Lymphocytopenia and Cytotoxic Therapy in Patients with Advanced Ovarian Cancer
Alexei N. Shoutko,
Ludmila E. Yurkova,
Kseniya S. Borodulya,
Ludmila P. Ekimova
Issue:
Volume 3, Issue 3, May 2015
Pages:
47-51
Received:
13 April 2015
Accepted:
25 April 2015
Published:
12 May 2015
Abstract: The relationship between 5-year survival and the mean number of circulating lymphocytes during 1 month after beginning a combined therapy was investigated in 175 patients with advanced epithelial ovarian cancer to understand why myelosuppression caused by a cytotoxic treatment is almost inseparable from its benefit. Patients received a combined therapy consisting of primary cytoreductive surgery followed by different systemic treatments according to three schemes: conventional chemotherapy with cisplatinum and cyclophosphanum (CP), conventional chemotherapy with paclitaxel and carboplatinum (TP), or lower-half body irradiation (LHBI). The TP scheme included premedication with dexamethasone. The LHBI involve irradiation with a total dose of 9 Gy (3 Gy daily) in patients with primary disease. LHBI with a total dose of 1 Gy (0.1 Gy daily) was used for patients with primary disease or relapse. The LHBI treatment included five final courses of thiophosphamide/5-fluorouracil for patients with primary cancer or conventional local radiotherapy up to a total dose of 30 Gy (2 Gy daily) for relapsed patients. Survival curves were analyzed by exponential approximation, and 5-year exponential mortality rates were calculated. The mortality rates were compared with the relative decline in the mean number of circulating lymphocytes after 1 month of therapy. If pretreatment lymphocytopenia did not exceed 0.7 109 cells /L, a linear dependency of the exponential death rate from the relative deviation of cells in the range of 1.16 to 0.7 (p < 0.001) was observed. The inevitable side effect of cytotoxic cancer therapy in the form of lymphocytopenia sheds doubt on the actual existence of effective antineoplastic immunity; however, it provides a logical background of the morphogenic function of some circulating mononuclear cells in relation to proliferating tissues, including malignant tissues.
Abstract: The relationship between 5-year survival and the mean number of circulating lymphocytes during 1 month after beginning a combined therapy was investigated in 175 patients with advanced epithelial ovarian cancer to understand why myelosuppression caused by a cytotoxic treatment is almost inseparable from its benefit. Patients received a combined the...
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Cell Migration Induced by Native Type IV Collagen Requires PI3K/Akt2 and EGFR Activity in MDA-MB-231 Breast Cancer Cells
Emmanuel Reyes-Uribe,
Octavio Galindo-Hernandez,
Pedro Cortes-Reynosa,
Eduardo Perez Salazar
Issue:
Volume 3, Issue 3, May 2015
Pages:
52-62
Received:
6 May 2015
Accepted:
26 May 2015
Published:
16 June 2015
Abstract: Basement membrane (BM) is a specialized extracellular matrix (ECM) that separates epithelial cells from surrounding stroma and regulates various biological processes including morphology, growth, differentiation, adhesion and motility. Type IV collagen is the major component of BM, provides structural framework of all BMs and interacts with cell surface receptors including integrins and discoidin domain receptors (DDRs). The DDRs are receptor tyrosine kinases that get activated by collagens in their native triple-helical form and present sustained and slow activation kinetics. Particularly, DDR1 signaling mediates differentiation, immune response, migration and wound healing. However, the signal transduction pathways involved in cell migration induced by native IV collagen in breast cancer cells has been poorly studied. Here we demonstrate that native type IV collagen induces Akt2 and FAK activation through a DDR1, PI3K and epidermal growth factor receptor (EGFR)-dependent pathway in MDA-MB-231 breast cancer cells. In addition, cell migration induced by native type IV collagen requires PI3K, Akt2 and EGFR activity, whereas collagen IV also induces NFκB-DNA binding activity through a DDR1, PI3K, Akt2 and EGFR-dependent pathway. In summary, we demonstrate that migration induced by native type IV collagen requires PI3K/Akt2 and EGFR activity in MDA-MB-231 breast cancer cells.
Abstract: Basement membrane (BM) is a specialized extracellular matrix (ECM) that separates epithelial cells from surrounding stroma and regulates various biological processes including morphology, growth, differentiation, adhesion and motility. Type IV collagen is the major component of BM, provides structural framework of all BMs and interacts with cell su...
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