EPHA2, EPHA4, and EPHA7 Expression in Triple-Negative Breast Cancer.

Ongoing research continues to elucidate the complex role of ephrin receptors (EPHs) and their ligands (ephrins) in breast cancer pathogenesis, with their varying expression patterns implied to have an important impact on patients' outcome. The current study aims to investigate the clinical significance of EPHA2, EPHA4, and EPHA7 expression in triple-negative breast cancer (TNBC) cases. EPHA2, EPHA4, and EPHA7 protein expression was assessed immunohistochemically on formalin-fixed and paraffin-embedded (FFPE) TNBC tissue sections from 52 TNBC patients and correlated with key clinicopathologic parameters and patients' survival data (overall survival (OS); disease-free survival (DFS)).

High Pregnane X Receptor (PXR) Expression Is Correlated with Poor Prognosis in Invasive Breast Carcinoma.

Pregnane X Receptor (PXR) is involved in human cancer, either by directly affecting carcinogenesis or by inducing drug-drug interactions and chemotherapy resistance. The clinical significance of PXR expression in invasive breast carcinoma was evaluated in the present study. PXR protein expression was assessed immunohistochemically on formalin fixed paraffin-embedded breast invasive carcinoma tissue sections, obtained from 148 patients, and was correlated with clinicopathological parameters, molecular phenotypes, tumor cells' proliferative capacity, and overall disease-free patients' survival.

PAPOLA contributes to cyclin D1 mRNA alternative polyadenylation and promotes breast cancer cell proliferation.

Poly(A) polymerases add the poly(A) tail at the 3' end of nearly all eukaryotic mRNA, and are associated with proliferation and cancer. To elucidate the role of the most-studied mammalian poly(A) polymerase, poly(A) polymerase α (PAPOLA), in cancer, we assessed its expression in 221 breast cancer samples and found it to correlate strongly with the aggressive triple-negative subtype. Silencing PAPOLA in MCF-7 and MDA-MB-231 breast cancer cells reduced proliferation and anchorage-independent growth by decreasing steady-state cyclin D1 (CCND1) mRNA and protein levels.

Elevated Hu-Antigen Receptor (HuR) Expression is Associated with Tumor Aggressiveness and Poor Prognosis but not with COX-2 Expression in Invasive Breast Carcinoma Patients.

Hu-antigen R (HuR), a RNA-binding protein, is considered to play a crucial role in tumor development and progression by stabilizing or regulating a group of cellular mRNAs of cancer-related genes, such as cyclooxygenase-2 (COX-2). The present study aimed to evaluate the clinical significance of HuR and COX-2 expression in invasive breast carcinoma. HuR and COX-2 protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissue sections obtained from 121 patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival.

High Farnesoid X Receptor (FXR) expression is a strong and independent prognosticator in invasive breast carcinoma.

Farnesoid X Receptor (FXR), a nuclear receptor superfamily member, is related with bile acids, glucose and lipids metabolism and recently with cancer. In the present study the clinical significance of FXR expression in invasive breast carcinoma was evaluated. FXR protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissues obtained from 115 breast cancer patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression, as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival.

Glomerular expression of matrix metalloproteinases in AL-amyloidosis and association with renal function at the time of kidney biopsy.

Background: Matrix metalloproteinases (MMPs) have been implicated in the pathophysiology of various renal diseases, however, there are limited data regarding their role in renal AL-amyloidosis. In the present study, we evaluated the glomerular expression of MMPs in renal-biopsy specimens containing AL-amyloid deposits. We also examined the association of MMPs with renal function at the time of diagnostic renal biopsy.

Nestin involvement in tissue injury and cancer--a potential tumor marker?

Background: In eukaryotic cells, the cytoskeleton contains three major filamentous components: actin microfilaments, microtubules and intermediate filaments. Nestin represents one of the class VI intermediate filament proteins. Clinical and molecular analyses have revealed substantial information regarding the presence of Nestin in cells with progenitor or stem cell properties.

Effect of Smad pathway activation on podocyte cell cycle regulation: an immunohistochemical evaluation.

Background: Mature podocytes are in cell cycle arrest and their inability to proliferate successfully is a consequence of negative cell-cycle regulators' expression, such as p57. Phosphorylated smad2/smad3 (pSmad2/3) is an intracellular heteromeric mediator of transforming growth factor beta (TGF-β) signals and, together with co-activators such as P300, regulates gene transcription, including cell cycle regulator proteins.

Methods: In order to investigate Smad pathway activation and podocyte cell cycle regulation in glomerular injury, we studied the glomerular immunohistochemical expression of p57, pSmad2/3 and P300 in samples from 67 patients with various types of glomerulonephritis (GN) and 10 normal kidney tissue specimens.

Effect of BRCA1 immunohistochemical localizations on prognosis of patients with sporadic breast carcinomas.

Our purpose was to investigate the expression pattern of BRCA1 protein in sporadic breast carcinomas, as well as the clinicopathological and prognostic value of its subcellular localizations. Immunohistochemistry was performed on paraffin embedded tissue specimens from 111 sporadic, invasive breast carcinomas to detect the expression of the proteins BRCA1, ER, PR, erbB2, p53 and Ki67. BRCA1 protein was detected in the nuclei and the cytoplasm of the tumor cells.

Y-box-binding protein 1 (YB1) in breast carcinomas: relation to aggressive tumor phenotype and identification of patients at high risk for relapse.

Aims: To investigate the expression pattern of Y-box-binding protein 1 (YB1) in breast carcinomas, its clinicopathological and prognostic value, and its association with the breast cancer stem cell phenotype [CD44(+)/CD24(-/low)].

Methods And Results: Immunohistochemistry was performed on 225 paraffin embedded specimens of invasive breast carcinomas to detect the expression of the proteins YB1, ER, PR, HER2, p53, Ki67, bcl-2, CD44 and CD24. YB1 protein was detected in the nuclei, the cytoplasm and the stroma of the tumor cells.

Rapamycin ameliorates proteinuria and restores nephrin and podocin expression in experimental membranous nephropathy.

Objective: Recent studies have shown a beneficial effect of rapamycin in passive and active Heymann Nephritis (HN). However, the mechanisms underlying this beneficial effect have not been elucidated.

Methods: Passive Heymann Nephritis (PHN) was induced by a single intravenous infusion of anti-Fx1 in 12 Sprague-Dawley male rats.

Tissue factor expression in neutrophil extracellular traps and neutrophil derived microparticles in antineutrophil cytoplasmic antibody associated vasculitis may promote thromboinflammation and the thrombophilic state associated with the disease.

Objectives: Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is characterised by neutrophil activation. An elevated prevalence of venous thromboembolic events has been reported in AAV. Because of the critical role of neutrophils in inflammation associated thrombosis, we asked whether neutrophil tissue factor (TF) may be implicated in the thrombotic diathesis in AAV.

Depletion of B lymphocytes in idiopathic membranous glomerulopathy: results from patients with extended follow-up.

Aims: To assess the long-term therapeutic benefit of temporary depletion of B lymphocytes in patients with idiopathic membranous glomerulopathy (MGN) and search for potential predictors of response.

Patients And Methods: The patients included had been diagnosed with biopsy-proven MGN in the absence of secondary causes. Estimated glomerular filtration rate should be above 30 ml/min/1.

An immunohistochemical evaluation of the proteins Wnt1 and glycogen synthase kinase (GSK)-3β in invasive breast carcinomas.

Aims: Our purpose was to investigate, in breast carcinomas, the prognostic importance of the proteins Wnt1 and glycogen synthasekinase (GSK)-3β, and their associations with classic clinicopathological indices.

Methods And Results: Immunohistochemistry was performed on paraffin-embedded tissue specimens from 288 invasive breast carcinomas to detect the expression of the proteins Wnt1, GSK3β, oestrogen receptor (ER), progesterone receptor (PR), erbB2, p53, Ki67, caspase-3 and β-catenin. Both Wnt1 and GSK3β were detected predominantly in the cytoplasm of the invasive tumour cells and the in-situ component, while GSK3β was also detected in the stromal fibroblasts.

Cyclin D1 in invasive breast carcinoma: favourable prognostic significance in unselected patients and within subgroups with an aggressive phenotype.

Aims:   To study the clinicopathological and prognostic value of cyclin D1 overexpression in patients with breast carcinoma.

Methods And Results:   Immunohistochemistry was performed on paraffin-embedded tissue specimens from 290 invasive breast carcinomas to detect the proteins cyclin D1, oestrogen receptor (ER), progesterone receptor (PR), p53, c-erbB2, and topoisomerase IIα (topoIIα). Cyclin D1 staining was quantified using a computerized image analysis method.

Exon 8 amplification of epidermal growth factor receptor (EGFR) in invasive breast carcinomas.

Aims: The rate of EGFR amplification in breast cancer ranges between 0% and 15%. Recent studies have focused on the amplification status of cytosine-adenine (CA) repeats in intron 1 of the gene and correlated it with increased EGFR protein. The aim of this study was to investigate, for the first time, the significance of coding exon 8 amplification of EGFR in invasive breast cancer.

Early treatment with glucocorticoids or cyclophosphamide retains the slit diaphragm proteins nephrin and podocin in experimental lupus nephritis.

Renal podocytes and their slit diaphragms ensure the integrity of renal basement membrane and prevent urinary protein loss. We have previously reported that decreases of the podocyte slit diaphragm proteins nephrin and podocin represent early events in the podocytopathy of lupus nephritis (LN). We asked whether immunosuppressive agents such as glucocorticoids and cyclophosphamide may have direct effects on podocytes.

Prognostic significance of phosphorylated STAT-1 expression in premenopausal and postmenopausal patients with invasive breast cancer.

Aims:   STAT-1 is the first member of the family of signal transducers and activators of transcription (STATs). In breast cancer experimental models, an apoptotic and antiproliferative effect has been demonstrated. Our aim was to study the role of phosphorylated STAT-1 (pSTAT-1) in invasive breast carcinoma and its prognostic significance in premenopausal and postmenopausal patients.

Rapamycin induced ultrastructural and molecular alterations in glomerular podocytes in healthy mice.

Background: In the normal kidney, rapamycin is considered to be non-nephrotoxic. In the present study, we investigated whether rapamycin is indeed non-nephrotoxic by examining the ultrastructural and molecular alterations of podocytes in healthy mice.

Methods: Balb/c mice were given three different intraperitoneal doses of rapamycin for 1 week (dose model)-low-dose group: 1 mg/kg/day, intermediate-dose (ID) group: 1.

Differential effect of the expression of TGF-β pathway inhibitors, Smad-7 and Ski, on invasive breast carcinomas: relation to biologic behavior.

The aim of our study was to investigate the expression of Smad-7 and Ski proteins in invasive breast carcinomas, to determine their clinicopathological value and their influence on carcinomas biologic behavior. Immunohistochemistry was applied on 150 invasive breast carcinomas to detect the expression of Smad-7 and Ski. Their correlation to clinicopathologic parameters and markers of metastasis was statistically processed using chi-squared test.

Urinary interleukin-6 (IL-6) and transforming growth factor (TGF-β) levels in corticosteroidtreated patients with IgA nephropathy.

Background: Interleukin-6 (IL-6) and transforming growth factor-β (TGF-β) are implicated in the progression of IgA nephropathy, which is usually treated with corticosteroids.

Patients And Methods: Urinary IL-6 and TGF-β were measured in 21 proteinuric patients with IgA nephropathy, before and after treatment with corticosteroids, to estimate the activity of the disease after remission of proteinuria.

Results: Urinary IL-6 and TGF-β levels at diagnosis were significantly higher in patients with IgA nephropathy compared to healthy subjects.

Podocyte main slit diaphragm proteins, nephrin and podocin, are affected at early stages of lupus nephritis and correlate with disease histology.

Renal podocytes and their slit diaphragms ensure the integrity of the renal basement membrane that forms the barrier to urinary protein loss. A putative disruption of the slit diaphragm and its main protein components, nephrin and podocin, may be implicated in the pathogenesis of lupus nephritis (LN). We studied the glomerular protein expression of nephrin and podocin in NZB/W LN mice by Western blot and immunofluorescence; mRNA levels were measured by real-time PCR.

Statins and prostate cancer: molecular and clinical aspects.

The field of the potential applications of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) beyond their unambiguous cardiovascular beneficial effects is steadily increasing. In this regard, statins have also been shown to possess anti-inflammatory, immunomodulatory, antioxidant and growth inhibitory properties. Regarding their role in carcinogenesis, both preclinical and clinical studies report conflicting results.

Effective treatment of antiphospholipid syndrome with plasmapheresis and rituximab.

With the exception of the catastrophic antiphospholipid syndrome (APS), the management of patients with APS has been largely supportive aiming at avoiding a recurrent thrombotic event; it is noteworthy that data concerning therapy targeting the triggering factor (the antiphopsholipid antibodies) are scarce. We report a case of APS manifested as recurrent fetal losses, ischemic stroke and renal dysfunction with concomitant nephrotic syndrome successfully treated with the combination of plasmapheresis and anti-CD20 antibody.

Interstitial nephritis and nephrogenic diabetes insipidus in a patient treated with pemetrexed.

We present a case of interstitial nephritis and nephrogenic diabetes insipidus (NDI) in a patient treated with pemetrexed (500 mg/m(2)) for non-small cell lung cancer. Renal impairment and diabetes insipidus appeared after the first treatment cycle while he totally received four cycles of chemotherapy. There was not any significant myelosuppression and the patient was on regular supplementation with folic acid and vitamin B(12).