Male breast cancer: a report of 127 cases at a Moroccan institution

Background: Male breast cancer (MBC) is a rare disease representing less than 1% of all malignancies in men and only 1% of all incident breast cancers. Our study details clinico-pathological features, treatments and prognostic factors in a large Moroccan cohort. Findings: One hundred and twenty-seven patients were collected from 1985 to 2007 at the National Institute of Oncology in Rabat, Morocco. Median age was 62 years and median time for consultation 28 months. The main clinical complaint was a mass beneath the areola in 93, 5% of the cases. Most patients have an advanced disease. Ninety-one percent of tumors were ductal carcinomas. Management consisted especially of radical mastectomy; followed by adjuvant radiotherapy and hormonal therapy with or without chemotherapy. The median of follow-up was 30 months. The evolution has been characterized by local recurrence; in twenty two cases (17% of all patients). Metastasis occurred in 41 cases (32% of all patients). The site of metastasis was the bone in twenty cases; lung in twelve cases; liver in seven case; liver and skin in one case and pleura and skin in one case. Conclusion: Male breast cancer has many similarities to breast cancer in women, but there are distinct features that should be appreciated. Future research for better understanding of this disease at national or international level are needed to improve the management and prognosis of male patients

Huntingtin CAG expansion impairs germ layer patterning in synthetic human 2D gastruloids through polarity defects

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expansion of the CAG repeats in the huntingtin gene (HTT). Although HD has been shown to have a developmental component, how early during human embryogenesis the HTT-CAG expansion can cause embryonic defects remains unknown. Here, we demonstrate a specific and highly reproducible CAG length-dependent phenotypic signature in a synthetic model for human gastrulation derived from human embryonic stem cells (hESCs). Specifically, we observed a reduction in the extension of the ectodermal compartment that is associated with enhanced activin signaling. Surprisingly, rather than a cell-autonomous effect, tracking the dynamics of TGFβ signaling demonstrated that HTT-CAG expansion perturbs the spatial restriction of activin response. This is due to defects in the apicobasal polarization in the context of the polarized epithelium of the 2D gastruloid, leading to ectopic subcellular localization of TGFβ receptors. This work refines the earliest developmental window for the prodromal phase of HD to the first 2 weeks of human development, as modeled by our 2D gastruloids

WNT signaling memory is required for ACTIVIN to function as a morphogen in human gastruloids

Self-organization of discrete fates in human gastruloids is mediated by a hierarchy of signaling pathways. How these pathways are integrated in time, and whether cells maintain a memory of their signaling history remains obscure. Here, we dissect the temporal integration of two key pathways, WNT and ACTIVIN, which along with BMP control gastrulation. CRISPR/Cas9-engineered live reporters of SMAD1, 2 and 4 demonstrate that in contrast to the stable signaling by SMAD1, signaling and transcriptional response by SMAD2 is transient, and while necessary for pluripotency, it is insufficient for differentiation. Pre-exposure to WNT, however, endows cells with the competence to respond to graded levels of ACTIVIN, which induces differentiation without changing SMAD2 dynamics. This cellular memory of WNT signaling is necessary for ACTIVIN morphogen activity. A re-evaluation of the evidence gathered over decades in model systems, re-enforces our conclusions and points to an evolutionarily conserved mechanism

Tuberculin responses in children with allergic diseases

Background: The prevalence of allergic disorders has been increasing over the last 30 years, especially in developed countries. One factor associated with this rise may be the decline of many childhood infections. We investigated tuberculin responses in allergic children in order to see the development of delayed-type hypersensitivity reactions to tubercule bacillus infection. Methods: The study sample was composed of 106 allergic and 100 nonallergic children vaccinated with bacille Calmette-Guerin (BCG). The standard Mantoux test was applied to all children. The reactions were read after 72 h by measuring the diameter of the wheal. Results: The wheal size was 6.29 ± 5.09 mm (mean ± SD) in allergic children, and 2.79 ± 2.96 mm in nonallergic children. The difference between the two groups was significant (P < 0.001). In children with a single BCG scar, the mean purified protein derivative (PPD) wheal size for allergic children was 4.77 ± 4.79 mm, and for nonallergic children it was 2.48 ± 3.19 mm. The mean PPD wheal sizes in allergic and nonallergic children who had been vaccinated twice were 8.35 ± 4.80 mm and 3.33 = 2.44 mm, respectively. This difference was statistically significant (P < 0.05). In 27.35% of the allergic children and 6% of the nonallergic children, the positive tuberculin responses (PPD ? 10 mm) were recorded. The difference was significant (P < 0.05). Conclusions: Our results showed that response to tuberculin in BCG-immunized allergic children is higher than in BCG-immunized nonallergic children

Preliminary analysis of a phase II study of Paclitaxel and CHART in locally advanced non-small cell lung cancer

Paclitaxel (Taxol(R); Bristol-Myers Squibb) is one of the most active single agents for non-small cell lung cancer (NSCLC), and ideal in combination with radiation therapy. We designed a phase II study to determine the efficacy and toxicity of continuous hyperfractionated accelerated radiotherapy (CHART) and concurrent weekly Paclitaxel (T) in good performance status patients with unresectable stage III A and B NSCLC. T (60 mg/m(2)) was given as a 3-h infusion on days 1, 8, 15, 22, 29 and 36; CHART was started on day 15 with 150 cGy/fraction given three times a day for a total dose of 54 Gy in 12 days with no weekend break. Twenty patients were evaluable for acute toxicity. The major acute toxicities were esophagitis and pulmonary toxicity; 70% of the patients experienced grade 2-3 esophagitis and 50% experienced grade greater than or equal to 3 pulmonary toxicity. Grade 3 anemia developed in only one patient. Of the 17 patients evaluable for late toxicity, 12% of the patients had grade 3 pulmonary toxicity, one patient developed grade 4 esophagitis. Nineteen patients were evaluable response. The overall response rate was 84% (95% confidence interval, 60-97). CHART with concurrent weekly T seems to be an effective regimen, but tolerability needs to be documented with a larger number of patients and longer follow-up. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved

Radiation Therapy and Chemotherapy Results in Elderly Patients With Stage III Non-Small Cell Lung Cancer: Turkish Thoracic Radiation Oncology Group Study

58th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) -- SEP 25-28, 2016 -- Boston, MAWOS: 000387655803461Amer Soc Radiat Onco