Gold-palladium core@shell nanoalloys: experiments and simulations.

In this work, we report a facile synthesis route, structural characterization, and full atomistic simulations of gold-palladium nanoalloys. Through aberration corrected-STEM, UV-vis spectroscopy and EDS chemical analysis, we were able to determine that Au(core)-Pd(shell) bimetallic nanoparticles were formed. Using different computational approaches, we were capable of establishing how the size of the core and the thickness of the shell will affect the thermodynamic stability of several core-shell nanoalloys. Finally, grand canonical simulations using different sampling procedures were used to study the growth mechanism of Pd atoms on Au seeds of different shapes.

HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients.

BACKGROUND: In metastatic colorectal cancer (mCRC), KRAS is the only validated biomarker used to select patients for administration of epidermal growth factor receptor (EGFR)-targeted therapies. To identify additional predictive markers, we investigated the importance of HER2, the primary EGFR dimerisation partner, in this particular disease. METHODS: We evaluated the HER2 gene status by fluorescence in situ hybridisation (FISH) in 170 KRAS wild-type mCRC patients treated with cetuximab or panitumumab. RESULTS: Depending on HER2 gene copy number status, patients showed three distinct cytogenetic profiles: 4% of patients had HER2 gene amplification (R:HER2/CEP17 ≥ 2) in all neoplastic cells (HER2-all-A), 61% of patients had HER2 gain due to polysomy or to gene amplification in minor clones (HER2-FISH+*), and 35% of patients had no or slight HER2 gain (HER2-FISH-). These subgroups were significantly correlated with different clinical behaviours, in terms of response rate (RR; P=0.0006), progression-free survival (PFS; P<0.0001) and overall survival (OS; P<0.0001). Patients with HER2-all-A profile experienced the worst outcome, patients with HER2-FISH- profile showed an intermediate behaviour and patients with HER2-FISH+* profile were related to the highest survival probability (median PFS in months: 2.5 vs 3.9 vs 7.6, respectively; median OS in months: 4.2 vs 9.7 vs 13, respectively). CONCLUSION: HER2 gene copy number status may influence the clinical response to anti-EGFR-targeted therapy in mCRC patients.

Empiema causado por Salmonella typhimurium / Pleural empyema caused by Salmonella typhimurium: a case report

Salmonella species are commonly associated with acute gastroenteritis due to ingestion of contaminated food or water. Extraintestinal infections are less frequent, and most of them occur in immunocompromised patients. We report a case of pleural empyema caused by Salmonella typhimurium, without previous diarrhea or fever. The patient evolved favorably after receiving adequate treatment.

El género Salmonella se caracteriza por causar infecciones en el tracto gastrointestinal, debido a la ingesta de alimentos o agua contaminada. También puede causar, con menor frecuencia, infecciones localizadas en diferentes órganos; esto se asocia con inmunodepresión. En este caso se describe un paciente con infección pleuropulmonar por Salmonella typhimurium, que no reportó antecedentes de diarrea previa. Evolucionó favorablemente con tratamiento adecuado.

Assessment of breast cancer opportunistic screening by clinical-pathological indicators: a population-based study.

BACKGROUND: Although some clinical-pathological features of breast cancers, such as the incidence of ductal cancer in situ (DCIS) and the diameter of invasive tumours, are sensitive indicators of early detection, comprehensive population-based studies of opportunistic screening are needed. METHODS: Cases of DCIS or invasive breast cancer diagnosed in 1996-2007 were identified from the Ticino Cancer Registry (south of Switzerland). Time trends of age-adjusted incidence and mortality, as well as main clinical-pathological features, such as tumour diameter, AJCC stage and histological grade, were analysed. RESULTS: A total of 3047 incident cases of female breast cancer were identified. The proportion of DCIS with respect to invasive cases increased from 5.8% in the period 1996-2001 to 6.4% in the period 2002-2007. The median tumour size of invasive cancers decreased from 20 mm in 1996-2001 to 18 mm in 2002-2007 (P<0.0001). An increase in well/moderately differentiated invasive tumours, from 67% in the period 1996-2001 to 73% in 2002-2007 (P<0.001), was detected and resulted in an Annual Percentage Change of incidence of 2.8 (95% confidence interval: 1.3; 4.3). CONCLUSION: An opportunistic screening strategy can lead to an improvement of prognostic features at diagnosis, but these features are still less favourable than those achieved by organised screening programmes.

Differing deregulation of EGFR and downstream proteins in primary colorectal cancer and related metastatic sites may be clinically relevant.

Cetuximab and panitumumab efficacy in metastatic colorectal cancer (mCRC) may be influenced by EGFR gene status and/or deregulation of its downstream signalling proteins detected in primary tumour. However, metastasis might have different molecular patterns with respect to primary tumour, possibly affecting the prediction of EGFR-targeted therapy efficacy. We analysed primary tumour and metastasis in 38 mCRC patients. Twelve cases were cetuximab/panitumumab treated. EGFR gene status and protein expression were investigated through fluorescent in situ hybridisation and immunohistochemistry (IHC), K-Ras/BRAF mutations by sequencing and PTEN expression by IHC. We observed EGFR gene deregulation in 25 out of 36 primary tumours and 29 out of 36 metastases, K-Ras mutations in 16 out of 37 cancers and in 15 out of 37 metastases, BRAF mutations in 2 out of 36 cancers and 2 out of 36 metastases and PTEN loss in 8 out of 38 cancers and 12 out of 38 metastases. For the first time in literature, we show that primary colorectal cancer and paired metastasis may exhibit difference with respect to EGFR pathway deregulation mechanisms possibly implying a different response to cetuximab or panitumumab treatment. The investigation of treated patients confirms this hypothesis. We therefore suggest that the analysis of metastatic lesion should be considered in patient management as well as in designing future clinical trials aimed to investigate the effect of anti-EGFR monoclonal antibodies in the treatment of mCRC.

Life expectancy of women with lupus nephritis now approaches that of the general population.

Immunosuppressive treatment has changed the prognosis of Lupus nephritis over time, but improvement in prognosis is difficult to analyze in different historical periods, and should be better demonstrated in comparison with life expectancy of sex-and age-matched people. Long-term patient and renal survival of 90 patients diagnosed with Lupus nephritis at our center from 1968 to 2001 with a follow-up time of 14+/-8 years was retrospectively evaluated. Patient and kidney survival significantly increased over time. Multivariate analyses show that risks of patient and renal death decreased by 8% at each year of follow-up, and increased by more than 5 time in patients aged > 30 years at diagnosis. As only 14 patients were men, relative survival as compared to that of the sex- and age-matched general population of the Piedmont Region was calculated for the 76 women. Improvement in the survival of the cohort of women was seen at any time of follow-up: in particular, it was sharply lower in the first period (relative survival at 5, 10 and 15 years = 0.784, 0.665, and 0.620, respectively) and increased in the second (relative survival at 5, 10 and 15 years = 0.939, 0.921, and 0.850, respectively) nearly approaching that expected for the general population, i.e. 0.993, 0.983 and 0.967, respectively. Taken together, our data allow us to draw the conclusion that life expectancy in women with Lupus nephritis has improved over time, paralleling an improved awareness of the disease and a significant increase in steroid pulse therapy as induction/remission phase. Improvement in survival is for the first time demonstrated to cover the gap with life expectancy of the general population for women with Lupus nephritis.

Breast cancer classification according to immunohistochemical markers: clinicopathologic features and short-term survival analysis in a population-based study from the South of Switzerland.

BACKGROUND: Breast cancer may be classified into distinct molecular subtypes based on gene expression profiling and/or immunophenotypic characteristics. Aim of the study was to investigate prevalence, clinicopathologic features and overall survival (OS) of molecular subtypes, in a large European population-based study. PATIENTS AND METHODS: All invasive breast cancers from 2003 to 2007 were selected from the files of Ticino Cancer Registry. Molecular subtypes were defined by immunohistochemical markers. Clinicopathological characteristics and short-term OS were analyzed. RESULTS: Of 1214 invasive breast cancers, 73.2% were luminal A subtype, 13.8% luminal B, 7.4% basal like and 5.6% Her2/neu. Basal like presented largely in premenopausal women and displayed aggressive features, such as large tumor size, poorly differentiated cancers, high Ki-67 proliferation index and the worst 24-month OS. Luminal A included the highest percentage of patients >70, the highest proportion of stage I tumors and well/moderately differentiated lesions. Her2/neu was more frequent in postmenopausal women and showed the highest percentage of positive lymph nodes and stage IV cases. CONCLUSION: This is a comprehensive European population-based study on breast cancer molecular subtypes. We provide strong evidence that the molecular classification is useful for clinical management and superior to World Health Organization classification in terms of short-term prognostic value.

Population-based incidence and mortality cancer trends (1986-1997) from the network of Italian cancer registries.

The objective of this study was to analyse incidence and mortality cancer trends in the Italian Network of Cancer Registries (about 8,000,000 inhabitants) during the period 1986-1997. Included were 525,645 newly diagnosed cancers and 269,902 cancer deaths (subjects > 14 years). Joinpoints (points in time where trend significantly changes from linearity) were found and estimated annual percentage changes (EAPC) used to summarize tendencies. Overall cancer incidence increased in both sexes and cancer mortality significantly decreased (since 1991 among men). Lung cancer showed significantly decreasing incidence (EAPC = -1.4%) and mortality (EAPC = -1.6%) among men and increasing trends among women. In women, breast cancer incidence significantly increased (EAPC= +1.7%) and mortality decreased since 1989 (EAPC= -2.0%). Stomach cancer incidence and mortality decreased in both sexes. Prostate incidence sharply increased since 1991 and mortality decreased. Colon cancer incidence increased and rectum mortality decreased significantly in both sexes. Significant increases in incidence were also found for kidney (up to 1991 among men), urinary bladder, skin epithelioma, melanoma, liver (up to 1993 among men), pancreas, mesothelioma, Kaposi's sarcoma (up to 1995 among men), testis, thyroid, non-Hodgkin's lymphomas and multiple myeloma. Mortality significantly decreased for cancers of the oral cavity and pharynx, oesophagus, liver (women), larynx (men), bone, cervix (since 1990), central nervous system, urinary bladder, thyroid, Hodgkin's lymphomas and leukaemias (men). Non-Hodgkin's lymphoma mortality increased in both sexes. In conclusion, most of the changes seen can be explained as the effect of changes in smoking habits and of the extension of secondary prevention activities. The Italian health care system will also have to cope with growing cancer diagnostic and therapeutic needs due to population ageing.

Survival analysis of childhood tumours: data from the Italian cancer registries.

This study shows the childhood cancer survival rates of 1,315 cases incident in the 1990-1994 period in Italy. The observed survival shows an increase over the previous period in almost all diagnostic groups. In particular, 5-year survival attained 72% overall, 78% for acute lymphatic leukaemia, about 100% for Hodgkin's disease, 70% for non Hodgkin's lymphomas, 64% for central nervous system tumours, 87% for retinoblastoma, 80% for renal tumours, 67% for hepatic tumours, 71% for bone tumours, and 70% for soft tissue sarcomas. Finally, the findings are comparable to those in other countries (USA, Great Britain, Australia, Slovakia) and they show a progressive improvement in survival.