Breast cancer survival in Soweto, Johannesburg, South Africa: A receptor-defined cohort of women diagnosed from 2009 to 11.

BACKGROUND: South Africa's public healthcare system is better equipped to manage breast cancer than most other SSA countries, but survival rates are unknown. METHODS: A historical cohort of 602 women newly diagnosed with invasive breast carcinoma during 2009-2011 at Chris Hani Baragwanath Academic Hospital, Soweto, Johannesburg, was followed using health systems data to December 2014. 'Overall survival' time was defined from diagnosis to death or terminal illness. Cox regression was used to estimate hazard ratios (HR) associated with woman and tumour characteristics. RESULTS: During a median 2.1 years follow-up (IQR 0.5-3.8), 149 women died or were classified terminally ill; 287 were lost-to-follow-up. 3-year survival was 84% for early stage (I/II) and 56% for late stage (III/IV) tumours (late v early: HR 2.8 (95% confidence interval (CI): 1.9-4.1), however the 42% cumulative losses to follow-up over this period were greater for late stage, half of which occurred within 6 months of diagnosis. After mutual adjustment for stage, grade, age, receptor subtype and HIV status, lower survival was also associated with triple negative (HR 3.1 (95% CI: 1.9-5.0)) and HER2-enriched (2.5 (95% CI: 1.4-4.5)) compared to ER/PR+ HER2- tumours, but not with age or HIV-infection (1.4 (95% CI: 0.8, 2.3)). CONCLUSION: In this South African cohort, breast cancer survival is suboptimal, but was better for early stage and hormone receptor-positive tumours. Efforts to reduce clinic losses in the immediate post-diagnosis period, in addition to early presentation and accelerated diagnosis and treatment, are needed to prevent breast cancer deaths, and survival improvements need to be monitored using prospective studies with active follow-up.

In vitro inhibition of angiogenesis by antibodies directed against the 37kDa/67kDa laminin receptor.

The 37kDa/67kDa laminin receptor (LRP/LR) is a central receptor mediating interactions between tumour cells and the basement membrane and is thereby a key player in adhesion and invasion, essential processes in metastatic cancer. To affect continued tumour growth, tumours induce angiogenesis for the constant delivery of nutrients and oxygen. This study aims to determine the blocking effect of the anti-LRP/LR specific antibody, W3 on the angiogenic potential of HUVE (human umbilical vein endothelial) cells. Flow cytometric analysis revealed that 97% of HUVE cells display cell surface LRP/LR. An angiogenesis assay was conducted employing HUVE cells seeded on the basement membrane reconstituent Matrigel™ supplemented with the pro-angiogenic factor vascular endothelial growth factor (VEGF). Post 18h incubation at 37°C tubular structures, namely tube lengths were assessed. Treatment of established tubular structures with 100 µg/ml anti-LRP/LR specific antibody completely blocked angiogenesis. Our findings suggest a central role of the 37kDa/67kDa LRP/LR in tube formation and recommends anti-LRP/LR specific antibodies as potential therapeutic tools for treatment of tumour angiogenesis.

Downregulation of the non-integrin laminin receptor reduces cellular viability by inducing apoptosis in lung and cervical cancer cells.

The non-integrin laminin receptor, here designated the 37-kDa/67-kDa laminin receptor (LRP/LR), is involved in many physiologically relevant processes, as well as numerous pathological conditions. The overexpression of LRP/LR on various cancerous cell lines plays critical roles in tumour metastasis and angiogenesis. This study investigated whether LRP/LR is implicated in the maintenance of cellular viability in lung and cervical cancer cell lines. Here we show a significant reduction in cellular viability in the aforementioned cell lines as a result of the siRNA-mediated downregulation of LRP. This reduction in cellular viability is due to increased apoptotic processes, reflected by the loss of nuclear integrity and the significant increase in the activity of caspase-3. These results indicate that LRP/LR is involved in the maintenance of cellular viability in tumorigenic lung and cervix uteri cells through the blockage of apoptosis. Knockdown of LRP/LR by siRNA might represent an alternative therapeutic strategy for the treatment of lung and cervical cancer.

Patented biological approaches for the therapeutic modulation of the 37 kDa/67 kDa laminin receptor.

IMPORTANCE OF THE FIELD: The 37/67 kDa laminin receptor precursor/laminin receptor (LRP/LR) represents a multifunctional protein located on the cell surface, in the cytosol and the nucleus. The receptor acts as a mediator for cell adhesion, cell proliferation and cell differentiation. It is a key player in invasion and adhesion, major functions of several important metastatic cancer types. The receptor hampers apoptosis thereby favoring cancer progression. LRP/LR plays a major role as a cell surface receptor in prion disorders and may be of considerable importance for other neurodegenerative diseases such as Alzheimer's disease. A series of viruses including Sindbis virus, Dengue virus and Adeno-associated virus use LRP/LR as attachment receptors. Bacteria and Candida albicans use the receptor for pathogenesis. AREAS COVERED IN THIS REVIEW: Background and patented biological approaches for therapeutic modulation of LRP/LR in neurodegenerative diseases, cancer, viral disorders, bacterial and yeast infections. WHAT THE READER WILL GAIN: A comprehensive review of the role of LRP/LR in infectious and non-infectious diseases and an insightful assessment of published or patented biological approaches for the therapeutic modulation of LRP/LR. TAKE HOME MESSAGE: Molecular tools such as antibodies directed against LRP/LR have the potential to act as promising alternative therapeutics for the treatment of various diseases.