Gemcitabine is one of the most widely used pyrimidine analogues, with a well-established role as a first- and second-line treatment of several types of tumors. Several preclinical and clinical studies have been done to obtain information on molecular determinants of gemcitabine activity and metabolism, in order to predict whether this drug will be effective and safe for the individual patient. Among these molecular determinants, the mRNA and protein expression of equilibrative transporter-1 (ENT1) and ribonucleotide reductase (RR) emerged as possible predictors of drug activity in studies on pancreatic and non-small cell lung cancer. However, cytidine deaminase polymorphisms and activity were correlated with clinical outcome and severe toxicities, whereas further studies should evaluate both P53 dependent and independent pathways involved in gemcitabine induced apoptosis. Improved knowledge on these determinants is critical for the optimal development of combination of gemcitabine with other conventional or biological therapies, as well as to exploit the radiosensitizing potential of gemcitabine. Emerging technologies such as massive parallel sequencing, gene expression arrays and proteomics may identify novel biomarkers in tumor material, while polymorphisms and phenotyping analysis should unravel factors involved in drug toxicity. Validation of these markers in preclinical models should be used for the appropriate patient enrolment into subsequent prospective studies. Hopefully, novel pharmacogenetic biomarkers will be validated in these prospective studies and used to select cancer patients to be treated with gemcitabine-based regimens in the near future or to enroll them in studies with prodrugs in order to bypass resistance mechanisms.

Background Cancer-care health professionals are at great risk of workplace stress and high burnout levels. Only a few studies were studying the prevalence of workplace stress and burnout in medical oncologists in Egypt. The aim of the work is to study the prevalence of burnout levels and work stress among medical oncologists working at multi-centers in Egypt (Cairo, Menoufia, Fayoum, and Assiut university hospitals). A cross-sectional study was conducted on a total of 100 medical oncologists at four medical oncology centers in Egypt. Self-administered Maslach Burnout Inventory (MBI) questionnaire and Workplace Stress Scale (WSS) were used to assess the burnout and stress levels respectively among the participants. Results Out of 100 participants, 32% were overall burnout positive as they met the criteria for all the burnout subscales. The percentages of emotional exhaustion, depersonalization, and reduced personal capacity were 30%, 30%, and 25%, respectively. About 60% were having job stress. The present study showed that younger age (≤ 40 years), female gender, being single, with no children, junior physicians (residents or physicians < 10 years in practice), with work time directed to both patient care and research, and those with more than 6 shifts per month were associated with higher burnout and workplace stress. Conclusion Medical oncologists experienced high burnout levels and workplace stress. More studies are needed to assess these problems in large scales to try to mitigate them.

TAS-102 (trifluorothymidine [TFT] and thymidine phosphorylase inhibitor [TPI] in a molar ratio of 1:0.5) has activity in 5-fluorouracil resistant colon cancer. TPI is added to increase TFT's bioavailability. TFT has a dual mechanism of action by inhibiting thymidylate synthase and by its incorporation into DNA. Interesting radiosensitizing effects of TPI were recently reported. The aim of our study was to determine whether TP expression would affect radiosensitivity and to characterize the effect of TPI. Two bladder cancer cell lines RT112 (TP negative) and RT112/TP (TP overexpression) were tested for drug sensitivity and radiosensitivity (clonogenic assay), with and without TFT and/or TPI. Expression of γ H2AX was used as marker for DNA damage. RT112 cells were not more sensitive to TFT then RT112/TP cells. TPI alone did not inhibit cell growth of RT112 even at 100 μM, but inhibited that of RT112/TP by 27%. In both RT112 and RT112/TP cells 10 μM TPI did not or slightly affect radiosensitivity, but 100 μM TPI alone enhanced the radiation response (p<.05). TFT alone at 1 μM and in combination with 10 μM TPI did not affect the radiation response of both cell lines. TPI alone induced expression of ϒH2AX, which was increased in combination with radiation. In conclusion, TPI enhanced radiosensitivity at high concentrations, independent of TP expression, while TFT and TPI at a low concentration did not affect the radiosensitivity of RT112 and RT112/TP cell lines.

some cases, morphologic distinction between MAC and reactive mesothelial cells (RMC) is challenging, as both may show wide range of morphologic variations, or only few suspicious cells might be seen (Ikeda et al., 2011). In such doubtful cases, application of immunohistochemical markers to cell blocks allows more precise diagnosis of