Uncovering the genomic heterogeneity of multifocal breast cancer

Multifocal breast cancer (MFBC), defined as multiple synchronous unilateral lesions of invasive breast cancer, is relatively frequent and has been associated with more aggressive features than unifocal cancer. Here, we aimed to investigate the genomic heterogeneity between MFBC lesions sharing similar histopathological parameters. Characterization of different lesions from 36 patients with ductal MFBC involved the identification of non‐silent coding mutations in 360 protein‐coding genes (171 tumour and 36 matched normal samples). We selected only patients with lesions presenting the same grade, ER, and HER2 status. Mutations were classified as ‘oncogenic’ in the case of recurrent substitutions reported in COSMIC or truncating mutations affecting tumour suppressor genes. All mutations identified in a given patient were further interrogated in all samples from that patient through deep resequencing using an orthogonal platform. Whole‐genome rearrangement screen was further conducted in 8/36 patients. Twenty‐four patients (67%) had substitutions/indels shared by all their lesions, of which 11 carried the same mutations in all lesions, and 13 had lesions with both common and private mutations. Three‐quarters of those 24 patients shared oncogenic variants. The remaining 12 patients (33%) did not share any substitution/indels, with inter‐lesion heterogeneity observed for oncogenic mutation(s) in genes such as PIK3CA, TP53, GATA3, and PTEN. Genomically heterogeneous lesions tended to be further apart in the mammary gland than homogeneous lesions. Genome‐wide analyses of a limited number of patients identified a common somatic background in all studied MFBCs, including those with no mutation in common between the lesions. To conclude, as the number of molecular targeted therapies increases and trials driven by genomic screening are ongoing, our findings highlight the presence of genomic inter‐lesion heterogeneity in one‐third, despite similar pathological features. This implies that deeper molecular characterization of all MFBC lesions is warranted for the adequate management of those cancers. © 2015 The Authors. Pathological Society of Great Britain and Ireland.     

Antinociceptive, anti-inflammatory and antipyretic effects of Solanum nigrum chloroform extract in animal models

AIM: The present study was carried out to evaluate the antinociceptive, anti-inflammatory and antipyretic effects of chloroform extract of Solanum nigrum leaves using various animal models. METHODS: The extract was prepared by soaking (1:20; w/v) the air-dried powdered leaves (20 g) in chloroform for 72 hrs followed by evaporation (40 degrees C) under reduced pressure to dryness (1.26 g) and then dissolved (1:50; w/v) in dimethylsulfoxide (DMSO). The supernatant, considered as the stock solution with dose of 200 mg/kg, was diluted using DMSO to 20 and 100 mg/kg, and all doses were administered (s.c.; 10 ml/kg) in mice/rats 30 min prior to tests. RESULTS: The extract exhibited significant (p<0.05) antinociceptive activity when assessed using the abdominal constriction, hot plate and formalin tests. The extract also produced significant (p<0.05) anti-inflammatory and antipyretic activities when assessed using the carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests. Overall, the activities occurred in a dose-independent manner. CONCLUSION: The present study demonstrated that the lipid-soluble extract of S. nigrum leaves possessed antinociceptive, anti-inflammatory and anti-pyretic properties and confirmed the traditional claims.     

Primary Immunodeficiency Disorders: Survey of Pediatricians in Kuwait

INTRODUCTION: Early diagnosis of primary immunodeficiency disorders (PID) is critical so life saving interventions can be implemented to avoid significant morbidity and mortality. Unfortunately, they are frequently misdiagnosed, which results into significant delay in diagnosis. This study aimed to determine the knowledge and practice of pediatricians in Kuwait about PID. MATERIALS AND METHODS: A 66-item self-administered questionnaire was designed and distributed to the pediatricians working at all six governmental hospitals to measure their knowledge and practice about PID. A total of 244 pediatricians (78.4%; 143 males and 101 females) participated in the study. The mean age of participants was 40 years, and the mean number of years working in pediatrics was 13 years. The mean overall score was 59.6%, whereas the mean score in clinical presentation section was 63%, in associated diseases and syndromes section 58%, and in laboratory investigations section 51%. Only 26% of the participants answered correctly at least 2/3 of the questions (67% of the questions). CONCLUSION: This survey demonstrates that there is universal deficiency in both the knowledge and practice of pediatricians in the field of PID. Implementation of strategies to improve the awareness of pediatricians about PID is critical so early therapeutic interventions can be done to improve the health and prevent morbidity and mortality.     

Hybrid procedure in pseudoaneurysm of the descending thoracic aorta in Hospital Kuala Lumpur

Conventional open repair for Thoracoabdominal aortic aneurysm (TAA) is associated with high morbidity and mortality. Spinal cord ischemia (SCI), renal failure, bowel ischemia and mortality are established complications following this procedure. With the advent of endovascular stent technology, various novel approaches have been described to reduce these complications, namely fenestrated stent graft and hybrid procedure. We present a case of hybrid procedure in a pseudoaneurysm of descending thoracic aorta done in Kuala Lumpur Hospital.     

Microencapsulation of lime (Citrus aurantifolia) oil for antibacterial finishing of cotton fabric

Functional cotton fabric incorporated with antibacterial microcapsules of lime (C. aurantifolia) essential oil (LO) was prepared. The coacervation method, employing two biopolymers of alginate and gelatin as the shells, was preferentially selected to produce the LO microcapsules, whereas immobilization of the LO microcapsules onto the fabric was done using the pad–dry–cure method using various concentrations of citric acid binder. The antibacterial inhibition zone of the functional fabric was subsequently analysed using the Kirby Bauer method. The LO microcapsules were produced with a yield, encapsulation efficiency (EE), and oil content (OC) of 47 ± 4%, 84 ± 11%, and 58 ± 4%, respectively. The homogenous spherical and soft microcapsules (1.554 μm) bonded effectively by 4% citric acid onto the surface of the fabric and detached back by only 3% after 15 cycles of washing. Overall, the optimized functional fabric exhibited the highest antibacterial activities among others against typical skin bacteria, such as S. aureus, E. coli, K. pneumoniae, and S. epidermidis, and thus it can be potentially applied to obtain antibacterial functional textile.

Functional cotton fabric incorporated with antibacterial microcapsules of lime (C. aurantifolia) essential oil (LO) was prepared.     

Absence of p53 Gene Expression in Selenium Molecular Prevention of Chemically Induced Hepatocarcinogenesis in Rats

Background/Aim:

p53 pathway is thought by many researchers to be critically involved in selenium''s chemoprevention or in hepatocarcinogenesis. The aim of this study was to investigate the gene expression of p53, p21 and B-cell lymphoma-2 (bcl-2) using preventive and therapeutic approaches of selenium in chemically induced hepatocarcinogenesis in rats.

Materials and Methods:

Rats were divided randomly into six groups: Negative control, positive control (diethyl nitrosamine +2-acetylaminofluorene), preventive group, preventive control (respective control for preventive group), therapeutic group and therapeutic control (respective control for therapeutic group). p53, p21 and bcl-2 genes on liver tissues were measured using real-time polymerase chain reaction.

Results:

The expression of p53 was only significant in the therapeutic control. The expression of bcl-2 was insignificant in all the groups. p21 expression was significant in all the groups except the preventive group.

Conclusions:

The selenium molecular mechanism for liver cancer prevention is not through the p53 pathway. Also, the absence of p53 is not necessary for chemically induced liver cancer in rats.