2015, 30 patients were enrolled into the study. Ten patients failed screening primarily due to inadequate tumor tissue availability. Of the remaining 20 patients, 19 were assigned into 6 different chemotherapy doublets, and achieved an RR of 28%, with a DCR rate of 78%. The median PFS and OS were 5.78 and 8.21 months, respectively. Conclusions: The incorporation of biomarkers into a treatment algorithm is feasible and resulted in a PFS and OS similar to other doublet therapies for patients with metastatic pancreatic cancer. Based on the results from this pilot study, a larger phase II randomized trial of molecularly targeted therapy versus physicians' choice of standard of care has been initiated in the second-line setting (NCT02967770)., Competing Interests: No competing financial interests exist.

Injection drug users (IDU) are widely believed to have accelerated the looming HIV/AIDS epidemic now faced by the Russian Federation and countries of the former Soviet Union. However, IDUs may be heterogeneous with regard to risk behaviors, and a subpopulation may be responsible for the majority of blood-borne pathogen transmission. We studied 926 adult injection drug users (IDU) from the cities of Tbilisi, Batumi, and Poti in Georgia, a small country in the Caucuses region between the Black and Caspian Seas, between 1997 and 1998. Study participants were administered a confidential questionnaire and were tested for antibody to HIV, hepatitis C virus (HCV), hepatitis B virus surface antigen (HBsAg), and hepatitis B core antibody (anti-HBc). Five (0.5%) individuals were positive for HIV; 539 (58.2%), for HCV; 67 (7.2%), for HBsAg; and 475, for (51.3%) anti-HBc. Surveyed individuals, 88.7%, reported sharing needles with others, and needle sharing with more than 10 other individuals versus no sharing was a highly significant predictor (OR: 278.12, 95% CI: 77.57, 997.20) of HCV seropositivity. In adjusted analysis, individuals who usually injected stolen medical/synthetic drugs had significantly lower odds of HCV (OR: 0.38, 95% CI: 0.22, 0.68) and HBV (OR: 0.58, 95% CI: 0.37, 0.90) than individuals most commonly injecting opium. Despite some limitations, these results suggest the presence of substantial heterogeneity between different injection drug-using groups in Georgia. Identification of high-risk IDU subpopulations is vital to efficiently target risk reduction programs and to prevent confounding by risk status in large HIV/AIDS behavioral intervention and vaccine trials.