Prostate cancer metastasis: role of the host microenvironment in promoting epithelial to mesenchymal transition and increased bone and adrenal gland metastasis

BACKGROUND: The ARCaP cell line was established from the ascites fluid of a patient with metastatic prostate cancer. This study characterized the host microenvironmental role in cancer progression, epithelial to mesenchymal transition (EMT), and bone and adrenal metastasis in parental ARCaP and its derived cell subclones. METHODS: Cytogenetic profiles, growth, migration, invasion, cellular interaction, drug sensitivities, and gene expression of ARCaP cell subclones were compared. In vivo gene expression, behavior, and metastasis of ARCaP subclones were analyzed by serial intracardiac injections into SCID mice. RESULTS: ARCaP(E) cells, with cobblestone morphology, underwent EMT through cellular interaction with host bone and adrenal gland. Lineage-derived ARCaP(M) cells, with spindle-shape fibroblastic morphology, exhibited decreased cell adhesion and increased metastasis to bone and adrenal gland. Cytogenetic analyses of parental and ARCaP subclones confirmed their clonality. CONCLUSIONS: ARCaP uniquely models the molecular basis of prostate cancer bone and adrenal metastases and epithelial to mesenchymal transition.     

Immunohistochemical and molecular genetic study on epithelioid glioblastoma: Series of seven cases with review of literature

Epithelioid glioblastoma (e-gbm) is a recently described variant of glioblastoma (GBM) which is associated with short survival and now added as a provisional entity to WHO 2016 classification of CNStumors. About half of these tumors show characteristic BRAF-V600E mutation. However, unlike conventional GBMs, e-gbm lack specific diagnostic and prognostic markers. Hence, we aimed to molecularly characterize these tumors. An extensive review of literature was performed.In a multi-institutional effort, all the cases of glioblastoma of year 2017 were reviewed. Cases with predominant epithelioid morphology were analysed. Seven cases of e-gbm (adults:4 and pediatric: 3) were identified. Duration of symptoms varied from 2 weeks to one month. Radiologically, all cases were supratentorial, contrast enhancing with solid and cystic appearance. Majority of the cases were immunopositive for GFAP (71%), EMA (71%), S100 (71%) and vimentin (85%). All the cases showed ATRX, INI-1 and H3K27me3 expression. BRAFV600Emutation was seen in 28% of cases. TERT mutation was seen in 40% cases, while one case showed EGFR amplification. H3F3A mutations and PTEN deletions were seen in none. Although e-gbms are rare, epithelioid morphology of a CNS tumor in a young adult or children with areas of necrosis needs thorough histomorphological and genetic workup.     

Targeting myocardial reperfusion injuries with cyclosporine in the CIRCUS Trial – pharmacological reasons for failure

The mitochondrial permeability transition (mPTP) is a key feature of cardiac cell death in ischaemia‐reperfusion injury (I/R). The mPTP blocker, cyclosporine A (CsA), has been shown to give protection against reperfusion‐induced myocardial necrosis and troubles generated by acute coronary artery repermeabilization. Nevertheless, the results of the CIRCUS trial (Does Cyclosporine Improve Clinical Outcome in ST‐Elevation Myocardial Infarction Patients) seem to go against this hypothesis. Pharmacological reasons linked to CsA pharmacokinetics and pharmacodynamics could be suggested. First, it could be explained by a limited diffusion of the drug in the area at risk, due to the only inclusion of patients with a TIMI 0 or 1 coronary blood flow in the anterior territory and the absence of collateral perfusion. Second, to explain a low tissue diffusion of the compound, blood cell capture and high metabolism could be suggested. Moreover, CsA is highly metabolized by cytochrome P450 3A4 (CYP3A4), a polymorphic enzyme leading to variations of C_max and AUC between 10–20% in patients using CsA. Finally, CsA blocks calcineurin, a protein implied in I/R damage but calcineurin inhibition could contribute to protection towards I/R damage only when Rcan1, a calcineurin natural inhibitor, expression is low. The results of the CIRCUS trial are disappointing and could contribute to the withdrawal of the mPTP blockade pharmacological strategy as a way to protect the myocardium from I/R lesions. Nevertheless, many pharmacological insights could have contributed to an increased variability and, as a consequence, an important reduction of the pharmacological power of the study.     

Non small cell lung cancer (NSCLC): current status and future prospects

The incidence of lung cancer is rising dramatically and it is now the commonest cause of mortality and morbidity not only in the industrialised countries, but in developing nations like India as well. Tobacco smoking has consistently been demonstrated to be an important aetiological factor, though lung cancer occurs in non-smokers also. In spite of great advances in radiological and molecular diagnostic techniques, the ideal screening marker for early detection of lung cancer has still not been found. Histological diagnosis and staging is essential for selecting the mode of therapy in patients with lung cancer. Stages I and II are amenable to surgery. However, advanced stage III and IV need an individualised combination of surgery, chemotherapy and radiotherapy. With a better understanding of the cellular mechanisms operating in carcinogenesis, newer target specific modalities are being developed and tested in order to stem this disease, which threatens to assume epidemic proportions.     

A monokine regulates colony-stimulating activity production by vascular endothelial cells

Human umbilical vein endothelial cells were cultured in supernatants of peripheral blood monocytes that had been cultured for 3 days with and without lactoferrin. Colony-stimulating activity (CSA) was measured in supernatants of the endothelial cell cultures and appropriate control cultures using normal, T-lymphocyte-depleted, phagocyte-depleted, low- density bone marrow cells in colony growth (CFU-GM) assays. Monocyte- conditioned medium contained a nondialyzable, heat labile factor that enhanced 4-15--fold the production of CSA by endothelial cells. The addition of lactoferrin to monocyte cultures reduced the activity of this monokine by 69%. Lactoferrin did not inhibit CSA production by monokine-stimulated endothelial cells. Therefore, vascular endothelial cells are potent sources of CSA, the production of CSA by these cells is regulated by a stimulatory monokine, and the production and/or release of the monokine is inhibited by lactoferrin, a neutrophil- derived putative feedback inhibitor of granulopoiesis. Inasmuch as a similar monokine is known to stimulate CSA production by fibroblasts and T lymphocytes, we suggest that mononuclear phagocytes play a pivotal role in the regulation of granulopoiesis by recruiting a variety of cell types to produce CSA.     

再发骨质疏松性椎体压缩骨折保守治疗患者出院后生存质量

目的：对比初次和再发骨质疏松性椎体压缩骨折(osteoporotic vertebral compression fractures,OVCFs)患者保 守治疗的生存质量,了解再次骨折对此类患者生存质量各方面的影响。方法：回顾性观察治疗OVCFs后出现再骨折 的患者30名(再骨折组)和同时期行保守治疗OVCFs后未发生再骨折的基本条件相似的患者30例(对照组),比较两组出 院后3个月时SF-36简明健康健康状况调查表的调查结果。结果：再骨折组治疗后的8个维度均不同程度较对照组变差 (均P<0.01)。结论：再骨折组患者的生存质量明显低于对照组,并且会进一步影响患者的心理预期、情绪和社会活动 的各个方面。     

Comparison of lesion sizes produced by cryoablation and open irrigation radiofrequency ablation catheters

Introduction: The relative lesion sizes created by large electrode cryoablation catheter and irrigated radiofrequency (RF) ablation are not known. The purpose of this study was to directly compare lesion sizes created by cryoablation and irrigated RF under controlled conditions.
Methods and Results : Ablation lesions were created in freshly harvested porcine left ventricular myocardium in a blood-filled tissue bath using an 8-mm-tip cryoablation catheter and a 3.5-mm-tip open-irrigated RF ablation catheter. Lesions were created under all permutations of the following conditions: electrode orientation vertical (perpendicular) or horizontal (parallel) to the tissue, electrode contact pressure at 6 or 20 g, and blood flow at 0.2 or 0.4 m/s over the electrode-tissue interface. The largest lesion volumes created with cryoablation were 961 ± 103 mm³, compared with the largest lesions volumes created with RF of 680 ± 48 mm³ (P < 0.001). The 3-way interactions among electrode orientation, contact pressure, and superfusate blood velocity accounted for the variation in lesion volumes for both catheters (both r²= 0.97, both P < 0.0001). The greater contact pressure increased lesion size for both cryoablation and RF. For cryoablation, lesion sizes were increased by the horizontal orientation and by the lower blood flow velocity. For open-irrigated RF, lesion sizes were significantly reduced by the horizontal orientation, however.
Conclusions : Depending on conditions of electrode orientation, contact pressure, and blood velocity, either 8-mm-tip cryoablation or open-irrigated RF may produce the larger lesion volumes. Open-irrigated RF lesion sizes are reduced in the horizontal catheter orientation.