Zoledronic Acid Elicits Proinflammatory Cytokine Profile in Osteolytic Prostate Cancer Cells

Zoledronic acid (ZA), a bisphosphonate used to prevent skeletal fractures in patients with cancers, was demonstrated to induce apoptosis in a number of cancer cells. Our previous study showed that ZA also induces autophagic cell death in metastatic prostate cancer cells. However, the clinical trials using ZA in the treatment of metastatic prostate cancer did not have a longer diseases-free period. Since most of ZA was attracted to the bone after administration, we hypothesized that local prostate cancer cells may evolve prosurvival pathways upon low concentration of ZA treatment. In this study, we investigated the inflammatory effects of ZA on osteolytic PC3 prostate cancer cell, since inflammation was reported to be related to cancer development and survival. Exposure of PC3 cells to various concentrations of ZA resulted in induction of apoptosis and autophagy. The expression of inflammatory biomarkers including interleukin 6 (IL-6), cyclooxygenase-2 (COX-2), and NF-κB was remarkably upregulated in response to ZA treatment in a dose- and time-dependent manner. The production of IL-6 was elevated upon ZA treatment. The antiapoptotic protein Bcl2 was increased with parallel increased level of IL-6. Our data suggest that treatment with low concentrations of ZA enhances the inflammatory profile and may serve as a prosurvival signaling pathway in PC3 cells.

Do Foxp3+ Regulatory T Cells (Treg Cells) Play a Role in the Immunopathogenesis of Primary/Idiopathic Minimal Change Disease?

Minimal change disease constitutes a major cause of nephrotic syndrome. It is regarded as a non-immune-complex mediated primary glomerulopathy and pathogenetically is characterised by podocyte injury and effacement of foot processes; therefore, it is also classified as a type of podocytopathy. T cell dysfunction with increased levels of a soluble glomerular permeability factor has been proposed to play a major role in the pathogenesis of minimal change disease. It has been therefore suggested that a dysfunction of regulatory T cells, the orchestrators of immune homeostasis, could be implicated in perpetuating T cell activation in this condition. However, the actual contribution of regulatory T cell dysfunction in the immunopathogenesis of primary minimal change disease is still largely unclear. We here propose a theoretical model based on the available evidence.

A Comparative Histochemical Study of Mucous Cells in Odontogenic Cysts

The diagnosis of a glandular odontogenic cyst (GOC) on an incisional biopsy continues to remain a diagnostic challenge for the histopathologist. A marker for distinguishing GOC from odontogenic cysts with mucous metaplasia is thus needed in routine pathology practice. This study aimed to determine the histochemical composition of the mucous cells in the GOC and to compare the findings with the mucous cells in odontogenic cysts that show overlapping histomorphological features with the GOC. GOCs (), dentigerous cysts (DCs) (), and radicular cysts (RCs) () with mucous metaplasia were stained using the combined alcian blue(pH 2.5)-PAS histochemical technique. The cysts were evaluated for the frequencies of acidic- (type I), neutral- (type II) and mixed- (acidic and neutral (type III)) mucin containing cells. Significant differences were found between the levels of type I, type II, and type III mucous cells within the 3 cyst types, GOC (), DC (), and RC (), which all showed a predominance of type III mucous cells. There were, however, no significant differences for each mucous cell type between the 3 cyst types. GOC thus appears to share the same histochemical mucin phenotype with the mucous cells in DC and RC.

Selenium Status in Patients Receiving Short-Term Parenteral Nutrition: Frequency of Deficiency and Response to a Standard Supplementation Regimen

Background. This study aimed to determine the prevalence and correlates of Se deficiency in patients referred for parenteral nutrition (PN) and to assess the response to a standard supplementation regimen. Methods. Adult patients (53) were recruited prior to commencing a PN regimen delivering 32 µg (0.4 µmol) Se per 24–36 h. Serum Se concentrations were measured before and daily during PN. Results. At baseline 49 (92%) patients had serum Se concentrations below the reference range (0.9–1.65 μmol/L). Se concentrations climbed during PN from 0.49±0.23 (mean ± SD) to 0.57±0.22 μmol/L (P<0.05), but in 48 (91%) patients the concentrations remained low at post-PN. Taking a Se concentration below 0.6 μmol/L as indicative of depletion in the presence of an acute phase response (APR), 37 (70%) patients had Se depletion at baseline and in 27 (51%), levels remained low at post-PN. Baseline serum Se predicted the length of hospital stay (r=-0.36, P<0.05). Increased “malnutrition universal screening tool” score predicted low Se (r=-0.93, P<0.05). Conclusions. Patients referred for PN have a high prevalence of Se deficiency, even when the APR is taken into account. Se supplementation of 32 µg Se per 24–36 h is insufficient for most patients. Baseline serum Se may have prognostic value.

Immunohistochemical Expression of Mast Cells Using c-Kit in Various Grades of Oral Submucous Fibrosis

Oral submucous fibrosis (OSF) is a high risk precancerous condition characterized by changes in the connective tissue fibers of lamina propria and deeper parts of mucosa. Mast cells are local residents of connective tissue and have been identified to participate in fibrotic process. These cells produce pharmacologically active substances necessary for the physiological function of our body in response to various stimuli as and when required and also play a significant role in the pathogenesis of oral diseases. Ten healthy volunteers and 30 clinically diagnosed OSF cases with histopathological confirmation were included in the study. Immunohistochemical (c-kit) as well as acidified toluidine blue staining techniques were used to evaluate density and expression of mast cells. The mast cell density assessed using c-kit and toluidine blue showed significant difference in various stages of OSF. In general the mean number of mast cells obtained using c-kit was found to be more than that obtained using toluidine blue in various stages of OSF. The comparison of mast cell densities using immunohistochemistry (c-kit) and toluidine blue stain confirmed that c-kit is a more reliable technique to assess mast cell density in OSF.

Molecular Biology of Breast Cancer in the Horn of Africa: Case Series—A Pilot Study of Breast Cancer from Eritrea

Background. Recently, gene expression profiling and its surrogate immunohistochemistry (IHC) markers classified breast cancer into four distinct molecular subtypes, which have different prognoses, targeted therapies, and/or clinical outcomes. Objective. To conduct a preliminary study, to correlate the clinical pathological profiles and taxonomy of molecular subtypes of breast cancer in Eritrea, in the Horn of Africa. Design. Review of pathology reports from Jan. 1 to Nov. 30, 2009, provided 22 cases of microscopically confirmed invasive breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Cytokeratin 5/6). Result. Twenty patients were female and most of them (68%) were under 50 years at presentation. 90% were invasive invasive carcinoma of no special type and were histological grade 3. The molecular subtypes were luminal A (55%), luminal B (5%), HER2 (5%), basal-like (10%), and unclassified (25%). Triple negative carcinoma (basal-like and unclassified combined) was 35%, mostly (71%) in women under 50 years with grade 3 tumours. Conclusion. Breast carcinoma in Eritrean women presents at a younger age and with a high histologic grade. The two predominant molecular subtypes are luminal A and triple negative. Determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Eritrean women with breast cancer.

Small Bowel Imaging: Clinical Applications of the Different Imaging Modalities—A Comprehensive Review

In the last years, MR and CT techniques have been optimized for small bowel imaging and are playing an increasing role in the evaluation of small bowel disorders. In comparison to traditional barium fluoroscopic examinations, spatial and temporal resolution is now much more improved partially thanks to modern bowel distending agents. However, there is a global interest in implementing techniques that either reduce or eliminate radiation exposure. This is especially important in patients with chronic diseases such as inflammatory bowel disease who may require multiple studies over a lifetime. Owing to the excellent soft tissue contrast, direct multiplanar imaging capabilities, new ultrafast breath-holding pulse sequences, lack of ionizing radiation, and availability of a variety of oral contrast agents, MR is well suited to play a critical role in the imaging of small bowel disorders.

Role of HPV-16 in Pathogenesis of Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma and Correlation of p16INK4A Expression in HPV-16 Positive Cases: An Immunohistochemical Study

The objective of current study is to evaluate the role of HPV-16 in the pathogenesis of oral epithelial dysplasias (OED) and oral squamous cell carcinoma (OSCC) by immunohistochemistry (IHC) and to know whether HPV-16 participates in disruption of the regulation of p16 INK4A suppressor protein in OED and OSCC by IHC. Histopathologically diagnosed 20 cases of OED and 20 cases of OSCC were selected from amongst the patients attending the OPD of Vasantdada Patil Dental College and Hospital, Sangli. Biopsy tissue section were then tested for HPV-16 by IHC. HPV-16 positive tissue sections were then again tested by p16 by IHC. Overall 22.5% of cases in our study were found to be positive for HPV 16 which includes 10% of cases of OED and 35% cases of OSCC. Amongst the HPV 16 positive cases, more than 60% of cells were positive for p16INK4A IHC in OED (50%) and OSCC (85.71%). Thus, HPV 16 participates in disruption of the regulation of p16INK4A suppressor protein and can be used as surrogate biomarker for detection of HPV infection in OED and OSCC.

Confocal Laser Endomicroscopy: Applications in Clinical and Translational Science—A Comprehensive Review

Confocal laser endomicroscopy (CLE) is a novel tool in the endoscopist’s armamentarium. It allows on-site histological information. The ability of gastroenterologists to interpret such microscopic information has been demonstrated in multiple studies from the upper and lower gastrointestinal tract. Recently, the field of application has expanded to provide hepatobiliary and intra-abdominal CLE imaging. CLE allows “smart,” targeted biopsies and is able to guide endoscopic interventions. But CLE is also translational in its approach and permits functional imaging that significantly impacts on our understanding of gastrointestinal diseases. Molecular imaging with CLE allows detection and characterization of lesions and may even be used for prediction of response to targeted therapy. This paper provides a comprehensive review over current applications of CLE in clinical applications and translational science.

Investigation of Tenascin Expression in Endometriosis

Objective. To evaluate the serum and tissue levels and local expression pattern of tenascin, a high molecular weight extracellular matrix protein, in eutopic and ectopic endometrium from patients with and without endometriosis and to compare the proliferative and secretory phase differences. Materials and Methods. Thirty women with endometriosis and fifteen women without endometriosis undergoing surgery for benign indications were included in the study. Serum and tissue levels and proliferative and secretory phase expression patterns of tenascin in the ectopic and eutopic endometrium were analyzed with immunohistochemistry and immunoassays. The results were compared with Mann-Whitney U test. P values <0.05 were considered as statistically significant. Results. Tenascin expression was detected in both of eutopic and ectopic endometrium of women with and without endometriosis. In immunohistochemical staining, intense staining of tenascin was observed in glandular cells of eutopic and ectopic endometrial tissue samples of both groups during secretory phase (P<0.01). Eutopic and ectopic tissue levels of tenascin were higher than serum tenascin levels only secretory phase (P=0.02). There was no significant difference between groups for tissue and serum levels of tenascin during cycle phases. Conclusion. Tenascin expression showed cyclic change on eutopic and ectopic endometrium.