Benefit of adjuvant chemotherapy in patients with special histology subtypes of triple-negative breast cancer: a systematic review

Breast Cancer Research and Treatment - Breast cancer (BC) is a leading cause of morbidity, disability, and mortality in women, worldwide; triple-negative BC (TNBC) is a subtype traditionally...     

Pilot-scale production of a highly thermostable α-amylase enzyme from Thermotoga petrophila cloned into E. coli and its application as a desizer in textile industry

In this study, the industrial applications of a highly thermostable α-amylase as a desizer in the textile industry was evaluated. The cloned gene was expressed in different media (ZBM, LB, ZYBM9, and ZB) with IPTG (isopropyl β-d-1-thiogalactopyranoside) used as an inducer. Lactose was also used as an alternate inducer for the T7 promoter system in E. coli. For the large-scale production of the enzyme, different parameters were optimized. The maximum enzyme production was achieved when the volume of medium was 70% of the total volume of fermenter with a 2.0 vvm air supply and 20% dissolved oxygen at a 200 rpm agitation rate. Under all the optimized conditions, the maximum enzyme production was 22.08 U ml⁻¹ min⁻¹ with lactose (200 mM) as an inducer in ZBM medium. The desizing potential of the purified α-amylase enzyme was calculated with different enzyme concentrations (50–300 U ml⁻¹) at different temperatures (50–100 °C), and pHs (4–9) with varying time intervals (30–120 min). The highest desizing activity was found when 150 U ml⁻¹ enzyme units were utilized at 85 °C and at 6.5 pH for 1 h.

Thermostable recombinant α-amylase was produced in a large scale for the desizing of cotton cloth in the textile industry.     

Possible benefits of high-dose chemotherapy and autologous stem cell transplantation for adults with recurrent medulloblastoma

In an attempt to improve the dismal prognosis of adults with recurrent medulloblastoma, six patients were treated with aggressive salvage therapy including high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). At relapse, all patients underwent surgical debulking followed by HDCT/ASCT and then radiotherapy when possible. The treatment plan included two cycles of HDCT/ASCT; first with cyclophosphamide, etoposide and carboplatin (CECb) and then 2 months later with cyclophosphamide and thiotepa (CT). Three of the six patients received the planned therapy. One patient experienced severe toxicity requiring life-sustaining therapy. This patient developed multi-organ dysfunction including multiple enhancing lesions in both cerebral hemispheres that slowly resolved over several months. Two other patients did not mobilize sufficient stem cells for two ASCT procedures. They received one ASCT conditioned with cyclophosphamide, thiotepa and carboplatin (CTCb). Three of six patients had a complete response (CR); the other three had a partial response (PR). Following the first ASCT, median duration of response was 13.5 months (range 9-29 months) and median survival was 21.5 months (range 12-42 months). There was no treatment-related mortality. We conclude that HDCT/ASCT with CECb-CT or CTCb is active against recurrent medulloblastoma in adults and may be associated with prolonged remissions. Multiple enhancing cerebral lesions on brain MRI early post-HDCT/ASCT may be a consequence of the treatment rather than metastatic disease.     

A novel mechanism for regulating hepatic glycogen synthesis involving serotonin and cyclin-dependent kinase-5

Hepatic autonomic nerves regulate postprandial hepatic glucose uptake, but the signaling pathways remain unknown. We tested the hypothesis that serotonin (5-hydroxytryptamine [5-HT]) exerts stimulatory and inhibitory effects on hepatic glucose disposal. Ligands of diverse 5-HT receptors were used to identify signaling pathway(s) regulating glucose metabolism in hepatocytes. 5-HT had stimulatory and inhibitory effects on glycogen synthesis in hepatocytes mediated by 5-HT1/2A and 5-HT2B receptors, respectively. Agonists of 5-HT1/2A receptors lowered blood glucose and increased hepatic glycogen after oral glucose loading and also stimulated glycogen synthesis in freshly isolated hepatocytes with greater efficacy than 5-HT. This effect was blocked by olanzapine, an antagonist of 5-HT1/2A receptors. It was mediated by activation of phosphorylase phosphatase, inactivation of glycogen phosphorylase, and activation of glycogen synthase. Unlike insulin action, it was not associated with stimulation of glycolysis and was counteracted by cyclin-dependent kinase (cdk) inhibitors. A role for cdk5 was supported by adaptive changes in the coactivator protein p35 and by elevated glycogen synthesis during overexpression of p35/cdk5. These results support a novel mechanism for serotonin stimulation of hepatic glycogenesis involving cdk5. The opposing effects of serotonin, mediated by distinct 5-HT receptors, could explain why drugs targeting serotonin function can cause either diabetes or hypoglycemia in humans.     

The prevalence and break down of narrow anterior chamber angle pathology presenting to a general ophthalmology clinic

To approximate the breakdown of narrow anterior chamber angle conditions, on general ophthalmology clinics, in the predominantly white population of the South East Kent region in the United Kingdom.A review was done of all patients attending a secondary care ophthalmology general clinic over a 3-year period. Patients were assessed with: slitlamp biomicroscopy with indentation gonioscopy; SD optical coherence tomography, Humphrey visual field analyzer, and high frequency ultrasound and categorized into various narrow angle conditions. These were: narrow Van Herrick but open angle; primary narrow angle but nonoccludable; primary angle closure suspect; primary angle closure; chronic narrow angle glaucoma; plateau iris configuration; plateau iris syndrome, and phacomorphic narrow angle.A total of 14,520 patients were referred to the clinic, of those 10,491 attended and were analyzed. Six hundred seventy four (6.4%) of the patients had some form of narrow angle condition in at least 1 eye. The majority of these patients were at relative low risk of pathology such as nonoccludable narrow angles (359/53.3%) and narrow Van Herrick but open angles (93/13.8%). 8.8% of all the narrow angle patients had primary angle closure suspect or primary angle closure. Plateau iris pathology was seen in 68 (10.1%) of patients with 18 (26%) having confirmed plateau iris syndrome after peripheral iridotomy. Phacomorphic pathology was confirmed in 75 (11.1%) patients.Narrow angle patients form a significant proportion (6.4%) of those attending general ophthalmology clinic in the predominantly white population in the South East Kent Region of the United Kingdom. The majority of these (67.1%) are at a relatively low risk of developing acute or chronic angle closure glaucoma. Of the remaining patients 8.8% have primary angle closure suspect or primary angle closure and 2.9% have already progressed to chronic narrow angle closure glaucoma. Plateau iris pathology and phacomorphic glaucoma account for the remainder of the presentations.     

Cost-effectiveness of breast cancer screening programme for women in rural China

In low and middle-income countries mammographic breast cancer screening is prohibitively expensive and a cheaper alternative option is to use ultrasound as the primary screening test. In 2009, China launched a breast cancer screening programme for rural women aged 35–64 years with clinical breast examination coupled with ultrasound as the primary tool. Our study aimed to analyse the cost-effectiveness of breast screening compared to no screening among Chinese rural women. We developed a Markov model to estimate the lifetime costs and effects for rural women aged 35 years from a societal perspective. Asymptomatic women in the intervention arm were screened every 3 years before age 64 years. Breast cancer in the non-screening arm can only be diagnosed on presentation of symptoms. Parameter uncertainty was explored using one-way and probabilistic sensitivity analyses. Compared to no screening, breast cancer screening cost $186.7 more and led to a loss of 0.20 quality-adjusted life years (QALYs). Breast screening was more expensive and did harm to health among rural women with an incremental cost-effectiveness ratio (ICER) of $-916/QALY. The sensitivity analysis identified utility loss from false positives as the factor that most influenced the results, but this did not affect the conclusions. In a rural setting with such low breast cancer incidence, screening for asymptomatic disease is not cost-effective with current screening tools. Priority should be given to ensure that symptomatic women have proper access to diagnosis and treatment at an early stage as this will lead to mortality reductions without the usual screening harms.