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The successful treatment of cancer in a disseminated stage using chemotherapy is limited by the occurrence of drug resistance, often mediated by anti-apoptotic mechanisms. Thus the challenge is to pinpoint the underlying key factors and to develop therapies for their direct targeting. Protein kinase C (PKC) enzymes are promising candidates, as some PKCs were shown to be involved in regulation of apoptosis. Our studies and others have shown that PKC? is an anti-apoptotic kinase, able to confer protection on tumour cells against stress and chemotherapy. We have demonstrated that PKC? shuttles between the cytoplasm and the nucleus and that upon DNA damage is tethered at the nuclear membrane. The C1b domain mediates translocation of PKC? to the nuclear envelope and, similar to the full-length protein, could also confer protection against cell death. Furthermore, its localization in cell and nuclear membranes in breast cancer biopsies of neoadjuvant-treated breast cancer patients was an indicator for poor survival and a predictor for the effectiveness of treatment. PKC? is also a novel biomarker for poor prognosis in non-small-cell lung cancer (NSCLC). Thus PKC? presents a potential target for therapy where inhibition of its activity and/or translocation to membranes could interfere with the resistance to chemotherapy. [ABSTRACT FROM AUTHOR]

Background & Aims: We aimed to identify early clinical, laboratory, and endoscopic factors associated with sustained remission in children with ulcerative colitis (UC) treated with infliximab. Methods: We performed a post hoc analysis of data collected from 51 children (6–17 years old) with moderate-to-severe UC treated with infliximab for 1 year in the T72 clinical trial. The primary outcome was steroid-free remission at weeks 30 and 54 of treatment, which was based on patient and physician assessments. We compared the ability of the Pediatric UC Activity Index (PUCAI, a noninvasive clinical index), levels of C-reactive protein (CRP), and mucosal healing to predict which patients would be in steroid-free sustained remission after 1 year of treatment. Results: Week 8 PUCAI scores best predicted which patients would be in steroid-free remission after 1 year of treatment; 9 of 17 patients who had PUCAI scores <10 points were in sustained remission (53%), compared with 4 of 20 who had PUCAI scores ≥10 (20%) (P = .036). Mucosal healing at week 8 was associated with steroid-free remission at 1 year, but this did not reach significance; 7 of 16 patients with mucosal healing were in remission after 1 year (44%), compared with 6 of 21 without mucosal healing (29%) (P = .34). The area under the receiver operating characteristic curve values for association with steroid-free sustained remission were 0.70 for the PUCAI (95% confidence interval [CI], 0.53–0.88), 0.56 for mucosal healing (95% CI, 0.36–0.76), and 0.44 for level of CRP (95% CI, 0.24–0.65). By using a multivariable logistic regression model, the week 8 PUCAI was the only factor associated with steroid-free remission at 1 year (P = .038). PUCAI-defined remission had a high degree of concordance with complete mucosal healing at week 8 (33% of patients were in remission according to the PUCAI vs 31% with mucosal healing). Conclusion: On the basis of a post hoc analysis of data from the T72 clinical trial on the effect of infliximab in pediatric patients with UC, the PUCAI was no less predictive of sustained remission than mucosal healing at week 8, and both were superior to CRP level. Routine endoscopic evaluation in children with UC who are in complete clinical remission (ie, PUCAI <10 points) may not be necessary. [Copyright &y& Elsevier]

Colorectal cancer is the most common cancer of the gastrointestinal tract. It is considered as a biological model of a certain type of cancerogenesis process in which progression from an early to late stage adenoma and cancer is accompanied by distinct genetic alterations. Clinical and pathological parameters commonly used in clinical practice are often insufficient to determine groups of patients suitable for personalized treatment. Moreover, reliable molecular markers with high prognostic value have not yet been determined. Molecular studies using DNAbased microarrays have identified numerous genes involved in cell proliferation and differentiation during the process of cancerogenesis. Assessment of the genetic profile of colorectal cancer using the microarray technique might be a useful tool in determining the groups of patients with different clinical outcomes who would benefit from additional personalized treatment. The main objective of this study was to present the current state of knowledge on the practical application of gene profiling techniques using microarrays for determining diagnosis, prognosis and response to treatment in colorectal cancer. [ABSTRACT FROM AUTHOR]