Publications by authors named "Ahad Muhammadnejad"

30 Publications

  • Page 1 of 1

Neuroprotective phosphatidylserine liposomes alleviate depressive-like behavior related to stroke through neuroinflammation attenuation in the mouse hippocampus.

Psychopharmacology (Berl) 2021 Feb 11. Epub 2021 Feb 11.

Division of Research and Development, Pharmin USA, LLC, San Jose, CA, USA.

Objective: To investigate the protective effect of phosphatidylserine liposomes (PSL) on post-stroke (ST) injuries such as neuroinflammation and depression in mice.

Methods: Brain ischemia was induced via the right unilateral common carotid artery occlusion model. Then, behavioral assessments including the forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant-like effect of PSL. Moreover, inflammatory cytokines changes in the hippocampus including TNF-α and IL-10 levels as well as the number of survived neurons were evaluated in ST mice using immunohistochemistry (IHC).

Results: A significant reduction of the immobility time in both behavioral tests indicated the antidepressant activity of PSL. Moreover, the number of viable neurons increased significantly with PSL treatment, which was similar to control group, compared to the untreated ST group. IHC analysis of ST mice receiving PSL showed a significant reduction in TNF-α and IL-10 levels in the inflamed hippocampus of mice.

Conclusion: Oral PSL may improve post-stroke depression (PSD) through its anti-inflammatory properties.
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http://dx.doi.org/10.1007/s00213-021-05783-1DOI Listing
February 2021

Combination therapy of phosphatidylserine liposome with cyclosporine A improves nephrotoxicity and attenuates delayed-type hypersensitivity response.

Life Sci 2021 Jan 18;265:118780. Epub 2020 Nov 18.

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

This study aimed to evaluate the antioxidant capacity of phosphatidylserine liposome (PS) against oxidative stress due to cyclosporine A (CsA) and concurrent administration of PS and CsA on the attenuation of immune response. The effect of oral PS was evaluated on biochemical and oxidative renal markers and histopathology of nephrotic rats receiving CsA. The effect of co-administration of PS with CsA was also assessed on DTH (delayed-type hypersensitivity) reaction of immunized rats. The cytokines production level of IL-2 (Interleukin-2) and IFN-γ (Interferon gamma) was measured in immunized rat's splenocytes. PS treatment significantly (P < 0.05) reduced Cr and BUN of serum and MDA (malondialdehyde) in kidney tissue, and increased SOD (superoxide dismutase) and CAT (Catalase) of kidney tissue in CsA-nephrotic rats. Histopathology data indicated significantly (P < 0.05) nephrotoxicity improvement after 25-day treatment with PS. Furthermore, CsA plus PS administration significantly reduced DTH response and cytokines production of IL-2 and IFN-γ in immunized rats. In conclusion, coadministration of CsA plus PS may overcome oxidative stress and improve the performance of organ transplantation or autoimmune therapy.
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http://dx.doi.org/10.1016/j.lfs.2020.118780DOI Listing
January 2021

Significance of E-cadherin and Vimentin as epithelial-mesenchymal transition markers in colorectal carcinoma prognosis.

EXCLI J 2020 26;19:917-926. Epub 2020 Jun 26.

Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.

Colorectal cancer is the most common malignancy of the gastrointestinal tract with very high mortality. One of the most distinguishing features for the establishment of an epithelial-mesenchymal transition phenotype is the alteration of mesenchymal markers and structural adhesion proteins. We investigated the level of Vimentin and E-cadherin expression in relation to invasion and metastasis on colorectal cancer patients. Tissue specimens were collected consecutively from thirty-nine colorectal carcinoma patients during surgeries. The patients were diagnosed and treated between 2013 and 2016. In order to histological staging, tissue sections were prepared from formalin-fixed paraffin-embedded blocks and stained with Hematoxylin and Eosin. Also for evaluating the epithelial-mesenchymal transition markers, E-cadherin and Vimentin, all patient samples were stained and detected via immunohistochemistry, and afterwards the results were analyzed to determine whether these markers could be useful prognostic markers for predicting colorectal cancer patient outcomes. The expression of Vimentin as a mesenchymal marker along with rising grade of cancer, pathological stages, and metastasis to regional lymph nodes increased furthermore, in cancers with vascular invasion, Vimentin value was high. Reversely, the expression of E-cadherin with climbing grade, stages and colon cancer categories decreased and also in cancers with vascular invasion reduced. Variation of the markers had no relation to age and sex. In summary, along with cancer progression level of Vimentin expression varies inversely with E-cadherin expression and by increasing metastasis and invasion the Vimentin expression elevates. Further evaluation in this area might lead to a good method for predicting progressive clone cancer.
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http://dx.doi.org/10.17179/excli2020-1946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355153PMC
June 2020

P16INK4A Immunohistochemistry as a Gold Standard for Cervical Cancer and Precursor Lesions Screening.

Iran J Public Health 2020 Feb;49(2):312-322

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: High-risk (HR) Human papillomaviruses (HPVs) are known as the main factors implicated in the pathogenesis of cervical preinvasive and invasive lesions. Therefore, the presence or absence of HR-HPV can be followed for the prognosis of low-grade and high-grade squamous intraepithelial lesions. Since the overexpression of p16INK4a protein depends on the presence of transcriptionally-active HPV, and due to its availability and simple interpretation, it may be considered as a proper marker to diagnose cervical cancer.

Methods: An immunohistochemical analysis of p16INK4a was performed in 72 cervical tissue specimens at Imam Khomeini Complex Hospital (Tehran, Iran) from 2016 to 2018. The performance parameters were calculated and compared using receiving operating characteristics curve (ROC) details.

Results: p16INK4a is significantly up-regulated in the cervical cancer samples in comparison with that in normal samples. Moreover, the ROC data showed the potential ability of p16INK4a under determined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. The molecular typing disclosed the attendance of HPV DNA in 44.4% of cases (32/72) with a predominance of HPV type 16.

Conclusion: The molecular biomarker p16INK4a can be a good candidate for the early diagnosis and prognosis of cervical cancer in HPV-infected patients. Considering the increase in the expression level of p16INK4a in cancer and precancer tissues, p16INK4a may be used for early detection of cervical cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231710PMC
February 2020

Expression of Diverse Angiogenesis Factor in Different Stages of the 4T1 Tumor as a Mouse Model of Triple-Negative Breast Cancer.

Adv Pharm Bull 2020 Jun 18;10(2):323-328. Epub 2020 Feb 18.

Cancer Biology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Triple-negative breast cancer (TNBC) is specified by high vascularity and repetitious metastasis. Although several studies have indicated that angiogenesis has an important role in invasive breast cancer, a suitable model of TNBC that can show the exact onset of angiogenesis factors still needs to be developed. The purpose of this study is to determine the expression level of angiogenesis factors in different clinical stages of the 4T1 tumor as TNBC mouse model. Twenty mice were injected by the 4T1 cell line, and four mice selected as healthy controls. Following by tumor induction, the mice were randomly put into four groups, each contains four mice. Once the tumor volume reached to the early stage (<100 mm), intermediate stage (100-300 mm), advanced stage (300-500 mm), and end stage (>500 mm), they were removed by surgery. Then, the expression levels of Hif1α, VEGFR1, and VEGFR2 genes, as well as tumor markers of VEGF, bFGF and CD31, were evaluated by qPCR and immunohistochemistry (IHC) respectively. The statistical analysis was done by SPSS version 16. TNBC tumors were confirmed and multi-foci metastasis in the lung were seen. The mRNA and protein expression levels of the angiogenesis factors increased in the early stage and as the tumor grew, their expression level enhanced dramatically. The 4T1 syngeneic mouse tumor may serve as an appropriate TNBC model for further investigation of the angiogenesis and therapies. Moreover, angiogenesis factors are induced before the advanced stage, and anti-angiogenesis therapy is necessary to be considered at the first line of treatment in TBNC.
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http://dx.doi.org/10.34172/apb.2020.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191227PMC
June 2020

Human cytomegalovirus infection in Iranian glioma patients correlates with aging and tumor aggressiveness.

J Med Virol 2020 08 4;92(8):1266-1276. Epub 2020 Feb 4.

Department of Molecular Genetics, Cancer Biology Research Center, Cancer Institute of Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.

Human cytomegalovirus (HCMV), as a ubiquitous and opportunistic virus, is a matter for consideration in broad-spectrum diseases, specifically in immunocompromised individuals. In recent decades, many studies that have evaluated the role of HCMV in inflammation and malignancies, especially in high-grade gliomas, have reported inconsistent results. Thus, this study was conducted to analyze 97 primary gliomas for human CMV UL83 gene and protein through TaqMan real-time polymerase chain reaction and immunohistochemistry, respectively. The results were positive for the UL83 gene and pp65 protein in 71% and 24% of samples, respectively. The frequency of HCMV was significantly higher in glioblastomas than other glioma grades (P < .01 and P < .05 for the UL83 gene and protein, respectively). In addition, the association between the prevalence of HCMV and aging strengthened the virus reactivation hypothesis in gliomas. In conclusion, a high frequency of HCMV infection was found in gliomas that correlated with tumor aggressiveness and age. This study recommends a thorough investigation to determine HCMV infection in gliomas to improve the existing knowledge of its role in glial tumors, its prognostic value, and possible efficient antiviral target therapy.
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http://dx.doi.org/10.1002/jmv.25673DOI Listing
August 2020

A novel hydrazide compound exerts anti-metastatic effect against breast cancer.

Biol Res 2019 Aug 6;52(1):40. Epub 2019 Aug 6.

Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran.

Background: There are currently a number of barriers hindering the successful treatment of breast cancer, including the metastatic spread of cancer cells. In looking for new anticancer agents, we reported two novel hydrazide derivatives with anti-cancer activity in human breast cancer cells. The current study aims to explore the therapeutic potential of the most effective one, N'-((5-nitrothiophen-2-yl)methylene)-2-(phenylthio)benzohydrazide (compound B), on metastatic breast cancer, which is resistant to available chemotherapeutics.

Methods: 4T1 mammary carcinoma cells were inoculated into the fat pad mammary of 5-7-week-old female BALB/c mice and then the effective compound was intraperitoneally administered for 4 weeks. Proliferation index and angiogenesis in tumor and lung tissues were examined with immunohistochemistry. In vitro assessments were also carried out to evaluate the effect of the compound on invasion of MDA-MB-231 cells.

Results: Our results demonstrated that this effective derivative significantly inhibited invasion of MDA-MB-231 cells in vitro as shown by Matrigel assay and quantitative real-time method for MMP-9 expression after 48 h of treatment. Daily administration of the compound suppressed the growth of primary tumor and its metastasis to lung, which was confirmed by H&E experiment at a dose of 1 mg/kg in a well-known metastatic model of 4T1 breast cancer in syngeneic BALB/c mice. These outcomes were supported by the immunohistochemical examinations of the tumor and lung tissues of mice. Tumors and lungs in mice treated with the effective compound showed a reduced proliferation index and a smaller microvessel density compared to the control.

Conclusion: This study highlights an anti-metastatic role for a novel hydrazide derivative in both in vitro and in vivo models of breast cancer.
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http://dx.doi.org/10.1186/s40659-019-0247-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683344PMC
August 2019

AGS cell line xenograft tumor as a suitable gastric adenocarcinoma model: growth kinetic characterization and immunohistochemistry analysis.

Iran J Basic Med Sci 2018 Jul;21(7):678-681

Cancer Biology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Objectives: Gastric cancer is the third leading cause of cancer-related death worldwide. The overall survival rate of patients is poor because gastric cancers are usually diagnosed at the late stages. Therefore, further research is needed and appropriate research tools are required to develop novel therapeutic approaches.

Materials And Methods: Eight female athymic nude mice with a background were used in this study. AGS cells were inoculated into the flank. The tumor volumes were calculated and growth curves were drawn. When the volume of the tumors reached 1000 mm3, the animals were humanely euthanized with CO gas. After harvesting, tumors were analyzed with Hematoxylin and Eosin (H&E) and immunohistochemistry (IHC). A pathologist confirmed tumor entity through H&E staining. Tumors were evaluated for expression of HER-2, P53, Ki-67, CD34, cytokeratin 8 (CK8), vimentin, estrogen receptor (ER), and progesterone receptor (PR) utilizing immunohistochemistry.

Results: The tumor take rate was 62.5%, mean doubling time was 40.984 d, and the latency period was 30.62 days. The H&E staining results showed highly malignant hyperchromatin epithelial cells. IHC assessment showed the mutation status of P53 gene. The expression score of the CK8 protein in the tumor cells was +3. Vimentin protein was not expressed and changes in mesenchymal phenotype were not observed. Ki-67 IHC indicated that the proliferation rate was >43% and angiogenesis was defined as high MVD.

Conclusion: The respective AGS xenograft model provides an opportunity to understand the pattern of tumor growth as well as to evaluate new gastric cancer therapies in studies.
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http://dx.doi.org/10.22038/IJBMS.2018.22938.5835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098953PMC
July 2018

Antitumor Effects of Umbelliprenin in a Mouse Model of Colorectal Cancer.

Iran J Pharm Res 2018 ;17(3):976-985

Department of Pharmacology, school of medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Umbelliprenin is a sesquiterpene coumarin with vitro anti-carcinogenic activities. The aim of this study was to investigate the antitumor effects of umbelliprenin in animal models of colorectal cancer. The cytotoxic effects of umbelliprenin were explored on CT26 and L929by MTT assay. In this study, colorectal tumors developed in mice by intradermal injection of CT26 cell line. Tumor size, serum levels of IFN-γ and IL-4 by ELISA, and Ki-67, MMP2, MMP9, VEGF and E-cadherin markers by IHC method were evaluated. The results showed that umbelliprenin inhibited the cancer cells in a concentration-dependent manner. IC50 Evaluation showed that L929 cells were more resistant to Umbelliprenin than CT26 cells. Umbelliprenin treatment in both tumor-bearing mice and control normal mice showed significantly increased IFN-γ and decreased IL-4( < 0.05). The pathologic findings had shown that the E-cadherin marker in the umbelliprenin treated cancerous mice were significantly higher compared to the control group ( < 0.05) while the expression of Ki-67 marker was reduced significantly ( < 0.05). Markers involved in angiogenesis including VEGF, MMP2, and MMP-9 in the cancerous mice group treated with umbelliprenin showed a significant decrease compared to the control group ( < 0.05). Metastasis to lung and liver was reduced in umbelliprenin treated group. Our results showed that umbelliprenin inhibited CT26 tumor cells The reduction of tumor size, angiogenesis, and proliferation markers and the absence of metastasis represents the antitumor effects of umbelliprenin on colorectal cancer. The results showed that umbelliprenin can be considered as a good candidate for the treatment of colorectal cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094438PMC
January 2018

Umbelliprenin shows antitumor, antiangiogenesis, antimetastatic, anti-inflammatory, and immunostimulatory activities in 4T1 tumor-bearing Balb/c mice.

J Cell Physiol 2018 11 24;233(11):8908-8918. Epub 2018 May 24.

Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Umbelliprenin (UMB) has shown various pharmacological properties in vitro. We investigated the antineoplastic and immunostimulatory effects of UMB in 4T1 mammary-tumor-bearing mice. Two-hundred microliter of UMB (12.5 mg/ml) was intraperitoneally administrated to healthy and tumor-bearing female Balb/c mice for a period of 18 days. Data was analyzed using GraphPad Prism 5 software for Windows (version 5, La Jolla, CA). UMB caused a significant decrease in tumor size (P < 0.01). Serum interferon gamma (IFNγ) was augmented in both healthy and tumor-bearing animals (P < 0.01), and IL-4 declined in healthy animals (P < 0.01) treated with UMB. Expressions of Ki-67, VEGF, CD31, MMP2, MMP9, VCAM1, and NF-κB were significantly decreased in tumors from UMB-treated animals (P < 0.001), whereas E-Cadherin and TNFR1 expressions were markedly increased (P < 0.001). The rates of liver and lung metastases in UMB-administrated animals were smaller compared to the control. UMB can potently inhibit tumor growth, angiogenesis, metastasis, and inflammation and potentiate an antitumor immune response in vivo. However, further investigations are required to evaluate the UMB mechanisms of action in cancerous cells.
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http://dx.doi.org/10.1002/jcp.26814DOI Listing
November 2018

Long‑term behavioral, histological, biochemical and hematological evaluations of amyloid beta‑induced Alzheimer's disease in rat.

Acta Neurobiol Exp (Wars) 2018 ;78(1):51-59

Cancer Biology Research Center, Cancer research Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.

Alzheimer's disease (AD) is a mental impairment and neural degeneration which causes progressive loss of memory and cognitive functions. This age‑dependent illness is associated with extracellular amyloid plaques accumulation and twisted neurofibrillary tangles. Amyloid plaques are experimentally generated in animal models in order to investigate the disease process. In this study, we followed a rat model of AD for over a year. Wistar rats were divided randomly into two groups as control group (surgery without injection Aβ), and experimental group (two‑sided intrahippocampal amyloid‑beta injection into hippocampus). From each group, three animals were investigated 42 days after injection, and the remaining four animals were studied after one year. All animals were tested for learning abilities and memory. Finally, samples from blood, brain, heart, kidney, liver, colon and spleen were examined. In the experimental group, the size of amyloid plaques were increased significantly after one year \\r\\nand learning abilities and memory were concomitantly decreased. Onsets of various other conditions such as liver and kidney disorders, diabetes, and metabolic syndrome were observed, which indicates that the animals may be prone to cardiovascular disorders and ischemia.
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September 2018

Atorvastatin attenuates TNBS-induced rat colitis: the involvement of the TLR4/NF-kB signaling pathway.

Inflammopharmacology 2016 Jun 2;24(2-3):109-18. Epub 2016 Apr 2.

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.

Aim: The aim of the present study is to explore whether atorvastatin improves intestinal inflammation through the inhibition of the TLR4/NFkB signaling pathway in TNBS-induced rat colitis.

Methods: Acute colitis was induced by intra-rectal administration of 100 mg/kg TNBS dissolved in 0.25 ml of 50 % ethanol. Twenty four hours after colitis induction, saline, atorvastatin (20 and 40 mg/kg) and sulfasalazine (100 mg/kg) were given to the animals by oral route. This was repeated daily for 1 week. Body weight changes, macroscopic and microscopic lesions were assessed. MPO and TNF-α activities were detected by immunohistochemistry (IHC) and the expression level of TLR4, MyD88 and NF-κB p65 proteins were measured by western blotting analysis.

Results: Atorvastatin and sulfasalazine reduced the body weight loss, macroscopic and microscopic lesions. Additionally, both drugs decreased the expression of MPO and TNF-α positive cells in the colon tissue. Furthermore, they inhibited the TNBS-induced expression of TLR4, MyD88 and NF-κB p65 proteins.

Conclusions: It is suggested that the anti-inflammatory effect of atorvastatin on TNBS-induced rat colitis may involve the inhibition of the TLR4/NFkB signaling pathway.
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http://dx.doi.org/10.1007/s10787-016-0263-6DOI Listing
June 2016

Renal Sympathetic Denervation by CT-scan-Guided Periarterial Ethanol Injection in Sheep.

Cardiovasc Intervent Radiol 2015 Aug 6;38(4):977-84. Epub 2015 May 6.

Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Imam Khomeini Hospital Complex, Tehran University of Medical Sciences (TMUS), Tehran, 1419733141, Iran,

Background: Renal nerves are a recent target in the treatment of hypertension. Renal sympathetic denervation (RSD) is currently performed using catheter-based radiofrequency ablation (RFA) and because this method has limitations, percutaneous magnetic resonance (MR)-guided periarterial ethanol injection is a suggested alternative. However, few studies have been conducted on the effectiveness of percutaneous ethanol injection for RSD.

Aim: To evaluate the feasibility, efficacy, and complications of computed tomography (CT)-guided periarterial ethanol injection.

Methods: Ethanol (10 ml, 99.6%) was injected around the right renal artery in six sheep under CT guidance with the left kidney serving as a control. Before and after the intervention, the sheep underwent MR imaging studies and the serum creatinine level was measured. One month after the intervention, the sheep were euthanized and norepinephrine (NE) concentration in the renal parenchyma was measured to evaluate the efficacy of the procedure. The treated tissues were also examined histopathologically to evaluate vascular, parenchymal, and neural injury.

Results: The right kidney parenchymal NE concentration decreased significantly compared with the left kidney after intervention (average reduction: 40%, P = 0.0016). Histologic examination revealed apparent denervation with no other vascular or parenchymal injuries observed in the histological and imaging studies.

Conclusion: Effective and feasible RSD was achieved using CT-guided periarterial ethanol injection. This technique may be a potential alternative to catheter-based RFA in the treatment of hypertension.
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http://dx.doi.org/10.1007/s00270-015-1109-0DOI Listing
August 2015

Injection of insulin amyloid fibrils in the hippocampus of male Wistar rats: report on memory impairment and formation of amyloid plaques.

Neurol Sci 2015 Aug 19;36(8):1411-6. Epub 2015 Mar 19.

Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, 1411413137, Tehran, Iran.

Amyloid fibrils result from a particular type of protein aggregation, and have been linked with various disorders, including neurodegenerative ones. In the case of Alzheimer's disease, amyloid beta (abeta) fibrils are detected in patients' brain, in the amyloid plaques. These fibrils can be produced in vitro, and their injection into animals' brains generates an animal model of Alzheimer's disease. Based on the structural similarity of amyloid fibrils that are formed from different proteins, we hypothesized that injecting insulin amyloid fibrils into rats' brains could result in amyloid plaque formation. Fourteen male Wistar rats were divided into control and experimental groups (n = 7). The experimental group was bilaterally injected with insulin amyloid in the hippocampus. Seven days after injection, a shuttle box test was performed and the experimental group's memory was found to be impaired. Histological investigation of these rats' brain showed the formation of amyloid plaques in the hippocampus. A limited test has provided preliminary evidence for the stability of these plaques up to 35 days. Further complementary studies are required to fully validate the proposed procedure, which is simple and relatively low cost, and could be suggested as an alternative to models generated with abeta fibrils.
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http://dx.doi.org/10.1007/s10072-015-2169-2DOI Listing
August 2015

Feasibility assessment of in vitro chemoresponse assay on stereotactic biopsies of glioblastoma multiforms: a step towards personalized medicine.

Iran J Basic Med Sci 2014 Nov;17(11):922-5

Virology Department, Pasteur Institute of Iran, Tehran, Iran.

Objectives: P In vitro chemosensitivity and resistance assays (CSRAs) are a promising tool for personalized treatment of glioblastoma multiform (GBM). These assays require a minimum of 1 to 2 g of tumor specimen for testing, but this amount is not always accessible. We aimed to assess the feasibility and validity of utilizing stereotactic biopsies of GBM in CSRAs.

Materials And Methods: Single cell suspension was prepared from 1 g weight explants of the established xenograft tumor of GBM. Also, primary culture was carried out on 35 mg weight specimens, as a surrogate for stereotactic biopsies. Then, chemoresponse profile of cells obtained by direct cell disaggregation and primary culture was determined using temozolomide and carmustine by clonogenic assay.

Results: There was no statistically significant difference in the cytotoxicity of temozolomide and carmustine between cells obtained from both methods.

Conclusion: This work supports the feasibility of using stereotactic biopsies of GBM in CSRAs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4328103PMC
November 2014

First pathological study of canine primary breast lymphoma and the description of its clinicopathological characteristics as an animal model for human primary breast lymphoma.

Biomed Rep 2015 Jan 9;3(1):75-77. Epub 2014 Oct 9.

Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Imam-Khomeini Hospital Complex, Tehran 1419733141, Iran.

Canine breast cancer (BC) and human BC are the most prevalent tumors in female dogs and humans, respectively. Several studies have indicated that canine BC is a good model for human BC. Unlike breast carcinomas, human primary breast lymphoma (PBL) is a rare tumor, but no case of canine PBL has been reported thus far. The current study presents a case of canine MC of the primary non-Hodgkin lymphoma (NHL) type for the first time and subsequently questions the theory of considering it as a model for human PBL. A 2-cm tumor was surgically removed from the left caudal abdominal mammary gland of a 6-year-old female dog of the terrier breed. Microscopic examination did not show any sign for the epithelial origin of the tumor. By contrast, histomorphological view and molecular pathological evaluation by immunohistochemistry showed that the tumor was of the diffuse large B-cell lymphoma (DLBCL) type [cluster of differentiation 19 (CD19), CD20, CD10, B-cell lymphoma 6, CD3, CD15]. According to the World Health Organization classification, DLBCL is considered to be an NHL. Canine NHL is common in dogs and certain investigators believe that the biological behavior and clinical course is extremely similar to human NHL, and therefore, consider it as a model of human NHL. To the best of our knowledge, the current study is the first report of canine PBL. As the most significantly reported human PBL histotype is the DLBCL type, the histomorphological and immunophenotyping characteristics of canine PBL in the study considerably match with human PBL and raise the hypothesis that it can be a model for human PBL.
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http://dx.doi.org/10.3892/br.2014.369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251144PMC
January 2015

Expression of α4, αv, β1 and β3 integrins during the implantation window on blastocyst of a mouse model of polycystic ovarian syndromes.

Iran J Reprod Med 2014 Sep;12(9):623-32

Department of Anatomical sciences, Medical Sciences Faculty, Tarbiat Modares University, Tehran, Iran.

Background: It has been hypothesized that blastocyst integrin expression changes can affect the spontaneous miscarriage in polycystic ovarian syndromes (PCOS).

Objective: In this study, the profile of integrin genes and proteins was investigated on blastocyst of the PCOS experimental mouse model.

Materials And Methods: 30 NMRI female mice were equally divided into 3 groups: control, experimental [PCOS that was injected estradiol valerate (40 mg/kg)]. After 8 weeks, each group was hyper stimulated by PMSG and HCG. Vaginal plaque was checked, and mice were investigated 5 days after the test. Progesterone and estradiol levels were determined; α4, αv, β1 and β3 integrin genes and protein of blastocysts were examined by real time PCR method and immunohistochemistry, respectively.

Results: Estradiol level was significantly increased (p≤0.035) in PCOS group. Based on our finding, the ratio of genes' expressions αv, β3, β1 and α4 in PCOS to control group was 0.479±0.01, 0.5±0.001, 2.7±0.4 and 1.023±0.2 respectively. Genes expression showed a great difference (p≤0.001) between β3, β1 and αv in PCOS compared to other groups. αv and β3 integrin proteins expressed in all groups but intensity of these proteins in PCOS groups, was lower than other groups.

Conclusion: Pattern of αv and β3 integrins expression on the mouse blastocyst surface has an important effect during the implantation window. This pattern has changed in PCOS model and might have a great influence on implantation failure. Therefore, this experimental study suggests that a great attention to this problem may be essential in patients who are involved.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248147PMC
September 2014

Assessment of α4, αv, β1 and β3 integrins expression throughout the implantation window phase in endometrium of a mouse model of polycystic ovarian syndromes.

Iran J Reprod Med 2014 Oct;12(10):687-94

Department of Anatomical sciences, Medical Sciences Faculty, Tarbiat Modares University, Tehran, Iran.

Background: Endometrial integrin expression changes might be a reason for implantation failure in polycystic ovarian syndromes (PCOS). Objective : Assessment of integrin genes and proteins expression upon endometrium in the PCOS experimental mouse model was the main goal of this study.

Materials And Methods: 30 NMRI female mice were equally divided into control, experimental (PCOS; received estradiol valerate (40 mg/kg)) and sham group (received; olive oil). After 8 weeks, each group was hyper stimulated by 7 IU PMSG and then, after 48hrs, 7 IU HCG was injected. Vaginal plaque was checked. After 5 days, Progesterone and estradiol levels and endometrial tissues were investigated to evaluate of α4, αv, β1 and β3 integrins gene and protein by qPCR method and immunohistochemistry, respectively.

Results: Tissue samples were assessed and showed that level of progesterone was significantly decreased in PCOS group. RESULTS of molecular part in the amount of αv, β3, β1 and α4 gene expressions showed a great difference in β3 and αv genes expressions between experimental groups. αv, β3, α4 and β1 proteins in the endometrial stroma in the control group were expressed, but they were not detected in PCOS group.

Conclusion: According to the results, integrins had different expression patterns in different areas of the endometrium; such as epithelial and stromal. It seems that in PCOS, this pattern has changed and the results might have a great influence on implantation failure. Therefore, this study suggests that a great attention to this problem may be essential in patients who are involved.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248155PMC
October 2014

Effects of nitric oxide modulating activities on development of enteric nervous system mediated gut motility in chick embryo model.

J Biosci 2014 Dec;39(5):835-48

Department of Pharmacology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran,

The enteric nervous system (ENS) arises from the enteric neural crest-derived cells (ENCCs), and many molecules and biochemical processes may be involved in its development. This study examined the effects of modulating embryonic nitric oxide (NO) activity on the intestinal motility induced by ENS. One-hundred-and-twenty fertilized chicken eggs were assigned to three main groups and incubated at 37 degrees Centigrade and 60 percent humidity. The eggs were treated with NG-nitro-Larginine methyl ester (L-NAME), sodium nitroprusside (SNP), L-arginine (L-Arg) or vehicle from days 3 (1st group), 7 (2nd group) and 10 (3rd group) of incubation and continued up to day 18. On day 19, the embryos were sacrificed, the jejunal and colorectal segments were taken and the intestinal motility was assessed using isolated organ system. The intestinal motility was recorded normally and following cholinergic, adrenergic and non-adrenergic non-cholinergic (NANC) stimulations. The ENS structure was assessed by immunohistochemistry (IHC) using glial fibrillary acidic protein (GFAP). Rhythmic intestinal contractions were seen in all treatment groups, but inhibition of NO in the LNAME- treated embryos caused significant decrease (p less than 0.01) in the frequency and amplitude of the contraction. The responsiveness to adrenergic, cholinergic and NANC stimulations was also significantly decreased (p less than 0.05). The GFAP expression was significantly (p less than 0.05) reduced in the L-NAME-treated embryos. This study showed that the inhibition of NO caused a deficient development of the ENS, leading to a decrease in the frequency and amplitude of the intestinal contractions and reduced the responsiveness to adrenergic, cholinergic and NANC signalling.
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http://dx.doi.org/10.1007/s12038-014-9474-4DOI Listing
December 2014

Effect of three decellularisation protocols on the mechanical behaviour and structural properties of sheep aortic valve conduits.

Adv Med Sci 2014 Sep 26;59(2):299-307. Epub 2014 Aug 26.

Pediatric Urology Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Purpose: To determine the best method for decellularisation of aortic valve conduits (AVCs) that efficiently removes the cells while preserving the extracellular matrix (ECM) by examining the valvular and conduit sections separately.

Material/methods: Sheep AVCs were decellularised by using three different protocols: detergent-based (1% SDS+1% SDC), detergent and enzyme-based (Triton+EDTA+RNase and DNase), and enzyme-based (Trypsin+RNase and DNase) methods. The efficacy of the decellularisation methods to completely remove the cells while preserving the ECM was evaluated by histological evaluation, scanning electron microscopy (SEM), hydroxyproline analysis, tensile test, and DAPI staining.

Results: The detergent-based method completely removed the cells and left the ECM and collagen content in the valve and conduit sections relatively well preserved. The detergent and enzyme-based protocol did not completely remove the cells, but left the collagen content in both sections well preserved. ECM deterioration was observed in the aortic valves (AVs), but the ultrastructure of the conduits was well preserved, with no media distortion. The enzyme-based protocol removed the cells relatively well; however, mild structural distortion and poor collagen content was observed in the AVs. Incomplete cell removal (better than that observed with the detergent and enzyme-based protocol), poor collagen preservation, and mild structural distortion were observed in conduits treated with the enzyme-based method.

Conclusions: The results suggested that the detergent-based methods are the most effective protocols for cell removal and ECM preservation of AVCs. The AVCs treated with this detergent-based method may be excellent scaffolds for recellularisation.
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http://dx.doi.org/10.1016/j.advms.2014.08.004DOI Listing
September 2014

Expression of vimentin filaments in canine malignant mammary gland tumors: A simulation of clinicopathological features of human breast cancer.

Biomed Rep 2014 Sep 8;2(5):725-728. Epub 2014 Jul 8.

Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Science, Tehran 1419733141, Iran.

Canine malignant mammary gland tumors (CMMGTs) are the most common malignancies observed in females. Several biological similarities have been reported between CMMGTs and human breast cancer (HBC). The present study aimed to assess the correlation of vimentin filaments overexpression, as part of the process of epithelial-mesenchymal transition (EMT) and the clinicopathological characteristics in CMMGTs. The clinicopathological characteristics of 42 CMMGTs were collected. Paraffin-embedded blocks underwent immunohistochemistry staining, which was performed using vimentin (to assess the evolution of the EMT process), Ki-67 (for evaluation of tumor proliferation) and cluster of differentiation 34 (CD34) (for evaluation of angiogenesis) antibodies. The tumor stage, grade, vascular invasion, margin status, rate of expression of the vimentin filaments, microvessel density-CD34 and proliferation rate data were obtained. Finally, the association between the expression of the vimentin filaments and those parameters was resolved statistically. A significant association was shown between the overexpression of the vimentin filaments and tumor size (r=0.71, P=0.03), tumor grade (r=0.80, P=0.021), angiogenesis (r=0.57, P=0.043), proliferation coefficient (r=0.06, P=0.001) and vascular invasion (r=0.76, P=0.043). Vimentin overexpression did not statistically correlate with the tumor stage or the margin status. Similar to the findings of the present study, certain recent studies have indicated that vimentin filament expression in HBC and CMMGTs is associated with the severity of cancer. Thus, spontaneous canine mammary tumor models appear to be an appropriate animal model for breast cancer research, and the results of the present study could aid to reinforce the association.
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http://dx.doi.org/10.3892/br.2014.312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106566PMC
September 2014

HeLa cell line xenograft tumor as a suitable cervical cancer model: growth kinetic characterization and immunohistochemistry array.

Arch Iran Med 2014 Apr;17(4):273-7

Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Tehran, Iran.

Background: Cervical cancer is the seventh most common malignancy in both genders combined and the third most common cancer in women. Despite significant progress in treatments, cervical cancer is not completely curable. Therefore, further research is necessary in this area. Animal models are one of the most practical tools in the field of cancer research. The present study aimed to characterize the growth behavior and surface markers of HeLa cells after heterotopic and systemic inoculation to athymic nude mice.

Methods: Ten 6-week old female athymic C57BL/6 nude mice were used in this study. HeLa cells were inoculated into the flank or tail vein. The tumor volume was calculated and growth curves were drawn. Tumor-bearing mice were sacrificed and the lesions obtained after harvesting were analyzed in a pathology lab. Subsequently, one slide per tumor was stained with hematoxylin and eosin (H&E) and other slides were stained immunohistochemically by cytokeratins (CK), vimentin, P53, CD34, and Ki-67.

Results: Tumor take rate, mean doubling time and latency period were 94.4%, 5.29 ± 3.57 days and 15.27 days, respectively. H&E results revealed highly malignant hyperchromatin epithelial cells. Immunohistochemical examination of the heterotopic tumors indicated greater expression of CK and less expression of vimentin compared to the metastatic ones. Sixty percent of cells were P53-positive and more than 80% were Ki-67-positive. CD34 expression indicated the intensity of angiogenesis in tumor.

Conclusion: This study represents a comprehensive description of a HeLa xenograft model for in vivo investigations, enabling researchers to assess new treatments for cervical cancer.
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http://dx.doi.org/014174/AIM.0010DOI Listing
April 2014

Cochlear damages caused by vibration exposure.

Iran Red Crescent Med J 2013 Sep 5;15(9):771-4. Epub 2013 Sep 5.

Cancer Research Center, Iran Cancer Institute, Tehran University of Medical Sciences, Tehran, IR Iran.

Background: Many industrial devices have an excessive vibration which can affect human body systems. The effect of vibration on cochlear histology has been as a debatable problem in occupational health and medicine.

Objectives: Due to limitation present in human studies, the research was conducted to survey the influence of vibration on cochlear histology in an animal model.

Materials And Methods: TWELVE ALBINO RABBITS WERE EXPERIMENTED AS: Vibration group (n = 6; exposed to 1.0 m.s(-2) r.m.s vertical whole-body vibration at 4 - 8 Hz for 8 hours per day during 5 consecutive days) versus Control group (n = 6; the same rabbits without vibration exposure). After finishing the exposure scenario, all rabbits were killed by CO2 inhalation; their cochleae were extracted and fixed in 10% formaldehyde for 48 hours, decalcified by 10% nitric acid for 24 hours. Specimens were dehydrated, embedded, sectioned 5 µm thick and stained with Hematoxylin and Eosin for light microscopy observations.

Results: Severely hydropic degenerated and vacuolated inner hair cells (IHCs) were observed in vibration group compared to the control group. Inter and intracellular edema was appeared in supporting cells (SC). Nuclei of outer hair cells (OHCs) seemed to be pyknotic. Slightly thickened basilar membrane (BM) was probably implied to inter cellular edematous. Tectorial Membrane (TM) was not affected pathologically.

Conclusions: Whole-body vibration could cause cochlear damages in male rabbits, though vibration-induced auditory functional effects might be resulted as subsequent outcome of prolonged high level vibration exposures.
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http://dx.doi.org/10.5812/ircmj.5369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929808PMC
September 2013

Angiogenesis markers in breast cancer--potentially useful tools for priority setting of anti-angiogenic agents.

Asian Pac J Cancer Prev 2013 ;14(12):7651-6

Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran E-mail :

Background: Breast cancer is the most common malignancy among women in both developed and developing countries. The burden is increasing in low-income and middle-income countries (LMCs) and threatens the public health of such societies. Introduction of expensive monoclonal antibodies to cancer treatment regimens poses a real challenge in the health systems of LMCs. Despite controversy of cost-effectiveness of bevacizumab in breast cancer, some studies indicate gain of patients from this drug. The present study aimed to propose a priority setting model for administration of anti-angiogenic agents in breast cancer via assessment of tumor angiogenesis by the microvessel density (MVD) method and associations with clinicopathological characteristics (including simultaneous mutations of TP53 and HER-2 genes).

Materials And Methods: Age, axillary lymph nodes status, tumor size, stage and grade, estrogen and progesterone receptors status, HER-2/neu status (by immunohistochemistry and FISH test), TP53 mutation, Ki-67 (for proliferation assay) and CD34 (for angiogenesis assay) were assessed in 111 breast cancer patients. The molecular subtype of each tumor was also determined and correlations of simultaneous mutations of HER-2 and p53 genes with angiogenesis and other clinicopathological characteristics were evaluated.

Results: There were significant associations between simultaneous mutations of HER-2 and p53 genes and all other parameters except tumor size. The degree of angiogenesis in the ERBB2 subtype was greater than the others. Younger patients showed a higher angiogenesis rate rather those older than 50 years.

Conclusions: Our results demonstrated that patients with simultaneous mutations of HER-2 and p53 genes, those with ERBB2 molecular subtype and also younger women (often triple negative) seem more eligible for obtaining anti-angiogenic agents. These results suggest a model for priority setting of patients with breast cancer for treatment with anti-angiogenic drugs in LMCs.
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http://dx.doi.org/10.7314/apjcp.2013.14.12.7651DOI Listing
September 2014

Detection of HER2 status in breast cancer: comparison of current methods with MLPA and real-time RT-PCR.

Asian Pac J Cancer Prev 2013 ;14(12):7621-8

Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran E-mail :

Human epidermal growth factor receptor (HER) status is an important prognostic factor in breast cancer. There is no globally accepted method for determining its status, and which method is most precise is still a matter of debate. We here analyzed HER2 mRNA expression by quantitative reverse transcription-PCR (qRT-PCR) and HER2 DNA amplification using multiplex ligation-dependent probe amplification (MLPA). In parallel, we performed a routine evaluation of HER2 protein by immunohistochemistry (IHC). To assess the accuracy of the RT-PCR and MLPA techniques, a combination of IHC and fluorescence in situ hybridization (FISH) was used, substituting FISH when the results of IHC were ambiguous (2+) and for those IHC results that disagreed with MLPA and qRT-PCR, this approach being termed IHC-FISH. The IHC results for four samples were not compatible with the MLPA and qRT-PCR results; the MLPA and qRT-PCR results for these samples were confirmed by FISH. The correlations between IHC-FISH and qRT-PCR or MLPA were 0.945 and 0.973, respectively. The ASCO/CAP guideline IHC/FISH correlation with MLPA was (0.827) and with RT-PCR was (0.854). The correlations between the IHC results (0, 1+ as negative, and 3+ as positive) and qRT-PCR and MLPA techniques were 0.743 and 0.831, respectively. Given the shortcomings of IHC analysis and greater correlations between MLPA, qRT-PCR, and FISH methods than IHC analysis alone with each of these three methods, we propose that MLPA and real-time PCR are good alternatives to IHC. However a suitable cut-off point for qRT- PCR is a prerequisite for determining the exact status of HER2.
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September 2014

Establishment of a patient-derived Wilms' tumor xenograft model: a promising tool for individualized cancer therapy.

J Pediatr Urol 2014 Feb 26;10(1):123-9. Epub 2013 Aug 26.

Pediatric Urology Research Center, Children's Center of Excellence, Department of Pediatric Urology, Islamic Republic of Iran. Electronic address:

Objective: Lack of appropriate approaches that reliably predict response of Wilms' tumor (WT) to anticancer agents remains a major deficiency in clinical practice of individualized cancer therapy. The aim of this study was to establish a patient-derived tumor tissue (PDTT) xenograft model of WT for individualized chemotherapeutic regimen selection in accordance with the patient's tumor nature.

Material And Methods: Tumor specimens of a primary WT were orthotopically implanted into three nude mice, and after 4 weeks xenografts were harvested for serial heterotopic transplantation in 20 nude mice that were divided into three experimental groups and one control group. In vitro and in vivo chemosensitivity to doxorubicin, actinomycin-D, and vincristine were evaluated. Hematoxylin and eosin (H&E) staining and immunohistochemical examination with desmin, vimentin, myogenin, and neuron-specific enolase (NSE) were also applied to determine histological stability of the xenograft during serial transplantation compared with the original tumor tissue.

Results: The xenograft model was successfully established. Histopathologic characteristics of the xenograft tumors were similar to the patient's tumor. Early passage of the PDTT showed a similar chemosensitivity pattern to the original tumor tissue.

Conclusions: PDTT xenograft of WT provides an appropriate model for individualized cancer therapeutic regimen selection by means of its biological stability compared with original patient's tumor.
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http://dx.doi.org/10.1016/j.jpurol.2013.07.009DOI Listing
February 2014

Correlation of microvessel density with nuclear pleomorphism, mitotic count and vascular invasion in breast and prostate cancers at preclinical and clinical levels.

Asian Pac J Cancer Prev 2013 ;14(1):63-8

Cancer Research Centre, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.

Background: Tumor angiogenesis correlates with recurrence and appears to be a prognostic factor for both breast and prostate cancers. In the present study, we aimed to investigate the correlation of microvessel density (MVD), a measure of angiogenesis, with nuclear pleomorphism, mitotic count, and vascular invasion in breast and prostate cancers at preclinical and clinical levels.

Methods: Samples from xenograft tumors of luminal B breast cancer and prostate adenocarcinoma, established by BT-474 and PC-3 cell lines, respectively, and commensurate human paraffin-embedded blocks were obtained. To determine MVD, specimens were immunostained for CD-34. Nuclear pleomorphism, mitotic count, and vascular invasion were determined using hematoxylin and eosin (HandE)-stained slides.

Results: MVD showed significant correlations with nuclear pleomorphism (r=0.68, P=0.03) and vascular invasion (r=0.77, P=0.009) in breast cancer. In prostate cancer, MVD was significantly correlated with nuclear pleomorphism (r=0.75, P=0.013) and mitotic count (r=0.75, P=0.012). In the breast cancer xenograft model, a significant correlation was observed between MVD and vascular invasion (r=0.87, P=0.011). In the prostate cancer xenograft model, MVD was significantly correlated with all three parameters (nuclear pleomorphism, r=0.95, P=0.001; mitotic count, r=0.91, P=0.001; and vascular invasion, r=0.79, P=0.017; respectively).

Conclusions: Our results demonstrate that MVD is correlated with nuclear pleomorphism, mitotic count, and vascular invasion at both preclinical and clinical levels. This study therefore supports the predictive value of MVD in breast and prostate cancers.
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http://dx.doi.org/10.7314/apjcp.2013.14.1.63DOI Listing
December 2013

Therapeutic potential of human induced pluripotent stem cell-derived mesenchymal stem cells in mice with lethal fulminant hepatic failure.

Cell Transplant 2013 5;22(10):1785-99. Epub 2013 Feb 5.

Department of Anatomical Sciences, Tarbiat Modares University, Tehran, Iran.

Large-scale production and noninvasive methods for harvesting mesenchymal stem cells (MSCs), particularly in elderly individuals, has prompted researchers to find new patient-specific sources for MSCs in regenerative medicine. This study aims to produce MSCs from human induced pluripotent stem cells (hiPSCs) and to evaluate their therapeutic effects in a CCl4-induced mouse model of fulminant hepatic failure (FHF). hiPSC-MSCs have shown MSC morphology, antigen profile and differentiation capabilities, and improved hepatic function in our model. hiPSC-MSC-transplanted animals provide significant benefit in terms of survival, serum LDH, total bilirubin, and lipid peroxidation. hiPSC-MSC therapy resulted in a one-third reduction of histologic activity index and a threefold increase in the number of proliferating hepatocytes. This was accompanied by a significant decrease in the expression levels of collagen type I, Mmp13, Mmp2, and Mmp9 genes and increase in Timp1 and Timp2 genes in transplanted groups. hiPSC-MSCs secreted hepatocyte growth factor (HGF) in vitro and also expressed HGF in evaluated liver sections. Similar results were observed with human bone marrow (hBM)-derived MSCs. In conclusion, our results have demonstrated that hiPSC-MSCs might be valuable appropriate alternatives for hBM-MSCs in FHF liver repair and support liver function by cell therapy with a large-scale production capacity, patient-specific nature, and no invasive MSC harvesting.
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http://dx.doi.org/10.3727/096368912X662462DOI Listing
April 2014

Prevalence of HER-2-positive invasive breast cancer: a systematic review from Iran.

Asian Pac J Cancer Prev 2012 ;13(11):5477-82

Genetics Research Center, Biostatistics Department, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

Background: The HER-2/neu gene is altered in 15-20% of breast cancer patients. Immunohistochemistry (IHC) is considered to be the most cost-effective method for HER-2 detection in many countries. Approximately 8,000 new cases of breast cancer are observed annually in Iran. The aims of this study were to conduct a systematic review of the literature on the rate of HER-2-positive breast cancer diagnosed by IHC in Iran.

Methods: A systematic search of the medical literature using the Medline/PubMed, ISI and SID databases revealed articles published in the English and Persian languages evaluating HER-2-positive breast cancer in Iran.

Results: From 22 studies, 3,033 patients were evaluated, of whom 1,350 were diagnosed as HER-2-positive by IHC HER-2 testing. The mean percentage of HER-2-positive patients was 44.5%, which is higher than that recorded in international statistics. Results of this meta-analysis showed a significant heterogeneity between ratios. There was a statistically significant difference between the results of pre- and post implementation of 2007 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline. IHC HER-2 testing has been performed in Iran for over 10 years. Similar to many other countries, before establishment of an infrastructure for IHC diagnostic tests, HER-2 testing was routinely performed in Iran. Our study showed that the statistics reported from Iran varied widely; for instance, the rate of HER-2-positive cases varied from 23.3% to 81.0%.

Conclusions: Our results demonstrate that the lack of standardization and harmonization of this test have led to marked variations in breast cancer diagnosis in Iran.
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http://dx.doi.org/10.7314/apjcp.2012.13.11.5477DOI Listing
July 2013

Overexpression of her-2/neu in malignant mammary tumors; translation of clinicopathological features from dog to human.

Asian Pac J Cancer Prev 2012 ;13(12):6415-21

Department of Pathology, Faculty of Specialized Veterinary Sciences, Science Research Branch, Islamic Azad University, Tehran, Iran.

Background: Canine mammary gland tumors (CMGTs) are the most common tumor found in bitches. Changes in HER-2/neu genes in human breast cancer (HBC) lead to decrease in disease-free survival (DFS) and overall survival rate (OSR). Previous studies have demonstrated that the biological behavior of malignant mammary gland tumors (MMGTs) is similar to that of HBC. The present study aimed at evaluating the relationship between overexpression of HER-2/neu and clinicopathological features in MMGTs to represent a model of prognostic factors for HBC.

Materials And Method: The clinicopathological data of 35 MMGTs were obtained. Immunohistochemical staining with HER-2, Ki-67 and CD34 markers was conducted with sections from paraffin-embedded blocks. According to standard protocols, histological type, grade, margin status, lymphovascular invasion (LVI), HER-2/ neu score, proliferation rate and microvessel density (MVD) of tumors were determined and the association of HER-2/neu overexpression with these parameters was assessed statistically.

Results: The IHC results showed that 12 (34.3%) cases were HER-2/neu positive. Statistical analyses indicated a significant relationship between HER-2 positivity and tumor grade (p=0.043), which also was demonstrated with cancer stage (p=0.035), tumor margin involvement (p=0.016), proliferation index (p=0.001) and MVD (p=0.001); however, there was no statistical relationship between LVI and tumor size. Overexpression of the HER-2/neu gene in MMGTs results in similar biological behavior as that of HBC; as a result, these tumors have can be considered to have important similarities in clinicopathological characteristics.

Conclusions: MMGTs can be regarded as an HBC animal model. Further studies in this field would result in new treatments that could be beneficial for both dogs and humans.
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http://dx.doi.org/10.7314/apjcp.2012.13.12.6415DOI Listing
October 2014