Lessons Learned This study showed that carefully selected patients with locally advanced and metastatic forms of malignant melanoma and renal cell carcinoma could potentially have long‐term disease control with a tag‐7 gene‐modified tumor cells‐based vaccine. Randomized clinical trials in patients whose tumors produce low amounts of immunosuppressive factors are needed to confirm this hypothesis in both the adjuvant and metastatic settings. Background Immunotherapy may produce long‐lasting effects on survival and toxicity. The magnitude of efficacy may be dependent on immune factors. We analyzed the results of a phase I/II study of a tag‐7 gene‐modified tumor cells‐based vaccine (GMV) in patients with malignant melanoma (MM) or renal cell carcinoma (RCC) with biomarker analysis of immunosuppressive factors (ISFs) production by their tumor cells. Methods From 2001 to 2014, 80 patients received GMV: 68 with MM and 12 with RCC. Treatment in the metastatic setting included 61 patients (MM, 51; RCC, 10), and treatment in the adjuvant setting (after complete cytoreduction) included 19 patients (MM, 17; RCC, 2). Twenty‐six patients were stage III (33%), and 54 (67%) were stage IV. The patients’ tumor samples were transferred to culture, transfected with tag‐7 gene, and inactivated by radiation. The produced product was injected subcutaneously every 3 weeks until progression or 2 years of therapy. ISFs were measured in the supernatants of the tumor cell cultures and used as predictive factors. Results No major safety issues or grade 5 adverse events (AEs) were seen. One grade 4 and two grade 3 AEs were registered. No AEs were registered in 89.4% of treatment cycles. No delayed AE was found. The 5‐year overall survival (OS) in the intention‐to‐treat population was 25.1%. There were no differences between MM OS and RCC OS (log rank, p = .44). Median OS in the metastatic setting was 0.7 years and in the adjuvant setting was 3.1 years. Classification trees were built on the basis of ISF production (Fig. 1). The median OS was 6.6 years in the favorable prognosis (FP) group (major histocompatibility complex class I polypeptide‐related sequence A [MICA] level ≤582 pg/mL, n = 15) and 4.6 months in the unfavorable (UF) group (MICA level >582 pg/mL, n = 12; p < .0001). No significant differences were found between classification trees based on ISFs (transforming growth factor β1 [TGF‐β1], interleukin‐10 [IL‐10], and vascular endothelial growth factor [VEGF]). In patients with stage III–IV MM with FP, median OS was 2.3 years, with 31% patients alive at 10 years (Fig. 2) in the UF group (0.4 years; log rank, p = 1.94E−5). No FP patients received modern immunotherapy. Conclusion GMV showed high results in carefully selected patients with low ISF (TGF‐β1, IL‐10, and VEGF) production. The method should be further investigated in patients with FP.
Background. Various tumor control genes and microRNAs (miRNa) play an important role in the development and progression of colorectal cancer (CRC). the expression of these genes can differ significantly in tumor and adjacent healthy tissues. there is no exact data at what distance from the tumor the adjacent healthy tissue is located in terms of gene expression.The aim of the investigation was to study the tumor control genes (E2F3, TGFB, NFKB, KLF-12, EGFR and MMP9), as well as the microRNA genes (microRNA-15, -16, -21 and -210) expression profiles in tumor and adjacent healthy tissues.Material and methods. the study included 19 patients diagnosed with colorectal cancer. the tumor control genes (E2F3, TGFB, NFKB, KLF-12, EGFR and MMP9), as well as the miRNA genes (miRNA-15, -16, -21 and -210) expression levels were investigated in tumor and adjacent normal tissue samples taken during colonoscopy.Results. a decrease in the level of expression of E2F3 (median 3,73, Q1-Q3 2,64 Reu vs. median 6.5, Q1-Q3 6,39 REU, p=0,01) and miRNA-16 (median 2,83, Q1-Q3 4,74 REU vs. median 4,29, Q1-Q3 3,73 REU, p=0,027) and an increase in the expression level of miRNA-21 (median 2,64, Q1-Q3 1,38 REU vs. median 1,41, Q1-Q3 1,21 REU, p<0,001) were found in tumor tissue compared to normal tissue of patients with CRC.Conclusion. significant differences in the E2F3, miRNA-16 and miRNA-21 gene expressions were revealed. an increased level of E2F3 and miRNA-16 expressions at a distance of 1–2 cm from the tumor may be a predictor of tumor recurrence and progression, and an increased miRNA-21 expression in tumor tissue as compared to adjacent tissue may be a negative prognostic factor. this information can be used in further clinical research.
The review presents the data on the specifics of mechanism of action, classification, and clinical manifestations of neurotoxicity effect. The most significant features of specific side effects when using taxanes in different treatment regimens, including cumulative doses, are considered. The proven methods of treatment and prevention of neuropathy caused by anticancer drugs are discussed.
Петербургский клинический научно-практический центр специализированных видов медицинской помощи (онкологический)», Санкт-Петербург, Россия РЕЗЮМЕ В обзоре представлены данные о классификации, механизмах развития и клинических проявлениях нейротоксичности. Проанализированы основные особенности нейротоксичности при использовании таксанов, включая кумулятивные дозы. Рассмотрены доказанные методы лечения и профилактики нейропатии, вызванной цитостатическими препаратами.
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