Work on rodents demonstrated that steep upregulation of KCC2, a neuron-specific Cl extruder of cation-chloride cotransporter (CCC) family, commences in supraspinal structures at around birth, leading to establishment of hyperpolarizing GABAergic responses. We describe spatiotemporal expression profiles of the entire CCC family in human brain. KCC2 mRNA was observed already at 10th postconceptional week (PCW) in amygdala, cerebellum, and thalamus. KCC2-immunoreactive (KCC2-ir) neurons were abundant in subplate at 18 PCW. By 25 PCW, numerous subplate and cortical plate neurons became KCC2-ir. The mRNA expression profiles of α- and β-isoforms of Na-K ATPase, which fuels cation-chloride cotransport, as well of tropomyosin receptor kinase B (TrkB), which promotes developmental upregulation of KCC2, were consistent with data from studies on rodents about their interactions with KCC2. Thus, in human brain, expression of KCC2 and its functionally associated proteins begins in early fetal period. Our work facilitates translation of results on CCC functions from animal studies to human and refutes the view that poor efficacy of anticonvulsants in the term human neonate is attributable to the lack of KCC2. We propose that perinatally low threshold for activation of Ca-dependent protease calpain renders neonates susceptible to downregulation of KCC2 by traumatic events, such as perinatal hypoxia ischemia.

Reactive stromal changes that occur in different human cancers might play a role in local tumor spreading and progression. Studies done on various human cancers have shown activated stromal cell phenotypes, modified extracellular matrix (ECM) composition, and increased microvessel density. Furthermore, they exhibit biological markers consistent with stroma at the site of wound repair. In prostate cancer, stroma is composed of fibroblasts, myofibroblasts, endothelial cells and immune cells. Predominant cells in the tumorous stroma are, however, fibroblasts/myofibroblasts. They are responsible for the synthesis, deposition and remodeling of the ECM. Epithelial tumorous cells, in interaction with stromal cells and with the help of various molecules of ECM, create a microenvironment suitable for cancer cell proliferation, movement, and differentiation. In this review, we discussed the role of different stromal components in prostate cancer as well as their potential prognostic and therapeutic significance.

Aims To further characterise biphasic squamoid renal cell carcinoma (RCC), a recently proposed variant of papillary RCC. Methods and results We identified 28 tumours from multiple institutions. They typically showed two cell populations—larger cells with eosinophilic cytoplasm and higher‐grade nuclei, surrounded by smaller, amphophilic cells with scanty cytoplasm. The dual morphology was variable (median 72.5% of tumour, range 5–100%); emperipolesis was found in all cases. The male/female ratio was 2:1, and the median age was 55 years (range 39–86 years). The median tumour size was 20 mm (range 9–65 mm). Pathological stage pT1a was found in 21 cases, pT1b in three, and pT3a and pT3b in one each (two not available). Multifocality was found in 32%: multifocal biphasic RCC in one case, biphasic + papillary RCC in two cases, biphasic + clear cell RCC in three cases, biphasic + low‐grade urothelial carcinoma of the renal pelvis in one case, and biphasic + Birt–Hogg–Dubé syndrome in one case. Positive immunostains included: PAX8, cytokeratin (CK) 7, α‐methylacyl‐CoA racemase, epithelial membrane antigen, and vimentin. Cyclin D1 was expressed only in the larger cells. The Ki67 index was higher in the larger cells (median 5% versus ≤1%). Negative stains included: carbonic anhydrase 9, CD117, GATA‐3, WT1, CK5/6, and CK20; CD10 and 34βE12 were variably expressed. Gains of chromosomes 7 and 17 were found in two evaluated cases. Follow‐up was available for 23 patients (median 24 months, range 1–244 months): 19 were alive without disease, one was alive with recurrence, and one had died of disease (two had died of other causes). Conclusions Biphasic papillary RCC is a rare variant of papillary RCC, and is often multifocal.

Chronic inflammation is associated with both benign conditions and cancer. Likewise, inflammatory cells are quite common in benign prostatic hyperplasia (BPH) and prostatic tissue harboring cancer. Triggers that activate inflammatory pathways in the prostate remain a subject of argument and are likely to be multifactorial, some of these being bacterial antigens, different chemical irritations, and metabolic disorders. Acute and chronic inflammation in prostate leads to accumulation of immunocompetent cells, mainly T lymphocytes and macrophages, but also neutrophils, eosinophils, and mast cells, depending on the type of offending agent. Inflammatory processes activate hyperproliferative programs resulting in nodules seen in BPH, but are also important in creating suitable microenvironment for cancer growth and progression. Inflammatory cells have mostly been shown to have a protumoral effect such as tumor-associated macrophages, but some cell types such as mast cells have antitumoral effects. This review outlines the recent findings and theories supporting the role of inflammatory responses as drivers of both benign and malignant epithelial processes in the prostate gland.