Loading...
 
Toggle Health Problems and D

Chemotheraphy not work as well with low Vitamin D (colon cancer this time) – Aug 2018

Vitamin D Deficiency has a Negative Impact on Cetuximab-Mediated Cellular Cytotoxicity against Human Colon Carcinoma Cells

Targeted Oncology, pp 1–9 DOI https://doi.org/10.1007/s11523-018-0586-x
Lorenzo MortaraMarzia B. GariboldiAnnalisa BosiMarco BregniGraziella PinottiLuigina GuastiAlessandro SquizzatoDouglas M. NoonanElena MontiEmail authorLeonardo Campiotti


Background
Hypovitaminosis D is associated with an adverse prognosis in colon cancer patients, possibly due to the effects of the vitamin on the immune system. Antibody-dependent cell-mediated cytotoxicity (ADCC) significantly contributes to the anti-tumor effects of monoclonal antibodies, including cetuximab, an epidermal growth factor receptor (EGFR)-targeted monoclonal antibody that is frequently added to chemotherapy in the treatment of colon cancer.

Objective: The present study evaluates the association between vitamin D serum levels and the ability of ex vivo NK cells to support cetuximab-mediated ADCC in colon cancer cell lines.

Methods: Blood samples were obtained from 124 healthy volunteers and serum vitamin D was determined by RIA. NK cells were isolated from each sample and added to human colorectal carcinoma cells with or without cetuximab, and ADCC was assessed using a colorimetric lactate dehydrogenase assay.

Results
Correlation analysis indicates a significant, gender- and age-independent association between vitamin D levels and cetuximab-induced ADCC on HT29 cells, where NK cells from samples with vitamin D < 20 ng/mL are significantly less efficient in inducing ADCC. A confirmatory study on two additional colon cancer cell lines yielded similar results.

Conclusions: These data suggest that vitamin D supplementation in vitamin-deficient/insufficient colorectal cancer patients could improve cetuximab-induced ADCC.

24 of the References

  • 6. Kennel KA, Drake MT. Vitamin D in the cancer patient. Curr Opin Support Palliat Care. 2013;7(3):272–7.
  • 7. Fang S, Sui D, Wang Y, Liu H, Chiang YJ, Ross MI, et al. Association of vitamin D levels with outcome in patients with melanoma after adjustment for C-reactive protein. J Clin Oncol. 2016;34(15):1741–7.
  • 8. Wang W, Li G, He X, Gao J, Wang R, Wang Y, et al. Serum 25-hydroxyvitamin D levels and prognosis in hematological malignancies: a systematic review and meta-analysis. Cell Physiol Biochem. 2015;35(5):1999–2005.
  • 9. Li M, Chen P, Li J, Chu R, Xie D, Wang H. Review: the impacts of circulating 25-hydroxyvitamin D levels on cancer patient outcomes: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2014;99(7):2327–36.
  • 10. Yao S, Kwan ML, Ergas IJ, Roh JM, Cheng TD, Hong CC, et al. Association of Serum Level of vitamin D at diagnosis with breast Cancer survival: a case-cohort analysis in the pathways study. JAMA Oncol. 2017;3(3):351–7.
  • 11. Fuchs MA, Yuan C, Sato K, Niedzwiecki D, Ye X, Saltz LB, et al. Predicted vitamin D status and colon cancer recurrence and mortality in CALGB 89803 (alliance). Ann Oncol. 2017;28(6):1359–67.
  • 12. Kelly JL, Salles G, Goldman B, Fisher RI, Brice P, Press O, et al. Low serum vitamin D levels are associated with inferior survival in follicular lymphoma: a prospective evaluation in SWOG and LYSA studies. J Clin Oncol. 2015;33(13):1482–90.
  • 14. Bessler H, Djaldetti M. 1α,25-Dihydroxyvitamin D3 modulates the interaction between immune and colon cancer cells. Biomed Pharmacother. 2012;66(6):428–32.
  • 15. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.
  • 16. O'Connell JB, Maggard MA, Ko CY. Colon cancer survival rates with the new American joint committee on Cancer sixth edition staging. J Natl Cancer Inst. 2004;96(19):1420–5.
  • 17. Vogel A, Hofheinz RD, Kubicka S, Arnold D. Treatment decisions in metastatic colorectal cancer - beyond first and second line combination therapies. Cancer Treat Rev. 2017;59:54–60.
  • 18. Ciombor KK, Bekaii-Saab T. A comprehensive review of sequencing and combination strategies of targeted agents in metastatic colorectal cancer. Oncologist. 2018;23(1):25–34.
  • 19. Brandi G, De Lorenzo S, Nannini M, Curti S, Ottone M, Dall'Olio FG, et al. Adjuvant chemotherapy for resected colorectal cancer metastases: literature review and meta-analysis. World J Gastroenterol. 2016;22(2):519–33.
  • 20. Sartore-Bianchi A, Loupakis F, Argiles G, Prager GW. Challenging chemoresistant metastatic colorectal cancer: therapeutic strategies from the clinic and from the laboratory. Ann Oncol. 2016;27(8):1456–66.
  • 29. Trotta AM, Ottaiano A, Romano C, Nasti G, Nappi A, De Divitiis C, et al. Prospective evaluation of Cetuximab-mediated antibody-dependent cell cytotoxicity in metastatic colorectal Cancer patients predicts treatment efficacy. Cancer Immunol Res. 2016;4(4):366–74.
  • 35. Teleni L, Baker J, Koczwara B, Kimlin MG, Walpole E, Tsai K, et al. Clinical outcomes of vitamin D deficiency and supplementation in cancer patients. Nutr Rev. 2013;71(9):611–21.
  • 36. DeMille DM, Piscitelli M, Ocker A, Vuong C, Hartner L, Lynch MP. Vitamin D deficiency in the oncology setting. J Community Support Oncol. 2014;12(1):13–9.
  • 37. Ahmad II, Trikudanathan G, Feinn R, Anderson JC, Nicholson M, Lowe S, et al. Low serum vitamin D: a surrogate marker for advanced Colon adenoma? J Clin Gastroenterol. 2016;50(8):644–8.
  • 38. Skender S, Bohm J, Schrotz-King P, Chang-Claude J, Siegel EM, Steindorf K, et al. Plasma 25-Hydroxyvitamin D3 levels in colorectal Cancer patients and associations with physical activity. Nutr Cancer. 2017;69(2):229–37.
  • 39. Maalmi H, Walter V, Jansen L, Chang-Claude J, Owen RW, Ulrich A, et al. Relationship of very low serum 25-hydroxyvitamin D3 levels with long-term survival in a large cohort of colorectal cancer patients from Germany. Eur J Epidemiol. 2017;32(11):961–971.
  • 40. Maalmi H, Ordóñez-Mena JM, Schöttker B, Brenner H. Serum 25-hydroxyvitamin D levels and survival in colorectal and breast cancer patients: systematic review and meta-analysis of prospective cohort studies. Eur J Cancer. 2014;50(8):1510–21.
  • 41. McCullough ML, Zoltick ES, Weinstein SJ, Fedirko V, Wang M, Cook NR, et al. Circulating vitamin D and colorectal cancer risk: an international pooling project of 17 cohorts. J Natl Cancer Inst. 2018. https://doi.org/10.1093/jnci/djy087.
  • 43. Kimmie N, VA P, Kaori S, Chen Y, HB W, Donna N, et al. Vitamin D status and survival of metastatic colorectal cancer patients: results from CALGB/SWOG 80405 (Alliance). J Clin Oncol. 2015;33(15 S)3503–3503.

Created by admin. Last Modification: Wednesday June 19, 2019 21:41:09 GMT-0000 by admin. (Version 3)