Metabolically healthy/unhealthy obesity and breast cancer: A possible role of plasma-derived extracellular vesicles on the cancerous behavior of triple-negative breast cancer.

PURPOSE: Obesity has known detrimental effects on breast cancer (BC) development and progression. However, it's essential to consider the obesity phenotype based on metabolic health. This study aims to evaluate the impact of circulating extracellular vesicles (EVs) from women with metabolically healthy or unhealthy normal weight, overweight, and obesity on MDA-MB-231 cell migration, invasion, and apoptosis. METHODS: Plasma EVs were isolated from different obesity phenotypes in women. EVs were characterized and EVs uptake by MDA-MB-231 cells was assessed. MDA-MB-231 cell lines were treated with EVs obtained from various studied groups, and migration, invasion, MMP-2 and MMP-9 activity, Bax and Bcl-2 mRNA expression, p-53 and Thr55 p-p53 protein expression, and apoptosis were assessed. RESULTS: EVs from obese individuals, regardless of phenotype, increased invasion and MMP-2 activity compared to healthy normal-weight EVs. Normal-weight EVs led to higher invasion under unhealthy conditions. BC cell migration was enhanced by EVs from healthy obese individuals compared to healthy normal-weight EVs. EVs from unhealthy obese women exhibited significantly lower p53/p-p53 levels and reduced apoptosis compared to healthy obese groups. CONCLUSION: It appears that EVs from both normal-weight women with unhealthy conditions and those with obesity or overweight, irrespective of metabolic status, worsened the cancerous behavior of TNBC cells. Therefore, considering metabolic health, in addition to BMI, is crucial for understanding obesity-related disorders.

Higher expression of SALL4-A isoform is correlated with worse outcomes and progression of the disease in subtype of testicular germ cell tumours.

BACKGROUND: The transcription factor SALL4 is associated with embryonic pluripotency and has proposed as a novel immunohistochemistry (IHC) marker for diagnosing germ cell tumours. SALL4 comprises three isoforms, and SALL4-A being the full-length isoform. Studying its isoforms could revolutionize testicular cancer prognosis and subtype differentiation. METHODS: The expression and clinical significance of isoform 'A' of SALL4 was evaluated in 124 testicular germ cell tumours (TGCTs) subtypes, adjacent 67 normal tissues and 22 benign tumours, using immunohistochemistry on tissue microarrays (TMA). RESULTS: A statistically significant higher expression of nuclear and cytoplasmic SALL4-A was detected in TGCTs histological subtypes and benign tumours compared to the normal tissues. Seminoma and yolk sac tumours had the highest nuclear and cytoplasmic expression of SALL4-A. A significant correlation was detected between the higher nuclear expression of SALL4-A and increased pT stages (P = 0.026) in seminomas. Whereas in embryonal carcinomas, cytoplasmic expression of SALL4-A was associated with the tumour recurrence (P = 0.04) and invasion of the epididymis (P = 0.011). CONCLUSIONS: SALL4-A isoform expression in the cytoplasm and nucleus of TGCTs may be associated with histological differentiation. In the seminoma subtype of TGCTs, higher expression of SALL4-A may be used as a predictive indicator of poorer outcomes and prognosis.

Non-invasive Body Contouring Technologies: An Updated Narrative Review.

INTRODUCTION: Nowadays, a lot of body contouring devices and methods are introduced all over the world. The object of the present narrative review was to update and classify existing evidence on these methods and devices. METHODS: We searched databases including PubMed, Cochrane, and Google Scholar for 11 essential keywords, including cryolipolysis, high-intensity focused ultrasound (HIFU), shock wave, low-level laser therapy (LLLT), radiofrequency (RF), capacitive resistive electrical transfer (TECAR), high-intensity focused electromagnetic (HIFEM), electromyostimulation (EMS), carboxytherapy, mesotherapy, and acupuncture and their abbreviations, in addition to obesity, overweight, cellulite, subcutaneous fat, and body contouring. RESULTS: Totally 193 references were used in 11 main topics. CONCLUSION: In order to help physicians with finding the best evidence in different methods, the data were summarised in 11 topics. Furthermore, FDA-approved devices, side effects and common protocols were described in each section. LEVEL OF EVIDENCE I: This journal requires that authors 39 assign a level of evidence to each article. For a full 40 description of these Evidence-Based Medicine ratings, 41 please refer to the Table of Contents or the online 42 Instructions to Authors www.springer.com/00266 .

Significant co-expression of putative cancer stem cell markers, EpCAM and CD166, correlates with tumor stage and invasive behavior in colorectal cancer.

BACKGROUND: The crucial oncogenic role of cancer stem cells (CSCs) in tumor maintenance, progression, drug resistance, and relapse has been clarified in different cancers, particularly in colorectal cancer (CRC). The current study was conducted to evaluate the co-expression pattern and clinical significance of epithelial cell adhesion molecules (EpCAM) and activated leukocyte cell adhesion (CD166 or ALCAM) in CRC patients. METHODS: This study was carried out on 458 paraffin-embedded CRC specimens by immunohistochemistry on tissue microarray (TMA) slides. RESULTS: Elevated expression of EpCAM and CD166 was observed in 61.5% (246/427) and 40.5% (164/405) of CRC cases. Our analysis showed a significant positive association of EpCAM expression with tumor size (P = 0.02), tumor stage (P = 0.007), tumor differentiate (P = 0.005), vascular (P = 0.01), neural (P = 0.01), and lymph node (P = 0.001) invasion. There were no significant differences between CD166 expression and clinicopathological parameters. Moreover, the combined analysis demonstrated a reciprocal significant correlation between EpCAM and CD166 expression (P = 0.02). Interestingly, there was a significant positive correlation between EpCAM/CD166 phenotypes expression and tumor stage (P = 0.03), tumor differentiation (P = 0.05), neural, and lymph node invasion (P =0.01). CONCLUSIONS: The significant correlation of EpCAM and CD166 expression and their association with tumor progression and aggressive behavior is the reason for the suggestion of these two CSC markers as promising targets to promote novel effective targeted-therapy strategies for cancer treatment in the present study.

Production and characterization of a new specific monoclonal antibody against A-isoform of SALL4: A novel emerging testicular cancer marker.

SALL4 transcription factor plays an important role to maintain the pluripotent and self-renewal of embryonic stem cells. It contributes to the growth of many cancers and embryonic development. With the exception of spermatogonia, SALL4 expression is silenced in most adult tissues after birth; nevertheless, it is re-expressed in a subset of different solid malignancies. SALL4 is a new, precise biomarker for testicular germ cell cancers that was just introduced. The whole isoform of SALL4 is called SALL4-A. Regarding the lack of antibody against human SALL4 isoforms, the pattern of expression, the role of each isoform remain unknown. Furthermore, in isoform specific evaluations, we aimed, for the first time, to produce and characterize mAb against human SALL4-A. Immunization of mice were performed with a selected 33-mer synthetic peptide of SALL4-A conjugated with KLH. Hybridoma cells were screened by ELISA for positive reactivity with SALL4-A peptide. From the ascites fluid of mice that had been injected with hybridoma cells, anti-SALL4-A mAbs were isolated using a protein G column. Reactivity of the mAbs was evaluated using the peptide and SALL4-A recombinant protein by ELISA and IHC on testicular cancer tissue as positive control, and normal kidney, stomach and prostate tissues as negative control. The produced mAb could well detect SALL4-A in testicular cancer tissues using IHC, while the reactivity was negative in normal kidney, stomach and prostate tissues. Using ELISA, the mAb affinity for the peptide and SALL4-A recombinant protein was assessed, and it was shown to be reasonably high. The mAb detected SALL4-A in nucleus and cytoplasm of several cancer cells and spermatogonia in testicular cancer tissue. In addition, it could recognize SALL4-A recombinant protein. Our produced monoclonal antibody against isoform-A of human SALL4 can specifically recognize SALL4-A using either IHC or ELISA. We hope that this mAb could help researchers in isoform-specific study of human SALL4.

Food Addiction and Binge Eating Disorder in Relation to Dietary Patterns and Anthropometric Measurements: A Descriptive-Analytic Cross-Sectional Study in Iranian Adults with Obesity.

Obesity is associated with maladaptive eating behaviors, including food addiction (FA) and binge eating disorder (BED). However, the key factors influencing the development of maladaptive eating behaviors remain unknown. Adherence to specified dietary patterns has been suspected of making indirect impacts. This study investigates the association of FA and BED with dietary patterns and anthropometric measurements among 400 Iranian adults (aged 18-60; 66.25% women) living with obesity (body mass index [BMI] ≥ 30 kg/m2). The Binge Eating Scale and Yale Food Addiction Scale were used to measure BED and FA. A validated 147-item semi-quantitative food frequency questionnaire underwent principal component analysis and identified three major dietary patterns: mixed, unhealthy, and healthy dietary pattern. After adjusting for confounders, higher adherence to unhealthy dietary patterns was associated with an increased risk of FA, while higher adherence to healthy dietary patterns was associated with a lower risk of FA. Also, those within obesity class III had a significantly higher risk of FA and BED than those in obesity class I. This study suggests that adherence to an unhealthy dietary pattern may be associated with a higher risk of FA. It also highlights the link between higher BMI and maladaptive eating behaviors.

Reduced cytoplasmic expression of MAGE-A2 predicts tumor aggressiveness and survival: an immunohistochemical analysis.

BACKGROUND: Melanoma antigen gene A2 (MAGE-A2) is one of the most cancer-testis antigens overexpressed in various types of cancers. Silencing the MAGE-A2 expression inhibited the proliferation of prostate cancer (PCa) cells and increased the chemosensitivity. However, the expression pattern of MAGE-A2 in PCa tissue samples and its prognostic and therapeutic values for PCa patients is still unclear. METHODS: In this study, for the first time, the staining pattern and clinical significance of MAGE-A2 were evaluated in 166 paraffin-embedded prostate tissues, including 148 cases of PCa and 18 cases of high-grade prostatic intraepithelial neoplasia (HPIN), by immunohistochemical analysis. RESULTS: The simultaneous expression of both nuclear and cytoplasmic patterns of MAGE-A2 with different staining intensities was observed among studied cases. Increased expression of MAGE-A2 was significantly found in PCa tissues compared to HPIN cases (P < 0.0001). Among PCa samples, the strong staining intensity of nuclear expression was predominantly observed in comparison with cytoplasmic expression in PCa tissues (P < 0.0001). A significant and inverse correlation was found between the cytoplasmic expression of MAGE-A2 and increased Gleason score (P = 0.002). Increased cytoplasmic expression of MAGE-A2 was associated with longer biochemical recurrence-free survival (BCR-FS) and disease-free survival (DFS) of patients (P = 0.002, P = 0.001, respectively). In multivariate analysis, Gleason score and cytoplasmic expression of MAGE-A2 were independent predictors of the BCR-FS (P = 0.014; P = 0.028, respectively). CONCLUSIONS: Taken together, cytoplasmic expression of MAGE-A2 was inversely proportional to the malignant grade and duration of recurrence of the disease in patients with PCa.

Expression profiling of RTL1 in human breast cancer tissues and cell lines.

Breast cancer (BC) is the most common cancer in females. In this regard, the identification of molecular alterations driving BC is an immediate need for developing effective immunotherapeutic tools. Here we investigated the expression of a placenta-specific protein, Retrotransposon-like 1 (RTL1) in a series of BC tissues and cell lines. RTL1-specific polyclonal antibody was generated and characterized. Using tissue microarray immunohistochemistry, expression of RTL1 in a total of 147 BC and 36 non-malignant breast tissues was investigated and the association of patient's clinicopathological parameters with RTL1 expression was then examined. Expression of RTL1 in four BC cells was assessed by flow cytometry, immunofluorescent staining and Western blotting. We observed a mixture pattern of nuclear and cytoplasmic RTL1 expression in most tissues examined, however nuclear expression was found to be dominant pattern of expression. The level of nuclear RTL1 expression was significantly higher in BC tissues (P < 0.001). A statistically significant association between nuclear RTL1 expression and histological grade and vascular invasion was found (P < 0.001 and P < 0.05). All cell lines expressed RTL1 with varying degrees at their surface. The most invasive BC cell line MDA-MB-231, compared to T-47D, SKBR3 and MCF7 expressed higher levels of RTL1 at their surface. Cells with a low level of surface expression, expressed high levels of intracellular RTL1 expression. Our antibody reacted with a specific band of about 125 KD in normal human placenta and all cell lines examined. In contrast to placenta, two additional bands were also observed in cancer cell lines. Our results showed for the first time that RTL1 is differentially expressed in BC compared to non-malignant breast tissues and is associated with a higher grade and vascular invasion. In BC cells with high metastatic and invasive potential, this antigen is mostly confined to cell surface compartment indicating the possibility of using antibody-based immunotherapy for advanced metastatic BC patients.

Translation and validation of the Persian version of Godin Leisure-Time Exercise Questionnaire in patients with multiple sclerosis.

STUDY DESIGN: Psychometric study. OBJECTIVE: The purpose of this study is to translate, culturally adapt and evaluate the validity and reliability of the Persian (Farsi) version of GLTEQ in patients with multiple sclerosis. METHODS: This study had three phases, including translation of the questionnaire into Persian and making cultural adaptation, evaluation of pre-final version of questionnaire's comprehensibility in a pilot study, and investigation of reliability and validity of the final version of the translated questionnaire. Content validity, and convergent validity (correlations among the Persian version of GLTEQ and Global physical activity questionnaire (GPAQ), and international physical activity questionnaire (IPAQ)) and after all test-retest reliability were studied. RESULTS: The subjects were 87 MS patients. The Persian version demonstrated moderate to good convergent validity; the correlation coefficient between the Persian version and GPAQ was r=0.64 (p<0.001), and between the Persian version and IPAQ was r=0.59 (p<0.001). The test-retest reliability was strong (Intra-class Correlation (ICC) value ranged between 0.908 and 0.992). Besides, its face validity and content validity were acceptable. CONCLUSIONS: The Persian version of GLTEQ is a valid and reliable instrument to assess physical activity in patients with MS. This questionnaire can be a step toward standardization of physical activity measurement in patients with MS. Also, in research, it provides the possibilities to carry on a comparative study across cultures using the same outcome measure.

Increased cytoplasmic expression of DLL4 is associated with favorable prognosis in colorectal cancer.

Aims: DLL4 of the Notch pathway is a key regulator of VEGF expression, which mediates tumor neovascularization and stem cell self-renewal in colorectal cancer (CRC). The authors investigated the association of DLL4 expression with the clinicopathological characteristics and survival outcomes of CRC patients. Methods: DLL4 expression level was evaluated in 199 CRC samples using immunohistochemistry analysis of tissue microarrays. Results: The high expression of DLL4 was inversely associated with distant metastasis (p < 0.029), tumor recurrence (p < 0.04) and longer overall survival following curative surgery compared with those with low DLL4 expression with 95% CI (log-rank test: p = 0.050). In univariate analysis, histological grade (hazard ratio: 3.859; 95% CI: 1.081-13.784; p = 0.038) was a strong prognostic risk factor, affecting the overall survival of CRC patients. Conclusion: The authors' results demonstrate that DLL4 expression might be considered a favorable prognostic factor for overall survival in CRC patients.

Effect of Face-to-Face Education on Knowledge, Attitudes, and Practices Toward "Traffic Light" Food Labeling in Isfahan Society, Iran.

Emerging noncommunicable diseases (NCDs) with premature mortality are one of the major concerns in health supervising organizations of the world. High intake of energy, salt, sugar, fat, and trans fatty acids are introduced as dietary risk factors of NCDs. The status of food risk factors is presented in Traffic Light (TL) food labeling through colors of red, yellow, and green as the signs of stop, wait and watch and go, respectively. This stepwise interventional study examined whether TL education can result in choosing healthier food via assessing the impact of face-to-face educational sessions on knowledge, attitudes, and practices of 673 respondents toward TL food labeling through a self-administered and structured questionnaire. Paired t test or alternatively Wilcoxon test was used to evaluate the influence of education in total scores of knowledge, attitudes, and practices in test-retest. Results indicated that before education, the average of the scores for the knowledge, attitudes, and practices was 1.003 ± 0.69, 10.97 ± 1.86, and 1.60 ± 1.84, respectively. After education, the scores were increased to 8.72 ± 3.11, 15.95 ± 2.64, and 8.42 ± 1.69. Significant differences in the scores of the respondents were observed before and after education (p < .05). This study revealed that the intervention of education had positive effect on the knowledge, attitudes, and practices of the studied population. Even though general awareness about the food risk factors of NCDs existed, special education is required to make public TL and food labeling information usage as an actual guidance for every food item in Iran.

Association study between common variations in some candidate genes and prostate adenocarcinoma predisposition through multi-stage approach in Iranian population.

BACKGROUND: Prostate cancer is one of the five common cancers and has the second incidence rate and the third mortality rate in Iranian population. The purpose of this study was to evaluate the association of rs16901979, rs4242382 and rs1447295 on 8q24 locus, rs2735839 (KLK3 gene) and rs721048 (EHBP1 gene) with prostate adenocarcinoma through multi-stage approach to identify the polymorphisms associated with prostate cancer and use them as screening factors. Screening tests can identify people who may have a chance of developing the disease before detection and any symptoms. METHODS: The case-control study included 103 cases (prostate adenocarcinoma) and 100 controls (benign prostatic hyperplasia). Tetra-primer ARMS-PCR was used to genotyping of each participant. A Multi-stage approach was used for efficient genomic study. In this method, a smaller number of people can be used. Chi-squared, Fisher's exact test and logistic regression were used to investigate the SNPs associated with prostate cancer and Gleason score. RESULTS: In the first stage (59 men), the frequency of polymorphisms rs16901979, rs4242382, rs1447295, rs2735839 and rs721048 in the prostate adenocarcinoma group was evaluated compared to the control group (P-value < 0.3) in order to select meaningful polymorphisms. There was not any significant difference between genotype frequency rs16901979 (P = 0.671) and rs721048 (P = 0.474) in the case group compared to BPH. Therefore, these polymorphisms were eliminated, and in the second step (144 men), rs4242382, rs2735839 and rs1447295 were evaluated (P-value < 0.05). According to the total population (203 men), there was significant difference between genotype frequency rs4242382 (P = 0.001), rs2735839 (P = 0.000) and rs1447295 (P = 0.005) even after using Bonferroni correction (p = 0.016). The effect of these three polymorphisms on prostate cancer was not modified by age and PSA. There was a significant difference between the allelic frequency of A vs G (rs4242382, rs2735839) at all classes of Gleason score and A vs C (rs1447295) at Gleason score ≥ 8. CONCLUSIONS: The results of this study for rs2735839, rs4242382 and rs1447295 indicate the association of these polymorphisms with prostate adenocarcinoma predisposition in Iranian population. Exposure effect is homogeneous between different ages and PSA level categories. These three polymorphisms should be studied in a larger population to confirm these results.

Cytoplasmic expression of B7-H3 and membranous EpCAM expression are associated with higher grade and survival outcomes in patients with clear cell renal cell carcinoma.

B7-H3 and EpCAM are overexpressed in cancer and play a role in tumorigenesis and metastasis. In this study, the membranous, cytoplasmic and nuclear expression levels of B7-H3 and EpCAM biomarkers were mapped in three major subtypes of renal cell carcinoma (RCC). Expression of B7-H3 and EpCAM were evaluated using immunohistochemistry in RCC samples on tissue microarrays (TMAs), including clear cell RCCs (ccRCCs), type I and II papillary RCCs (pRCCs), and chromophobe RCCs (chRCCs). The association between B7-H3 and EpCAM expression and clinicopathological features as well as survival outcomes was determined. There was a statistically significant difference between B7-H3 and EpCAM expression among the different RCC subtypes. In ccRCC, higher cytoplasmic expression of B7-H3 was significantly associated with increase in nucleolar grade, lymph node invasion (LNI), invasion of the Gerota's fascia, and tumor necrosis, while no association was found with the membranous and nuclear expression. Moreover tumors with cytoplasmic expression of B7-H3 tended to have a worse prognosis for disease-specific survival (DSS) than those with membranous expression. In case of EpCAM, increased membranous expression of EpCAM was associated with nucleolar grade and tumor necrosis in ccRCC. Additionally, membranous EpCAM expression added prognostic value in patients with ccRCC who had high nucleolar grade versus low nucleolar grade. Moreover, membranous EpCAM expression was found to be an independent favorable prognostic marker for progression-free survival (PFS) in ccRCC. Our results demonstrated that higher cytoplasmic B7-H3 and membranous EpCAM expression are clinically significant in ccRCC and are associated with more aggressiveness tumor behavior.

Immunofluorescent labeling of CD20 tumor marker with quantum dots for rapid and quantitative detection of diffuse large B-cell non-Hodgkin's lymphoma.

Fluorescent semiconductor quantum dots (QDs) are newfound nanocrystal probes which have been used in bioimaging filed in recent years. The purpose of this study is to evaluate the diagnostic value of specific QDs coupled to rituximab monoclonal antibody against CD20 tumor markers for patients with diffuse large B-cell lymphoma (DLBCL). In current study rituximab-conjugated quantum dots (QDs-rituximab) were prepared against CD20 tumor markers for detection of CD20-positive cells (human Raji cell line) using flowcytometry. A total of 27 tumor tissue samples were collected from patients with DLBCL and 27 subjects with negative pathological tests as healthy ones, which stained by QD-rituximab. The detection signals were obtained from QDs using fluorescence microscopy. The flowcytometry results demonstrated a remarkable difference in fluorescent intensity and FL2-H + (CD20-positive cells percentage) between two groups. Both factors were significantly higher in Raji in comparison with K562 cell line (P < 0.05). Lot of green fluorescence signals was observed due to the selectively binding of QD-rituximab to CD20 tumor markers which overexpressed in tumor tissues and a few signals observed on the defined healthy ones. Based on these observations the cut-off point was 46.8 dots and the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 89.5%, 91.3%, and 100%, respectively (LR+, 9.52; LR-, 0). The QD -rituximab could be beneficial as a bioimaging tool with high sensitivity to provide an accurate molecular imaging technique for identifying CD20 tumor markers for early diagnosis of the patients with DLBCL.

Co-expression of TLR-9 and MMP-13 is associated with the degree of tumour differentiation in prostate cancer.

In vitro experiments demonstrated that stimulation of Toll-like receptor 9 (TLR-9) by synthetic TLR-9 ligands induces the invasion of TLR-9-expressing prostate cancer cells through matrix metalloproteinase 13 (MMP-13). However, the clinical value of TLR-9 and MMP-13 co-expression in the pathophysiology of the prostate is unknown. In the study, we evaluated the expression levels and clinical significance of the TLR-9 and MMP-13 in a series of prostate tissues. One hundred and eighty prostate tissues including prostate cancer (PCa) (n = 137), high-grade prostatic intraepithelial neoplasia (HPIN) (n = 18) and benign prostatic hyperplasia (BPH) (n = 25) were immunostained for the TLR-9 and MMP-13 markers. Subsequently, the correlation between the TLR-9 and MMP-13 staining scores and clinicopathological parameters was obtained. Higher expressions of TLR-9 and MMP-13 were found in PCa and high-grade prostatic intraepithelial neoplasia compared to benign prostatic hyperplasia tissues. Among PCa samples, a positive relationship was revealed between the MMP-13 expression and Gleason score (P < 0.001). There was a significant correlation between TLR-9 expression and regional lymph node involvement (P = 0.04). The expression patterns of TLR-9 and MMP-13 markers demonstrated a reciprocal significant correlation between the two markers in the same series of prostate samples (P < 0.001). Furthermore, the Gleason score of TLR-9high /MMP-13high and TLR-9low /MMP-13low phenotypes showed a significant difference (P = 0.002). Higher expressions of TLR-9 and MMP-13 can confer aggressive behaviour to PCa. Therefore, these markers may be used as a valuable target for tailored therapy of PCa.

Increased expression of DCLK1, a novel putative CSC maker, is associated with tumor aggressiveness and worse disease-specific survival in patients with bladder carcinomas.

Doublecortin-like kinase 1 (DCLK1) has been characterized as a novel potential cancer stem cell (CSC) marker in several types of cancer. It is considered as one of the most specific markers for distinguishing colorectal CSCs from normal stem cells. Yet, there are limited reports on the role of DCLK1 as a putative CSC marker in bladder cancer. Using immunohistochemistry, DCLK1 expression was examined in a well-defined tissue microarray series of 472 bladder cancer tissues. The association between DCLK1 protein expression and clinicopathological features, as well as survival outcomes, was assessed. Our findings showed strong, moderate, and weak DCLK1 expression in 123 (26.1%), 230 (48.7%), and 119 (25.2%) of the bladder cancer specimens, respectively. Higher expression of DCLK1 was significantly associated with increase in histological grade (P ≤ .001), pT stage (P = .014), lamina propria (P = .006), and lamina propria/muscularis (L/M) involvement (P = .014). On multivariate analysis, pT stage (P < .001), histological grade (P = .021), and lamina propria involvement (P = .001) were independent prognostic factors in DCLK1 expression. Moreover, the expression of DCLK1 was found to be an independent marker of poor prognosis for disease- specific survival (DSS) (P = .048) in bladder carcinomas. Our observations showed that DCLK1 expression was associated with more aggressive tumor behavior, more advanced disease, and poorer DSS in patients with bladder carcinomas. However, any potential clinical applications of DCLK1 as a novel target molecule in bladder cancer patients would require further investigations.

High GD2 expression defines breast cancer cells with enhanced invasiveness.

INTRODUCTION: Breast cancer is the most frequently diagnosed cancer among women. Cancer stem cells (CSCs) are suggested to be responsible for tumor initiation, progression, metastasis, recurrence and drug resistance. This study was conducted to evaluate the clinical significance of GD2, a newly suggested CSC marker and two other traditional CSC markers, CD44 and CD24 in breast cancer patients. MATERIAL AND METHODS: A total of 168 primary breast cancer tissues were evaluated in terms of GD2, CD44 and CD24 expression using tissue microarray. Then, the correlation of expression levels of these markers with patients' clinicopathological characteristics was assessed. RESULTS: Higher GD2 expression was mainly found in patients with advanced histological grade (p = 0.02), presence of lymph node invasion (p = 0.04), larger size of tumors (p = 0.04) and older age (p = 0.04). Breast cancer samples with advanced histological grade also showed higher CD44 (p = 0.03) and CD24 expression (p = 0.05). A significant positive association was found between increased CD24 expression and lymph node involvement (p = 0.01). Furthermore, GD2-high/CD44-high/CD24-low phenotype was frequently seen in breast cancer samples with positive lymph node involvement (p = 0.05). CONCLUSION: In summary, increased expression of GD2 may define more aggressive tumor behavior in breast cancer. GD2 can well be considered as a diagnostic and prognostic marker in breast cancer.

Molecular Detection of Pathogens Causing Sexually Transmissible Infections in Patients with Prostate Cancer and Hyperplasia by Quantitative TaqMan Real-Time PCR Assay.

BACKGROUND: Prostate cancer is considered the most prevalent cancer among men. Recent studies suggest that sex-ually transmissible infections (STIs) may be related to prostate carcinogenesis. Therefore, the aim of this study was to investigate whether STI pathogens (Atopobium vaginae (ATO), Neisseria gonorrhoeae (NG), Chlamydia tra-chomatis (CT), Treponema pallidum (TP), Ureaplasma urealyticum (UU), Gardnerella vaginalis (GV), Herpes Sim-plex Virus (HSV), Cytomegalovirus (CMV), Human herpesvirus (HHV), Human papillomavirus (HPV), and Tricho-monas vaginalis (TV)) presence in prostate tissues are associated with the risk of prostate cancer. METHODS: Paraffin-embedded prostate tissues obtained from patients with hyperplasia and prostate cancer were extracted. Determination of infectious microorganisms of interest was done by quantitative TaqMan real-time PCR assay. RESULTS: STI DNA was detected in 53/243 (21.8%) of the prostate tissues samples (ATO 3.7%, UU 2.88%, GV 2.46%, HSV-2 2.05%, CT 2.05%, CMV 1.64%, NG 1.64%, TP 1.64%, HHV-8 1.23%, HPV 1.23%, and TV 1.23%.) The statistical analysis revealed significant correlation between prevalence of Gardnerella vaginalis (GV) and Herpes Simplex Virus (HSV-2) between hyperplasia and cancerous groups (p = 0.02), respectively. CONCLUSIONS: No statistically significant difference was observed in the prevalence of most candidate infectious or-ganisms between hyperplasia and cancerous groups except for GV and HSV-2. It appears that inflammation in the prostate gland is more associated with prostate hyperplasia than prostate cancer. According to the role of in-fectious microorganisms in induction of chronic inflammation, we cannot exclude the importance of these patho-gens in progression of cancer. More studies are required to explore the associations of cancer with different infec-tious organisms.

Comorbidity of gastrointestinal disorders, migraine, and tension-type headache: a cross-sectional study in Iran.

Migraine can be accompanied by some gastrointestinal (GI) disorders. In this study, we aimed to investigate the relationship between migraine and tension-type headache (TTH) and different lower and upper GI disorders as well as non-alcoholic fatty liver (NAFLD) and cholelithiasis. This cross-sectional study included 1574 overweight and obese participants who were referred to the Obesity Research Center of Sina Hospital, Tehran, Iran. The diagnosis of migraine and TTH was made by an expert neurologist based on the international classification of headache disorders-III ß (ICHD III ß). GI disorders, including irritable bowel syndrome (IBS), constipation, heartburn, dyspepsia, non-alcoholic fatty liver (NAFLD), and cholelithiasis, were diagnosed by a gastroenterology specialist. The overall mean age of participants was 37.44 ± 12.62. A total of 181 (11.5%) migraine sufferers (with and without aura) and 78 (5%) TTH subjects were diagnosed. After adjusting for potential confounders by multivariable regression models, migraine had significant association with IBS (OR = 5.16, 95% CI = 2.07-12.85, P = 0.000), constipation (OR = 3.96, 95% CI = 2.25-6.99, P = 0.000), dyspepsia (OR = 4.12, 95% CI = 2.63-6.45, P = 0.000), and heartburn (OR = 5.03, 95% CI 2.45-10.33, P = 0.000), while the association between migraine and NAFLD was marginally significant (OR = 2.03, 95% CI = 0.98-4.21, P = 0.055). Furthermore, the prevalence of NAFLD (OR = 2.93, 95% CI 1.29-6.65, P = 0.010) and dyspepsia (OR = 4.06, 95% CI = 2.24-7.34, P = 0.000) was significantly higher in TTH patients than the headache-free group. These findings show an association between GI disorders and primary headaches especially migraine and are, therefore, of value to the management of migraine and TTH. Further studies should investigate the etiology of the relationship between all subtypes of primary headaches and GI disorders.

Cytoplasmic expression of CD133 stemness marker is associated with tumor aggressiveness in clear cell renal cell carcinoma.

Prominin-1 (CD133) is one of the most commonly used markers for cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. However, the clinical and prognostic significance of CSCs in renal cell carcinoma (RCC) remains unclear. The aim of this study was to investigate the expression patterns and prognostic significance of the cancer stem cell marker CD133 in different histological subtypes of RCC. CD133 expression was evaluated using immunohistochemistry in 193 well-defined renal tumor samples on tissue microarrays, including 136 (70.5%) clear cell renal cell carcinomas (CCRCCs), 26 (13.5%) papillary RCCs, and 31 (16.1%) chromophobe RCCs. The association between CD133 expression and clinicopathological features as well as the survival outcomes was determined. There was a statistically significant difference between CD133 expression among the different RCC subtypes. In CCRCC, higher cytoplasmic expression of CD133 was significantly associated with increase in grade, stage, microvascular invasion (MVI) and lymph node invasion (LNI), while no association was found with the membranous expression. Moreover, on multivariate analysis, TNM stage and nuclear grade were independent prognostic factors for overall survival (OS) in cytoplasmic expression. We showed that higher cytoplasmic CD133 expression was associated with more aggressive tumor behavior and more advanced disease in CCRCC but not in the other examined subtypes. Our results demonstrated that higher cytoplasmic CD133 expression is clinically significant in CCRCC and is associated with increased tumor aggressiveness and is useful for predicting cancer progression.