Immunolocalization of PTCH protein in odontogenic cysts and tumors

The human patched gene (PTCH) functions in both embryologic development and tumor suppression. PTCH mutations have been found in odontogenic keratocysts. However, the expression and localization of the protein product of the gene have not been determined in odontogenic tumors and cysts. We investigated 68 odontogenic lesions by immunohistochemistry, and compared their PTCH expression with that in basal cell carcinomas. All odontogenic lesions, including two keratocysts with truncating mutations, were positive for PTCH. Different types of lesions had different amounts of staining. Lack of staining was noted in the majority of basal cell carcinomas. Taken together, these data suggest that odontogenic keratocysts arise with heterozygous mutations of the PTCH gene.     

La conscience autonoétique dans les métastases cérébrales : regards croisés sur le voyage mental dans le temps

This paper focused on the importance of autonoetic consciousness or mental time travel, as a sense of a subjective experience of time in patients with brain metastases (BM). In particular, the common feature between prospective memory (i.e., “remember to remember”) and time perspective (i.e., time profile) may lie in mental time travel. In line with recent studies, they were explored as two psychological and neuropsychological determinants of quality of life in patients with BM. Finally, research perspectives and clinical supports were proposed.     

Physical activity and sedentary behavior in relation to lung cancer incidence and mortality in older women: The Women's Health Initiative

Physical activity has been associated with lower lung cancer incidence and mortality in several populations. We investigated these relationships in the Women's Health Initiative Observational Study (WHI‐OS) and Clinical Trial (WHI‐CT) prospective cohort of postmenopausal women. The WHI study enrolled 161,808 women aged 50–79 years between 1993 and 1998 at 40 U.S. clinical centers; 129,401 were eligible for these analyses. Cox proportional hazards models were used to assess the association of baseline physical activity levels [metabolic equivalent (MET)‐min/week: none <100 (reference), low 100 to <500, medium 500 to <1,200, high 1,200+] and sedentary behavior with total lung cancer incidence and mortality. Over 11.8 mean follow‐up years, 2,148 incident lung cancer cases and 1,365 lung cancer deaths were identified. Compared with no activity, higher physical activity levels at study entry were associated with lower lung cancer incidence [p = 0.009; hazard ratios (95% confidence intervals) for each physical activity category: low, HR: 0.86 (0.76–0.96); medium, HR: 0.82 (0.73–0.93); and high, HR: 0.90 (0.79–1.03)], and mortality [p < 0.0001; low, HR: 0.80 (0.69–0.92); medium, HR: 0.68 (0.59–0.80); and high, HR: 0.78 (0.66–0.93)]. Body mass index (BMI) modified the association with lung cancer incidence (p = 0.01), with a stronger association in women with BMI < 30 kg/m². Significant associations with sedentary behavior were not observed. In analyses by lung cancer subtype, higher total physical activity levels were associated with lower lung cancer mortality for both overall NSCLC and adenocarcinoma. In conclusion, physical activity may be protective for lung cancer incidence and mortality in postmenopausal women, particularly in non‐obese women.     

XPC (A2920C), XPF (T30028C), TP53 (Arg72Pro), and GSTP1 (Ile105Val) polymorphisms in prognosis of cutaneous melanoma

Tumor Biology - This study aimed to evaluate whether XPC A2920C, XPF T30028C, TP53 Arg72Pro, and GSTP1 Ile105Val polymorphisms alter outcomes of cutaneous melanoma (CM) patients. DNA from 237 CM...     

Occurrence and outcome of de novo metastatic breast cancer by subtype in a large,diverse population

Purpose

To examine the occurrence and outcomes of de novo metastatic (Stage IV) breast cancer, particularly with respect to tumor HER2 expression.

Methods

We studied all 6,268 de novo metastatic breast cancer cases diagnosed from 1 January 2005 to 31 December 2011 and reported to the California Cancer Registry. Molecular subtypes were classified according to HER2 and hormone receptor (HR, including estrogen and/or progesterone receptor) expression. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) of Stage IV versus Stage I–III breast cancer; Cox proportional hazards regression was used to assess relative hazard (RH) of mortality.

Results

Five percent of invasive breast cancer was metastatic at diagnosis. Compared to patients with earlier stage disease, patients with de novo metastatic disease were significantly more likely to have HER2+ tumors (HR+/HER2+: OR 1.29, 95 % CI 1.17–1.42; HR?/HER2+: OR 1.40, 95 %CI 1.25–1.57, vs. HR+/HER2?). Median survival improved over time, but varied substantially across race/ethnicity (Asians: 34 months; African Americans: 6 months), neighborhood socioeconomic status (SES) (highest: 34 months, lowest: 20 months), and molecular subtype (HR+/HER2+: 45 months; triple negative: 12 months). In a multivariable model, triple negative (RH 2.85, 95 % CI 2.50–3.24) and HR?/HER2+ (RH 1.60, 95 % CI 1.37–1.87) had worse, while HR+/HER2+ had similar, risk of all-cause death compared to HR+/HER2? breast cancer.

Conclusions

De novo metastatic breast cancer was more likely to be HER2+. Among metastatic tumors, those that were HER2+ had better survival than other subtypes.

     

Innate immunity and aging

Advanced age is associated with defects in all of the cells of the innate immune system, including numbers, function, and early stages of activation. This review, presents the current state of the field on the impact of age on the innate immune system. The analysis of the literature suggests that a dysfunctional innate immune system is a contributing factor to aberrant outcomes after injury or infection and to the development of many of the diseases observed in the elderly. Gaining an understanding of the nature of the defects in innate immune cells may allow the development of therapeutic strategies aimed to restore innate immune function in aged individuals.