Babak Behnam - Academia.edu (original) (raw)

Papers by Babak Behnam

Frontiers in Bioscience-Landmark

Cancer whose major problems are metastasis, treatment resistance, and recurrence is the leading c... more Cancer whose major problems are metastasis, treatment resistance, and recurrence is the leading cause of death worldwide. Tumorinitiating stem cells (TiSCs) are a subset of the tumor population responsible for tumor resistance and relapse. Understanding the characteristics and shared features between tumor-initiating stem cells (TiSCs) and long-lived postmitotic cells may hold a key to better understanding the biology of cancer. Postmitotic cells have exited the cell cycle and are transitioned into a non-dividing and terminally differentiated state with a specialized function within a tissue. Conversely, a cancer cell with TiSC feature can divide and produce a variety of progenies, and is responsible for disease progression, tumor resistance to therapy and immune system and disease relapse. Surprisingly, our comprehensive evaluation of TiSCs suggests common features with long-lived post-mitotic cells. They are similar in structure (primary cilia, high mitochondrial content, and being protected by a barrier), metabolism (autophagy and senescence), and function (immunoescape and/or immune-privileged by a blood barrier). In-depth exploration showed how mitochondrial metabolism contributes to these shared features, including high energy demands arising from ciliary and microtubular functionality, increased metabolic activity, and movement. These findings can assist in decoding the remaining properties which offer insights into the biology of TiSCs, with potential implications for enhancing cancer treatment strategies and patient prognosis.

Energy is needed by cancer cells to stay alive and communicate with their surroundings. The prima... more Energy is needed by cancer cells to stay alive and communicate with their surroundings. The primary organelles for cellular metabolism and energy synthesis are mitochondria. Researchers recently proved that cancer cells can steal immune cells' mitochondria using nanoscale tubes. This finding demonstrates the dependence of cancer cells on normal cells for their living and function. It also denotes the importance of mitochondria in cancer cells’ biology. Emerging evidence has demonstrated how mitochondria are essential for cancer cells to survive in the harsh tumor microenvironment, evade the immune system, obtain more aggressive features, and resist treatments. For instance, functional mitochondria can improve cancer resistance against radiotherapy by scavenging the released reactive oxygen species. Therefore, targeting mitochondria can potentially enhance oncological outcomes, according to this notion. The patients' reactions to radiation are varied, ranging from a complete response to even cancer progression during treatment. This concept illustrates how different levels of mitochondrial metabolism might contribute to this heterogeneity. Considering this notion can help to improve personalized oncological treatments. This article outlines the importance of mitochondrial metabolism in cancer biology and personalized treatments.

Many investigators all around the world are working to find the best and novel methods for cancer... more Many investigators all around the world are working to find the best and novel methods for cancer treatment. Among them some are trying to reduce the treatment side effects from which patients are suffering. The side effects of Gamma-Ray on skin appear in forms of different ...

Cancer drug discovery and develogment, Dec 10, 2016

Development of new technologies is taking cancer research on a new journey in which plenty of mys... more Development of new technologies is taking cancer research on a new journey in which plenty of mysterious aspects of cancer biology are being unraveled. To defeat cancer, we first need to understand the biology of this smart complex system, which often hijacks several programs to proliferate, invade, escape the immune system and colonize distant organs. Therefore, studying cancer cells in every step of tumor development (including primary tumor formation, invasion, circulation and metastatic colonization) is absolutely essential. Analysis of human-derived cancer models in primary site, circulation or metastatic lesions outside their host is one of the most promising ways to understand these complexities. The most common currently used and more recently developed cancer cell lines consist of primary patient-derived tumor xenograft (PDTX), circulating tumor cells isolation and analyzes, and primary tumor organoids. In this chapter we provide a brief update of some of the most important advances in studying and treatment of cancer using new technologies.

Journal of pediatric nephrology, Jul 4, 2016

Idiopathic nephrotic syndrome is a heterogeneous disease with a spectrum of age at presentation, ... more Idiopathic nephrotic syndrome is a heterogeneous disease with a spectrum of age at presentation, phenotype, renal pathology, and response to treatment. Many mutations are recognized to be implicated in sporadic or hereditary forms. The aim of this review was to summarize the results of the genetic studies which have already been carried out in Iran considering their limitations. A literature search was conducted from March 1970 to September 2015 through MEDLINE, EMBASE, Google Scholar, Google, Iran Medex, Magiran, and SID. Eleven studies were relevant. Three articles were excluded due to insufficient data, duplicated case, and a syndromic nephrotic case without genetic studies. Our results showed that in the southwest of Iran, 80% of the patients had mutations in NPHS1 while in Fars Province, one third showed mutations in NPHS2 when all exons were assessed. In two different studies conducted in one center in Tehran, no mutation was detected in exon 5 but when all exons were studied, more than 65% had hot spot mutation in exon 8 of NPHS2. Interestingly, none of adolescents with FSGS showed mutation in p.R229Q (NPHS2, exon 5). This review revealed that both NPHS1 and NPHS2 were prevalent in Iranian children with SRNS. No mutation of p.R229Q was reported in Iranian adolescent with SRNS.

Cancers

Energy is needed by cancer cells to stay alive and communicate with their surroundings. The prima... more Energy is needed by cancer cells to stay alive and communicate with their surroundings. The primary organelles for cellular metabolism and energy synthesis are mitochondria. Researchers recently proved that cancer cells can steal immune cells’ mitochondria using nanoscale tubes. This finding demonstrates the dependence of cancer cells on normal cells for their living and function. It also denotes the importance of mitochondria in cancer cells’ biology. Emerging evidence has demonstrated how mitochondria are essential for cancer cells to survive in the harsh tumor microenvironments, evade the immune system, obtain more aggressive features, and resist treatments. For instance, functional mitochondria can improve cancer resistance against radiotherapy by scavenging the released reactive oxygen species. Therefore, targeting mitochondria can potentially enhance oncological outcomes, according to this notion. The tumors’ responses to anticancer treatments vary, ranging from a complete res...

Breast Cancer Research and Treatment, 2017

We investigated the role of glial cell line-derived neurotrophic factor (GDNF) in compensating tr... more We investigated the role of glial cell line-derived neurotrophic factor (GDNF) in compensating trastuzumab (TZMB)-induced apoptosis in HER2 ? breast cancer (BC) cells using xenograft tumors. We generated BC xenografts in nude mice using samples from three patients selected based on their HER2 status and response to TZMB therapy. TZMB treatment resulted in shrinkage of the HER2 ? TZMB-sensitive xenograft tumor but not the HER2or HER2 ? TZMB-resistant ones. GDNF neutralized TZMB activity and induced growth in all tumors. Three distinct cell lines were derived from these tumors and named, respectively, TZMB-sensitive (TSTC), HER2-(HNTC), and TZMB-resistant (TRTC). Over 50% of TRTC but 1% of TSTC cells expressed CD44, whereas 84% of TSTC were CD24 ? compared to only 1% of TRTC, despite comparable levels of HER2 detected in both. TZMB induced profound morphological changes toward apoptosis in TSTC but not in TRTC or HNTC. However, GDNF significantly compensated TZMB-mediated TSTC cell loss and promoted growth by 37 and 50%, respectively, in TSTC and TRTC. Inhibition of SRC by Saracatinib (SARC) blocked GDNF function and accelerated TZMBmediated cell death in TSTC, but GDNF continued promoting TRTC growth. These changes paralleled with expression levels of the key molecules involved in growth and apoptosis. Collectively, we found in our xenograft samples that firstly SRC mediates GDNF pro-survival functions by bridging RET-HER2 crosstalk in TZMB-responsive BC tumors. Secondly, SARC-TZMB interactions can synergistically eradicate such tumor cells; and thirdly, GDNF can support antibody resistance by acting independent from SRC in tumors with poor HER2 response to TZMB therapy.

Andrologia, 2015

Testicular cancer is the most common cancer affecting men in reproductive age, and cisplatin is o... more Testicular cancer is the most common cancer affecting men in reproductive age, and cisplatin is one of the major helpful chemotherapeutic agents for treatment of this cancer. In addition, exposure of testes cancer cells to cisplatin could potentially eliminate tumour cells from germ cells in patients. The aim of this study was to evaluate the effect of cisplatin on viability of mouse acute lymphoblastic leukaemia cell line (EL‐4) and neonatal mouse spermatogonial cells in vitro. In this study, the isolated spermatogonial stem cells (SSC) and EL‐4 were divided into six groups including control (received medium), sham (received DMSO in medium) and experimental groups which received different doses of cisplatin (0.5, 5, 10 and 15 μg ml−1). Cells viability was evaluated with MTT assay. The identity of the cultured cells was confirmed by the expression of specific markers. Our finding showed that viability of both SSC and EL‐4 cells was reduced with the dose of 15 μg/ml when compared to the control group (P ≤ 0.05). Also, the differences between the IC50 in doses 10 and 15 μg/ml at different time were significant (P ≤ 0.05). The number of TUNEL‐positive cells was increased, and the BAX and caspase‐3 expressions were upregulated in EL4 cells for group that received an effective dose of cisplatin). In conclusion, despite the dramatic effects of cisplatin on both cells, spermatogonial stem cells could form colony in culture.

Journal of cell science & therapy, 2015

TSGA10 is overexpressed in some cancers, during neural development, in embryogenesis, and in seve... more TSGA10 is overexpressed in some cancers, during neural development, in embryogenesis, and in several tissues with actively dividing cells. TSGA10 protein localization to the sperm tail has been previously described. The protein is cleaved into two parts, which appear to play different functions in the sperm tail: the 27-KDa N-terminal is localized to the fibrous sheath in the principal piece, whereas its 55-KDa C-terminal of the TSGA10 forms filaments, decreases transcriptional activity of hypoxia-inducible factor (HIF)-1-alpha and accumulates in the midpiece of mature spermatozoa. Using colocalization, and coimmunoprecipitation assays, we show that TSGA10 interacts with 'Outer Dense Fiber 2' (ODF2), a centrosome scaffold component associated with mother centrioles. Also, our yeast two-hybrid assay shows that the full-length TSGA10 protein and its 55-KDa C-terminus portion predominantly interact with ODF2. However, the truncated N-terminus 27-KDa fibrous sheath component of TSGA10 fails to bind ODF2. Our experiments examining the localization of TSGA10, demonstrated that the full length TSGA10 protein localizes to perinuclear structures, colocalizes with γ-tubulin, and associates with the centrosome and basal body. The TSGA10 55-KDa C-terminus, but not its 27-KDa N-terminus also localizes to the centrosome and basal body. Our Real-time PCR data indicated that the levels of TSGA10 and ODF2 genes expressions correlate, in mice testes. Finally, we propose that TSGA10 is a ciliary-centrosomal protein and therefore is a good candidate for further investigation in ciliopathies, as well as, cancer biology.

worldwide international science conferences and events. Established in the year 2007 with the sol... more worldwide international science conferences and events. Established in the year 2007 with the sole aim of making the information on Sciences and technology ‘Open Access’, OMICS Group publishes 500 online open access scholarly journals in all aspects of Science, Engineering, Management and Technology journals. OMICS Group has been instrumental in taking the knowledge on Science & technology to the doorsteps of ordinary men and women. Research Scholars, Students, Libraries, Educational Institutions, Research centers and the industry are main stakeholders that benefitted greatly from this knowledge dissemination. OMICS Group also organizes 500 International conferences annually across the globe, where knowledge transfer takes place through debates, round table discussions, poster presentations, workshops, symposia and exhibitions. About OMICS International Conferences OMICS International is a pioneer and leading science event organizer, which publishes around 500 open access journals a...

Iranian journal of kidney diseases, 2018

Complement C3 glomerulopathy refers to a disease process in which abnormal control of complement ... more Complement C3 glomerulopathy refers to a disease process in which abnormal control of complement activation or degradation results in predominant C3 fragment deposition within the glomerulus and causes glomerular damage. Abnormal control of the complement alternative pathway is a well-established risk factor for the occurrence of C3 glomerulonephritis. It is the first reported case in Iran with multiple mutations in complement factor H, with one of these mutations we have expected in hemolytic uremic syndrome rather than C3 glomerulopathy Genetic analysis showed that the molecular abnormalities of factor H led to complement factor H malfunction that were polymorphous and not restricted to the C-terminal domains of the protein.

American journal of human genetics, Jan 2, 2018

Interferon regulatory factor 2 binding protein-like (IRF2BPL) encodes a member of the IRF2BP fami... more Interferon regulatory factor 2 binding protein-like (IRF2BPL) encodes a member of the IRF2BP family of transcriptional regulators. Currently the biological function of this gene is obscure, and the gene has not been associated with a Mendelian disease. Here we describe seven individuals who carry damaging heterozygous variants in IRF2BPL and are affected with neurological symptoms. Five individuals who carry IRF2BPL nonsense variants resulting in a premature stop codon display severe neurodevelopmental regression, hypotonia, progressive ataxia, seizures, and a lack of coordination. Two additional individuals, both with missense variants, display global developmental delay and seizures and a relatively milder phenotype than those with nonsense alleles. The IRF2BPL bioinformatics signature based on population genomics is consistent with a gene that is intolerant to variation. We show that the fruit-fly IRF2BPL ortholog, called pits (protein interacting with Ttk69 and Sin3A), is broadl...

Korean Journal of Pediatrics, 2016

Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive neurocutaneous disorder with worldwi... more Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive neurocutaneous disorder with worldwide incidence of 0.4 per 100,000 people. It is characterized by the triad of congenital ichthyosis, spastic diplegia or quadriplegia, and mental retardation. Herein we report a 2-year-old male child with SLS, asthma, and recurrent pneumonia. SLS was confirmed by a molecular genetics study that revealed a deletion mutation in the ALDH3A2 gene. An ALDH3A2 gene mutation results in dysfunction of the microsomal enzyme fatty aldehyde dehydrogenase and impaired metabolism and accumulation of leukotriene B4, which is a key molecule and a pro-inflammatory mediator in developing allergic diseases, especially asthma. An increased level of leukotriene B4 has been reported in SLS patients. As far as we are aware, this is the first report of SLS associated with asthma and recurrent pneumonia. In conclusion, pediatricians should be aware of and evaluate patients with SLS for possible associated asthma and allergic disorders.

The American Journal of Human Genetics, 2019

Like living organisms, cancer cells require energy to survive and interact with their environment... more Like living organisms, cancer cells require energy to survive and interact with their environment. Mitochondria are the main organelles for energy production and cellular metabolism. Recently, investigators demonstrated that cancer cells can hijack mitochondria from immune cells. This behavior sheds light on a pivotal piece in the cancer puzzle, the ‘dependence’ on the normal cells. This article illustrates the benefits of new, functional mitochondria for cancer cells that urge them to hijack mitochondria. It describes how functional mitochondria help cancer cells’ survival in the harsh tumor microenvironment, immune evasion, progression, and treatment resistance. Recent evidence has put forward the pivotal role of mitochondria in cancer stem cells’ metabolism. This theory highlights the mitochondria in cancer biology and explains how targeted anti-mitochondrial treatments can improve oncological outcomes.

Prader�Willi Syndrome (PWS) is a complex genetic disorder with different manifestations in infa... more Prader�Willi Syndrome (PWS) is a complex genetic disorder with different manifestations in infancy and childhood including obesity, type 2 diabetes mellitus, mild to moderate intellectual impairment and learning disabilities. In this syndrome, growth hormone therapy improves outcomes. For the first time, here we report an 11-year-old boy with PWS who presented with three episodes of unilateral facial palsy after starting growth hormone therapy. © 2017 The Authors

JIMD Reports, 2022

Citrullinemia type 1 is an autosomal recessive metabolic disease caused by ASS1 gene mutations en... more Citrullinemia type 1 is an autosomal recessive metabolic disease caused by ASS1 gene mutations encoding argininosuccinic acid synthetase enzyme which is within the pathway of arginine and nitric oxide biosynthesis. Disease confirmation was done by ASS1 gene mutation analysis using next-generation sequencing, DNA Sanger sequencing. The study group was 17 citrullinemia type 1 patients from 10 unrelated families referred to Iranian National Society for Study on Inborn Errors of Metabolism's clinic between 2008 and 2020. Clinical, laboratory, and molecular data were retrospectively evaluated. Eleven different ASS1 gene mutations were detected in 13 (76%) of 17 neonatal, three (18%) of 17 late infantile, and one (6%) of 17 asymptomatic patients. Severe developmental delay and intractable seizures despite metabolic control was outcome of neonatal form survivor. Two late infantile form patients live metabolically controlled with quite normal performance. DNA mutations are as follows: seven missense, one nonsense, and two insertion/deletion mutations in 12, two, and three patients, respectively. Five novel mutations were detected including a homozygous GG deletion in exon 12 (c.790_791delGG;p. Gly264Profs*3) and a homozygous mutation in exon 7 (c.440C>T; p. Met147Thr), both causing infantile (late onset) form; a homozygous mutation in exon 6 (c.1130T>C; p.Met376Thr) causing neonatal form; two compound heterozygote mutations in exon 14 (c.1167_1168insC:p.Gly390Argfs*22& c.1186T>A; p.Ser396Thr) causing asymptomatic form. Five (38%) patients with classic neonatal form had mutation in exon 14 of ASS1 (c.1168G>A; p. Gly390Arg). Classic neonatal was the most common form of disease in

Molecular Genetics and Metabolism, 2021

Iranian Journal of Basic Medical Sciences, 2015

Objective(s): Intracerebral injection of bone marrow stromal cells (BMSCs) is being investigated ... more Objective(s): Intracerebral injection of bone marrow stromal cells (BMSCs) is being investigated as a therapeutic tool to prevent Alzheimer’s disease (AD). Our aim was to investigate the effects of BMSCs by intrathecal injection in AD rat model. Materials and Methods: BMSCs were obtained from the bone marrow of Wistar rat and transplanted into AD rat model via intrathecal injection. The rat model had received an injection of β amyloid into the hippocampus for histological and immunohistochemical studies. Results: Histological examination of the brains in transplanted rats compared to controls demonstrated the migration of BrdU-labeled BMSCs from the site of delivery, confirmed the differentiation of BMSCs transplanted cells into the cholinergic neurons, and increased number of healthy and decreased number of dark neurons. Conclusion: Our results showed that BMSCs intratechal administration could be a promising method for treatment of Alzheimer’s disease in rat model.

Frontiers in Bioscience-Landmark

Cancer whose major problems are metastasis, treatment resistance, and recurrence is the leading c... more Cancer whose major problems are metastasis, treatment resistance, and recurrence is the leading cause of death worldwide. Tumorinitiating stem cells (TiSCs) are a subset of the tumor population responsible for tumor resistance and relapse. Understanding the characteristics and shared features between tumor-initiating stem cells (TiSCs) and long-lived postmitotic cells may hold a key to better understanding the biology of cancer. Postmitotic cells have exited the cell cycle and are transitioned into a non-dividing and terminally differentiated state with a specialized function within a tissue. Conversely, a cancer cell with TiSC feature can divide and produce a variety of progenies, and is responsible for disease progression, tumor resistance to therapy and immune system and disease relapse. Surprisingly, our comprehensive evaluation of TiSCs suggests common features with long-lived post-mitotic cells. They are similar in structure (primary cilia, high mitochondrial content, and being protected by a barrier), metabolism (autophagy and senescence), and function (immunoescape and/or immune-privileged by a blood barrier). In-depth exploration showed how mitochondrial metabolism contributes to these shared features, including high energy demands arising from ciliary and microtubular functionality, increased metabolic activity, and movement. These findings can assist in decoding the remaining properties which offer insights into the biology of TiSCs, with potential implications for enhancing cancer treatment strategies and patient prognosis.

Energy is needed by cancer cells to stay alive and communicate with their surroundings. The prima... more Energy is needed by cancer cells to stay alive and communicate with their surroundings. The primary organelles for cellular metabolism and energy synthesis are mitochondria. Researchers recently proved that cancer cells can steal immune cells' mitochondria using nanoscale tubes. This finding demonstrates the dependence of cancer cells on normal cells for their living and function. It also denotes the importance of mitochondria in cancer cells’ biology. Emerging evidence has demonstrated how mitochondria are essential for cancer cells to survive in the harsh tumor microenvironment, evade the immune system, obtain more aggressive features, and resist treatments. For instance, functional mitochondria can improve cancer resistance against radiotherapy by scavenging the released reactive oxygen species. Therefore, targeting mitochondria can potentially enhance oncological outcomes, according to this notion. The patients' reactions to radiation are varied, ranging from a complete response to even cancer progression during treatment. This concept illustrates how different levels of mitochondrial metabolism might contribute to this heterogeneity. Considering this notion can help to improve personalized oncological treatments. This article outlines the importance of mitochondrial metabolism in cancer biology and personalized treatments.

Many investigators all around the world are working to find the best and novel methods for cancer... more Many investigators all around the world are working to find the best and novel methods for cancer treatment. Among them some are trying to reduce the treatment side effects from which patients are suffering. The side effects of Gamma-Ray on skin appear in forms of different ...

Cancer drug discovery and develogment, Dec 10, 2016

Development of new technologies is taking cancer research on a new journey in which plenty of mys... more Development of new technologies is taking cancer research on a new journey in which plenty of mysterious aspects of cancer biology are being unraveled. To defeat cancer, we first need to understand the biology of this smart complex system, which often hijacks several programs to proliferate, invade, escape the immune system and colonize distant organs. Therefore, studying cancer cells in every step of tumor development (including primary tumor formation, invasion, circulation and metastatic colonization) is absolutely essential. Analysis of human-derived cancer models in primary site, circulation or metastatic lesions outside their host is one of the most promising ways to understand these complexities. The most common currently used and more recently developed cancer cell lines consist of primary patient-derived tumor xenograft (PDTX), circulating tumor cells isolation and analyzes, and primary tumor organoids. In this chapter we provide a brief update of some of the most important advances in studying and treatment of cancer using new technologies.

Journal of pediatric nephrology, Jul 4, 2016

Idiopathic nephrotic syndrome is a heterogeneous disease with a spectrum of age at presentation, ... more Idiopathic nephrotic syndrome is a heterogeneous disease with a spectrum of age at presentation, phenotype, renal pathology, and response to treatment. Many mutations are recognized to be implicated in sporadic or hereditary forms. The aim of this review was to summarize the results of the genetic studies which have already been carried out in Iran considering their limitations. A literature search was conducted from March 1970 to September 2015 through MEDLINE, EMBASE, Google Scholar, Google, Iran Medex, Magiran, and SID. Eleven studies were relevant. Three articles were excluded due to insufficient data, duplicated case, and a syndromic nephrotic case without genetic studies. Our results showed that in the southwest of Iran, 80% of the patients had mutations in NPHS1 while in Fars Province, one third showed mutations in NPHS2 when all exons were assessed. In two different studies conducted in one center in Tehran, no mutation was detected in exon 5 but when all exons were studied, more than 65% had hot spot mutation in exon 8 of NPHS2. Interestingly, none of adolescents with FSGS showed mutation in p.R229Q (NPHS2, exon 5). This review revealed that both NPHS1 and NPHS2 were prevalent in Iranian children with SRNS. No mutation of p.R229Q was reported in Iranian adolescent with SRNS.

Cancers

Energy is needed by cancer cells to stay alive and communicate with their surroundings. The prima... more Energy is needed by cancer cells to stay alive and communicate with their surroundings. The primary organelles for cellular metabolism and energy synthesis are mitochondria. Researchers recently proved that cancer cells can steal immune cells’ mitochondria using nanoscale tubes. This finding demonstrates the dependence of cancer cells on normal cells for their living and function. It also denotes the importance of mitochondria in cancer cells’ biology. Emerging evidence has demonstrated how mitochondria are essential for cancer cells to survive in the harsh tumor microenvironments, evade the immune system, obtain more aggressive features, and resist treatments. For instance, functional mitochondria can improve cancer resistance against radiotherapy by scavenging the released reactive oxygen species. Therefore, targeting mitochondria can potentially enhance oncological outcomes, according to this notion. The tumors’ responses to anticancer treatments vary, ranging from a complete res...

Breast Cancer Research and Treatment, 2017

We investigated the role of glial cell line-derived neurotrophic factor (GDNF) in compensating tr... more We investigated the role of glial cell line-derived neurotrophic factor (GDNF) in compensating trastuzumab (TZMB)-induced apoptosis in HER2 ? breast cancer (BC) cells using xenograft tumors. We generated BC xenografts in nude mice using samples from three patients selected based on their HER2 status and response to TZMB therapy. TZMB treatment resulted in shrinkage of the HER2 ? TZMB-sensitive xenograft tumor but not the HER2or HER2 ? TZMB-resistant ones. GDNF neutralized TZMB activity and induced growth in all tumors. Three distinct cell lines were derived from these tumors and named, respectively, TZMB-sensitive (TSTC), HER2-(HNTC), and TZMB-resistant (TRTC). Over 50% of TRTC but 1% of TSTC cells expressed CD44, whereas 84% of TSTC were CD24 ? compared to only 1% of TRTC, despite comparable levels of HER2 detected in both. TZMB induced profound morphological changes toward apoptosis in TSTC but not in TRTC or HNTC. However, GDNF significantly compensated TZMB-mediated TSTC cell loss and promoted growth by 37 and 50%, respectively, in TSTC and TRTC. Inhibition of SRC by Saracatinib (SARC) blocked GDNF function and accelerated TZMBmediated cell death in TSTC, but GDNF continued promoting TRTC growth. These changes paralleled with expression levels of the key molecules involved in growth and apoptosis. Collectively, we found in our xenograft samples that firstly SRC mediates GDNF pro-survival functions by bridging RET-HER2 crosstalk in TZMB-responsive BC tumors. Secondly, SARC-TZMB interactions can synergistically eradicate such tumor cells; and thirdly, GDNF can support antibody resistance by acting independent from SRC in tumors with poor HER2 response to TZMB therapy.

Andrologia, 2015

Testicular cancer is the most common cancer affecting men in reproductive age, and cisplatin is o... more Testicular cancer is the most common cancer affecting men in reproductive age, and cisplatin is one of the major helpful chemotherapeutic agents for treatment of this cancer. In addition, exposure of testes cancer cells to cisplatin could potentially eliminate tumour cells from germ cells in patients. The aim of this study was to evaluate the effect of cisplatin on viability of mouse acute lymphoblastic leukaemia cell line (EL‐4) and neonatal mouse spermatogonial cells in vitro. In this study, the isolated spermatogonial stem cells (SSC) and EL‐4 were divided into six groups including control (received medium), sham (received DMSO in medium) and experimental groups which received different doses of cisplatin (0.5, 5, 10 and 15 μg ml−1). Cells viability was evaluated with MTT assay. The identity of the cultured cells was confirmed by the expression of specific markers. Our finding showed that viability of both SSC and EL‐4 cells was reduced with the dose of 15 μg/ml when compared to the control group (P ≤ 0.05). Also, the differences between the IC50 in doses 10 and 15 μg/ml at different time were significant (P ≤ 0.05). The number of TUNEL‐positive cells was increased, and the BAX and caspase‐3 expressions were upregulated in EL4 cells for group that received an effective dose of cisplatin). In conclusion, despite the dramatic effects of cisplatin on both cells, spermatogonial stem cells could form colony in culture.

Journal of cell science & therapy, 2015

TSGA10 is overexpressed in some cancers, during neural development, in embryogenesis, and in seve... more TSGA10 is overexpressed in some cancers, during neural development, in embryogenesis, and in several tissues with actively dividing cells. TSGA10 protein localization to the sperm tail has been previously described. The protein is cleaved into two parts, which appear to play different functions in the sperm tail: the 27-KDa N-terminal is localized to the fibrous sheath in the principal piece, whereas its 55-KDa C-terminal of the TSGA10 forms filaments, decreases transcriptional activity of hypoxia-inducible factor (HIF)-1-alpha and accumulates in the midpiece of mature spermatozoa. Using colocalization, and coimmunoprecipitation assays, we show that TSGA10 interacts with 'Outer Dense Fiber 2' (ODF2), a centrosome scaffold component associated with mother centrioles. Also, our yeast two-hybrid assay shows that the full-length TSGA10 protein and its 55-KDa C-terminus portion predominantly interact with ODF2. However, the truncated N-terminus 27-KDa fibrous sheath component of TSGA10 fails to bind ODF2. Our experiments examining the localization of TSGA10, demonstrated that the full length TSGA10 protein localizes to perinuclear structures, colocalizes with γ-tubulin, and associates with the centrosome and basal body. The TSGA10 55-KDa C-terminus, but not its 27-KDa N-terminus also localizes to the centrosome and basal body. Our Real-time PCR data indicated that the levels of TSGA10 and ODF2 genes expressions correlate, in mice testes. Finally, we propose that TSGA10 is a ciliary-centrosomal protein and therefore is a good candidate for further investigation in ciliopathies, as well as, cancer biology.

worldwide international science conferences and events. Established in the year 2007 with the sol... more worldwide international science conferences and events. Established in the year 2007 with the sole aim of making the information on Sciences and technology ‘Open Access’, OMICS Group publishes 500 online open access scholarly journals in all aspects of Science, Engineering, Management and Technology journals. OMICS Group has been instrumental in taking the knowledge on Science & technology to the doorsteps of ordinary men and women. Research Scholars, Students, Libraries, Educational Institutions, Research centers and the industry are main stakeholders that benefitted greatly from this knowledge dissemination. OMICS Group also organizes 500 International conferences annually across the globe, where knowledge transfer takes place through debates, round table discussions, poster presentations, workshops, symposia and exhibitions. About OMICS International Conferences OMICS International is a pioneer and leading science event organizer, which publishes around 500 open access journals a...

Iranian journal of kidney diseases, 2018

Complement C3 glomerulopathy refers to a disease process in which abnormal control of complement ... more Complement C3 glomerulopathy refers to a disease process in which abnormal control of complement activation or degradation results in predominant C3 fragment deposition within the glomerulus and causes glomerular damage. Abnormal control of the complement alternative pathway is a well-established risk factor for the occurrence of C3 glomerulonephritis. It is the first reported case in Iran with multiple mutations in complement factor H, with one of these mutations we have expected in hemolytic uremic syndrome rather than C3 glomerulopathy Genetic analysis showed that the molecular abnormalities of factor H led to complement factor H malfunction that were polymorphous and not restricted to the C-terminal domains of the protein.

American journal of human genetics, Jan 2, 2018

Interferon regulatory factor 2 binding protein-like (IRF2BPL) encodes a member of the IRF2BP fami... more Interferon regulatory factor 2 binding protein-like (IRF2BPL) encodes a member of the IRF2BP family of transcriptional regulators. Currently the biological function of this gene is obscure, and the gene has not been associated with a Mendelian disease. Here we describe seven individuals who carry damaging heterozygous variants in IRF2BPL and are affected with neurological symptoms. Five individuals who carry IRF2BPL nonsense variants resulting in a premature stop codon display severe neurodevelopmental regression, hypotonia, progressive ataxia, seizures, and a lack of coordination. Two additional individuals, both with missense variants, display global developmental delay and seizures and a relatively milder phenotype than those with nonsense alleles. The IRF2BPL bioinformatics signature based on population genomics is consistent with a gene that is intolerant to variation. We show that the fruit-fly IRF2BPL ortholog, called pits (protein interacting with Ttk69 and Sin3A), is broadl...

Korean Journal of Pediatrics, 2016

Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive neurocutaneous disorder with worldwi... more Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive neurocutaneous disorder with worldwide incidence of 0.4 per 100,000 people. It is characterized by the triad of congenital ichthyosis, spastic diplegia or quadriplegia, and mental retardation. Herein we report a 2-year-old male child with SLS, asthma, and recurrent pneumonia. SLS was confirmed by a molecular genetics study that revealed a deletion mutation in the ALDH3A2 gene. An ALDH3A2 gene mutation results in dysfunction of the microsomal enzyme fatty aldehyde dehydrogenase and impaired metabolism and accumulation of leukotriene B4, which is a key molecule and a pro-inflammatory mediator in developing allergic diseases, especially asthma. An increased level of leukotriene B4 has been reported in SLS patients. As far as we are aware, this is the first report of SLS associated with asthma and recurrent pneumonia. In conclusion, pediatricians should be aware of and evaluate patients with SLS for possible associated asthma and allergic disorders.

The American Journal of Human Genetics, 2019

Like living organisms, cancer cells require energy to survive and interact with their environment... more Like living organisms, cancer cells require energy to survive and interact with their environment. Mitochondria are the main organelles for energy production and cellular metabolism. Recently, investigators demonstrated that cancer cells can hijack mitochondria from immune cells. This behavior sheds light on a pivotal piece in the cancer puzzle, the ‘dependence’ on the normal cells. This article illustrates the benefits of new, functional mitochondria for cancer cells that urge them to hijack mitochondria. It describes how functional mitochondria help cancer cells’ survival in the harsh tumor microenvironment, immune evasion, progression, and treatment resistance. Recent evidence has put forward the pivotal role of mitochondria in cancer stem cells’ metabolism. This theory highlights the mitochondria in cancer biology and explains how targeted anti-mitochondrial treatments can improve oncological outcomes.

Prader�Willi Syndrome (PWS) is a complex genetic disorder with different manifestations in infa... more Prader�Willi Syndrome (PWS) is a complex genetic disorder with different manifestations in infancy and childhood including obesity, type 2 diabetes mellitus, mild to moderate intellectual impairment and learning disabilities. In this syndrome, growth hormone therapy improves outcomes. For the first time, here we report an 11-year-old boy with PWS who presented with three episodes of unilateral facial palsy after starting growth hormone therapy. © 2017 The Authors

JIMD Reports, 2022

Citrullinemia type 1 is an autosomal recessive metabolic disease caused by ASS1 gene mutations en... more Citrullinemia type 1 is an autosomal recessive metabolic disease caused by ASS1 gene mutations encoding argininosuccinic acid synthetase enzyme which is within the pathway of arginine and nitric oxide biosynthesis. Disease confirmation was done by ASS1 gene mutation analysis using next-generation sequencing, DNA Sanger sequencing. The study group was 17 citrullinemia type 1 patients from 10 unrelated families referred to Iranian National Society for Study on Inborn Errors of Metabolism's clinic between 2008 and 2020. Clinical, laboratory, and molecular data were retrospectively evaluated. Eleven different ASS1 gene mutations were detected in 13 (76%) of 17 neonatal, three (18%) of 17 late infantile, and one (6%) of 17 asymptomatic patients. Severe developmental delay and intractable seizures despite metabolic control was outcome of neonatal form survivor. Two late infantile form patients live metabolically controlled with quite normal performance. DNA mutations are as follows: seven missense, one nonsense, and two insertion/deletion mutations in 12, two, and three patients, respectively. Five novel mutations were detected including a homozygous GG deletion in exon 12 (c.790_791delGG;p. Gly264Profs*3) and a homozygous mutation in exon 7 (c.440C>T; p. Met147Thr), both causing infantile (late onset) form; a homozygous mutation in exon 6 (c.1130T>C; p.Met376Thr) causing neonatal form; two compound heterozygote mutations in exon 14 (c.1167_1168insC:p.Gly390Argfs*22& c.1186T>A; p.Ser396Thr) causing asymptomatic form. Five (38%) patients with classic neonatal form had mutation in exon 14 of ASS1 (c.1168G>A; p. Gly390Arg). Classic neonatal was the most common form of disease in

Molecular Genetics and Metabolism, 2021

Iranian Journal of Basic Medical Sciences, 2015

Objective(s): Intracerebral injection of bone marrow stromal cells (BMSCs) is being investigated ... more Objective(s): Intracerebral injection of bone marrow stromal cells (BMSCs) is being investigated as a therapeutic tool to prevent Alzheimer’s disease (AD). Our aim was to investigate the effects of BMSCs by intrathecal injection in AD rat model. Materials and Methods: BMSCs were obtained from the bone marrow of Wistar rat and transplanted into AD rat model via intrathecal injection. The rat model had received an injection of β amyloid into the hippocampus for histological and immunohistochemical studies. Results: Histological examination of the brains in transplanted rats compared to controls demonstrated the migration of BrdU-labeled BMSCs from the site of delivery, confirmed the differentiation of BMSCs transplanted cells into the cholinergic neurons, and increased number of healthy and decreased number of dark neurons. Conclusion: Our results showed that BMSCs intratechal administration could be a promising method for treatment of Alzheimer’s disease in rat model.