Publications by authors named "Amir-Hossein Jafarian"

61 Publications

Application of inulin/Eudragit RS in 5-ASA pellet coating with tuned, sustained-release feature in an animal model of ulcerative colitis.

Int J Pharm 2021 Feb 2;597:120347. Epub 2021 Feb 2.

Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

A tunable release of 5-aminosalicylic acid (5-ASA) could bring therapeutic benefits in the treatment of inflammatory bowel disease (IBD). A 3 factorial design was used to achieve a tuned delivery of 5-ASA pellets in the small and large intestine using a coating composed of inulin/Eudragit RS (RS). The ratio of inulin/RS and coating level were independent variables while the dependent variables were the percent of drug release at pH 1.2 in 2 h and total release of drug in 10 h at pH 6.8. 5-ASA release from pellets was examined at different pH levels and the therapeutic efficacy of the optimum pellets was compared to 5-ASA pellets of Pentasa in rats with ulcerative colitis. The inulin/RS of 18/82 at a coating level of 16% was found to be the optimum for delivery of the drug to the small and large intestine. The coated pellets offered a superior therapeutic outcome compared to uncoated pellets and Pentasa in terms of colitis activity index (CAI), and the colon's tissue enzymes of GSH and MDA. The optimum coating composed of inulin and RS could offer a tuned sustained release of 5-ASA throughout the small and large intestine with the sensitivity of drug release to microbial degradation.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120347DOI Listing
February 2021

Matrix metalloproteinase-9 (MMP-9) Expression in Non-Small Cell Lung Carcinoma and Its Association with Clinicopathologic Factors.

Iran J Pathol 2020 16;15(4):326-333. Epub 2020 Jul 16.

Pathology Department, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background & Objective: Matrix metalloproteinases-9 (MMP-9) is one of the most important enzymes to breakdown extracellular matrix which plays a major role in tumor invasion and metastasis. This study aimed to determine tumor MMP-9 expression in non-small-cell lung carcinoma (NSCLC) and whether it is associated with histopathologic factors and has prognostic value to affect overall survival (OS).

Methods: The specimens of 92 patients with NSCLC diagnosis were included. Tumor sections were stained by immunohistochemistry method. Using scores for the percentage of cells positively stained and the intensity of staining, MMP-9 expression total score was classified as low-score (scores of 0 to 2), moderate-score (scores of 3 to 5), or high-score (scores of 6 or 7). OS was defined as the time interval since the diagnosis of NSCLC to the status at the last follow-up (dead or alive). The follow up period was up to 70 months.

Results: About 74% of undifferentiated specimens (grade III tumors) showed high scores for MMP-9 expression which was significantly higher than moderately differentiated tumors (25% had high scores for MMP-9 expression) and well differentiated ones which did not have high scores (<0.001). A total of 74 patients (80.4%) died during the follow-up period. Of this, 36% had high scores for MMP-9 expression. In contrast, none of the patients who were alive at the last follow-up had high scores for MMP-9 expression (<0.001). Median OS was significantly lower in high score group (6 months) compared to moderate score (9 months) and high score group (15 months) (<0.001).

Conclusion: MMP-9 expression may serve as a significant prognostic factor for mortality and overall survival in NSCLC. Undifferentiated tumors significantly express higher MMP-9 immunohistochemically.
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http://dx.doi.org/10.30699/ijp.2020.95177.1940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477682PMC
July 2020

Evaluation of CD133 and CD56/NCAM expression in Wilms tumor and their association with prognostic factors.

Iran J Basic Med Sci 2020 Jul;23(7):853-857

Department of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: To validate certain markers for cancer stem cell populations and their clinical importance in Wilms tumor (WT).

Materials And Methods: Immunohistochemical study for CD133 and CD56/NCAM was performed on forty-six cases of WT that were diagnosed between 1999 and 2015, and the association of these markers with survival and prognostic factors was analyzed.

Results: Thirty-four (73.9%) of WTs were positive for CD133 and thirty-nine (84.8%) were positive for CD56/NCAM. A significant positive correlation between CD133 and CD56/NCAM expression and the National Wilms Tumor Stage (NWTS) and death was found. Moreover, overall survival time was significantly correlated with CD133 and CD56/NCAM H-score, NWTS stage, and death.

Conclusion: It seems that CD133 and CD56/NCAM expressions can be used as strong prognostic parameters for the survival of patients with WT and can be used to predict WT patients' stage. Moreover, their targeted therapies can abolish cancer stem cells in children with recurrent tumors.
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http://dx.doi.org/10.22038/ijbms.2020.41468.9804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395190PMC
July 2020

Primary Synovial Sarcoma Presenting as a Huge Mass: A Report of a Rare Case and Review of Literature.

Arch Bone Jt Surg 2020 May;8(3):454-456

Endoscopic and Minimally Invasive Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Primary synovial sarcoma of mediastinum is very rare among soft tissue sarcomas. Only a few cases have been reported in the literatures. The best treatment is still unclear, but, surgical resection is the main therapy. In this article we report a case of a 20*20 cm (2000gr) primary giant mediastinal synovial sarcoma in a 42 year-old man. We performed radical excision of the tumor and the metastasis.
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http://dx.doi.org/10.22038/ABJS.2019.14130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358235PMC
May 2020

Tropisetron ameliorates cyclophosphamide-induced hemorrhagic cystitis in rats.

Eur J Pharmacol 2020 Sep 1;883:173310. Epub 2020 Jul 1.

Pharmaceutical Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Hemorrhagic cystitis is one of the most important complications of cyclophosphamide, a drug widely used in cancer chemotherapy and bone marrow transplantation. 5-HT antagonists are anti-emetic agents and have been shown to have notable anti-inflammatory and antioxidant properties. This study was designed to investigate the possible protective effects of tropisetron against cyclophosphamide-induced hemorrhagic cystitis in rats. Hemorrhagic cystitis was induced in female rats by cyclophosphamide (270 mg/kg). Tropisetron (2.5, 5 and 7.5 mg/kg), granisetron (2.5 and 5 mg/kg), and ondansetron (5 mg/kg) were injected 15 min before, 4 and 8 h after cyclophosphamide. To evaluate the role of alpha7 nicotinic acetylcholine receptor (α7nAChR), its antagonist, methyllycaconitine (5 mg/kg) was administered 30 min before tropisetron. After 24 h, animals were killed under anesthesia. Macroscopic and histological changes were evaluated. Malondialdehyde (MDA), glutathione (GSH) and Evans blue were measured spectrophotometrically. Furthermore, the protein levels of p38 mitogen-activated protein kinases (P38 MAPK), p-P38, signal transducer and activator of transcription 3 (STAT3), p-STAT3 and Poly (ADP-ribose) polymerase (PARP) were determined using Western blot. Cyclophosphamide administration significantly induced histopathological damages and increased MDA, p-p38/p38, p-STAT3/STAT3, and PARP levels compared with the saline group. Tropisetron treatment diminished histopathological injuries as well as MDA level, and STAT3 activity compared to cyclophosphamide treated rats. Co-administration of methyllycaconitine with tropisetron, partially or completely reversed the protective effects of tropisetron. Our results showed that prophylactic administration of tropisetron markedly ameliorated the cyclophosphamide-induced bladder hemorrhage and inflammation in rats. These effects of tropisetron were α7nAChR dependent.
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http://dx.doi.org/10.1016/j.ejphar.2020.173310DOI Listing
September 2020

in Idiopathic Pulmonary Fibrosis.

Iran J Pathol 2020 ;15(1):30-33

Department of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background & Objective: Idiopathic pulmonary fibrosis (IPF) is a chronic and uniformly fatal interstitial lung disease with incompletely understood pathogenesis. Several studies have given the evidence for and against viral cofactors in the pathogenesis of Idiopathic pulmonary fibrosis. In this study (EBV) and (HHV-8) have been studied for a possible role in the pathogenesis of IPF.

Methods: Polymerase chain reaction (PCR) was employed for the detection of EBV and HHV-8 in 58 formalin-fixed paraffin-embedded lung tissue specimens (29 controls and 29 IPF specimens).

Results: EBV DNA was present in the lung tissue of 6 out of 29 (20.7%) IPF specimens compared with 1 out of 29 (3.4%) controls (=0.102). The HHV-8 gene was identified in 3 out of 29 (10.3%) cases of IPF specimens. The control group showed no evidence of HHV-8 gene (=0.227).

Conclusion: Although multiple studies are strongly suggestive of a role for EBV and HHV-8 in the development of IPF, there was no statistically significant difference in the prevalence of EBV and HHV-8 DNA in the IPF specimens and controls in this study.
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http://dx.doi.org/10.30699/IJP.2019.77233.1728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995674PMC
January 2020

The Relationship between Tissue Thioredoxin Reductase Activity and the Psoriasis Area and Severity Index.

Indian J Dermatol 2020 Jan-Feb;65(1):29-32

Department of Dermatology, Mashhad University of Medical Sciences, Mashhad, Iran.

Introduction: Psoriasis is an autoimmune disease. The important role of oxidative stress in the pathogenesis of psoriasis had been investigated in different studies. Thioredoxin reductase (TrxR) is a selenocysteine-containing enzyme which is involved in the protection of cells against oxidative stress. Here, we investigated the TrxR activity in skin lesions of psoriatic patients and the possible correlation between this activity and the severity of the disease that was scored based on the Psoriasis Area and Severity Index (PASI).

Materials And Methods: TrxR activity was determined using TrxR colorimetric method based on the reduction of 5,5'-dithiobis-(2-nitrobenzoic acid) to 5-thio-2-nitrobenzoic acid by TrxR using nicotinamide adenine dinucleotide phosphate in 20 psoriatic patients (11 men and 9 women) aged 38.9 ± 12.6 years. For evaluating the disease severity, PASI score system (mild [PASI <10], moderate [PASI 10-20], or severe [PASI >20]) was utilized that was based on three factors including thickness, erythema, and scaling of lesions.

Results: Our results revealed that the TrxR activity between different groups of psoriatic patients (according to the PASI score) was statistically significant and it was higher in psoriatic patients with mild disease (correlation coefficient = -0.85).

Conclusion: These results further strengthen the association between psoriasis and oxidative stress. The increased level of TrxR could be due to the protective effect of this enzyme against the inflammatory process and oxidative stress. Moreover, TrxR could be used as a novel marker for evaluating psoriasis severity.
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http://dx.doi.org/10.4103/ijd.IJD_327_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986113PMC
February 2020

The Relationship Between Fibroblastic Growth Factor Receptor-1 (FGFR1) Gene Amplification in Triple Negative Breast Carcinomas and Clinicopathological Prognostic Factors.

Iran J Pathol 2019 22;14(4):299-304. Epub 2019 Sep 22.

Department of Pathology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background & Objective: In Triple-Negative Breast Cancers (TNBCs), estrogen receptor (ER), progesterone receptor (PR) and HER2/neu genes are not expressed. Fibroblastic Growth Factor Receptor-1 (FGFR1) gene product is a protein that acts as a receptor of thyrosin kinase. It plays a role in the proliferation, differentiation, and migration of malignant cells. The objective was to evaluate the possible relation between FGFR1 over-expression and amplification in TNBCs and other clinicopathological variables.

Methods: In this cross sectional study, purposive sampling was used to collect eighty-four TNBC specimens from mastectomy specimens collected between 2013 and 2017. Tissue microarrays were evaluated for FGFR1 over-expression and amplification respectively by immunohistochemistry (IHC) staining and real time Polymerase Chain Reaction (PCR). The needed clinical and paraclinical information were obtained from patients' files. To analyze the correlation among prognostic factors, we used a wide range of different statistic methods, namely Chi-square test, independent t-test, Fisher's exact test, and ANOVA.

Results: FGFR1 over-expression was found in 15 of the 84 samples (17.9%). FGFR1 gene amplification was observed in 33.3% (28 of 84) of the samples. We found no association between FGFR1 and clinicopathological parameters, including tumor grade, stage, and patient survival (>0.005).

Conclusion: FGFR1 over-expression and amplification may not be related to clinicopathological parameters, namely age, stage, and grade of the cancer not to mention TNBC survival. Using FGFR1 as a prognostic factor in TNBCs requires further study.
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http://dx.doi.org/10.30699/ijp.2019.96713.1952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824770PMC
September 2019

Effect of Intravenous Lipid Emulsion on Clozapine Acute Toxicity in Rats.

J Pharmacopuncture 2019 Sep 30;22(3):147-153. Epub 2019 Sep 30.

Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: Many studies have been reported the efficacy of intravenous lipid emulsion (ILE) as an antidote on acute lipophilic drug toxicity. Clozapine, highly lipophilic dibenzodiazepine neuroleptics, is an important medication in the schizophrenia therapy regimen. Acute intoxication with antipsychotics is one of the main reasons for the referral of poisoned patients to the hospital. We expected that ILE could be used for the therapy of acute clozapine intoxicated patients.

Methods: We used two groups of consisting of six male rats. Both groups received a toxic dose of clozapine (40 mg/kg) intravenously, via the tail vein. After 15 minutes, they were treated with intravenous infusion of 18.6 mg/kg normal saline (NS group), or 18.6 mg/kg ILE 20% (ILE group). We evaluated blood pressure (BP) and heart rate by power lab apparatus through the tail artery, ataxia by a rat rotary circle, seizure scores and death in multiple times after starting clozapine administration. For biochemical and pathological evaluations the samples of tissue and blood were taken.

Results: Our results demonstrated that ILE 20% could return hypotension-induced clozapine better than normal saline. Furthermore, ataxia and seizure have rectified more rapidly and deaths reduced. Clozapine administration causes pancreatitis and lung injury but fat emulsion did not show an optimal effect on tissue damages caused by clozapine toxicity.

Conclusion: In conclusion, ILE can remove toxic signs of clozapine same as other lipophilic medicines, however, clinical uses of ILE for this intention requires more appraisement to determine the precise implication and safety.
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http://dx.doi.org/10.3831/KPI.2019.22.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820469PMC
September 2019

Effects of ethanolic extract of oleo-resin in a rat model of streptozotocin-induced diabetes.

Res Pharm Sci 2019 Apr 8;14(2):138-145. Epub 2019 Mar 8.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, I.R. Iran.

Previous studies have shown that some plants in the genus of (Apiaceae) have antidiabetic effects. The present work was aimed to evaluate effects of oleo-resin in a rat model of streptozotocin-induced diabetes. Male Wistar rats were randomized into five groups (n = 6): normal control, diabetic control, diabetic rats treated with insulin (3 IU/day), and diabetic rats treated with 100 or 400 mg/kg/day of an ethanolic extract of the oleo-resin. After 4 weeks, blood samples were collected for measuring fasting blood glucose (FBG), lipid profile, aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, blood urea nitrogen, and creatinine. In addition, levels of lipid peroxidation, thiol groups, and superoxide dismutase (SOD) activity were evaluated in the liver and kidney. At the end of the fourth week, the level of FBG in rats treated with 100 mg/kg of the extract was lower than that in diabetic control rats (273 ± 39 mg/dL 471 ± 32 mg/dL). Administration of insulin and the extract had no significant effects on the serum lipids. Insulin and both doses of the extract significantly reduced the activity of ALT. In addition, the extract inhibited lipid peroxidation in the kidney and restored the elevated level of SOD in the liver and kidneys. oleo-resin has the potential to prevent or delay the complications of diabetes by inhibiting the progression of hyperglycemia and attenuating oxidative stress-induced damage in the liver and kidneys.
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http://dx.doi.org/10.4103/1735-5362.253361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791176PMC
April 2019

Correction to: Isolated Human and Livestock Echinococcus granulosus Genotypes Using Real-Time PCR of cox1 Gene in Northeast Iran.

Acta Parasitol 2019 09;64(3):686

Department of Parasitology and Mycology, School of Medicine, Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Unfortunately, the affiliation of Majid Fasihi‑Harandi needs to be edited.
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http://dx.doi.org/10.2478/s11686-019-00133-wDOI Listing
September 2019

Vascular Mimicry Expression in Invasive Ductal Carcinoma; A New Technique for Prospect of Aggressiveness.

Iran J Pathol 2019 1;14(3):232-235. Epub 2019 Aug 1.

Department Of Pathology, Cancer Molecular Pathology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background & Objective: In vascular (vasculogenic) mimicry (VM), tumoral cells mimic the endothelial cells and form the extracellular matrix-rich tubular networks. It has been proposed that VM is more extensive in aggressive tumors. This study was designed to investigate the rate of VM expression in the stromal cells of invasive ductal carcinoma (IDC) and to find its relationship with other clinicopathological factors.

Methods: In this cross-sectional study, 120 patients with histopathologic diagnosis of IDC who received mastectomy were included. The VM expression was determined by immunohistochemistry (IHC). The clinicopathologic data including age, tumor size, histological grade, clinical stage, axillary lymph node metastasis, hormonal receptors, and survival were documented.

Results: The mean (±SD) age of the patients was 51 (±13.83) years old. The stromal VM expression was detected in 16 of 120 patients (13.3%). Twelve specimens (75%) of positive VM expression group had grade 3 which was higher than negative VM expression group (9 cases, 8.65%; <0.001). The VM expression showed statistically significant relationship with higher histologic grade higher clinical stage (stage 3) of the tumor (62.5% vs. 87%; =0.003), the presence of axillary lymph node metastasis (95.6% vs. 55.8%; <0.001), and positive HER-2 (100% vs. 31.1%; <0.001); but not estrogen receptor (ER) or progesterone receptor (PR). However, age, tumor size and mortality rate were not significantly different among the patients with and without VM expression.

Conclusion: The stromal VM expression showed significant relationship with higher stage and grade of the tumor and the presence of nodal metastasis. The VM expression in IDC can be used as a marker for tumor aggressiveness.
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http://dx.doi.org/10.30699/ijp.2019.94997.1939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742743PMC
August 2019

Isolated Human and Livestock Echinococcus granulosus Genotypes Using Real-Time PCR of cox1 Gene in Northeast Iran.

Acta Parasitol 2019 Sep 19;64(3):679-685. Epub 2019 Sep 19.

Department of Parasitology and Mycology, School of Medicine, Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Purpose: Cystic echinococcosis (CE), caused by the metacestode of Echinococcus granulosus, is highly endemic over large parts of Iran. The purpose of this study was to investigate the prevalence rate of hydatidosis and mitochondrial cox1 real-time PCR with high-resolution melting curve (HRM) analysis of E. granulosus isolated from human and livestock.

Methods: In this cross-sectional study, 61 formalin-fixed paraffin-embedded tissue isolates were collected from human CE cases and 83 hydatid cysts from the liver and lung lesions of the livestock in Khorasan Razavi province, Northeast Iran. DNA was extracted from each isolate and amplified by real-time PCR and analyzed using the HRM method.

Results: The HRM analysis using the cox1 gene of 40 E. granulosus human isolates showed that 35 (87.5%), 4 (10%), and 1 (2.5%) of the isolates were categorized as G1, G3, and G6 genotypes, respectively. Out of the total 1342 livestock inspected, 39 (4%) goats and 44(12%) cattle were found harboring hydatid cysts all belonging to E. granulosus sensu stricto.

Conclusion: The results confirmed that the high prevalence of E. granulosus sensu stricto in intermediate hosts is remarkable in northeast of Iran coupled with the high prevalence of infection in livestock, which reinforced the need for hydatidosis control programs in this region.
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http://dx.doi.org/10.2478/s11686-019-00117-wDOI Listing
September 2019

Evaluation of Cyclooxygenase-2 Expression in Association with Clinical-Pathological Factors in Malignant Melanoma.

Iran J Pathol 2019 10;14(2):96-103. Epub 2019 Jan 10.

Associate Professor of Pathology, Department Of Pathology, Cancer Molecular Pathology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background And Objective: The primary goal of this study is to develop a rigorous understanding of the correlation between COX-2 expression and malignant melanoma prognostic factors.

Material And Methods: In this cross-sectional study, we analyzed 60 cases of cutaneous malignant melanoma. The related stained slides were reviewed by two pathologists. The results were interpreted according to the COX2 staining index (SI), tumor thickness (Breslow, Clark), number of mitoses per 10 hpf, and melanoma types. Gender, lymph node involvement, metastasis, and survival were considered as evaluation factors as well.

Results: The expression of the COX-2 protein was evident in 98.4% of cases. A strong Staining Index(SI) was reported in 60% of all melanomas, moderate staining was detected in 20.8% and weak staining in 10%; 1.6% of studied cases showed no staining. Benign nevus specimens showed no staining for the COX-2 enzyme.

Conclusion: We have demonstrated that COX-2 is strongly expressed in the majority of malignant melanomas and that the SI score of COX-2 is related to the number of mitoses, tumor thickness (based on Clark level and Breslow), melanoma sub-type, lymph node involvement, and metastases; No association was noted between the anatomic site, gender, and survival. COX-2 can be applied as a prognostic factor in malignant melanoma and a promising candidate for future target therapies.
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http://dx.doi.org/10.30699/IJP.14.2.96DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679669PMC
January 2019

PYGO2 as an independent diagnostic marker expressed in a majority of colorectal cancers.

J Histotechnol 2019 09 13;42(3):98-103. Epub 2019 May 13.

Department of Biology, Damghan Branch, Islamic Azad University , Damghan , Iran.

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers worldwide. Detection of CRC at the early stages of disease can play an important role in decrease of associated mortality rates. The Wnt signaling pathway is crucial for the progression of different cellular and developmental processes and Wnt pathway deregulation has been well characterized in a variety of cancers, particularly in CRC. The aim of this study was to analyze protein expression of Pygopus2 (PYGO2), the main transcription factor of Wnt pathway, in CRC tissues and evaluate its probable correlation with clinicopathological features of the patients. The expression pattern of PYGO2 was evaluated by immunohistochemistry in tumor tissues and their margin normal which is the piece of normal, or unaffected tissue excised from the surrounding the visible tumors in 46 CRC patients. A defined scoring system was applied to analyze immunostaining results. The expression of PYGO2 protein was detected in all tumor tissues. Furthermore, this expression was significantly higher in CRC samples than in normal tissues. There was a significant association between PYGO2 protein expression in CRC and tumor cell metastasis to the lymph nodes. Considering the significant expression of PYGO2 protein in colorectal tumor cells and its correlation with lymph node metastasis, this protein may be used as a biomarker for metastatic CRC as well as a putative therapeutic target to inhibit aggressiveness and metastasis of CRC.
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http://dx.doi.org/10.1080/01478885.2019.1610214DOI Listing
September 2019

Development, characterization and evaluation of topical methotrexate-entrapped deformable liposome on imiquimod-induced psoriasis in a mouse model.

Int J Pharm 2019 Oct 13;569:118623. Epub 2019 Aug 13.

Biotechnology Research Center, Pharmaceutical Technology Institute, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Nanotechnology Research Center, Pharmaceutical Technology Institute, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

The aim of this study was to prepare and characterize topical methotrexate (MTX) with different percentages (0.05%, 0.1%, 0.25% and 0.5%) entrapped in deformable liposomes using phosphatidylcholine and oleic acid. The effectiveness and sub-acute toxicity of these topical formulations were investigated in imiquimod (IMQ)-induced psoriasis in a mouse model (IMQP). The particle sizes of formulations were around 100 nm with a mean zeta potential of -72.87 mV. The entrapment efficiency (EE%) of MTX in liposomal formulations were more than 85%. Franz cell permeability studies indicated that permeation of MTX through the healthy BALB/c mice skin is very low; however, in the inflammatory skin, which was induced by IMQ it was significant (50%). Liposomal MTX (LM 0.05 and 0.1%) caused significant reduction of thickness score dose-dependently in IMQP compared to the injected MTX. Moreover, investigation of the inflammatory factor and pathological examinations of skin proved the superiority of the LM treating group. Pathological examinations also showed there are no toxicity in organs of the mice that received the LM. Blood cell count test didn't show any abnormality. MTX-entrapped deformable liposomes could be a topical option in future for the treatment of human psoriasis with a less toxicity and merit further investigations.
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http://dx.doi.org/10.1016/j.ijpharm.2019.118623DOI Listing
October 2019

Sentinel ode apping in on-small ell ung ancer sing an ntraoperative adiotracer echnique.

Asia Ocean J Nucl Med Biol 2019 ;7(2):153-159

Lung Disease Research Center, Faculty of Medicine, Mashhad University of Medicine Sciences, Mashhad, Iran.

Objectives: Lymph node metastases are the most significant prognostic factor in localized non-small cell lung cancer (NSCLC). Identification of the first nodal drainage site (sentinel node) may improve detection of metastatic nodes. Extended surgeries, such as lobectomy or pneumonectomy with lymph node dissection, are among the therapeutic options of higher acceptability. Sentinel node biopsy can be an alternative approach to less invasive surgeries. The current study was conducted to evaluate the accuracy of sentinel node mapping in patients with NSCLC using an intraoperative radiotracer techniques.

Methods: This prospective study was conducted on 21 patients with biopsy-proven NSCLC who were candidates for sentinel node mapping during 2012-2014. All patients underwent thoracoabdominal computed tomography, based on which they had no lymph node involvement. Immediately after thoracotomy and before mobilizing the tumor, peritumoral injection of 2mCi/0.4 mL Tc-99m- phytate was performed in 4 corners of tumor. After mobilization of the tumoral tissues, the sentinel nodes were searched for in the hillar and mediastinal areas using hand-held gamma probe . Any lymph node with in vivo count twice the background was considered as sentinel node and removed and sent for frozen section evaluation. All dissected nodes were evaluated by step sectioning and hematoxylin and eosin staining (H&E).The recorded data included age, gender, kind of pathology, site of lesion, number of dissected sentinel nodes, number of sentinel nodes, and site of sentinel nodes. Data analysis was performed in SPSS software (version 22).

Results: The mean age of the patients was 58.52±11.46 years with a male to female ratio of 15/6. The left lower lobe was the most commonly affected site (30.09%). Squamous cell carcinoma and adenocarcinoma were detected in 11 and 10 subjects, respectively. A total of 120 lymph nodes were harvested with the mean number of 5.71±2.9 lymph nodes per patient. At least one sentinel node was identified in each patient, resulting in a detection rate of 95.2%. The mean number of sentinel nodes per patient was 3.61±2. Frozen section results showed 100% concordance with the results of hematoxylin and eosin staining.

Conclusion: Based on the findings, sentinel node mapping can be considered feasible and accurate for lymph node staging and NSCLC treatment.
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http://dx.doi.org/10.22038/AOJNMB.2019.13195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661315PMC
January 2019

Acute and sub-acute toxicity evaluation of the root extract of Janisch.

Drug Chem Toxicol 2020 Nov 2;43(6):609-615. Epub 2019 Jul 2.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

Despite the widespread use of in herbal medicine, no study has yet examined its toxicity. The aim of this study is to evaluate the acute and sub-acute toxicity of hydroalcoholic extract of root. In acute toxicity experiment, female and male mice ( = 5/group/sex) were orally administrated with the extract at single doses of 300, 2000 and 3000 mg/kg and observed for 14 days. In the sub-acute study, the extract was orally administered daily at doses of 100 and 400 mg/kg to male rats ( = 8) for 4 weeks. During the acute toxicity test, there were no deaths or any signs of toxicity observed after administration of the extract at 300 mg/kg, which was the no-observed-adverse-effect level (NOAEL). The extract at a dose of 3000 mg/kg led to the death of one female and one male mouse (LD > 3000 mg/kg). In sub-acute toxicity experiment, the extract induced no mortality or significant changes in body weight, general behaviors, hematological parameters, serum biochemical factors (related to the kidney and liver function), and histopathology of the heart, liver, kidney, and brain up to the highest dose tested of 400 mg/kg (NOAEL). High-performance liquid chromatography-mass spectrometry revealed the presence of phenolic compounds, flavonoids, alkanes, and anthraquinones in the extract. In conclusion, short-term use of root does not appear to produce significant toxicity up to a dose of 400 mg/kg.
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http://dx.doi.org/10.1080/01480545.2018.1561713DOI Listing
November 2020

Bone defect healing is induced by collagen sponge/polyglycolic acid.

J Mater Sci Mater Med 2019 Mar 6;30(3):33. Epub 2019 Mar 6.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

We have evaluated the capability of a collagen/poly glycolic acid (PGA) scaffold in regeneration of a calvarial bone defects in rabbits. 4 bone critical size defects (CSD) were created in the calvarial bone of each rabbit. The following 4 treatment modalities were tested (1) a collagen/PGA scaffold (0.52% w/w); (2) the collagen/PGA scaffold (0.52% w/w) seeded with adipose-derived mesenchymal stem cells (AD-MSCs, 1 × 10 cells per each defect); (3) AD-MSCs (1 × 10 cells) no scaffold material, and (4) blank control. The rabbits were then divided into 3 random groups (of 5) and the treatment outcomes were evaluated at 4, 8 and 12 weeks. New bone formation was histologically assessed. Experimental groups were analyzed by CT scan and real-time PCR. Histological analysis of bone defects treated with collagen/PGA alone exhibited significant fibrous connective tissue formation at the 12 weeks of treatments (P ≤ 0.05). There was no significant difference between collagen/PGA alone and collagen/PGA + AD-MSCs groups. The results were confirmed by CT scan data showing healing percentages of 34.20% for the collage/PGA group alone as compared to the control group and no difference with collagen/PGA containing AD-MSCs (1 × 10 cells). RT-PCR analysis also indicated no significant differences between collagen/PGA and collagen/PGA + AD-MSC groups, although both scaffold containing groups significantly express ALP and SIO rather than groups without scaffolds. Although there was no significant difference between the scaffolds containing cells with non-cellular scaffolds, our results indicated that the Collagen/PGA scaffold itself had a significant effect on wound healing as compared to the control group. Therefore, the collagen/PGA scaffold seems to be a promising candidate for research in bone regeneration.
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http://dx.doi.org/10.1007/s10856-019-6235-9DOI Listing
March 2019

Overexpression of Lactate Dehydrogenase in the Saliva and Tissues of Patients with Head and Neck Squamous Cell Carcinoma.

Rep Biochem Mol Biol 2019 Jan;7(2):142-149

Dental Research Center, Mashhad University of Medical Science, Mashhad, Iran.

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy that is associated with high morbidity and mortality. Salivary lactate dehydrogenase (LDH concentration), as an expression of cellular necrosis, may be a special marker of lesions that occur with changes in the integrity of the oral mucosa. This study was performed to determine the accuracy of salivary LDH as a clinical marker for HNSCC detection and to investigate the relationship between salivary LDH levels and tissue tumor detection.

Methods: The case group consisted of 44 HNSCC patients and the control group consisted of 44 healthy subjects. The stage and grade of HNSCC were determined, and the LDH levels in collected saliva samples were measured in all subjects. The expression of LDH in tumors and healthy tissue margins was evaluated via immunohistochemistry.

Results: The expression of LDH in the saliva of patients with HNSCC is significantly higher than that in the saliva of the healthy control group. The expression of salivary LDH in patients with oral squamous cell carcinoma (OSCC) is significantly higher than that in the other patients and healthy individuals in the control group. The levels of salivary LDH in patients with SCC of the tongue and lower oral cavity were significantly higher than those in other patients affected with SCC in other parts of the head and neck (P<0.01).

Conclusion: As this enzyme increases simultaneously in both tumoral tissues and saliva, it can serve as a useful diagnostic marker for the early diagnosis and prediction of HNSCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374058PMC
January 2019

Molecular Status of BRAF Mutation in Prostate Adenocarcinoma: The Analysis of 100 Cases in North-East of IRAN.

Iran J Pathol 2018 25;13(4):415-421. Epub 2018 Sep 25.

Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background And Objective: mutations were studied in various populations for prostate carcinoma (PC); however, mutations in BRAF gene are unusual compared to . Oncogenic activating of BRAF mutations were studied lately in almost 0%10% of prostate cancer cases.

Methods: In this retrospective study, we gathered 100 formalin-fixed paraffin-embedded samples of prostate adenocarcinoma. A hundred archived samples of adjacent benign prostatic hyperplasia were chosen as normal control. This study was done in pathology laboratory of Qaem Hospital during 2013-2015.

Results: Total number of 200 PC and normal cases was investigated for BRAF V600E mutation. The BRAF V600E mutation was found in only 4 patients but it was not detected in normal cases. There were no significant differences between patient and control groups for this mutation (>0.99). The frequency of BRAF V600E mutation was not significant in different age groups (>0.285); the most frequency was related to the age range of 71-80. No significant difference was observed between tumor grade and BRAF mutation (=0.21).

Conclusion: According to our findings, BRAF gene mutations did not play essential role in PC. Therefore, anti-BRAF (V600E) could not be considered as a proper target for therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358555PMC
September 2018

KRAS Codon 12 and 13 Mutations in Gastric Cancer in the Northeast Iran.

Iran J Pathol 2018 17;13(2):167-172. Epub 2018 Jul 17.

Dept. of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background & Objective: mutations are reported in many types of cancers including pancreas, lung, colon, breast,and gastric (GC). High frequency of mutation is observed in the pancreas,colon, and lung cancers; they commonly arise in codon 12 and 13 of exon 2. Due to the lack of information about the frequency of mutations in the Northeast of Iran, the currentstudy aimed at evaluating frequency in cases with GC in this region.

Methods: A total of120 formalin-fixed, paraffin-embedded blocks of patients with GC were assessed. The assays to detect in codon 12 and13 were obtained through the peptide nucleic acid (PNA)-clamp.

Results: Totally 87 male and 33 female patients were analyzed in the current study. The mean age of the subjects was 55years.The most common tumoral fragment was located on the body with 48 cases (40%) and the less frequent was related to fondues with six cases (5%).Of the 120 GC samples, 16(13.3%) caseshad codon 12 mutation, and 16.7% had codon 13 mutations. There were no significant relationships between gender,age, and mutations in the studied specimens.

Conclusion: In conclusion, the overall frequency of codon 12 and 13 mutations in GC was 30% in the current study population.Frequency of codon 12 and 13 mutations hadsignificant correlation with tumors location. Different pathogenic mechanismsare suggested for GC according to tumor location. The current study resultsmay be an important diagnostic tool for physicians managing atrophic gastritis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339504PMC
July 2018

Promising effects of exosomes isolated from menstrual blood-derived mesenchymal stem cell on wound-healing process in diabetic mouse model.

J Tissue Eng Regen Med 2019 04 20;13(4):555-568. Epub 2019 Mar 20.

Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Wound healing is a complicated process that contains a number of overlapping and consecutive phases, disruption in each of which can cause chronic nonhealing wounds. In the current study, we investigated the effects of exosomes as paracrine factors released from menstrual blood-derived mesenchymal stem cells (MenSCs) on wound-healing process in diabetic mice. The exosomes were isolated from MenSCs conditioned media using ultracentrifugation and were characterized by scanning electron microscope and western blotting assay. A full thickness excisional wound was created on the dorsal skin of each streptozotocin-induced diabetic mouse. The mice were divided into three groups as follows: phosphate buffered saline, exosomes, and MenSC groups. We found that MenSC-derived exosomes can resolve inflammation via induced M1-M2 macrophage polarization. It was observed that exosomes enhance neoangiogenesis through vascular endothelial growth factor A upregulation. Re-epithelialization accelerated in the exosome-treated mice, most likely through NF-κB p65 subunit upregulation and activation of the NF-κB signaling pathway. The results demonstrated that exosomes possibly cause less scar formation through decreased Col1:Col3 ratio. These notable results showed that the MenSC-derived exosomes effectively ameliorated cutaneous nonhealing wounds. We suggest that exosomes can be employed in regenerative medicine for skin repair in difficult-to-heal conditions such as diabetic foot ulcer.
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http://dx.doi.org/10.1002/term.2799DOI Listing
April 2019

The protective activity of nanomicelle curcumin in bisphenol A-induced cardiotoxicity following subacute exposure in rats.

Environ Toxicol 2019 Mar 29;34(3):319-329. Epub 2018 Nov 29.

Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Bisphenol A (BPA), an estrogenic compound, is used in manufacture of polycarbonate plastics and epoxy resins. Curcumin, the active ingredient of turmeric, is a potent protective compound against cardiac diseases. In this study the protective effect of nanomicelle curcumin on BPA-induced subchronic cardiotoxicity in rats was evaluated. Rats were divided into 6 groups including control, nanomicelle curcumin (50 mg/kg, gavage), BPA (50 mg/kg, gavage), nanomicelle curcumin (10, 25, and 50 mg/kg) plus BPA. The treatments were continued for 4 weeks. Results revealed that BPA significantly induced histophatological injuries including focal lymphatic inflammation, nuclear degenerative changes and cytoplasmic vacuolation, increased body weight, systolic and diastolic blood pressures, malondialdehyde and Creatine phosphokinase-MB level and decreased glutathione content in comparison with control group. In addition, in electrocardiographic graph, RR, QT, and PQ intervals were increased by BPA. Western blot analysis showed that BPA up-regulated phosphorylated p38 (p38-mitogen-activated protein kinase) and JNK (c-jun NH terminal kinases), while down-regulated phosphorylated AKT (Protein Kinase B) and ERK1/2 (extracellular signal-regulated protein kinases 1 and 2). However, nanomicelle curcumin (50 mg/kg) significantly improved these toxic effects of BPA in rat heart tissue. The results provide evidence that nanomicelle curcumin showed preventive effects on subchronic exposure to BPA induced toxicity in the heart tissue in rats.
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http://dx.doi.org/10.1002/tox.22687DOI Listing
March 2019

Evaluation of CD30/CD4/CD8 in triple-negative invasive ductal carcinoma of breast in association with clinicopathological prognostic factors.

Indian J Pathol Microbiol 2018 Oct-Dec;61(4):500-504

Department of Pathology and Laboratory Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Triple-negative breast cancer (TNBC) lacks the benefits of receptor-targeted therapeutic strategies. The limitations in treatment options along with poor patients' outcome heighten the need for novel approaches. Due to recent concentration on the role of biomarkers in prognosis, treatment, and survival of various cancer subtypes, this study involves an investigation of CD4, CD8, and CD30 markers detected by immunohistochemistry in TNBCs and their association with clinicopathological and prognostic factors.

Materials And Methods: Tissue samples of 85 hormone receptor- and human epidermal growth factor receptor-2-negative ductal breast carcinomas extracted from the archive of pathology department. Regarding CD4/CD8 ratio, the infiltrated T-lymphocytes were investigated. The tumoral tissue regions were also identified to be immunohistochemically assessed for the CD30 expression levels.

Results: With an elevated CD4/CD8 ratio, a significant increase in lymph node involvement was observed (P < 0.05); in contrast, increased expression levels of CD8 were related to significant reduction of lymph node involvement. CD30 overexpression was found to be significantly associated with shortened overall survival (OS) and highly involvement of lymph nodes.

Conclusion: Following the progression in stage and grade of tumor, CD4/CD8 ratio and CD30 expression levels are increased and are accompanied by adverse prognosis and poor OS, while CD8-enhanced expression carries a favorable prognostic impact as it improves OS status. Therefore, all these findings could be of interest in the field of target therapy.
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http://dx.doi.org/10.4103/IJPM.IJPM_67_18DOI Listing
February 2019

Evaluation of serum level of substance P and tissue distribution of NK-1 receptor in endometrial cancer.

Mol Biol Rep 2018 Dec 17;45(6):2257-2262. Epub 2018 Sep 17.

Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Substance P (SP), a neuropeptide belonging to the tachykinin family, exerts different biological activities mainly through neurokinin-1 receptor (NK1R). The role of SP/NK1R system in tumoral growth and spread is reported in several cancers. We aimed to evaluate the serum SP concentration and NK1R tissue distribution in endometrial cancer, and to study the relationship between these factors with tumor size, lymph node involvement, disease stage and cancer grade. Recruiting 22 patients with endometrial cancer and 21 patients with leiomyoma as the control group, serum SP concentration was measured using an ELISA method, and NK1R tissue distributions were immunohistochemically analyzed. Serum SP concentration in patients was significantly higher than the control group (p-value = 0.005). The expression level of NK1R in tumoral tissue was more than normal tissue (p-value < 0.001). The NK1R expression had a significant relationship with lymph node involvement (p-value = 0.005) and disease stage (p-value = 0.017). The NK1R expression was higher in more advanced and less-differentiated tumors. SP/NK1R system seems to play a role in tumor growth and development in endometrial cancer. As well, the NK1R expression increased in endometrial cancer, and may be considered as a prognostic factor; but further studies are needed in this field.
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http://dx.doi.org/10.1007/s11033-018-4387-1DOI Listing
December 2018

Primary duodenal malignant melanoma: A case report.

Caspian J Intern Med 2018 ;9(3):312-315

Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Melanoma is a neoplasm derived commonly from melanocytic cells of skin. Although coetaneous presentation of malignant melanoma is easily recognizable, the presentation of melanoma in other organs is so confusing. In particular, when it metastasizes to other organs, many bizarre figures and unusual organs may be involved. In this report, we present a case of primary duodenal malignant melanoma.

Case Presentation: A 68-year-old man presented with a history of iron deficiency anemia. The upper gastrointestinal endoscopy showed a prominent papilla of duodenum along with an ulcerative lesion adjacent to second part of duodenum. Histopathologic evaluation showed a high-grade malignant neoplasm involving the bowel wall which was labeled for S100 protein and markers of melanocytic differentiation; Melan-A indicating the definitive diagnosis of malignant melanoma of the second portion of duodenal mucosa.

Conclusions: In patients with a history of iron deficiency anemia, any GI symptom should be evaluated carefully. However, the diagnosis of primary GI melanomas in patients without any history of melanoma is possible. Full medical investigations are recommended in these patients with primary mucosal lesions.
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http://dx.doi.org/10.22088/cjim.9.3.312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121338PMC
January 2018

The effects of vitamin B on the brain damages caused by methamphetamine in mice.

Iran J Basic Med Sci 2018 Apr;21(4):434-438

Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: Methamphetamine (METH) is a powerful stimulant drug that directly affects the brain and induces neurological deficits. B is a water-soluble vitamin (vit) that is reported to attenuate neuronal degeneration. The goal of the present study is to investigate the effect of vitamin B on METH's neurodegenerative changes.

Materials And Methods: Two groups of 6 animals received METH (10 mg/kg, interaperitoneally (IP)) four times with a 2 hr interval. Thirty mins before METH administration, vit B12 (1 mg/kg) or normal saline were injected IP. Animals were sacrificed 3 days after the last administration. Caspase proteins levels were measured by Western blotting. Also, samples were examined by TUNEL assay to detect the presence of DNA fragmentation. Reduced glutathione (GSH) was also determined by the Ellman method.

Results: The pathological findings showed that vit B attenuates the gliosis induced by METH. Vit B administration also significantly decreased the apoptotic index in the striatum and the cerebral cortex (<0.001). It also reduced caspase markers compared to the control (<0.01 and <0.001, respectively). Interestingly, co-administration of METH and Vit B elevates the levels of GSH in both regions of the brain and returned it to normal levels compared to the METH group.

Conclusion: The current study suggests that parenteral vit B at safe doses may be a promising treatment for METH-induced brain damage via inhibition of neuron apoptosis and increasing the reduced GSH level. Research focusing on the mechanisms involved in the protective responses of vit B can be helpful in providing a novel therapeutic agent against METH-induced neurotoxicity.
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http://dx.doi.org/10.22038/IJBMS.2018.23362.5897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960763PMC
April 2018

Evaluation of photoshop based image analysis in cytologic diagnosis of pleural fluid in comparison with conventional modalities.

Diagn Cytopathol 2018 Jul 19;46(7):578-583. Epub 2018 Apr 19.

Department of Pathology, Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences Medical Sciences, Mashhad, Iran.

Background: The aim of this study is to investigate and compare the results of digital image analysis in pleural effusion cytology samples with conventional modalities.

Materials And Methods: In this cross-sectional study, 53 pleural fluid cytology smears from Qaem hospital pathology department, located in Mashhad, Iran were investigated. Prior to digital analysis, all specimens were evaluated by two pathologists and categorized into three groups as: benign, suspicious, and malignant. Using an Olympus microscope and Olympus DP3 digital camera, digital images from cytology slides were captured. Appropriate images (n = 130) were separately imported to Adobe Photoshop CS5 and parameters including area and perimeter, circularity, Gray Value mean, integrated density, and nucleus to cytoplasm area ratio were analyzed.

Results: Gray Value mean, nucleus to cytoplasm area ratio, and circularity showed the best sensitivity and specificity rates as well as significant differences between all groups. Also, nucleus area and perimeter showed a significant relation between suspicious and malignant groups with benign group. Whereas, there was no such difference between suspicious and malignant groups.

Conclusion: We concluded that digital image analysis is welcomed in the field of research on pleural fluid smears as it can provide quantitative data to apply various comparisons and reduce interobserver variation which could assist pathologists to achieve a more accurate diagnosis.
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http://dx.doi.org/10.1002/dc.23952DOI Listing
July 2018

The Diagnostic Value of TTF-1, P63, HMWK, CK7, and CD56 Immunostaining in the Classification of Lung Carcinoma.

Iran J Pathol 2017 1;12(3):195-201. Epub 2017 Jul 1.

Dept. of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran.

Background & Objective: The histologic distinction of small cell from non-small cell lung carcinoma and correct identification of all subtype of lung carcinoma are very important in treatment management. The main method for histologic classification of lung tumors is based on morphology. However, in small bronchoscopic biopsies in particular, distinction is very difficult upon morphology alone. The current study aimed at evaluating the utility of a panel of antibodies, consisting of thyroid transcription factor (TTF-1), P63, high molecular weight keratin [HMWK (34βE12)], cytokeratin (CK7), and cluster of differentiation (CD56) for accurate distinction of bronchogenic carcinomas.

Methods: Bronchoscopic biopsies of 60 lung carcinoma cases including 20 small cell carcinomas, 20 adenocarcinomas, and 20 squamous cell carcinomas (SCCs) with typical morphologic features were selected. All these cases were immunohistochemically stained for TTF-1, P63, HMWK (34βE12), CK7, and CD56. All immunostained slides were scored as either positive or negative.

Results: The mean age of the patients was 60 years; ranged from 35 to 81. Sixteen patients were female and 44 were male. All adenocarcinomas were positive for CK7 and most of them (18/20; 90%) were positive for TTF-1. Most of small cell lung carcinomas were positive for TTF-1 (17/20; 85%), and CD56 (18/20; 90%). All squamous cell carcinomas (SCCs) were negative for TTF-1, but most of them were positive for HMWK (34βE12) and P63.

Conclusion: The obtained data showed that TTF-1, P63, CK7, CD56 and/or 34βE12 represent a useful panel of antibodies to identify lung carcinoma subtypes in small bronchoscopic biopsies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835366PMC
July 2017