Therapeutic effects of iNOS inhibition against vitiligo in an animal model.

Nitric oxide (NO) is involved in several biological processes, but its role in human melanogenesis and vitiligo need further studies. Previous studies revealed that exposure to UVA and UVB were capable of the inducing nitric oxide production in keratinocytes and melanocytes through the activation of constitutive nitric oxide synthase, whereas inducible nitric oxide synthase overexpression has been reported to play an important role in hyperpigmentary disorders. The aim of this study was to evaluate iNOS inhibitor aminoguanidine (AG) as a therapeutic agent in our mouse model of vitiligo. In this study, male C57BL/6J Ler-vit/vit mice were purchased to evaluate the effect of iNOS inhibitor (aminoguanidine) (50 and 100 mg/kg) and L-arginine (100 mg/kg) in a mouse model of vitiligo induced by monobenzone 40%. Moreover, we used phototherapy device to treat the mice with NBUVB as a gold standard.The findings revealed that monobenzone was capable of inducing depigmentation after 6 weeks. However, aminoguanidine in combination with monobenzone was decrease the effect of monobenzone, while L-arginine play a key role in promoting the effect of monobenzone (P<0.001). Based on the phototherapy, the efficacy of phototherapy significantly increased by adding L-arginine (P<0.05). Taken together, we suggest that iNOS inhibitor can be a novel treatment for the prevention and treatment of vitiligo by combination of NBUVB therapy, furthermore; NO agents like L-arginine could also increase the effectiveness of phototherapy. Taken together, this pilot study showed significant repigmentation of vitiligous lesions treated with iNOS inhibitor plus NBUVB therapy, where other aspect including expression of an inducible iNOS, NO and TNF levels remained to be evaluated in mice model.

The effect of histone deacetylase inhibitors on AHSP expression.

Alpha-hemoglobin stabilizing protein (AHSP) is a molecular chaperone that can reduce the damage caused by excess free α-globin to erythroid cells in patients with impaired ß-globin chain synthesis. We assessed the effect of sodium phenylbutyrate and sodium valproate, two histone deacetylase inhibitors (HDIs) that are being studied for the treatment of hemoglobinopathies, on the expression of AHSP, BCL11A (all isoforms), γ-globin genes (HBG1/2), and some related transcription factors including GATA1, NFE2, EKLF, KLF4, and STAT3. For this purpose, the K562 cell line was cultured for 2, 4, and 6 days in the presence and absence of sodium phenylbutyrate and sodium valproate. Relative real-time qRT-PCR analysis of mRNA levels was performed to determine the effects of the two compounds on gene expression. Expression of all target mRNAs increased significantly (p < 0.05), except for the expression of BCL11A, which was down-regulated (p < 0.05) in the cells treated with both compounds relative to the levels measured for untreated cells. The findings indicated that sodium valproate had a more considerable effect than sodium phenylbutyrate (p < 0.0005) on BCL11A repression and the up-regulation of other studied genes. γ-Globin and AHSP gene expression continuously increased during the culture period in the treated cells, with the highest gene expression observed for 1 mM sodium valproate after 6 days. Both compounds repressed the expression of BCL11A (-XL, -L, -S) and up-regulated GATA1, NFE2, EKLF, KLF4, STAT3, AHSP, and γ-globin genes expression. Moreover, sodium valproate showed a stronger effect on repressing BCL11A and escalating the expression of other target genes. The findings of this in vitro experiment could be considered in selecting drugs for clinical use in patients with ß-hemoglobinopathies.

Immunohistochemical Evaluation of ß-Catenin Marker in Papillary Thyroid Cancer: Clinicopathologic Significance.

BACKGROUND & OBJECTIVE: papillary thyroid cancer is the most common cancer of thyroid accounting for 75%-85% of all thyroid malignancies. Recently, ß-catenin has been determined to play a role in clinical course of human epithelial cancers. This study was designed to reveal the association of ß-catenin marker and papillary thyroid carcinoma behavior. METHODS: 63 paraffin blocks of papillary thyroid carcinoma were stained with ready to use monoclonal ß-catenin antibody according to manufacturer's instructions. Memberanous, cytoplasmic and nuclear staining was scored according to intensityof immunoreactivity. ß-catenin immunostaining association with clinical parameters like number of recurrences and cumulative dose of radioiodine therapy were analyzed using SPSS version 15. Histopathologic parameters like tumor stage, grade, capsular invasion, lymphovascular invasion, lymph node involvement, distant metastasis andother variables were also evaluated for association with ß-catenin immunoreactivity. RESULTS: 77.8% of papillay thyroid carcinoma were well differentiated and the remaining were poorly differentiated. Loss of ß-catenin membrane immunostaining depicted correlation with number of recurrences (P=0.023% , Pearson correlation=-0.285). Its loss of memberanous staining correlated similarly with cumulative dose of radioiodine (P= 0.046, Pearson correlation = -0.253). Loss of membranous ß-catenin was significantly associated with some histopathologic findings like nodal involvement (P<0.001), distant metastasis (P=0.003) and tumor dedifferentiation (P< 0.001). CONCLUSION: Loss of ß -catenin membranous staining and its cytoplasmic accumulation were associated with aggressive clinicopathologic behavior. The exact effect of radioiodine exposure on ß-catenin pathway remained to be determined in future.

Immunohistochemical distinction of metastases of renal cell carcinoma with molecular analysis of overexpression of the chemokines CXCR2 and CXCR3 as independent positive prognostic factors for the tumorigenesis.

Renal cell carcinoma (RCC) represents, on average, over 90% of all malignancies of the kidney that occur in adults in both sexes. Chemokine receptors expression has been found in many kinds of cancer and at tumor metastasis site. We determined CXCR2 and CXCR3 expression in RCC by immunohistochemistry method and analyzed the prognostic value of these markers. Our finding demonstrated that CXCR3 were highly overexpressed in renal cancer tissues compared with those adjacent normal kidney tissues (P < 0.001). The results showed that high expression of CXCR3 was markedly correlated with metastasis (P = 0.021) and tumor stage (P = 0.031). CXCR2 were overexpressed in renal cancer tissues compared with those adjacent normal kidney tissues (P < 0.001). Our result showed that CXCR2 expression was correlated with high grade (P = 0.024), advanced stage (P = 0.029) and metastasis (P = 0.018). The log-rank test revealed that high CXCR2 and CXCR3 expressions are related to poorer overall survival (P < 0.001; P < 0.001). In conclusion, this study indicates the correlation of CXCR3 and CXCR3 with progression of RCC. In addition, high CXCR3 andCXCR2 expressions were correlated with shorter overall survival. © 2016 IUBMB Life, 68(8):629-633, 2016.

Ovarian Hemangioma: a Rare Case Report and Review of the Literature.

Ovarian hemangiomas are benign and rare tumors of female genital tract with less than 60 reported cases in the literature. A 38- yr- old woman was admitted to Be'sat Hospital, Tehran, Iran in 2012, due to severe abdominal pain. Ultrasound evaluation revealed a 6 cm left ovarian cystic mass and serum tumor markers were normal. Then, left salpingo-oophorectomy was performed for the patient. Microscopic examination revealed a follicular cyst and an incidental cavernous hemangioma consisting thin-walled vascular channels filled with blood that lined with flatten endothelial cells. In IHC staining strong immunoreactivity for CD31 and CD34 were seen, finally, the diagnosis of primary ovarian hemangioma, cavernous-type was made. The clinicopathologic presentation of this unusual benign tumor is discussed.

Overexpression of interleukins IL-17 and IL-8 with poor prognosis in colorectal cancer induces metastasis.

Current evidences indicated that a group of soluble mediators called chemokines is involved in tumor growth and metastasis. The association of IL-8 with tumor cell migration was previously found, and its expression was related to angiogenesis, tumor progression, and metastasis in many kinds of carcinomas in human and animal models. Furthermore, it has been showed that IL-17 plays its role as either a proteome of tumor progression or antitumor indifferent cancer models. To investigate the messenger RNA (mRNA) expressions of IL-8 and IL-17 in patients with colorectal cancer (CRC) and non-tumor tissue, quantitative real-time PCR was used in the study. Our results showed that expression of IL-8 mRNA was significantly increased in tumor tissues (mean ± SD 3.84 ± 0.08) compared with adjacent normal mucosa (mean ± SD 1.17 ± 0.75, P = 0.001). Furthermore, a higher expression of IL-17 mRNA was found in tumor tissues (mean ± SD 2.73 ± 0.69) when compared with normal tissues (mean ± SD 1.06 ± 0.07, P = 0.001). Our findings indicated that advanced tumor-node-metastasis (TNM) stage (P = 0.024) and histological grade (poorly differentiated, P = 0.013) and distant metastasis (P = 0.001) were correlated with expression of IL-8. Moreover, high expression of IL-17 showed significant association with early stage CRC (TNM) (P = 0.038). In conclusion, the expression of IL-8 and IL-17 mRNAs was significantly increased in tumor tissues compared with adjacent normal tissues. We found that advanced TNM stage and histological grade and distant metastasis were correlated with expression of IL-8, while high expression of IL-17 showed significant association with early stage CRC (TNM) stage and overexpression of IL-8 may be associated with progression of CRC.

Downregulation of miR-148b as biomarker for early detection of hepatocellular carcinoma and may serve as a prognostic marker.

MicroRNAs (miRNAs) have a large number of various target genes in different cancer types, which may result in many biological functions. Thus, identifying the molecular mechanisms of miRNAs may effect on the complexity of cancer progression via regulation of gene. In the current study, we utilized real-time PCR to quantify the diction of miR-148b in trail hepatocellular carcinoma (HCC) specimen and normal tissues. Furthermore, we evaluated the relationship of miR-148b and clinicopathological features with survival of HCC patients. Therefore, we evaluated the level of miR-148b expression in 101 HCC patients and also in 40 normal control cases. The result suggested lower expression in tumor tissues than normal control tissues (0.96 ± 0.14; 1.84 ± 0.20, P < 0.05). Our findings suggest that the declined expression of miR-148b can considerably be linked to tumor node metastasis (TNM) stage (stages III and IV; P = 0.021) and vein invasion (P = 0.029). Nevertheless, miR-148b expression was not related to sex (P = 0.674), age (P = 0. 523), size of tumor (P = 0.507), liver cirrhosis, and histologic grade (P = 0.734). Survival analysis showed that low expression was remarkably related to overall survival (P = 0.012). Furthermore, multivariate survival test suggested that decline of miR-148b diction was linked to poor survival in HCC patients. Our results suggested that miR-148b is decreased in HCC. Therefore, we concluded that miR-148b may play its role in the prognosis of HCC.

Middle Ear Salivary Gland Choristoma: A Case Report.

Salivary gland choristoma of the middle ear cavity is a very rare condition. These lesions are a result of a defective embryonic development and their adjacent structures may be associated with abnormalities. Here we report a case of salivary gland choristoma of the middle ear who presented to Be'sat Hospital, Tehran, Iran in 2015 with unilateral conductive hearing loss. There are 41 case reports in English and non-English literature from 1961. Taylor and Martin reported the first case of middle ear salivary choristoma.

Survival analysis and prognosis for patients with serous and mucinous borderline ovarian tumors: 14-year experience from a tertiary center in Iran.

The aim of this study was to determine the prognosis and survival for patients with borderlineovarian tumor (BOT). A retrospective review of 30 patients with serous andmucinous BOT treated at or referred to our institution was performed. Fifteenpatients (50%) had serous, and the others had mucinous BOT. About 86% of allpatients in both groups were in stage I of the disease. The recurrent disease occurredin 7% and 21% of serous and mucinous tumors, respectively. All recurrences,except one in mucinous tumors, were found in advance stage disease. After amean of 37 and 52 months follow-up, the overall survival was 100% and 93%, anddisease-free survival was 93% and 79% for serous and mucinous tumors,respectively. In this series, advanced stage was associated with poorprognosis. However, to obtain more accurate information further studies withnumber of patients and longer follow-up is recommended.

Association between iron deficiency anemia and Helicobacter pylori infection among children under six years in Iran.

This study was conducted to evaluate the association between H. pylori infection and Iron deficiency anemia (IDA) among preschool children (age range: 40-75 months) at a tertiary referral hospital in Tehran.In a case-control study, the prevalence of H. pylori seropositivity was compared between 64 children with IDA diagnosis and 70 healthy non-anemic sex- and age-matched controls. Totally, 52 (81.3%) children with IDA and 10 (14.3%) non-anemic controls had a positive antibody level for H. pylori specific IgG and the difference between two groups was statistically significant (P<0.0001). H. pylori infection had a significant high prevalence among preschool patients with IDA. Eradication of H. pylori infection is recommended for patients with refractory IDA.

Cellular and biological evaluation and diagnostic immunohistochemistry of cytokeratin 15/19 expression in distinguishing cutaneous basal cell carcinoma.

Recent studies have investigated the expression of proliferative markers, but little is known about the expression of cytokeratin 15 and 19 in different histological subtypes of basal cell carcinoma (BCC). We conducted cellular, biological, clinicopathological and immunohistochemical analysis on the manifestations of 8 BCC by hematoxylin and eosin stain (H&E) staining and immunohistochemistry and reviewed relevant literature. Microscopically, the tumor cells were multiple remarkable foci of epidermolytic hyperkeratosis with large pleomorphic nuclei and scant cytoplasm together with peripheral palisading and forming solid nests. Furthermore, the most tumors were composed of highly cellular areas with a homogenous population of round, ovoid and spindle cells, hyperchromatic nuclei, high cellular pleomorphism, high mitotic index and various morphologic patterns. Moreover, the tumors displayed an invasive growth, with positive expression of Cytokeratin 19 (CK19) and negative expression of CK15. Our study revealed that the expression of CK19 was associated with progression and invasion in cases with BCC and immunohistochemistry is indispensable in distinguishing this tumor from other types of cutaneous carcinoma. To our best knowledge, it may be a considerable biomarker to assess invasiveness of cutaneous-surface BCC and to guide clinical management of such tumors.

Histopathological findings of endometrial specimens in abnormal uterine bleeding.

PURPOSE: The aim of this study was to assess the frequency of different histopathological findings obtained from dilatation and curettage (D&C) specimens in patients with abnormal uterine bleeding (AUB). METHODS: In a retrospective review of 591 specimens, the included subjects were all women with AUB who underwent D&C between 2002 and 2006 in Be'sat Hospital, Tehran, Iran. The pathological diagnoses were analyzed in four groups from normal to malignant endometrium. The pathological groups were evaluated for patients' characteristics including demographic data and medical history. RESULTS: The majority of patients (61.6%) were in the 41-50 year age group. Totally, 81.4% of patients had normal pathology. The disordered proliferative endometrium/polyps, hyperplasia, and malignant pathology were found in 15.4, 2.5, and 0.7% of specimens, respectively. The abnormal pathologies were seen more among patients with postmenopausal status, nulli-/primigravid women, and those with hypertension, diabetes, hypothyroidism, and polycystic ovary syndrome. CONCLUSIONS: The proliferative endometrium and secretory endometrium were the most common histopathological observations in AUB patients in our region, and except normal endometrium, disordered proliferative endometrium was the most common cause of AUB.