It has been suggested that tumor cells produce IL-8 as an autocrine growth factor, which promote tumor growth, tissue invasion and metastatic spread.7 Previous studies have revealed that highly metastatic solid tumors such as prostate,

Purpose: Previous studies have shown that estrogen prevents colon cancer in postmenopausal women, indicating a role in colorectal cancer carcinogenesis and tumor progression. We investigated the interactions between sex, age, ethnicity, and year of diagnosis on overall survival (OS) in patients with metastatic colorectal cancer (MCRC). Experimental Design: We screened 52,882 patients with MCRC from 1988 to 2004, using the Surveillance Epidemiology and End Results registry. Age at diagnosis, sex, ethnicity, tumor location, year of diagnosis, OS, and cancer-specific survival were evaluated using Cox proportional hazards model. The models were adjusted for marital status, tumor site, tumor differentiation, and treatment with radiation and/or surgery. Results: We observed that younger women (18-44 years old) with MCRC lived longer than younger men (17 months versus 14; P < 0.0001, log-rank test). In contrast, older women (55 years and older) had significantly worse OS than older men (7 months versus 9; P < 0.0001, log-rank test). In multivariate analysis, we found that gender discrepancies have widened in recent years; young women diagnosed after 2000 have improved cancer-specific survival, compared to men (hazard ratio, 0.778; 95% confidence interval, 0.669-0.904), but those diagnosed before 2000 benefit less (hazard ratio, 0.931; 95% confidence interval, 0.821-1.056). Conclusion: As one of the largest data sets analyzed to establish that younger women with MCRC survive longer than younger men, hormonal status not only seems to play an important role in the development and pathogenesis of colorectal cancer but also may be of prognostic significance. These data warrant further studies to determine the role of estrogen in colorectal cancer. ( The effect of gender on colorectal cancer (CRC) incidence is well established. At all ages, women are less likely to develop CRC than men (1, 2). Indeed, their risk is comparable to men 4 to 8 years younger in age (3). Variable environmental exposures and comorbidities may contribute to these findings; however, an alternate explanation is emerging.In the Women's Health Initiative trial, postmenopausal hormone use was associated with a 40% decrease in colorectal cancer (4). This association between hormone replacement therapy and colon cancer prevention is consistent with previous reports (5, 6). Hormones also protect premenopausal women, as oral contraceptive use reduces the risk of developing CRC by ∼20% (7, 8). The mechanism by which this occurs is unclear, but these findings parallel reports that menopause increases a woman's risk of developing colon cancer over premenopausal women of the same age (9).Gender differences in CRC extend to environmental sequelae, tumor biology, and therapeutic response. For example, obesity (10) and a sedentary lifestyle (11) increase the risk of colon cancer mostly in men. There is also evidence that tumorigenesis may be gender specific as women are more likely to develop right-sided tumors with the microsatelllite instability phenotyp...

these results are the first to indicate that the KRAS 3'UTR polymorphism may predict for cetuximab responsiveness in KRASwt mCRC patients, which warrants validation in other clinical trials.

Inactivated vaccines are commonly produced by incubating pathogens with chemicals such as formaldehyde or β-propiolactone. This is a time-consuming process, the inactivation efficiency displays high variability and extensive downstream procedures are often required. Moreover, application of chemicals alters the antigenic components of the viruses or bacteria, resulting in reduced antibody specificity and therefore stimulation of a less effective immune response. An alternative method for inactivation of pathogens is ionizing radiation. It acts very fast and predominantly damages nucleic acids, conserving most of the antigenic structures. However, currently used irradiation technologies (mostly gamma-rays and high energy electrons) require large and complex shielding constructions to protect the environment from radioactivity or X-rays generated during the process. This excludes them from direct integration into biological production facilities. Here, low-energy electron irradiation (LEEI) is presented as an alternative inactivation method for pathogens in liquid solutions. LEEI can be used in normal laboratories, including good manufacturing practice (GMP)- or high biosafety level (BSL)-environments, as only minor shielding is necessary. We show that LEEI efficiently inactivates different viruses (influenza A (H3N8), porcine reproductive and respiratory syndrome virus (PRRSV), equine herpesvirus 1 (EHV-1)) and bacteria (Escherichia coli) and maintains their antigenicity. Moreover, LEEI-inactivated influenza A viruses elicit protective immune responses in animals, as analyzed by virus neutralization assays and viral load determination upon challenge. These results have implications for novel ways of developing and manufacturing inactivated vaccines with improved efficacy.

Since its introduction more than 50 years ago by Heidelberger et al., the fluoropyrimidine 5-fluorouracil (5-FU) has remained the mainstay of therapeutic regimens used in the treatment of colorectal cancer and other human malignancies, with single-agent response rates of 20% to 25% in advanced disease stage. Pharmacogenomics has emerged as a useful tool to address interindividual gene variations by analyzing the interplay of host and tumor genotype and drug efficacy and toxicity. Having a reliable panel of prognostic and predictive markers will be critical in selecting an individualized and tailored chemotherapy regimen based on the particular tumor and host genotype. Although conflicting results have been reported, higher thymidylate synthase (TS) protein and mRNA expression levels in tumors have generally been associated with poor clinical outcome in patients treated with 5-FU -based chemotherapy regimens. However, the cause of the variability in TS expression still remains not fully understood, although several germ-line polymorphisms seem to affect the expression of TS, some of which have been found to have an effect on prognosis and the probability of response to 5-FU -based chemotherapy. This review will provide an update on pharmacogenomic studies of TS that were aimed at elucidating their role as prognostic and predictive markers.