The presence and impact of estrogen metabolism on the biology of triple-negative breast cancer

Purpose

While triple-negative breast cancer (TNBC) is negative for estrogen receptor alpha, a substantial proportion of carcinomas express estrogen receptor beta (ERβ); consequently, estrogen actions and metabolism may be relevant in this cancer subtype.

Methods

A cohort of 81 TNBC patients from Tohoku University Hospital, Japan were characterised with regard to the expression of estrogen receptor beta and enzymes known to modulate levels of estrogens in breast and other tissues (Aromatase, 17-beta- Hydroxysteroid dehydrogenases 1, 2 and 6). This was done at the protein level by means of immunohistochemistry. As this cohort has been previously characterised for androgens, this also allows for comparison between the expressions of estrogen-related proteins and of androgen-related proteins. Preliminary mechanistic studies in cell culture were also undertaken.

Results

17βHSD2 was detected in the highest number of cases followed by 17βHSD1, 17βHSD6 and aromatase. When comparing the expression of ERβ with that of the enzymes, it was positively correlated with the expression of 17βHSD6 (p < 0.05) and trended towards correlation with dual expression of 17βHSD1 and 2 (p < 0.07). 17βHSD1 was associated with significantly reduced tumour volume (p = 0.0025), while ERβ was associated with a trend towards reduced lymphovascular invasion, (p < 0.061). Interestingly, in survival analysis, 17βHSD6 expression was the only one of these five factors that influenced survival, with positive samples being associated with longer disease-free survival compared to those that were negative for 17βHSD6 (p < 0.05). In assessing associations with expression of proteins in the androgenic pathway, expression of aromatase appeared to be associated with androgenic pathways in TNBC patients (p < 0.05). Due to this association and the potential relevance to androgen-directed therapies in TNBC, we evaluated this interaction in vitro. We observed androgen-dependent upregulation of aromatase and ERβ in a subset of AR expressing TNBC cell lines (MDA-MB-453, SUM-185-PE and MFM-223).

Conclusion

Overall this study suggests the presence of, and a potential protective effect of estrogens in TNBC.

     

Study of lung functions in smokers and non-smokers in rural India

Smoking is a common habit prevalent in both the urban and rural areas in India. Smoking is a well-known risk factor for chronic obstructive pulmonary disease (COPD), a group of lung diseases that includes emphysema and chronic bronchitis. Pulmonary-function tests provide objective, quantifiable measures of lung function. The objective of the present study was to study and compare the pulmonary function tests among smokers and non-smokers in a rural area, to study the role of possible associated factors and relation of type, quantity and duration of smoking on the pulmonary function tests in Rural Maharashtra. The pulmonary function tests were assessed on computerized spirometer in 400 male subjects comprising of 200 smokers and 200 non smokers. Almost all the pulmonary function parameters were significantly reduced in smokers, more commonly in those aged 50 years and above. Obstructive pulmonary impairment was commonest among smokers. Thus by spirometry a spectrum of lung disorders may be detected at an early stage and subsequent morbidity can be minimized.     

Extraskeletal osteosarcoma of abdominal wall in a child

Compared with osteosarcoma of bone, extraskeletal osteosarcoma is rare and accounts for approximately 1% to 2 % of all soft tissue sarcomas. Osteosarcoma arising in soft tissues is exceedingly rare in children. The tumor most often affects older adults, involves the lower extremity, responds poorly to chemotherapy, and carries a grave prognosis. The authors describe a 4-year-old girl with an extraskeletal osteosarcoma in the lateral abdominal wall.     

Imaging of the pituitary: Recent advances

Pituitary lesions, albeit relatively infrequent, can significantly alter the quality of life. This article highlights the role of advanced imaging modalities in evaluating pituitary-hypothalamic axis lesions. Magnetic resonance imaging (MRI) is the examination of choice for evaluating hypothalamic-pituitary-related endocrine diseases. Advanced MR techniques discussed in this article include dynamic contrast-enhanced MRI, 3T MRI, magnetization transfer (MT) imaging, diffusion-weighted imaging (DWI), proton MR spectroscopy, fluorine-18 fluorodeoxyglucose-positron emission tomography, single-photon emission computed tomography, intraoperative MRI, and intraoperative real-time ultrasonography.     

Segregation of gustatory cortex in response to salt and umami taste studied through event-related potentials

In this study, we report gustatory event-related potentials in response to stimulation with monosodium glutamate (MSG) and salt (NaCl). We investigated differences in event-related potential related to stimulus quality, stimulus concentration, cortical topography, and participants' sex. Our results showed that amplitudes P1N1 and N1P2 were significantly larger in response to stimulation with NaCl compared with stimulation with MSG and the topographical distribution of amplitudes varied significantly for the two stimuli. In addition, responses were significantly larger in the right hemisphere compared with the left hemisphere for both stimuli, suggesting right hemispheric dominance for gustatory processing. In conclusion, this study shows significant differences in cerebral processing of MSG and NaCl in the human brain.     

Achieved systolic blood pressure in older people: a systematic review and meta-analysis

Background

It remains unclear into which level the systolic blood pressure (SBP) should be lowered in order to provide the best cardiovascular protection among older people. Hypertension guidelines recommendation on attaining SBP levels <150 mmHg in this population is currently based on experts’ opinion. To clarify this issue, we systematically reviewed and quantified available evidence on the impact of achieving different SBP levels <150 mmHg on various adverse outcomes in subjects aged ≥60 years old receiving antihypertensive drug treatment.

Methods

We searched 8 databases to identify randomized controlled trials (RCTs) and post-hoc analyses or subanalyses of RCTs reporting the effects of attaining different SBP levels <150 mmHg on the risk of stroke, acute myocardial infarction, heart failure, cardiovascular mortality and all-cause mortality in participants aged ≥60 years. We performed random-effects meta-analyses stratified by study design.

Results

Eleven studies (> 33,600 participants) were included. Compared with attaining SBP levels ≥140 mmHg, levels of 130 to <140 mmHg were not associated with lower risk of outcomes in the meta-analysis of RCTs, whereas there was an associated reduction of cardiovascular mortality (RR 0.72, 95% CI 0.59–0.88) and all-cause mortality (RR 0.86, 95% CI 0.75–0.99) in the meta-analysis of post-hoc analyses or subanalyses of RCTs. Limited and conflicting data were available for the SBP levels of <130 mmHg and 140 to <150 mmHg.

Conclusions

Among older people, there is suggestive evidence that achieving SBP levels of 130 to <140 mmHg is associated with lower risks of cardiovascular and all-cause mortality. Future trials are required to confirm these findings and to provide additional evidence regarding the <130 and 140 to <150 mmHg SBP levels.

     

In vitro bactericidal and TEM study of the interaction of Ag-modified titania with coliform bacteria

This research aimed to investigate in vitro photocatalytic bactericidal effect of Ag–TiO₂ nanocomposite using Escherichia coli as a model organism. Highly dispersed, Ag–TiO₂ nanocomposite is used with an average particle size of less than 20?nm. Bactericidal analysis was carried out in Luria Bertani medium on solid agar plates with various illumination time and different concentrations of Ag–TiO₂ nanocomposite. Transmission electron microscopic analysis of bacterial section was used to detect the effect of irradiation of Ag–TiO₂ nanocomposite on the ultra structure of the bacterial cell in order to reveal possible cellular damage. The mechanism underlying the action of photoexcited Ag–TiO₂ nanocomposite on E. coli cell membrane is also evaluated. The results confirmed that E. coli cells after the contact with Ag–TiO₂ nanocomposite were damaged since they showed membrane disorganization. This causes the enhanced level of membrane permeability leading to the build-up of Ag–TiO₂ nanocomposite in the bacterial membrane and also cellular internalization of these nanoparticles.     

Novel Piperine Derivatives with Antidiabetic Effect as PPAR‐γ Agonists

Piperine is an alkaloid responsible for the pungency of black pepper. In this study, piperine isolated from Piper nigrum L. was hydrolyzed under basic condition to obtain piperic acid and was used as precursor to carry out the synthesis of twenty piperine derivatives containing benzothiazole moiety. All the benzothiazole derivatives were evaluated for their antidiabetic potential by OGT test followed by assessment of active derivatives on STZ‐induced diabetic model. It was observed that nine of twenty novel piperine analogues ( 5b, 6a‐h) , showed significantly higher antidiabetic activity in comparison with rosiglitazone (standard). Furthermore, these active derivatives were evaluated for their action as PPAR‐γ agonists demonstrating their mechanism of action. The effects on body weight, lipid peroxidation, and hepatotoxicity after administration with active derivatives were also studied to further establish these derivatives as lead molecules for treatment of diabetes with lesser side‐effects.     

Isolated nasal septum necrosis caused by Aspergillus flavus in an immunocompromised child

Nontraumatic isolated nasal septal aspergillosis in the absence of sinusitis is a rare but serious infection in immunocompromised patients. Adequate management requires early diagnosis, prompt empiric antifungal therapy, and surgical debridement to prevent progression of life-threatening complications. With the increasing population of immunocompromised children, it is essential for timely management that clinicians have a high index of suspicion for this unusual presentation of aspergillosis.