C. Belda

Chemotherapy for colorectal cancer in the elderly: Whom to treat and what to use.

The median age at diagnosis of colorectal cancer is during the seventh decade, and the incidence of the disease increases continuously with age. However, as the age increases, the possibilities of receiving adequate cancer treatment diminish and the mortality rises. So, there is a huge need for defined treatment strategies in elderly patients with colorectal carcinoma. The geriatric population is a very heterogeneous group where patients with an excellent health status coexist with the patients with both co-morbidities and functional dependency. Therefore, it is necessary to personalize each treatment according to the degree of vulnerability of the elderly patients. It is essential to set up a multidimensional geriatric assessment in order to consider not only the stage of the disease, but also all the factors that may influence the survival and interfere with the treatment. The aim of this review is to discuss the potential benefits and issues of chemotherapy in the elderly patients affected with colorectal cancer.

Immunohistochemical analysis of tumour regression grade for rectal cancer after neoadjuvant chemoradiotherapy

Aim  Tumour regression grade (TRG) as defined by Rödel et al. has been used as an independent prognostic factor for rectal carcinoma after preoperative treatment by chemoradiotherapy (CRT). Determination of TRG 2 and 3, semiquantitatively defined as more or less than 50% tumour regression, respectively, does not appear to correlate with prognosis. The purpose of this study was to find an immunohistochemical pattern to permit improved stratification of intermediate responders defined by disease free (DFS) and overall survival (OS).

Irinotecan-cetuximab-bevacizumab as a salvage treatment in heavily pretreated metastatic colorectal cancer patients: a retrospective observational study.

Background: The objective was to evaluate the efficacy of irinotecan-cetuximab-bevacizumab in combination as a salvage treatment for heavily pretreated metastatic colorectal cancer patients. Methods: A total of 39 patients resistant to both oxaliplatin and irinotecan were included in this retrospective study. Treatment consisted of irinotecan 180/m2 every 14 days, weekly cetuximab standard dose and bevacizumab 5 mg/kg every 14 days. Results: Partial response was observed in 8 patients (20%), stable disease in 24 (61%) and progressive disease in 7 (18%). Overall response rate in KRAS wild type was 6/22 (27%) and in mutated KRAS it was 2/15 (13%). Median time to progression was 8 months (6.4–9.4) and median overall survival 12 months (10.1–13.8). Overall, grade 3–4 adverse events were observed in 24 patients (62%). Conclusions: This regimen is active and moderately well tolerated in heavily pretreated advanced colorectal patients. However, caution is advisable when interpreting these results, because they run against the findings of two large phase III trials.

DNA Methylation of miR-7 is a Mechanism Involved in Platinum Response through MAFG Overexpression in Cancer Cells

One of the major limitations associated with platinum use is the resistance that almost invariably develops in different tumor types. In the current study, we sought to identify epigenetically regulated microRNAs as novel biomarkers of platinum resistance in lung and ovarian cancers, the ones with highest ratios of associated chemo-resistance. Methods: We combined transcriptomic data from microRNA and mRNA under the influence of an epigenetic reactivation treatment in a panel of four paired cisplatin -sensitive and -resistant cell lines, followed by real-time expression and epigenetic validations for accurate candidate selection in 19 human cancer cell lines. To identify specific candidate genes under miRNA regulation, we assembled “in silico” miRNAs and mRNAs sequences by using ten different algorithms followed by qRT-PCR validation. Functional assays of site-directed mutagenesis and luciferase activity, miRNAs precursor overexpression, silencing by antago-miR and cell viability were performed to confirm their specificity in gene regulation. Results were further explored in 187 primary samples obtained from ovarian tumors and controls. Results: We identified 4 candidates, miR-7, miR-132, miR-335 and miR-148a, which deregulation seems to be a common event in the development of resistance to cisplatin in both tumor types. miR-7 presented specific methylation in resistant cell lines, and was associated with poorer prognosis in ovarian cancer patients. Our experimental results strongly support the direct regulation of MAFG through miR-7 and their involvement in the development of CDDP resistance in human tumor cells. Conclusion: The basal methylation status of miR-7 before treatment may be a potential clinical epigenetic biomarker, predictor of the chemotherapy outcome to CDDP in ovarian cancer patients. To the best of our knowledge, this is the first report linking the regulation of MAFG by miRNA-7 and its role in chemotherapy response to CDDP. Furthermore, this data highlights the possible role of MAFG as a novel therapeutic target for platinum resistant tumors.

Expression Profile as Predictor of Relapse after Adjuvant Treatment in Gastric Cancer

IntroductionTNM and histological subtype are the most important prognostic criteria in gastric cancer. In this study, we have tried to identify an immunohistochemical protein profile involved in gastric recurrence after a radical surgery.Materials and methodsIn this paper, protein panels involved in gastric carcinogenesis and progression was analyzed by immunohistochemistry expression: p53, Ki-67, Bcl-2, COX-2, c-erb-B2, EPO-R, E-cadherin, and β-catenin in 44 gastrectomy samples coming from gastrectomy pieces of patients diagnosed and operated on adenocarcinoma of the stomach followed by adjuvant treatment based on MacDonald chemoradiation regimen. An immunostaining profile that could predict the relapse after the end of adjuvant treatment was tried to find. These results have shown that the expression of the adverse prognostic protein profile based on positive p53 immunohistochemical expression and non-conserved E-cadherin/B-catenin staining is associated with tumor recurrence and a poor disease-free survival in operated gastric cancer patients with curative intent followed by adjuvant chemoradiation according to MacDonald’s regimen. A protein profile based on immunohistochemical expression of p53 and E-cadherin–B-catenin that has a significant correlation to disease-free survival was identified in gastric cancer samples.