Independent Prognostic and Predictive Role of Interstitial Macrophages in Kidney Biopsies of IgA Nephropathy Patients.

A relevant percentage of IgAN patients experience a progressive decline in kidney function. According to the KDIGO guidelines, proteinuria and eGFR are the only validated prognostic markers. The role of interstitial macrophages in kidney biopsies of IgAN patients and the outcome of patients treated with renin-angiotensin system inhibitors (RASBs) alone or combined with glucocorticoids were evaluated.

Bioradiotherapy with Cetuximab May Reduce the Risk of Neck Node Relapse in Locoregionally Advanced Laryngeal Glottic Carcinoma: May HER1-Profile Be Useful in the Bioselection of Patients?

The aim of the study was to evaluate survival in patients with advanced glottic laryngeal squamous cell carcinoma treated by bioradiotherapy (BioRT) with cetuximab and eventual salvage surgery (group A, n = 66) or upfront surgery (total laryngectomy or near-total laryngectomy) with or without postoperative radiotherapy (PORT) (group B, n = 66). The predictive role of HER1 expression in the bioselection of tumors was evaluated. Relapse-free (RFS), metastasis-free (MFS), overall (OS) survivals, salvageability, and rates of larynx preservation were analyzed.

Parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor type 1 in locally advanced laryngeal cancer as prognostic indicators of relapse and survival.

Background: Parathyroid hormone-related peptide (PTHrP) overexpression and poor patient outcome have been reported for many human tumors, but no studies are available in laryngeal cancer. Therefore, we studied the expression of PTHrP and its receptor, parathyroid hormone-related peptide receptor type 1 (PTH1R), in primary locally advanced laryngeal squamous cell carcinomas (LALSCC) also in relation to the clinical outcome of patients.

Methods: We conducted a retrospective exploratory study, using immunohistochemistry, on PTHrP, PTH1R and HER1 expressions in LALSCC of 66 patients treated with bio-radiotherapy with cetuximab.

Nuclear HER3 expression improves the prognostic stratification of patients with HER1 positive advanced laryngeal squamous cell carcinoma.

Background: Compared to the other members of human epidermal growth factor family receptors (HER), the role of HER3 has not been well defined in laryngeal cancer. The predictive and prognostic role of HER3 has been the focus of clinical attention but the research findings are contradictory, especially in laryngeal squamous cell carcinoma (LSCC). The variable localization of HER3 within cancer cells and the role of HER3 in primary and acquired resistance to HER1-targeted therapies remain unclear.

Primary cardiac synovial sarcoma: A review correlating outcomes with surgery and adjuvant therapy.

Background: Cardiac synovial sarcoma (CSS) is an extremely rare malignant tumor with a severe prognosis, due to frequent relapses and metastases. To obtain useful information for treatment protocols, we analyzed survival and therapy data from the cases reported in the literature.

Methods: A search of MEDLINE was performed throughout December 2018.

Minichromosome maintenance protein 7 and geminin expression: Prognostic value in laryngeal squamous cell carcinoma in patients treated with radiotherapy and cetuximab.

Background: Minichromosome maintenance protein 7 (MCM7) is a downstream of human epidermal growth receptor (HER1) signaling. We examined MCM7, geminin, and HER1 expression in patients with laryngeal squamous cell carcinoma (SCC) treated with radiotherapy and cetuximab.

Methods: MCM7, geminin, and HER1 were evaluated by immunohistochemistry on 61 patients with laryngeal SCC.

Minichromosome maintenance protein 7 as prognostic marker of tumor aggressiveness in pituitary adenoma patients.

Background: Ki-67 labeling index (LI) is currently regarded as a useful prognostic marker of pituitary adenoma (PA) clinical behavior, although its relevance as a reliable clinical indicator is far from being universally accepted, since both validations and criticisms are found in the literature. Minichromosome maintenance 7 (MCM7), a cell-cycle regulator protein, has been recently proposed as a marker of tumor aggressiveness in tumors from many sites, including the CNS. Therefore, we evaluated MCM7, in comparison to Ki-67, as a potential marker of clinical outcome in PA.

Abnormal megakaryopoiesis and platelet function in cyclooxygenase-2-deficient mice.

Previous studies suggest that cyclooxygenase-2 (COX-2) might influence megakaryocyte (MK) maturation and platelet production in vitro. Using a gene deletion model, we analysed the effect of COX-2 deficiency on megakaryopoiesis and platelet function. COX-2-/- mice (10-12 weeks old) have hyper-responsive platelets as suggested by their enhanced aggregation, TXA2 biosynthesis, CD62P and CD41/CD61 expression, platelet-fibrinogen binding, and increased thromboembolic death after collagen/epinephrine injection compared to wild-type (WT).

Hu/elav RNA-binding protein HuR regulates parathyroid hormone related peptide expression in human lung adenocarcinoma cells.

In 54 stage I and II human lung adenocarcinomas, HuR and PTHrP levels were positively correlated and the PTHrP-HuR status of the tumor was an independent prognostic marker of the clinical outcomes of patients. The possibility that HuR could upregulate PTHrP expression in lung adenocarcinoma was investigated by immunohistochemical, Western blot and RT-PCR analyses in HCC44 and DV90 human lung adenocarcinoma cell lines. In both cell lines, knockdown of HuR by specific siRNAs reduced PTHrP mRNAs and both cellular and secreted protein.

DHA induces apoptosis by altering the expression and cellular location of GRP78 in colon cancer cell lines.

n-3 polyunsaturated fatty acids exert growth-inhibitory and pro-apoptotic effects in colon cancer cells. We hypothesized that the anti-apoptotic glucose related protein of 78kDa (GRP78), originally described as a component of the unfolded protein response in endoplasmic reticulum (ER), could be a molecular target for docosahexaenoic acid (DHA) in these cells. GRP78 total and surface overexpression was previously associated with a poor prognosis in several cancers, whereas its down-regulation with decreased cancer growth in animal models.

Immunohistochemical expression patterns of the HER4 receptors in normal mucosa and in laryngeal squamous cell carcinomas: antioncogenic significance of the HER4 protein in laryngeal squamous cell carcinoma.

Objectives/hypothesis: The prognosis for laryngeal squamous cell carcinoma (LSCC) has not shown any improvement in the last 30 years because of inadequate prognostic stratification. Therefore, the detection of reliable molecular markers may have a significant impact on clinical practice. As promising data regarding HER1/EGFR have been published, the purpose of the present study was to elucidate the role of the other receptors of the HER family.

Expression of the RNA-binding protein HuR and its clinical significance in human stage I and II lung adenocarcinoma.

The ubiquitously expressed RNA-binding protein Hu antigen (HuR) participates in the post-transcriptional regulation of mRNAs bearing U- and AU-rich sequences. Expression of HuR is increased in cancers of the breast, colon, ovary and lung and cytoplasmic immunoreactivity for HuR was found to be closely related to poor outcomes in patients with these tumors. Since the regulation of HuR function is closely linked to its subcellular localization, we evaluated, by quantitative immunohistochemistry, the impact on clinical outcome of both nuclear and cytoplasmic levels (integrated density: ID) of HuR and of nuclear/cytoplasmic ratio (N/C) in 54 lung adenocarcinomas from stage I and II patients.

DHA induces apoptosis and differentiation in human melanoma cells in vitro: involvement of HuR-mediated COX-2 mRNA stabilization and β-catenin nuclear translocation.

The pro-inflammatory phenotype accompanying melanoma progression includes an enhanced expression of cyclooxygenase-2 (COX-2), which plays an important role in the acquisition of apoptosis resistance, and is a suitable target for melanoma prevention and therapy. We observed that the WM266-4 metastatic melanoma cell line showed a constitutive COX-2 expression higher than that of the primary WM115 cells, an increased cytosolic level of the COX-2 messenger RNA (mRNA)-stabilizer human antigen R (HuR) and a lower susceptibility to basal apoptosis. The transfection of HuR siRNA induced apoptosis and reduced COX-2 protein abundance in both the cells.

Lycopene regulation of cholesterol synthesis and efflux in human macrophages.

Hypercholesterolemia is one of the most important risk factors for atherosclerosis, and tomato lycopene has been suggested to have beneficial effects against such a disease, although the exact molecular mechanism is unknown. We tested the hypothesis that lycopene may exert its antiatherogenic role through changes in cholesterol metabolism. Incubation of THP-1 cells with lycopene (0.

Docosahexaenoic acid reverts resistance to UV-induced apoptosis in human keratinocytes: involvement of COX-2 and HuR.

The dramatic increase in the incidence of nonmelanoma skin cancer over the last decades has been related to the augmented exposure to ultraviolet (UV) radiation (UVR). It is known that apoptosis is induced as a protective mechanism after the acute irradiation of keratinocytes, whereas apoptotic resistance and carcinogenesis may follow the chronic exposure to UVR. We found that not all the human keratinocytes lines studied underwent apoptosis following acute exposure to UVR (10-60 mJ/cm(2)).

Prostaglandin E2 differentially modulates human platelet function through the prostanoid EP2 and EP3 receptors.

Activated human platelets synthesize prostaglandin (PG) E(2), although at lower rate than thromboxane A(2). PGE(2) acts through different receptors (EP1-4), but its role in human platelet function remains poorly characterized compared with thromboxane. We studied the effect of PGE(2) and its analogs on in vitro human platelet function and platelet and megakaryocyte EP expression.

Lycopene induces cell growth inhibition by altering mevalonate pathway and Ras signaling in cancer cell lines.

Several evidences suggest that cancer cells have abnormal cholesterol biosynthetic pathways and prenylation of small guanosine triphosphatase proteins. Tomato lycopene has been suggested to have beneficial effects against certain types of cancer, including that of prostate, although the exact molecular mechanism(s) is unknown. We tested the hypothesis that lycopene may exert its antitumor effects through changes in mevalonate pathway and in Ras activation.

Lycopene prevention of oxysterol-induced proinflammatory cytokine cascade in human macrophages: inhibition of NF-κB nuclear binding and increase in PPARγ expression.

It is now well accepted that oxysterols play important roles in the formation of atherosclerotic plaque, involving cytotoxic, pro-oxidant and proinflammatory processes. It has been recently suggested that tomato lycopene may act as a preventive agent in atherosclerosis, although the exact mechanism of such a protection is not clarified. The main aim of this study was to investigate whether lycopene is able to counteract oxysterol-induced proinflammatory cytokines cascade in human macrophages, limiting the formation of atherosclerotic plaque.

Expression of parathyroid hormone-related protein in human inflamed dental pulp.

Introduction: The aim of this study was to investigate the presence and the role of the parathyroid hormone-related protein (PTH-rP) in the inflamed pulp.

Materials And Methods: Thirty-four pulp tissue specimens (24 inflamed and 10 normal pulps) from extracted third molars were studied. The presence of PTH-rP was observed by using immunohistochemistry.

Prognostic significance and clinical relevance of the expression of the HER family of type I receptor tyrosine kinases in human laryngeal squamous cell carcinoma.

Introduction: The full clinical relevance of the expression pattern of HER family of type I receptor tyrosine kinases in laryngeal squamous cell carcinoma remains to be elucidated. We evaluated the clinical relevance of such parameter in our population.

Patients And Methods: This study examined the expression pattern of HER family receptor members by quantitative immunohistochemistry and the amount of the EGF binding sites by a radioligand binding assay, in the same group of 67 LSCC patients, analysing the correlation between the expression of the four HER receptors and the clinical and prognostic parameters.

Parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor type 1 expression in human lung adenocarcinoma.

Background: In many primary tumors, parathyroid hormone-related peptide (PTHrP) and PTHrP type 1 receptor (PTH1R) are coexpressed, supporting the possibility that PTHrP/PTH1R system can mediate important signals for tumor progression through paracrine/autocrine mechanisms. In non-small cell lung carcinoma the clinical relevance of the expression of PTH1R remains to be investigated.

Methods: Fifty-four lung adenocarcinomas of mixed histologic type from patients with stage I and II cancer were assayed by quantitative immunohistochemistry for the expression of PTHrP and PTH1R.

The contribution of cyclooxygenase-1 and -2 to persistent thromboxane biosynthesis in aspirin-treated essential thrombocythemia: implications for antiplatelet therapy.

We tested whether cyclooxygenase 2 (COX-2) expression and unacetylated COX-1 in newly formed platelets might contribute to persistent thromboxane (TX) biosynthesis in aspirin-treated essential thrombocythemia (ET). Forty-one patients on chronic aspirin (100 mg/day) and 24 healthy subjects were studied. Platelet COX-2 expression was significantly increased in patients and correlated with thiazole orange-positive platelets (r = 0.

Expression and subcellular localization of CRH and its receptors in human endometrial cancer.

CRH and its receptors are expressed in human normal endometrial cells, where they are associated to anti-proliferative progesterone-like activity. We aimed to investigate CRH, CRH-R1 and CRH-R2 expression and intracellular localization in human endometrial cancers and their relationships with tumor biological parameters. Surgical specimens were obtained from 51 untreated endometrial cancer patients and immunohistochemistry for CRH, CRH receptors, ER, PR and Ki-67 was performed.

Diminished expression of S100A2, a putative tumour suppressor, is an independent predictive factor of neck node relapse in laryngeal squamous cell carcinoma.

Purpose: In primary squamous cell carcinoma of the larynx (LSCC), Ca(2+) binding S100A2 protein underexpression was already found to be associated with poor tumour differentiation and shorter overall survival. In the present work, the role of S100A2 protein expression in the prediction of regional metastasis-free survival (MFS) was investigated to guide neck management in LSCC.

Experimental Design: Specimens of LSCC from 62 consecutive untreated patients were examined for S100A2 content by immunocytochemistry; the patients were followed up for a median of 44 months (range 2-90 months) after initial surgical resection.

No-glucose strategy influences posterior cranial fossa tumors' postoperative course: introducing the Glycemic Stress Index.

In a selected patient population, we evaluated the glycemic response to different infusional policies in the management of posterior cranial fossa tumor (PFT) removal. We analyzed the perioperative course, prospectically collected, of 137 children undergoing 150 surgical procedures. Patients were divided in two groups according to different intraoperative fluids (group A, 2.