Regulatory and Interacting Partners of PDLIM7 in Thyroid Cancer.

Enigma protein, encoded by the PDLIM7 gene, is overexpressed in thyroid cancer in a stage-dependent manner, suggesting a potential involvement in the initiation and progression of thyroid cancer. The Enigma interacts with several cellular pathways, including PI3K/AKT, MDM2, and BMP-1. The Enigma is regulated by microRNAs. Specifically, we showed that the Enigma protein upregulation corresponds to the downregulation of Let-7 family genes. There is limited research on the interactions and regulation of the Enigma with other proteins/genes in thyroid cancer tissues, indicating a gap in current knowledge. Our aim is to establish the Enigma as a biomarker. We also aim to study the interacting partners of the Enigma signaling pathways and their probable miRNA regulation in thyroid cancer progression. Using Western blotting, densitometric analysis, immunoprecipitation (IP), and reverse IP, we detected the protein expression and protein-protein interactions in the corresponding papillary thyroid carcinomas (PTCs). Utilizing real-time qPCR assay and Pearson's correlation test, we highlighted the correlation between PDLIM7 and Let-7g gene expression in the same tissues. The results showed the differential upregulations of the Enigma protein in different stages of PTCs compared to benign tissues along with AKT, VDR, BMP-1, and MDM2 proteins. Loss of DBP was observed in a subset of PTCs. Strong interactions of the Enigma with PI3K/AKT and MDM2 were noted, along with a weaker BMP-1 interaction. Pearson's correlation coefficient analysis between PDLIM7 and let-7g gene expression was significant (p < 0.05); however, there was a weak inverse correlation (r = -0.27). The study suggests the potential utility of the PDLIM7-qPCR assay as a biomarker for thyroid cancer. The Enigma's interactions with key signaling pathways may provide valuable insights into the development of thyroid cancer. The study contributes to understanding the molecular mechanisms involving the Enigma protein in thyroid cancer and highlights its potential as a biomarker.

Single vs. double drain in modified radical mastectomy: A randomized controlled trial.

Objectives: It was aimed to test the hypothesis that the use of a double drain results in less seroma formation, duration of the hospital stay, surgical site infection (SSI), postoperative pain, hematoma, flap necrosis compared to a single drain in patients undergoing modified radical mastectomy. Material and Methods: This parallel-group, single-institution randomized controlled trial was conducted at the department of surgery of our institute between April 2015 and July 2018. Women undergoing modified radical mastectomy were randomly allocated to either a single drain (n= 98) or double drain (n= 98). Results: Both groups were comparable for baseline variables such as age, co-morbidity, BMI, and tumor characteristics. The variables of single drain yielded no better outcomes compared to double drain with estimated blood loss (101.67 ± 25.14 vs.101.67 ± 24.40, p> 0.001), drain volume (898.81 ± 116.42 vs 803.97 ± 103.22 mL, p> 0.001), duration of surgery in minutes (103.19 ± 15.96, 103.19 ± 15.93) and seroma formation (13.4% vs 6.1%, p= 0.082). However, single drain yielded less postoperative pain (mean 2.5 ± 0.70 vs 5.22 ± 5.10, p <0.000). On multivariable Cox regression analysis, single drain was associated with a lower risk of significant postoperative pain [adjusted relative risk 0.14 (95% confidence interval (CI) 0.070-0.25)] and overall complications [adjusted relative risk 0.47, (95% CI 0.26-0.86)]. On multiple linear regression, the duration of drains in the single drain group was 0.01 days less than double drain (r2= 0.00, b= 0.388, p> 0.001). Conclusion: The use of a single drain significantly reduces postoperative discomfort and pain while demonstrating similar morbidity to the patient with two drains. We thus recommend preferential use of a single drain in modified radical mastectomy (NCT02411617).

N-Cubic q-Rung Orthopair Fuzzy Sets: Analysis of the Use of Mobile App in the Education Sector.

This study analyzes the description to examine the results of a new study and create the technique and also demonstrate the effectiveness of this technique. In this ever-changing world, students are increasingly encouraged to use mobile phones primarily to learn for educational purposes. The learning process is continuous and the goal has now been achieved. It has been replaced by online learning. Due to mobile phones as well as the many feature-oriented applications, students can study at their own place and use the application to spend their time understanding, because everything is accessible with a single click. To carry on the study we applied mobile applications for online education system. Now, because the traditional method is taken into consideration, it is normal to carry a bag full of books and copies and immerse yourself in the tradition of learning to write. However, it has been found that not all students learn when he takes notes. Therefore, we must make sure that the student focuses only on one thing at a time. To continue the research, we apply the N-cubic structure to q-rung orthopair fuzzy sets in multi-attribute group decision-making problems. This structure solves the problems of multi-attribute group decision-making techniques more generally.

MRI Findings and Topographic Distribution of Lesions in Metronidazole-Induced Encephalopathy.

Purpose This study aims to describe the magnetic resonance imaging (MRI) of the brain of five patients diagnosed with metronidazole-induced encephalopathy (MIE). In addition, the aim of our study was to better define the topographic distribution of lesions in MIE. Methods We retrospectively evaluated MRI findings before and after drug cessation in five patients diagnosed with MIE at Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India. The main MRI signal changes and lesion locations were studied. Results Among the patients observed, the average age of the patients with MIE was 55 years (range: 30-70 years). Cerebellar dysfunction, mainly ataxia, and altered mental status were seen in the majority of cases. The most frequently involved sites were the dentate nucleus (cerebellum), brain stem, and corpus callosum (splenium). In diffusion-weighted imaging (DWI), most lesions did not show true restricted diffusion, except for a solitary corpus callosum lesion. Conclusion Although drug-related side effects are more common with long-term use of metronidazole, they may also occur with high doses for short durations. The dentate nucleus, the splenium in the corpus callosum, and the brain stem are the most affected structures. Apart from a solitary lesion of the corpus callosum, all identified lesions were reversible at follow-up MRI after discontinuation of metronidazole. The clinical presentation and characteristic MRI changes are highly specific and can be correlated to make a rapid and more accurate diagnosis of this potentially treatable condition. Prognosis is excellent if detected early.

Aminoflavone upregulates putative tumor suppressor miR-125b-2-3p to inhibit luminal A breast cancer stem cell-like properties.

Metastatic breast cancer is incurable and often due to breast cancer stem cell (CSC)-mediated self-renewal. We previously determined that the aryl hydrocarbon receptor (AhR) agonist aminoflavone (AF) inhibits the expression of the CSC biomarker α6-integrin (ITGA6) to disrupt the formation of luminal (hormone receptor-positive) mammospheres (3D breast cancer spheroids). In this study, we performed miRNA-sequencing analysis of luminal A MCF-7 mammospheres treated with AF to gain further insight into the mechanism of AF-mediated anti-cancer and anti-breast CSC activity. AF significantly induced the expression of >70 microRNAs (miRNAs) including miR125b-2-3p, a predicted stemness gene regulator. AF-mediated miR125b-2-3p induction was validated in MCF-7 mammospheres and cells. miR125b-2-3p levels were low in breast cancer tissues irrespective of subtype compared to normal breast tissues. While miR125b-2-3p levels were low in MCF-7 cells, they were much lower in AHR100 cells (MCF-7 cells made unresponsive to AhR agonists). The miR125b-2-3p mimic decreased, while the antagomiR125b-2-3p increased the expression of stemness genes ITGA6 and SOX2 in MCF-7 cells. In MCF-7 mammospheres, the miR125b-2-3p mimic decreased only ITGA6 expression although the antagomiR125b-2-3p increased ITGA6, SOX2 and MYC expression. AntagomiR125b-2-3p reversed AF-mediated suppression of ITGA6. The miR125b-2-3p mimic decreased proliferation, migration, and mammosphere formation while the antagomiR125b-2-3p increased proliferation and mammosphere formation in MCF-7 cells. The miR125b-2-3p mimic also inhibited proliferation, mammosphere formation, and migration in AHR100 cells. AF induced AhR- and miR125b2-3p-dependent anti-proliferation, anti-migration, and mammosphere disruption in MCF-7 cells. Our findings suggest that miR125b-2-3p is a tumor suppressor and AF upregulates miR125b-2-3p to disrupt mammospheres via mechanisms that rely at least partially on AhR in luminal A breast cancer cells.

Differential Expression of Non-Coding RNA Signatures in Thyroid Cancer between Two Ethnic Groups.

Filipino Americans show higher thyroid cancer recurrence rates compared to European Americans. Although they are likely to die of this malignancy, the molecular mechanism has not yet been determined. Recent studies demonstrated that small non-coding RNAs could be utilized to assess thyroid cancer prognosis in tumor models. The goal of this study is to determine whether microRNA (miRNA) signatures are differentially expressed in thyroid cancer in two different ethnic groups. We also determined whether these miRNA signatures are related to cancer staging. This is a retrospective study of archival samples from patients with thyroid cancer (both sexes) in the pathology division from the last ten years at Loma Linda University School of Medicine, California. Deidentified patient demographics were extracted from the patient chart. Discarded formalin-fixed paraffin-embedded tissues were collected post-surgeries. We determined the differential expressions of microRNA in archival samples from Filipino Americans compared to European Americans using the state-of-the-art technique, HiSeq4000. By ingenuity pathway analysis, we determined miRNA targets and the pathways that those targets are involved in. We validated their expressions by real-time quantitative PCR and correlated them with the clinicopathological status in a larger cohort of miRNA samples from both ethnicities. We identified the differentially upregulated/downregulated miRNA clusters in Filipino Americans compared to European Americans. Some of these miRNA clusters are known to target genes that are linked to cancer invasion and metastasis. In univariate analysis, ethnicity and tumor staging were significant factors predicting miR-4633-5p upregulation. When including these factors in a multivariate logistic regression model, ethnicity and tumor staging remained significant independent predictors of miRNA upregulation, whereas the interaction of ethnicity and tumor staging was not significant. In contrast, ethnicity remained an independent predictor of significantly downregulated miR-491-5p and let-7 family. We provide evidence that Filipino Americans showed differentially expressed tumor-tissue-derived microRNA clusters. The functional implications of these miRNAs are under investigation.

Design and Prototyping of Genetically Encoded Arsenic Biosensors Based on Transcriptional Regulator AfArsR.

Genetically encoded biosensors based on engineered fluorescent proteins (FPs) are essential tools for monitoring the dynamics of specific ions and molecules in biological systems. Arsenic ion in the +3 oxidation state (As3+) is highly toxic to cells due to its ability to bind to protein thiol groups, leading to inhibition of protein function, disruption of protein-protein interactions, and eventually to cell death. A genetically encoded biosensor for the detection of As3+ could potentially facilitate the investigation of such toxicity both in vitro and in vivo. Here, we designed and developed two prototype genetically encoded arsenic biosensors (GEARs), based on a bacterial As3+ responsive transcriptional factor AfArsR from Acidithiobacillus ferrooxidans. We constructed FRET-based GEAR biosensors by insertion of AfArsR between FP acceptor/donor FRET pairs. We further designed and engineered single FP-based GEAR biosensors by insertion of AfArsR into GFP. These constructs represent prototypes for a new family of biosensors based on the ArsR transcriptional factor scaffold. Further improvements of the GEAR biosensor family could lead to variants with suitable performance for detection of As3+ in various biological and environmental systems.

The impact of hospital accreditation in selected Middle East countries: a scoping review.

PURPOSE: There is conflicting evidence concerning the impact of hospital accreditation programmes, including across the Middle East Region, where such programmes have been most recently implemented in Iran, Jordan and Saudi Arabia. This paper maps available evidence regarding the impact of hospital accreditation in these three countries and draws attention to knowledge gaps for consideration. DESIGN/METHODOLOGY/APPROACH: This scoping review was conducted in 2020, using the Arksey and O'Malley framework. Five research databases were searched, along with five government and accreditation agency websites. Searches were complemented by citation chaining. English and Arabic publications evaluating hospital accreditation in the selected countries were included. Commentaries and articles not based on primary data collection and reviews of existing registry data were excluded. There were no exclusions based on study design or methods. A descriptive numerical summary and thematic analysis were used to synthesise the literature. FINDINGS: studies were included. The majority (n = 35) were published since 2014 and conducted in Saudi Arabia (n = 16). Four themes emerged: organisational impacts, patient safety, quality of care, and patient satisfaction and experience. The literature generally highlights positive impacts of accreditation, but most studies were based solely on health professionals' subjective perceptions. "Organisational impacts" had the largest, and strongest body of supporting evidence, while "patient safety" had the least and most variable evidence. ORIGINALITY/VALUE: Opportunities to strengthen the design and evaluation of hospital accreditation programmes in the selected countries are highlighted. Additional experimental, mixed-method research is recommended to strengthen the evidence base and inform practical enhancements to hospital accreditation programmes in the region.

Differential expression of Vitamin D binding protein in thyroid cancer health disparities.

Thyroid cancer incidence, recurrence, and death rates are higher among Filipino Americans than European Americans. We propose that vitamin D binding protein (DBP) with multifunctionality with ethnic variability plays a key role within different ethnicities. In this study, we determined the correlation between differential DBP expression in tumor tissues and cancer staging in Filipino Americans versus European Americans. We assayed DBP expression by immunohistochemistry and analyzed the data with confocal microscopy on 200 thyroid cancer archival tissue samples obtained from both ethnicities. DBP-stable knockdown/gain-in-function assays were done by using DBP-shRNA/DBP-cDNA-expression in vitro. The majority of Filipino Americans presented with advanced tumor staging. In contrast, European Americans showed early staging and very few advanced tumors. A significantly low to no DBP staining was detected and correlated to the advanced staging in Filipino Americans. On the contrary, in the tumor tissues derived from European Americans, moderate to strong DBP staining was detected and correlated to early staging. When downregulation of the DBP gene in papillary thyroid cancer (PTC) cell lines was observed, tumor proliferation and migration were enhanced. On the other hand, the upregulation of the DBP gene decreased cell proliferation and migration in PTC cells. In conclusion, we determined a differential expression of an essential biological molecule (DBP) is linked to cancer staging in thyroid cancer health disparities in two ethnicities. Loss-of-DBP/gain-in-DBP-function influenced tumor progression. A future study is underway to determine the DBP regulation and its downstream pathways to elucidate strategies to eliminate the observed thyroid cancer health disparities.

Differential MicroRNA-Signatures in Thyroid Cancer Subtypes.

Thyroid cancer is one of the most common endocrine cancers, with an increasing trend in the last few decades. Although papillary thyroid cancer is the most frequent subtype compared with follicular or anaplastic thyroid cancer, it can dedifferentiate to a more aggressive phenotype, and the recurrence rate is high. The cells of follicular adenomas and follicular carcinomas appear identical in cytology, making the preoperative diagnosis difficult. On the other hand, anaplastic thyroid cancer poses a significant clinical challenge due to its aggressive nature with no effective therapeutic options. In the past several years, the roles of genetic alterations of thyroid tumors have been documented, with a remarkable correlation between genotype and phenotype, indicating that distinct molecular changes are associated with a multistep tumorigenic process. Besides mRNA expression profiles, small noncoding microRNA (miRNA) expression also showed critical functions for cell differentiation, proliferation, angiogenesis, and resistance to apoptosis and finally activating invasion and metastasis in cancer. Several high-throughput sequencing studies demonstrate that miRNA expression signatures contribute clinically relevant information including types of thyroid cancer, tumor grade, and prognosis. This review summarizes recent findings on miRNA signatures in thyroid cancer subtypes.

Anti-inflammatory Property of AMP-activated Protein Kinase.

BACKGROUND: One of the many debated topics in inflammation research is whether this scenario is really an accelerated form of human wound healing and immunityboosting or a push towards autoimmune diseases. The answer requires a better understanding of the normal inflammatory process, including the molecular pathology underlying the possible outcomes. Exciting recent investigations regarding severe human inflammatory disorders and autoimmune conditions have implicated molecular changes that are also linked to normal immunity, such as triggering factors, switching on and off, the influence of other diseases and faulty stem cell homeostasis, in disease progression and development. METHODS: We gathered around and collected recent online researches on immunity, inflammation, inflammatory disorders and AMPK. We basically searched PubMed, Scopus and Google Scholar to assemble the studies which were published since 2010. RESULTS: Our findings suggested that inflammation and related disorders are on the verge and interfere in the treatment of other diseases. AMPK serves as a key component that prevents various kinds of inflammatory signaling. In addition, our table and hypothetical figures may open a new door in inflammation research, which could be a greater therapeutic target for controlling diabetes, obesity, insulin resistance and preventing autoimmune diseases. CONCLUSION: The relationship between immunity and inflammation becomes easily apparent. Yet, the essence of inflammation turns out to be so startling that the theory may not be instantly established and many possible arguments are raised for its clearance. However, this study might be able to reveal some possible approaches where AMPK can reduce or prevent inflammatory disorders.

Sarcomas in the United States: Recent trends and a call for improved staging.

BACKGROUND AND OBJECTIVES: Sarcomas represent a heterogeneous group of tumors, and there is lack of data describing contemporary changes in patterns of care. We evaluated the epidemiology of sarcomas over 12 recent years. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was queried for sarcoma cases from 2002-2014. Patient, tumor and treatment factors, and trends over time were studied overall and by subtype. Univariable and multivariable logistic regression models and 5-year survival and cause-specific mortality (CSM) were summarized. RESULTS: There were 78,527 cases of sarcomas with an overall incidence of 7.1 cases per 100,000 people, increasing from 6.8 in 2002 to 7.7 in 2014. Sarcoma NOS(14.8%) and soft tissue(43.4%) were the most common histology and primary site, respectively. A majority of tumors were high-grade(33.6%) and >5 cm(51.3%). CSM was 28.6% and 5-year survival was 71.4%. Many patients had unknown-grade(42.2%), which associated with 2.6 times increased odds of no surgical intervention. CONCLUSIONS: This comprehensive national study highlights important trends including increasing incidence, changing histologic types, and underestimation of true incidence. A large proportion of sarcomas are inadequately staged (unknown-grade 42.2%) with lack of appropriate surgical treatment. Our study highlights need for standardization of care for sarcomas.

Linking obesity-induced leptin-signaling pathways to common endocrine-related cancers in women.

Obesity is related to many major diseases and cancers. Women have higher rates of obesity and obesity is linked to commonly occurring cancers in women. However, there is a lack of knowledge of the unique mechanism(s) involved in each type of cancer. The objective of this review is to highlight the need for novel experimental approaches and a better understanding of the common and unique pathways to resolve controversies regarding the role of obesity in cancer. In women, there is a link between hormones and obesity-associated genes in cancer development. Leptin is an obesity-associated gene that has been studied extensively in cancers; however, whether the defect is in the leptin gene or in its signaling pathways remains unclear. Both leptin and its receptor have been positively correlated with cancer progression in some endocrine-related cancers in women. This review offers an up-to-date and cohesive review of both upstream and downstream pathways of leptin signaling in cancer and a comprehensive picture of cancer pathogenesis in light of current evidence of leptin effects in several major types of cancer. This work is intended to aid in the design of better therapeutic strategies for obese/overweight women with cancer.

Exosomal survivin facilitates vesicle internalization.

Survivin, a member of the inhibitor of apoptosis (IAP) protein family plays a significant role in cell fate and function. It is significantly overexpressed in tumor cells and has been identified in most cancer cell types. A novel extracellular population has recently been identified and its function is still unknown. Emerging evidence continues to shed light on the important role the tumor microenvironment (TME) has on tumor survival and progression. This new population of survivin has been seen to enhance the tumor phenotype when internalized by recipient cells. In this paper, we sought to better understand the mechanism by which survivin is taken up by cancer cells and the possible role it plays in this phenomenon. We isolated the exosomal carriers of extracellular survivin and using a lipophilic stain, PKH67, we tracked their uptake with immunofluorescence and flow cytometry. We found that by blocking exosomal survivin, exosome internalization is reduced, signifying a novel function for this protein. We also discovered that the common membrane receptors, transferrin receptor, endothelin B receptor, insulin receptor alpha, and membrane glucocorticoid receptor all facilitate exosomal internalization. This understanding further clarifies the protein-protein interactions in the TME that may influence tumor progression and identifies additional potential chemotherapeutic targets.

AhR ligand aminoflavone suppresses α6-integrin-Src-Akt signaling to attenuate tamoxifen resistance in breast cancer cells.

More than 40% of patients with luminal breast cancer treated with endocrine therapy agent tamoxifen demonstrate resistance. Emerging evidence suggests tumor initiating cells (TICs) and aberrant activation of Src and Akt signaling drive tamoxifen resistance and relapse. We previously demonstrated that aryl hydrocarbon receptor ligand aminoflavone (AF) inhibits the expression of TIC gene α6-integrin and disrupts mammospheres derived from tamoxifen-sensitive breast cancer cells. In the current study, we hypothesize that tamoxifen-resistant (TamR) cells exhibit higher levels of α6-integrin than tamoxifen-sensitive cells and that AF inhibits the growth of TamR cells by suppressing α6-integrin-Src-Akt signaling. In support of our hypothesis, TamR cells and associated mammospheres were found to exhibit elevated α6-integrin expression compared with their tamoxifen-sensitive counterparts. Furthermore, tumor sections from patients who relapsed on tamoxifen showed enhanced α6-integrin expression. Gene expression profiling from the TCGA database further revealed that basal-like breast cancer samples, known to be largely unresponsive to tamoxifen, demonstrated higher α6-integrin levels than luminal breast cancer samples. Importantly, AF reduced TamR cell viability and disrupted TamR mammospheres while concomitantly reducing α6-integrin messenger RNA and protein levels. In addition, AF and small interfering RNA against α6-integrin blocked tamoxifen-stimulated proliferation of TamR MCF-7 cells and further sensitized these cells to tamoxifen. Moreover, AF reduced Src and Akt signaling activation in TamR MCF-7 cells. Our findings suggest elevated α6-integrin expression is associated with tamoxifen resistance and AF suppresses α6-integrin-Src-Akt signaling activation to confer activity against TamR breast cancer.

Beneficial Role of Citrus Fruit Polyphenols Against Hepatic Dysfunctions: A Review.

Alcoholic liver diseases and virus-induced hepatic dysfunctions are prevalent in western countries. Evidence also suggests that hyperglycemia and insulin resistance are key players in the development of hepatic diseases and their complications. Since the comorbid diseases like obesity, diabetes and vascular dysfunctions primarily affect liver, the modern therapies against other hepatic dysfunctions are becoming a major challenge to treat. In addition to these, polypharmacy and adverse drug reactions (ADRs) are further aggravating the phenomenon. Production of interleukins (IL) 1ß, tumor necrosis factors (TNF) α, nuclear factor (NF) κB, activator protein (AP) 1, macrophage inflammatory protein (MIP), toll-like receptor (TLR) 4, and several other harmful cytokines are often evaluated for clinical significance in hepatic complications as recommended by much evidence. On the other hand, transforming growth factors (TGF) ß, matrix metalloproteinases, and extracellular matrix- (ECM-) mediated hepatic fibrosis have been identified as major targets. However, modern medicines rely not only on synthetic compounds but also on herbal sources. Traditional therapies are gradually being acknowledged due to having fewer ADRs and other complications. Citrus fruits are generally seen all over the world and offer a great value as seasonal fruit. Several important biologically active components such as polyphenols, flavonols, carbohydrates, amino acids, and oils have been isolated from this family. Evidence suggests that polyphenol-based therapies have already proved their high potency against the production of inflammatory cytokines and profibrogenic factors. Along with the prevention of oxidative stress, these molecules hinder the generation of free radicals. Furthermore, polyphenols induce several defensive genes such as Nrf2, AMPK, superoxide dismutase, catalase, heme oxygenase (HO), Sirt1, and other important functional proteins to serve mitochondrial biogenesis. Therefore, this review will try to establish some molecular theories between citrus polyphenols and liver dysfunctions.

Pathologic significance of a novel oncoprotein in thyroid cancer progression.

BACKGROUND: The incidence of thyroid cancer is increasing worldwide, and there is an emerging need to develop accurate tools for diagnosis. Fine needle aspiration biopsy has greatly improved evaluation of thyroid nodules, but challenges with indeterminate lesions remain in up to 25% of biopsies. Novel tissue biomarkers may assist in improved nodule characterization. Microcalcifications occurring in thyroid cancers suggest proteins involved in bone formation may play a role in thyroid carcinogenesis. We evaluated the expression of the known osteogenic protein, Enigma, in thyroid cancer as a candidate oncoprotein and role in carcinogenesis based on association with other known oncoproteins such as bone morphogenetic protein-1 (BMP-1). METHODS: The expression of both Enigma and BMP-1 were evaluated by immunohistochemistry (IHC) in an equal number of benign (n = 120) and different histological subtypes of malignant (n = 120) human archival thyroid nodules with and without calcification. The colocalization of Enigma with BMP-1 was evaluated by confocal microscopy using the BZ analyzer. RESULTS: Enigma was strongly expressed in thyroid cancer tissue with a higher immunoreactive score in advanced thyroid cancer compared to less advanced and benign nodules. Enigma was localized either in cytoplasm or nucleus depending on the histological subtypes. Higher expression of Enigma was associated with the tumor size and lymph node involvement. There was clear and strong colocalization signal of Enigma and that of BMP-1. Expression of Enigma occurred without regard to calcification in cancer tissue. CONCLUSION: Enigma may serve as an oncoprotein marker, identifying benign from malignant thyroid tissue on FNA. Enigma may have a role in carcinogenesis of thyroid cancer independent of tissue calcification, possibly in relation to interaction with BMP-1.

Racial differences in the expression of inhibitors of apoptosis (IAP) proteins in extracellular vesicles (EV) from prostate cancer patients.

African-American men with prostate cancer typically develop more aggressive tumors than men from other racial/ethnic groups, resulting in a disproportionately high mortality from this malignancy. This study evaluated differences in the expression of inhibitors of apoptosis proteins (IAPs), a known family of oncoproteins, in blood-derived exosomal vesicles (EV) between African-American and European-American men with prostate cancer. The ExoQuick™ method was used to isolate EV from both plasma and sera of African-American (n = 41) and European-American (n = 31) men with prostate cancer, as well as from controls with no cancer diagnosis (n = 10). EV preparations were quantified by acetylcholinesterase activity assays, and assessed for their IAP content by Western blotting and densitometric analysis. Circulating levels of the IAP Survivin were evaluated by ELISA. We detected a significant increase in the levels of circulating Survivin in prostate cancer patients compared to controls (P<0.01), with the highest levels in African-American patients (P<0.01). African-American patients with prostate cancer also contained significantly higher amounts of EVs in their plasma (P<0.01) and sera (P<0.05) than European-American patients. In addition, EVs from African-American patients with prostate cancer contained significantly higher amounts of the IAPs Survivin (P<0.05), XIAP (P<0.001), and cIAP-2 (P<0.01) than EVs from European-American patients. There was no significant correlation between expression of IAPs and clinicopathological parameters in the two patient groups. Increased expression of IAPs in EVs from African-American patients with prostate cancer may influence tumor aggressiveness and contribute to the mortality disparity observed in this patient population. EVs could serve as reservoirs of novel biomarkers and therapeutic targets that may have clinical utility in reducing prostate cancer health disparities.

Uptake of lymphoma-derived exosomes by peripheral blood leukocytes.

Exosomes are nanosized lipid vesicles secreted into blood and other body fluids and serve as vehicles for intercellular communication. Despite being an important component of the tumor microenvironment (TME), exosomal targeting and uptake into recipient cells are still not fully understood. Few studies have looked at lymphoma exosomes and their interactions with circulating blood cells. In this study, we examine the exosomal uptake distribution among peripheral blood leukocytes (PBLs) using vesicles derived from a diffuse large B cell lymphoma cell line, WSU-DLCL2. Lymphoma cells survive, proliferate, and are protected from the cytotoxic effects of chemotherapeutic agents by soluble factors or by direct contact with inflammatory and stromal cells within the TME. In an attempt to close the gap in knowledge concerning lymphoma TME immunosuppression, we have treated normal human PBLs with PKH67-labeled lymphoma exosomes and monitored the uptake by measuring fluorescence at different time points using flow cytometry and fluorescent microscopy. Our results show that of the four populations examined, B cells and monocytes demonstrated uptake of PKH67-labeled exosomes, while T cells and NK cells displayed significantly less uptake.

Morbidity of colostomy reversal.

OBJECTIVE: To determine morbidity after colostomy reversal at a tertiary care hospital. METHODS: The retrospective case series was conducted at the Aga Khan University Hospital, Karachi, and comprised records of patients aged 15 years or more who underwent colostomy reversal from January 2003 to December 2011. Data was collected regarding demographics, procedure dates, indication, as well as type and location of colostomy. Details of colostomy reversal, including pre-operative, intra-operative and post-operative variables were recorded. RESULTS: The mean age of the 96 patients was 40±16 years; 72(75%) of them being males. The most frequent indications for fashioning of colostomy were bowel perforation in 53 (55.2%) and malignancy in 9(9.3%) patients. Intra-operative complications occurred in 5(5.2%) with bowel perforation in 3(3.1%) and bleeding in 2(2%) patients. Overall, 40(41.6%) patients had post-operative local complications; the most common being wound infection in 19(19.8%) followed by incisional hernia 15(15.6%). Patients who experienced post-operative complications had significantly longer hospital stay compared to those without complications (9±2.8 vs. 7±2.4days; p=0.038). CONCLUSIONS: Colostomy reversal was associated with non-negligible morbidity. The most common complications were wound infection and incisional hernia.