Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer

Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan.

Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for ‘sacituzumab govitecan’ and ‘clinical trial’.

Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer.     

Critical study of hair growth analysis with computer-assisted methods

BACKGROUND: Computer-assisted image analysis has been proposed for human hair growth studies. METHODS: The performances of Trichoscan, a commercially available automated system combining epiluminiscence microscopy with digital image analysis, developed for office-based hair growth measurements, have been evaluated comparatively on the same skin sites using standardized photographic equipment and calibrated processing for contrast-enhanced phototrichogram (CE-PTG) analysis. This reference method has been validated with scalp biopsies and histological examination of serial sectioning. RESULTS: Besides edge effects, hair fibres escaped the Trichoscan analysis for various reasons including, but not limited to, thickness, pigmentation, closeness and crossing. CONCLUSION: Most of these problems have been identified in the late 1980s and remain largely unsolved by the processing software that was evaluated in 2004. Therefore claims promoting the Trichoscan method for accurate hair measurements in clinical trials on scalp and body hair are not supported by the present investigation. The speed at which the analysis is performed is outweighed by the errors in signal detection. Therefore we suggest that improvements must be clearly documented before Trichoscan is established for quantified diagnostic purposes and detailed hair cycle monitoring during hair trials.     

Computed tomography and pulmonary function abnormalities in sickle cell disease.

The aim of this study was to determine whether patients with sickle cell disease (SCD) in steady state had pulmonary abnormalities seen on high-resolution computed tomography (HRCT) and whether any abnormalities correlated with contemporaneously diagnosed lung function abnormalities. A subsidiary question was whether the results of a noninvasive measure of haemolysis (end-tidal carbon monoxide (ETCO) levels) correlated with pulmonary function abnormalities. Thirty three patients with SCD, median (range) age 36 yrs (17-67 yrs) were examined. The degree of lobar volume loss and ground-glass opacification and prominence of central vessels on HRCT were quantitatively assessed. Pulmonary function was assessed by measurements of lung volumes, spirometry, gas transfer and oxygen saturation. ETCO levels were measured using an end-tidal CO monitor. Forced expiratory volume in one second (FEV1), forced vital capacity and total lung capacity significantly correlated with HRCT findings, particularly lobar volume loss. ETCO levels significantly negatively correlated with FEV1, vital capacity measured using a plethysmograph, specific airway conductance and arterial oxygen saturation measured by pulse oxymetry. In conclusion, the present results suggest that high-resolution computed tomography noninvasive assessment of haemolysis might be useful to identify sickle cell disease patients with respiratory function impairment.     

双波长紫外分光光度法测定贝母中腺苷和胸苷的含量

将4种贝母的甲醇提取物经薄层色谱法粗分离后,直接用双波长紫外分光光度法测定其含量。结果表明,该方法线性关系好,腺苷和胸苷标准曲线的相关系数均为0.9999,同时也发现平贝、炉贝和伊贝中腺苷都占核苷总量60%以上,而浙贝中仅占约40%,提示贝母生药的抗凝血活性可能与贝母中核苷类化合物的种类和含量的差别有关。     

The origin and nature of stromal osteoclast-like multinucleated giant cells in breast carcinoma: implications for tumour osteolysis and macrophage biology

The origin and nature of osteoclast-like multinucleated giant cells (OMGCs), in extraskeletal neoplasms, is uncertain. The ultrastructure, antigenic phenotype and function of OMGCsm in a breast carcinoma were studied in order to clarify the relationship between OMGCs, osteoclasts and other cells of the mononuclear phagocyte system (MPS). OMGCs resorbed cortical bone in a manner similar to osteoclasts. However, unlike osteoclasts, OMGCs did not possess a ruffled border or clear zone, and expressed HLA-DR and Fc receptors and CD14, CD16, CD18 and CD11 (p150,95) antigens. In addition, OMGCs failed to respond morphologically to calcitonin and were directly stimulated by parathyroid hormone (PTH) to increase bone resorption. These findings suggest that OMGCs are a specific type of macrophage polykaryon distinct from both osteoclasts and other types of inflammatory polykaryon. Occasional smaller (20-25 microns) macrophage-like cells were also associated with resorption pits. Bone resorption by OMGCs isolated from the breast indicates that a cell of the MPS can be transplanted to a new tissue location and perform a highly specialised function appropriate to an MPS cell of that tissue (i.e. the osteoclast). PTH stimulation of bone resorption by OMGCs suggests that PTH or a PTH-like protein, may be involved in the bone resorption and consequent hypercalcaemia associated with metastatic breast cancer.     

The impact of percutaneous transluminal angioplasty on the management of peripheral vascular disease

Percutaneous transluminal angioplasty is a well established technique with wide application, but its place in the overall management of peripheral vascular disease is not well defined. This study compares similar groups of patients with peripheral vascular disease in 1981 and 1984, before and after the introduction of the technique to a district general hospital. More patients are now being investigated and treated and this is almost entirely due to the availability of angioplasty. The rates for surgery have not changed. Percutaneous transluminal angioplasty should therefore be seen as a new and separate form of treatment for peripheral vascular disease, not necessarily influencing or replacing surgery, and requiring its own allocation of resources in accordance with the increase in the level of care afforded by the technique.