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.
Gender difference in survival of patients with gastric cancer is not well investigated. The aim of this study was to analyze the gender-related distribution of estrogen receptor alpha (ERα) and ...androgen receptor (AR) in the epithelium and stroma of intestinal-type gastric cancer.
Immunohistochemical analysis was performed in 60 patients (42% females).
In gastric cancer patients, frequency of ERα-positive cells was lower in epithelium than in healthy individuals, but not significantly. In stroma and epithelium, AR-positive cells were absent from samples of women with T1 and T2 stage disease, while in men, their frequency was significantly increased in stroma of those with T3 and T4 stages and was significantly higher compared to women. AR-positive cells in stroma were fibroblasts, myofibroblasts and mast cells.
To our knowledge, this study is the first to show gender differences in the distribution and frequency of AR-positive cells in neoplastic stroma of gastric cancer.
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.
Colorectal cancer (CRC) is the third most common cancer worldwide. The high mortality from CRC is mainly related to metastasis affecting distant organs and their function. Dissemination of tumor ...cells from the primary tumor and hematogeneous spread are considered crucial in the formation of tumor metastases. The analysis of circulating tumor cells (CTCs) and CTC clusters in the blood can be used for the early detection of invasive cancer. Moreover, CTCs have a prognostic significance in the monitoring of a malignant disease or the response to chemotherapy. This work presents an overview of the research conducted on CTCs with the aim of finding suitable detection systems and assessing the possibility of clinical applications in patients with CRC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Differentiation of noninvasive from invasive papillary urothelial carcinoma can be challenging due to inability of proper orientation and thermal damage of transurethrally obtained material. The aim ...of this study was to analyze the presence and extent of peritumoral retractions in pT1 compared to pTa papillary urothelial carcinoma. Since peritumoral retractions may result from altered expression profiles of extracellular matrix proteins, we additionally analyzed the expression of matrix metalloproteinase 2 (MMP-2) and interleukin 8 (IL-8) in these tumors. The study comprised 50 noninvasive (pTa) and 50 invasive (pT1) cases of transurethrally obtained primary papillary urothelial carcinomas. The invasive nature of nests showing peritumoral retractions was confirmed immunohistochemically using antibody against collagen IV. Staining for MMP-2 and IL-8 was evaluated semiquantitatively using immunohistochemical staining index, calculated by multiplying the percentage of positive cells and staining intensity. Peritumoral retractions were found in 32% of pT1 carcinomas but in none of the pTa carcinomas. All tumors showing peritumoral retraction were high grade tumors. There was no statistically significant correlation between the expression of MMP-2 or IL-8 and the presence of peritumoral retractions or stage of the tumor (pTa vs. pT1). A statistically significant but weak correlation was found between MMP-2 and IL-8 expression (χ2-test, p=0,015). There was no statistically significant correlation between the presence of peritumoral retractions or MMP-2 expression and tumor recurrence and progression. Our study shows that, in doubtful cases, when differentiating between pTa and pT1 stages of papillary urothelial carcinoma, the presence of peritumoral retractions could favor the diagnosis of invasive neoplasm.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
6.
Prostate Cancer—Focus on Cholesterol Škara, Lucija; Huđek Turković, Ana; Pezelj, Ivan ...
Cancers,
09/2021, Volume:
13, Issue:
18
Journal Article
Peer reviewed
Open access
Prostate cancer (PC) is the most common malignancy in men. Common characteristic involved in PC pathogenesis are disturbed lipid metabolism and abnormal cholesterol accumulation. Cholesterol can be ...further utilized for membrane or hormone synthesis while cholesterol biosynthesis intermediates are important for oncogene membrane anchoring, nucleotide synthesis and mitochondrial electron transport. Since cholesterol and its biosynthesis intermediates influence numerous cellular processes, in this review we have described cholesterol homeostasis in a normal cell. Additionally, we have illustrated how commonly deregulated signaling pathways in PC (PI3K/AKT/MTOR, MAPK, AR and p53) are linked with cholesterol homeostasis regulation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The choice of therapy for muscle-invasive bladder cancer (MIBC) could be influenced by the tumor's molecular subtype. Currently, well-defined consensus subtypes are based on tumor microarray mRNA ...data. Clearly defined and easy-to-use surrogate molecular subtypes, based on immunohistochemistry (IHC) performed on whole slides, are needed to make subtyping cost-effective and useful in routine work and future research. To aid in the development of a simple immunohistochemical classifier, a retrospective single-center series of 92 cases of localized bladder cancer was identified. Routine IHC for GATA3, cytokeratins 5 and 6 (CK5/6), and p16 was performed on whole tissue blocks containing muscle-invasive disease. Electronic medical records were retrieved and searched for clinical variables, treatment, and survival data. The mean age was 69.6 years, and 73% were males. Conservative treatment was used in 55% of cases, while cystectomy with chemotherapy was used in 45%. GATA3 and CK5/6 expression divided cases into broad luminal and basal subtypes, respectively, while p16 expression was used to subclassify luminal cases into luminal papillary and luminal unstable types according to the consensus molecular classification. When subtyped in this way, GATA3 and CK5/6 negative cases showed worse overall survival. Molecular subtyping of MIBC on whole slides containing muscle-invasive tumor using only three commonly used, consensus-based antibodies, is a feasible and cost-effective method for detecting subtypes of invasive bladder cancer. Future work combining morphological analysis and IHC is needed to fully translate the consensus molecular classification into a comprehensive, cost-effective subtyping strategy.
Prostate cancer (PCa) is the most commonly diagnosed neoplasm among men. Since it often resembles benign prostate hyperplasia (BPH), biomarkers with a higher differential value than PSA are required. ...Epigenetic biomarkers in liquid biopsies, especially miRNA, could address this challenge. The absolute expression of miR-375-3p, miR-182-5p, miR-21-5p, and miR-148a-3p were quantified in blood plasma and seminal plasma of 65 PCa and 58 BPH patients by digital droplet PCR. The sensitivity and specificity of these microRNAs were determined using ROC curve analysis. The higher expression of miR-182-5p and miR-375-3p in the blood plasma of PCa patients was statistically significant as compared to BPH (
= 0.0363 and 0.0226, respectively). Their combination achieved a specificity of 90.2% for predicting positive or negative biopsy results, while PSA cut-off of 4 µg/L performed with only 1.7% specificity. In seminal plasma, miR-375-3p, miR-182-5p, and miR-21-5p showed a statistically significantly higher expression in PCa patients with PSA >10 µg/L compared to ones with PSA ≤10 µg/L. MiR-182-5p and miR-375-3p in blood plasma show higher performance than PSA in discriminating PCa from BPH. Seminal plasma requires further investigation as it represents an obvious source for PCa biomarker identification.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Benign, atypical, or malignant chondroid syringoma (mixed tumor of the skin) have almost identical clinical presentation with similar histological features, except for infiltrative growth, and ...perineural and vascular invasion in the malignant type. Tumors with borderline features are described as atypical chondroid syringoma. Immunohistochemical profiles in all three types are similar, with the the main difference in the expression of the p16 stain. We present a case of an atypical chondroid syringoma in an 88-year-old female patient with a subcutaneous, painless nodule in the gluteal region and with diffuse, strong nuclear immunohistochemical staining for p16. To our knowledge, this is the first such reported case.
Neuroendocrine breast cancer (NEBC) is a group of rare tumors, which could benefit from therapy targeting the somatostatin receptors (SSTRs). In particular, SSTR2A and SSTR5 are potential targets ...given their consistent expression in gastrointestinal and pancreatic primary and metastatic neuroendocrine cancers. Currently, there are no studies describing the expression of SSTRs in NEBC. The purpose of our study was to characterize the immunohistochemical expression of SSTR2A and SSTR5 in a cohort of NEBC.
Thirty-one primary NEBC cases were analyzed, and SSTR2A and SSTR5 immunohistochemistry performed and scored using the modified immunoreactive score proposed by Remmele and Stanger.
All patients were females with a mean age of 66.6 years (SD = 14). 77% of cases were histological grade 2. SSTR2A showed a weak positivity in 11 cases (35.5%), moderate positivity in 6 cases (19.4%) and strong positivity in 5 cases (16.1%). Nine cases were negative for SSTR2A (29%). SSTR5 showed a weak positivity in 16 cases (51.6%), moderate positivity in 6 cases (19.4%), while no cases showed strong positivity. Nine cases were negative for SSTR5 (29%). Five cases were negative for both SSTR2A and SSTR5.
A weak to moderate SSTR2A and SSTR5 expression was observed in 50–70% of the cases. A subset of NEBCs with strong SSR2A expression may benefit from SSTRs targeted therapy. These results need further validation in a larger series including metastatic NEBC, to provide potential therapeutic targets for patients with advanced disease.
•We analyzed the immunohistochemical expression of SSTR2A and SSTR5 in women with neuroendocrine breast cancer.•We show expression of SSTR2A and SSTR5 in the majority of analyzed cases.•SSTR2A and SSTR5 could be potential therapeutic targets for localized and advanced neuroendocrine breast cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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