Publications

Abstract Aims To develop and to validate a Cancer Multimorbidity Score (CMS) predictive of mortality in elderly patients affected by solid tumor, by using population‐based administrative Italian databases. Methods Through administrative databases of Lombardy Region (Northern Italy), a cohort of patients aged ≥65 years with a new diagnosis of solid tumor during the period 2009–2014 was identified. Sixty‐one conditions and diseases, measured from hospital inpatient diagnosis and outpatient drug prescription within 2 years before cancer diagnosis in a training set randomly including 70% of the cohort patients were tested to predict 5‐year mortality using a Cox regression model. Regression coefficients were used for assigning a weight to the predictive conditions, selected by the LASSO method. Weights were summed up in order to produce an aggregate score (the CMS). CMS performance was evaluated on a validation set, including the remaining 30% of the cohort patients, in terms of discrimination and calibration. Results The study cohort included 148,242 cancer patients. Thirty conditions were selected as independent predictors of 5‐year mortality and were included in the computation of the CMS. The area under the receiving operating characteristics curve was 0.68, becoming 0.71 when considering 1‐year mortality as outcome and reaching values of 0.74 and 0.81 when focusing on patients with breast and prostate cancer, respectively. A strong increasing trend in mortality was observed with increasing CMS value. Conclusions CMS represents a new useful tool for identifying high‐risk elderly cancer patients in everyday clinical practice, as well as for risk adjustment in clinical and epidemiological studies.

Data on the role of aspirin on endometrial cancer risk are scanty. Here we provide additional information on the issue, using data from a multicentric Italian case-control study. The study was conducted between 1992 and 2006 in three Italian areas, on 442 cases with histologically confirmed endometrial cancer and 676 control women admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic, non-gynaecological, non-hormone-related conditions, providing information on aspirin use. Odds ratios (OR) of endometrial cancer and corresponding 95% confidence intervals were calculated using multiple logistic regression models, including terms for sociodemographic characteristics, body mass index and hormonal and reproductive factors. Regular aspirin use was reported by 28 (6.3%) cases and 46 (6.8%) controls, corresponding to a multivariate OR of 0.65 (95% confidence interval 0.37-1.11). There was no consistent pattern of risk with duration of use, nor with age at first use, time since first use or time since last use. Further, there was no difference in risk estimates across strata of body mass index. This study--the first one from a population outside North America--adds relevant information on the absence of a consistent association between aspirin use and endometrial cancer risk, even in high-risk overweight and obese women.

[This corrects the article DOI: 10.18632/oncotarget.5210.].

We have studied the expression of insulin-like growth fador type II (IGF-ll) and its autocrine role during the proliferation and differentiation of the CaCo-2 colon carcinoma cell line. ICE-Il RNA levels were high in proliferating cells and decreased by more than 10-fold when cells ceased to proliferate and differentiated. Immunoreadive ICE-Il protein was high in the conditioned media of proliferating cells and decreased 20-fold in the media of differentiated cells. Reduced ICE-Il expression was associated with a decrease in ICE-I receptor number that was high in proliferating cells (approximately 80,000 binding sites/cell) and reduced by 4-fold in differentiated cells. Exogenously added ICE-Il was able to stimulate proliferation of serum-deprived cells in a dose-dependent fashion. ICE-Il aded through the ICE-I receptor, since both basal and ICE-Il-stimulated cell proliferation was inhibited by the monoclonal antibody a-lR3, which blocks the binding sites of the ICE-I receptor. The inhibition of CaCo-2 basal cell growth by the a-lR3 antibody suggeststhat ICE-lI may ad as an autocrine growth fador for these cells.

The most recent scientific evidence supports the consumption of cow's milk and dairy products as part of a balanced diet. However, these days, the public and practicing physicans are exposed to a stream of inconsistent (and often misleading) information regarding the relationship between cow's milk intake and health in the lay press and in the media. The purpose of this article, in this context, is to facilitate doctor-patient communication on this topic, providing physicians with a series of structured answers to frequently asked patient questions. The answers range from milk and milk-derived products' nutritional function across the life span, to their relationship with diseases such as osteoporosis and cancer, to lactose intolerance and milk allergy, and have been prepared by a panel of experts from the Italian medical and nutritional scientific community. When consumed according to appropriate national guidelines, milk and its derivatives contribute essential micro- and macronutrients to the diet, especially in infancy and childhood where bone mass growth is in a critical phase. Furthermore, preliminary evidence suggests potentially protective effects of milk against overweight, obesity, diabetes, and cardiovascular disease, while no clear data suggest a significant association between milk intake and cancer. Overall, current scientific literature suggests that an appropriate consumption of milk and its derivatives, according to available nutritional guidelines, may be beneficial across all age groups, with the exception of specific medical conditions such as lactose intolerance or milk protein allergy. Key teaching points: Milk and its derivatives contribute essential micro and macronutrients to the diet, when consumed according to appropriate national guidelines, especially in infancy and childhood where bone mass growth is in a critical phase. Preliminary evidence suggests potentially protective effects of milk against overweight, obesity, diabetes and cardiovascular disease No clear data are available about the association between milk intake and cancer. Current scientific literature suggests that an appropriate consumption of milk and its derivatives may be beneficial at all ages, with the exception of specific medical conditions such as lactose intolerance or milk protein allergy.

This study shows evidence of a positive association between diabetes and colorectal cancer, mainly proximal colon cancer. Moreover, it indicates a negative association between colorectal cancer and metformin use and a positive association for insulin use.

Eps15 is an endocytic adaptor protein involved in clathrin and non-clathrin mediated endocytosis.In Caenorhabditis elegans and Drosophila melanogaster lack of Eps15 leads to defects in synaptic vesicle recycling and synapse formation.We generated Eps15-KO mice to investigate its function in mammals.Eps15-KO mice are born at the expected Mendelian ratio and are fertile.Using a large-scale phenotype screen covering more than 300 parameters correlated to human disease, we found that Eps15-KO mice did not show any sign of disease or neural deficits.Instead, altered blood parameters pointed to an immunological defect.By competitive bone marrow transplantation we demonstrated that Eps15-KO hematopoietic precursor cells were more efficient than the WT counterparts in repopulating B220 + bone marrow cells, CD19 2 thymocytes and splenic marginal zone (MZ) B cells.Eps15-KO mice showed a 2-fold increase in MZ B cell numbers when compared with controls.Using reverse bone marrow transplantation, we found that Eps15 regulates MZ B cell numbers in a cell autonomous manner.FACS analysis showed that although MZ B cells were increased in Eps15-KO mice, transitional and pre-MZ B cell numbers were unaffected.The increase in MZ B cell numbers in Eps15 KO mice was not dependent on altered BCR signaling or Notch activity.In conclusion, in mammals, the endocytic adaptor protein Eps15 is a regulator of B-cell lymphopoiesis.

Study findings suggest a protective effect of carotenoids against NPC in a low-risk population, adding further support to a possible beneficial role of a diet rich in fruits and vegetables in cancers of the head and neck.

Background Timely identification of lactose intolerance is crucial to prevent secondary complications. This study aimed to assess the diagnostic accuracy of three commonly used methods for detecting lactose malabsorption (LM): the lactose hydrogen breath test (LHBT), the lactose tolerance test (LTT), and the genetic test (GT). Methods Patients diagnosed with irritable bowel syndrome underwent fasting and post-lactose (20 g) evaluations, including measurements of breath hydrogen, blood glucose, and genotyping for the C/T-13910 polymorphism associated with lactase persistence in European populations. A sustained increase of breath hydrogen ≥20 ppm above baseline, a failure of plasma glucose to rise >20 mg/dL from fasting levels, and the presence of the C/T-13910 variant were defined as positive for LHBT, LTT, and GT, respectively. Results One hundred and eight patients (age 39 ± 14 years, 17 males) were enrolled. Eighty-eight had symptoms after lactose ingestion. Of these, 88 (100%) were LHBT and 69 (78%) were LTT positive. Of a subgroup of 33 patients undergoing GT, 27 presented symptoms and 25 tested positive. Sensitivity and specificity were 100% and 85% for LHBT, 78% and 48% for LTT, and 93% and 83% for GT. Conclusions: With observation times greater than 4 h, LHBT had higher sensitivity and specificity than LTT and GT.