Postpulmonary tuberculosis complications in South Africa and a potential link with pulmonary hypertension: Premise for clinical and scientific investigations

CITATION: Allwood, B. W. et al. 2018. Post-pulmonary tuberculosis complications in South Africa and a potential link with pulmonary hypertension : premise for clinical and scientific investigations. South African Medical Journal, 108(7):529, doi:10.7196/SAMJ.2018.v108i7.13359.The original publication is available at http://www.samj.org.zaThe magnitude of the pulmonary tuberculosis (TB) epidemic in South Africa (SA) and globally[1] has received increased attention. Efforts have been made to explore new and improved diagnostic[2] and treatment strategies,[3] but the story does not end with treatment, and TB frequently results in long-term lung damage.http://www.samj.org.za/index.php/samj/article/view/12339/8528Publisher's versio

T-cadherin loss promotes experimental metastasis of squamous cell carcinoma

T-cadherin is gaining recognition as a determinant for the development of incipient invasive squamous cell carcinoma (SCC). However, effects of T-cadherin expression on the metastatic potential of SCC have not been studied. Here, using a murine model of experimental metastasis following tail vein injection of A431 SCC cells we report that loss of T-cadherin increased both the incidence and rate of appearance of lung metastases. T-cadherin-silenced SCC metastases were highly disordered with evidence of single cell dissemination away from main foci whereas SCC metastases overexpressing T-cadherin developed as compact, tightly organised sheets. SCC cell adhesion to vascular endothelial cells (EC) in culture was increased for T-cadherin-silenced SCC and decreased for T-cadherin-overexpressing SCC. Confocal microscopy showed that T-cadherin-silenced SCC adherent on EC display an elongated morphology with long thin extensions and a high degree of intercalation within the EC monolayer, whereas SCC overexpressing T-cadherin formed poorly-spread multicellular aggregates that remain on the outer surface of the EC monolayer. T-cadherin-deficient SCC or human keratinocyte cells exhibited increased transendothelial migration in vitro which could be attenuated in the presence of EGFR inhibitor gefitinib. Our data suggest that loss of T-cadherin can increase metastatic potential and aggressiveness of SCC, possibly due to facilitating arrest and extravasation through the vascular wall and/or more efficient establishment of metastases in the new microenvironment

β-arrestin Kurtz inhibits MAPK and Toll signalling in Drosophila development

β-Arrestins are best known as adaptor proteins involved in GPCR signal transduction, although they are known to regulate multiple signalling cascades. In this study, Tipping et al identify a new function for the Drosophila β-arrestin as an inhibitor of both Toll and RTK pathways during development

Docetaxel and cisplatin combination chemotherapy in advanced carcinoma of the urothelium: A multicenter phase II study of the Hellenic Cooperative Oncology Group

Purpose: Both docetaxel and cisplatin have moderate activity in patients with advanced urothelial cancer. We performed a multicenter phase II study in order to assess the efficacy and toxicity of the combination of these two agents in patients with advanced carcinoma of the urothelium. Patients and methods: Sixty-six patients not amenable to curative surgery or irradiation were enrolled onto this cooperative group study and treated on an outpatient basis with docetaxel 75 mg/m(2) followed by cisplatin 75 mg/m(2), both administered intravenously. Granulocyte-colony stimulating factor was administered subcutaneously at a dose of 5 mu g/kg daily from day 5 until resolution of neutropenia. The chemotherapy was administered every three weeks for a maximum of six courses in patients without evidence of progressive disease. Results: Thirty-four of sixty-six patients (52%, 95% confidence interval 40%-64%) demonstrated objective responses, with eight achieving clinical complete responses and twenty-six partial responses. A multivariate logistic regression analysis indicated that the patients most likely to respond were those without lung metastasis and without weight loss before treatment. The median duration of response was 6.1 months and the median times to progression and survival for all patients were 5 and 8 months, respectively. Absence of anemia, of liver metastases and of weight loss correlated with longer survival. Grade greater than or equal to 3 toxicities included granulocytopenia in 33% of patients, anemia in 14%, diarrhea in 13% and emesis in 7% of patients. Conclusion: The combination of docetaxel and cisplatin appeared relatively well tolerated and moderately active in patients with advanced urothelial cancer. The patients most likely to benefit were those without weight loss and without lung or liver metastases