Cardiotoxic Profile and Arterial Stiffness of Adjuvant Chemotherapy for Colorectal Cancer.

BACKGROUND AND PURPOSE: Even though new cancer therapies have improved the overall survival, in some cases they have been associated with adverse effects, including increased cardiotoxicity. The purpose of the present study was to assess the cardiovascular effects of adjuvant chemotherapy for colorectal cancer and mainly the impact on arterial stiffness indices. MATERIAL AND METHODS: A total of 70 patients with non-metastatic colorectal cancer who were treated either with FOLFOX (n=16) or with XELOX (n=54) adjuvant chemotherapy were included in the study. All patients were subjected to full cardiovascular evaluation at the beginning and the end of chemotherapy. Arterial stiffness was assessed by means of pulse wave velocity (PWV) and augmentation index (Aix) and full laboratory examinations were conducted prior to, and soon after, the termination of chemotherapy. RESULTS: Patients exhibited significantly higher levels of carotid-radial PWV, carotid femoral RWV and Aix post-chemotherapy (p<0.001); these findings remained significant when examined separately in each treatment subgroup (FOLFOX, XELOX). The observed changes were independent of treatment regimen and baseline patient characteristics. Univariate regression analyses showed that baseline PWVc-r and PWVc-f were the only factors associated with PWVc-r and PWVc-f change, while Aix change was independent of its baseline value. CONCLUSION: There is a clear burden in arterial stiffness indices post-adjuvant chemotherapy for colorectal cancer in both chemotherapy groups. This is a finding of important clinical significance, however more prospective studies are required in order to encode the possible mechanisms involved.

IL-6 is associated to IGF-1Ec upregulation and Ec peptide secretion, from prostate tumors.

BACKGROUND: Ec peptide (PEc), resulting from the proteolytic cleavage of the IGF-1Ec isoform, is involved in prostate cancer progression and metastasis, whereas in muscle tissue, it is associated with the mobilization of satellite cells prior to repair. Our aim is to determine the physiological conditions associated to the IGF-1Ec upregulation and PEc secretion in prostate tumors, as well as, the effect of tumor PEc on tumor repair. METHODS: IGF-1 (mature and isoforms) expression was examined by qRT-PCR, both in prostate cancer cells co-incubated with cells of the immune response (IR) and in tumors. PEc secretion was determined by Multiple Reaction Monitoring. The effect of PEc, on mesenchymal stem cell (MSC) mobilization and repair, was examined using migration and invasion assays, FISH and immunohistochemistry (IHC). The JAK/STAT signaling pathway leading to the IGF1-Ec expression was examined by western blot analysis. Determination of the expression and localization of IL-6 and IGF-1Ec in prostate tumors was examined by qRT-PCR and by IHC. RESULTS: We documented that IL-6 secreted by IR cells activates the JAK2 and STAT3 pathway through IL-6 receptor in cancer cells, leading to the IGF-1Ec upregulation and PEc secretion, as well as to the IL-6 expression and secretion. The resulting PEc, apart from its oncogenic role, also mobilizes MSCs towards the tumor, thus promoting tumor repair. CONCLUSIONS: IL-6 leads to the PEc secretion from prostate cancer cells. Apart from its oncogenic role, PEc is also involved in the mobilization of MSCs resulting in tumor repair.

Association of CD133 polymorphisms and response to bevacizumab in patients with metastatic colorectal cancer.

BACKGROUND: Bevacizumab, an angiogenesis inhibitor is used in regimens for metastatic colorectal cancer (CRC). A minority of cancer cells with characteristics of cancer stem cells (CSC) may be responsible for progression and development of chemotherapy resistance in this disease. CD133 is a well-known CSC marker and is associated with angiogenesis, poor prognosis and resistance to chemotherapy. OBJECTIVE: The purpose of our study was to evaluate the association between the rs3130 and rs2286455 polymorphisms of the CD133 gene and the response, toxicity, and overall survival of patients with CRC on bevacizumab-based treatment. METHODS: Forty-three patients receiving bevacizumab, irinotecan and capecitabine and 15 patients receiving bevacizumab, irinotecan and 5-FU were included. Efficacy and toxicity were evaluated. KRAS mutation analysis and rs3130 and rs2286455 polymorphisms genotyping in the tumors and peripheral blood respectively were performed with PCR-RFLP. RESULTS: No association between KRAS mutated alleles and response was found. The rs3130 CC genotype was associated with reduced toxicity of treatments (p= 0.0017), and with lower overall survival on bevacizumab (p= 0.002). CONCLUSIONS: The CC genotype of rs3130 polymorphism in the CD133 gene can predict poorer overall survival in patients with metastatic CRC on bevacizumab which cannot be attributed to increased treatment toxicity.

Fertility after chemotherapy for ovarian germ cell tumours.

Gonadal function was assessed in 17 women who successfully completed chemotherapy with the POMB/ACE regimen (cisplatin, vincristine [Oncovin], methotrexate, bleomycin/actinomycin D, cyclophosphamide, etoposide) for ovarian germ cell tumours, and had a remaining ovary and uterus. A 20-year-old girl has not yet recovered menstruation 5 months off chemotherapy. All the remaining women whose mean age at start of chemotherapy was 21 (9-38) are now menstruating with a median time of recovery of 41/2 months after completion of chemotherapy. Five women have so far conceived after chemotherapy resulting in three full term normal deliveries of healthy infants, one termination of pregnancy, two miscarriages and one continuing pregnancy. Gonadal function does not appear to be permanently impaired in the majority of patients receiving POMB/ACE chemotherapy for ovarian germ cell tumours.

Fertility after chemotherapy for male and female germ cell tumours.

Gonadal function was assessed in fifty-nine men and thirty-one women who had successfully completed chemotherapy with the POMB/ACE regimen for germ cell tumours. Seventeen (81%) of the twenty-one men who had not received paraaortic radiotherapy, whose original tumour bulk was less than 5 cm and whose duration of chemotherapy was less than 6 months, recovered spermatogenesis compared with twelve (32%) of thirty-eight patients who had either larger tumour masses or longer courses of chemotherapy, or both. All but one of the seventeen women in whom menstruation could have been expected to recur are now menstruating. This study suggests that the great majority of patients treated with POMB/ACE chemotherapy for germ cell tumours will recover fertility.