Gene expression profiling of unresectable pancreatic cancer patients treated with gemcitabine, nab-paclitaxel, metformin, and dietary supplements (DS)

التفاصيل البيبلوغرافية
العنوان: Gene expression profiling of unresectable pancreatic cancer patients treated with gemcitabine, nab-paclitaxel, metformin, and dietary supplements (DS)
المؤلفون: Daneng Li, Holly Yin, Tamara Mirzapoiazova, Joseph Chao, Paul Frankel, Raju Pillai, Ravi Salgia, Orn Adalsteinsson, Steven Hirsh, Bolot Mambetsariev, Isa Mambetsariev, Stephen Shibata, Andrea Bild, Vincent Chung, Marwan Fakih, Prakash Kulkarni, Dean Lim
المصدر: Journal of Clinical Oncology. 38:736-736
بيانات النشر: American Society of Clinical Oncology (ASCO), 2020.
سنة النشر: 2020
مصطلحات موضوعية: Unresectable Pancreatic Cancer, Oncology, Cancer Research, medicine.medical_specialty, business.industry, Pilot trial, medicine.disease, Gemcitabine, Metformin, Gene expression profiling, Weight loss, Internal medicine, Pancreatic cancer, medicine, medicine.symptom, business, medicine.drug, Nab-paclitaxel
الوصف: 736 Background: Pancreatic cancer commonly causes weight loss and many patients take supplements to improve nutrition but also for any potential anticancer properties. We conducted a pilot trial evaluating a standardized combination of dietary supplements, metformin and gemcitabine plus nab-paclitaxel chemotherapy. Methods: The supplements were custom designed by a nutritionally trained oncologist. 17 supplements were given as 12 pills and 2 smoothie packets divided twice per day. Patients began metformin on day (D)-6 to evaluate GI tolerance before starting the DS on D-3. On D1, gemcitabine and nab-paclitaxel chemotherapy was administered at standard doses. Serum samples were collected D-6, C1D1, C3D1 and at the end of treatment. RNA was extracted from PBMC samples and a total of 48 samples were analyzed from 19 patients. NanoString Human Immune Profiling and PanCancer Pathways were performed to evaluate changes in gene expression with treatment. Results: The differential expression of genes was small with dietary supplements alone and in combination with chemotherapy. After 2 months of treatment, 17 genes were upregulated while 4 genes were down regulated. At the time of tumor resistance, 33 genes were upregulated while 17 genes were downregulated. We observed downregulation of tumor suppressor gene expression with upregulation in growth factor pathways. Interestingly, SPRY2 mRNA expression was also up regulated which functions as a negative feedback regulator of multiple receptor tyrosine kinases. Conclusions: Increasing number of genes were upregulated with continued treatment. The most common pathway affected was cell cycle and apoptosis. During the initial supplement run-in period from D-6 to C1D1, IL-8 mRNA expression was upregulated the most. IL-8 is a neutrophil chemotactic factor secreted by cells involved in the innate immune response as well as pancreatic cancer cells associated with a pro-inflammatory state. Treatment with gemcitabine and nab-paclitaxel decreased the IL-8 mRNA expression. Additional studies with longer course treatment with supplements alone would be required to explore its impact on differential gene expression.
تدمد: 1527-7755
0732-183X
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::0b8afec67a031b2312988954ce921e1e
https://doi.org/10.1200/jco.2020.38.4_suppl.736
رقم الأكسشن: edsair.doi...........0b8afec67a031b2312988954ce921e1e
قاعدة البيانات: OpenAIRE