Rho proteins belong to the small GTPases superfamily. They function as molecular switches that, in response to diverse stimuli, control key signaling and structural aspects of the cell. Although early studies proposed a role for Rho GTPases in cellular transformation, this effect was underestimated due to the fact that no genetic mutations affecting Rho-encoding genes were found in tumors. Recently, it has become evident that Rho GTPases participate in the carcinogenic process by either overexpression of some of the members of the family with oncogenic activity, downmodulation of other members with suggested tumor suppressor activity, or by alteration of upstream modulators or downstream effectors. Thus, alteration of the levels of expression of different members of the family of Rho GTPases has been detected in many types of human tumors leading to a great interest in the cellular effects elicited by these oncoproteins. This essay reviews the current evidence of dysregulation of Rho signaling by overexpression in human tumors.

This overview describes the principles of the 4th edition of the European Code against Cancer and provides an introduction to the 12 recommendations to reduce cancer risk. Among the 504.6 million inhabitants of the member states of the European Union (EU28), there are annually 2.64 million new cancer cases and 1.28 million deaths from cancer. It is estimated that this cancer burden could be reduced by up to one half if scientific knowledge on causes of cancer could be translated into successful prevention. The Code is a preventive tool aimed to reduce the cancer burden by informing people how to avoid or reduce carcinogenic exposures, adopt behaviours to reduce the cancer risk, or to participate in organised intervention programmes. The Code should also form a base to guide national health policies in cancer prevention. The 12 recommendations are: not smoking or using other tobacco products; avoiding second-hand smoke; being a healthy body weight; encouraging physical activity; having a healthy diet; limiting alcohol consumption, with not drinking alcohol being better for cancer prevention; avoiding too much exposure to ultraviolet radiation; avoiding cancer-causing agents at the workplace; reducing exposure to high levels of radon; encouraging breastfeeding; limiting the use of hormone replacement therapy; participating in organised vaccination programmes against hepatitis B for newborns and human papillomavirus for girls; and participating in organised screening programmes for bowel cancer, breast cancer, and cervical cancer.

Despite metastasis as an important cause of death in colorectal cancer patients, current animal models of this disease are scarcely metastatic. We evaluated whether direct orthotopic cell microinjection, between the mucosa and the muscularis layers of the cecal wall of nude mice, drives tumor foci to the most relevant metastatic sites observed in humans and/or improves its yield as compared with previous methods. We injected eight animals each tested human colorectal cancer cell line (HCT-116, SW-620, and DLD-1), using a especially designed micropipette under binocular guidance, and evaluated the take rate, local growth, pattern and rate of dissemination, and survival time. Take rates were in the 75 to 88% range. Tumors showed varying degrees of mesenteric and retroperitoneal lymphatic foci (57 to 100%), hematogenous dissemination to liver (29 to 67%) and lung (29 to 100%), and peritoneal carcinomatosis (29 to 100%). Tumor staging closely correlated with animal survival. Therefore, the orthotopic cell microinjection procedure induces tumor foci in the most clinically relevant metastatic sites: colon-draining lymphatics, liver, lung, and peritoneum. The replication of the clinical pattern of dissemination makes it a good model for advanced colorectal cancer. Moreover, this procedure also enhances the rates of hematogenous and lymphatic dissemination at relevant sites, as compared with previously described methods that only partially reproduce this pattern. Colorectal cancer cases represents 15% of all cancer types. Its poor prognosis and the consequence of its metastatic spread makes colorectal cancer the second most common cause of cancer death in western countries.1 However, genetically modified mouse models of colorectal cancer are scarcely or not metastatic.2,3 Moreover, more metastatic cancer models, such as surgical orthotopic implantation (SOI), experimental or spontaneous metastasis assays, and orthotopic cell injection also show limitations. Thus, although SOI of human colorectal cancer in nude mice yields liver metastasis, 4,5 it does not generate lung metastasis, nor mesenteric or retroperitoneal lymphatic metastasis, 6 and requires the previous expansion of the tumor in subcutaneous xenografts, [7][8][9] which may alter its growth and dissemination capacities. 10 On the other hand, the experimental metastasis assay or spontaneous metastasis assay, consisting of cell injection into the tail vein or footpad, are less physiological and usually generate tumor foci only at one single site. [11][12][13][14][15][16] Moreover, injection of colorectal cancer cells in the ileocolic vein or in the apical lymphoid follicle 12,17,18 limits metastases to liver and lymphatics, varying widely in their rate.We tested whether direct orthotopic cell microinjection (OCMI), between the mucosa and the muscularis externa

PurposeAfrica has low breast cancer incidence rates but high mortality rates from this disease due to poor survival. Delays in presentation and diagnosis are major determinants of breast cancer survival, but these have not been comprehensively investigated in Africa.MethodsMEDLINE, Embase, and Global Health were searched to identify studies reporting on delays in presentation and/or diagnosis of breast cancer published between January 1, 2000 and May 31, 2016. Data were synthesized in narrative, tabular, and graphical forms. Meta-analyses were not possible due to between-study differences in the way delays were reported.ResultsTwenty-one studies were included in the review. Study-specific average times between symptom recognition and presentation to a health care provider ranged from less than 1 to 4 months in North Africa and from less than 3 to greater than 6 months in sub-Saharan Africa. Study-specific average times from presentation to diagnosis were less than 1 month in North Africa but ranged from less than 3 to greater than 6 months in sub-Saharan Africa. Reported reasons for these delays included patient-mediated (e.g., socioeconomic factors) and health system–mediated factors (e.g., referral pathways).ConclusionsThis systematic review revealed marked delays in presentation and diagnosis of breast cancer in Africa. Identification of their drivers is crucial to the development of appropriate control strategies in the continent.

Lifestyle factors, including diet, have long been recognised as potentially important determinants of cancer risk. In addition to the significant role diet plays in affecting body fatness, a risk factor for several cancers, experimental studies have indicated that diet may influence the cancer process in several ways. Prospective studies have shown that dietary patterns characterised by higher intakes of fruits, vegetables, and whole-grain foods, and lower intakes of red and processed meats and salt, are related to reduced risks of death and cancer, and that a healthy diet can improve overall survival after diagnosis of breast and colorectal cancers. There is evidence that high intakes of fruit and vegetables may reduce the risk of cancers of the aerodigestive tract, and the evidence that dietary fibre protects against colorectal cancer is convincing. Red and processed meats increase the risk of colorectal cancer. Diets rich in high-calorie foods, such as fatty and sugary foods, may lead to increased calorie intake, thereby promoting obesity and leading to an increased risk of cancer. There is some evidence that sugary drinks are related to an increased risk of pancreatic cancer. Taking this evidence into account, the 4th edition of the European Code against Cancer recommends that people have a healthy diet to reduce their risk of cancer: they should eat plenty of whole grains, pulses, vegetables and fruits; limit high-calorie foods (foods high in sugar or fat); avoid sugary drinks and processed meat; and limit red meat and foods high in salt.