Nima Hemmat

Tabriz University of Medical Sciences

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Behzad Baradaran

Tabriz University of Medical Sciences

Hossein Bannazadeh Baghi

Tabriz University of Medical Sciences

Zahra Asadzadeh

Tabriz University of Medical Sciences

Afshin Derakhshani

Istituto Tumori Bari

Nicola Silvestris

Istituti di Ricovero e Cura a Carattere Scientifico

Ahad Mokhtarzadeh

Tabriz University of Medical Sciences

Amir Baghbanzadeh

Tabriz University of Medical Sciences

Oronzo Brunetti

Istituto Tumori Bari

Mahdi Abdoli Shadbad

Tabriz University of Medical Sciences

Behzad Baradaran

Tabriz University of Medical Sciences

Cooperative Institutions

Tabriz University of Medical Sciences

University of Tabriz

Tehran University of Medical Sciences

Shahid Beheshti University of Medical Sciences

Mashhad University of Medical Sciences

Islamic Azad University of Tabriz

Istituti di Ricovero e Cura a Carattere Scientifico

University of Bari Aldo Moro

Tarbiat Modares University

Istituto Tumori Bari

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Role of microRNAs in epidermal growth factor receptor signaling pathway in cervical cancer

Molecular Biology Reports (2020)

Nima Hemmat Ahad Mokhtarzadeh Mohammad Aghazadeh Farhad Jadidi‐Niaragh Behzad Baradaran

ErbB

10.1007/s11033-020-05494-4

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Citations (19)

siRNA-E6 sensitizes HPV-16-related cervical cancer through Oxaliplatin: an in vitro study on anti-cancer combination therapy

European journal of medical research (2023)

Parisa Shiri Aghbash Nima Hemmat Behzad Baradaran Hossein Bannazadeh Baghi

Persistent infection with high-risk Human papillomaviruses (HPV), such as hr-HPV-16 and hr-HPV-18, lead to cervical cancer, the fourth most common cancer in the world. In the present study, we investigated the alteration of E6 oncogene expression by E6-specific short interfering RNA (siRNA) combined with Oxaliplatin.The cervical cancer cell line, CaSki, was transfected with E6-siRNA, then treated with Oxaliplatin. The cellular genes, such as p53, MMP9, Nanog, and caspases expression, were assessed by quantitative real-time PCR. The cell death rate, cell cycle, and cell viability were assessed by Annexin V/PI staining, DAPI staining, and MTT test, respectively. Furthermore, colony formation assay and scratch test determined the stemness ability and cell metastasis, respectively.Combination therapy increased the re-expression of genes involved in the p53-dependent apoptosis pathway (increase in apoptosis to 44.2%), and reduced stemness and metastasis ability compared to either siRNA or Oxaliplatin monotherapy. Together, our results demonstrate that E6-siRNA and Oxaliplatin combination increased the cervical cancer cells' sensitivity to Oxaliplatin and decreased the survival rate, proliferation, and metastasis, and consequently escalated apoptosis rate, induced cell cycle arrest in the sub-G1 stage, and reduced the chemotherapy drug dosage.Inhibition of E6 oncogene expression and subsequent E6-siRNA with Oxaliplatin combination therapy could be a novel strategy for cervical cancer treatment.

DAPI

MTT assay

10.1186/s40001-023-01014-9

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Citations (11)

The cross-talk between tumor-associated macrophages and tumor endothelium: Recent advances in macrophage-based cancer immunotherapy

Biomedicine & Pharmacotherapy (2021)

Ali Baradaran Zahra Asadzadeh Nima Hemmat Amir Baghbanzadeh Mahdi Abdoli Shadbad

Tumor-associated macrophages (TAMs) are among the abundant cell populations of the tumor microenvironment (TME), which have pivotal roles in tumor development, chemoresistance, immune evasion, and metastasis. Growing evidence indicates that TAMs and the cross-talk between TAMs and tumoral endothelial cells can substantially contribute to tumor angiogenesis, which is considered a vital process for cancer development. Besides, tumoral endothelial cells can regulate the leukocyte infiltration to the TME in solid cancers and contribute to immune evasion. Therefore, targeting the immunosuppressive TAMs and the cross-talk between them can be a promising strategy for improving anti-tumoral immune responses. This review aims to summarize the biology of TAMs, their recently identified roles in tumor development/angiogenesis, and recent advances in macrophage-based cancer immunotherapy approaches for treating cancers.

Tumor-associated macrophage

Cancer Immunotherapy

10.1016/j.biopha.2021.112588

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Citations (23)

Coronavirus Disease 2019: A Brief Review of the Clinical Manifestations and Pathogenesis to the Novel Management Approaches and Treatments

Frontiers in Oncology (2020)

Omid Kooshkaki Afshin Derakhshani Andelé M. Conradie Nima Hemmat Savio George Barreto

The recent outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or Coronavirus Disease 2019 (COVID-19) inChina, which spread to the rest of the world, led the World Health Organization (WHO) to classify it as a global pandemic. COVID-19 belongs to the Bettacoronavirusgenus of Coronaviridae familyand is mainly spreads through the respiratory tract. Studies have now confirmed a human-to-human transmission as the primary pathway of spread. COVID-19 patients with a history of diseases like respiratory system diseases, immune deficiency, diabetes, cardiovascular disease, and cancer are prone to adverse events (admission to the intensive care unit (ICU) requiring invasive ventilation and even death). The current focus has been on the development of novel therapeutics,including antivirals, monoclonal antibodies, and vaccines. However, while there is undoubtedly an urgent need not to identify effective treatment options against infection with COVID-19, it is equally important to clarify management protocols for the other significant diseases these patients may suffer from, including cancer. This review summarizesthe current evidence about the epidemiology, pathogenesis, and management of patients with COVID-19. It also aims to provide the reader with insights into COVID-19 in pregnant patients and those with cancer outlining necessary precautions relevant to cancer patients. Finally, we provide the available evidence on the latest potent antiviral drugs and vaccines of COVID-19 and the ongoing drug trials.

Pandemic

Coronavirus

Coronaviridae

10.3389/fonc.2020.572329

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Citations (7)

The effect of Wnt/β-catenin signaling on PD-1/PDL-1 axis in HPV-related cervical cancer

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics (2022)

Parisa Shiri Aghbash Nima Hemmat Behzad Baradaran Ahad Mokhtarzadeh Vahdat Poortahmasebi

Infection with high-risk human papillomavirus (HPV), including HPV-16 and HPV-18, is the main cause of malignancies, such as cervical cancer. Viral oncoproteins encoded by HPV are expressed in HPV-positive cancers and associated with the early cancer stages and the transformation of normal cells. The signaling pathways involved in the transformation of normal cells to cancerous form and the subsequently expressed programmed cell death-ligand 1 (PD-L1) on the surface of the transformed cells lead to a disruption in recognition of tumor cells by the immune cell system, including T lymphocytes and dendritic cells which lead to the development of cervical cancer malignancy. These cells also produce modest levels of cytokines during exhaustion, tumor-infiltrating T CD4+ cells with high levels of PD-1 and CD39 release considerable quantities of cytokines. The Wnt/β-catenin signaling pathway, which controls the expression of genes involved in the tumor cells' markers, is demonstrated to be one of the most potent cancer stimulants. It leads to the evasion of the tumor cells from immune cell detection and ultimately avoids being recognized by dendritic cells or T-cells. PD-L1, as an inhibitory immune checkpoint, is essential for controlling immune system activity by inhibiting T-cells' inflammatory function. In the present review, we looked into how Wnt/β-catenin affects the expression of PD-L1 and related genes like c-MYC in cancer cells and its role in the development of HPV-induced malignancy. We hypothesized that blocking these pathways could be a potential immunotherapy and cancer prevention method.

Malignant Transformation

Immunosurveillance

10.32604/or.2022.026776

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Citations (16)

miRNA-21, an Important Regulator of Autoimmune Diseases

Current Molecular Medicine (2024)

Roghayeh Tofigh Reza Safaralizadeh Mohammad Ali Hosseinpour Feizi Nima Hemmat Behzad Baradaran

Abstract: miRNA-21 is regarded as both an abundant and highly conserved member of the microRNA (miRNA) family. It is expressed in virtually every cell and is responsible for critical regulatory actions that are important in health and disease. This microRNA has been shown to potentially have a role in the pathogenesis of several immune-related disorders, including autoimmune diseases, such as Multiple sclerosis and systemic lupus erythematosus, as two prominent examples of diseases that might be involved. In the current research, we looked at the role of miRNA-21, regarded as one of the most significant pathogenic miRNAs with a role in the development of autoimmune illness.

Pathogenesis

10.2174/0115665240290075240514164601

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Citations (1)

A Systematic Review on PD-1 Blockade and PD-1 Gene-Editing of CAR-T Cells for Glioma Therapy: From Deciphering to Personalized Medicine

Frontiers in Immunology (2022)

Mahdi Abdoli Shadbad Nima Hemmat Vahid Khaze Afshin Derakhshani Farzad Baradaran

Programmed cell death protein 1 (PD-1) can attenuate chimeric antigen receptor-T (CAR-T) cell-mediated anti-tumoral immune responses. In this regard, co-administration of anti-PD-1 with CAR-T cells and PD-1 gene-editing of CAR-T cells have been suggested to disrupt this inhibitory axis. Herein, we aim to investigate the advantages and disadvantages of these two approaches and propose a novel strategy to ameliorate the prognosis of glioma patients.Scopus, Embase, and Web of Science were systematically searched to obtain relevant peer-reviewed studies published before March 7, 2021. Then, the current study was conducted based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statements. The random-effect model was applied to evaluate the effect size of administrated agents on the survival of animal models bearing gliomas using RevMan version 5.4. The Cochran Q test and I2 were performed to assess the possible between-study heterogeneity. Egger's and Begg and Mazumdar's tests were performed to objectively assess potential asymmetry and publication bias using CMA version 2.Anti-PD-1 can substantially increase the survival of animal models on second-generation CAR-T cells. Also, PD-1 knockdown can remarkably prolong the survival of animal models on third-generation CAR-T cells. Regardless of the CAR-T generations, PD-1 gene-edited CAR-T cells can considerably enhance the survival of animal-bearing gliomas compared to the conventional CAR-T cells.The single-cell sequencing of tumoral cells and cells residing in the tumor microenvironment can provide valuable insights into the patient-derived neoantigens and the expression profile of inhibitory immune checkpoint molecules in tumor bulk. Thus, single-cell sequencing-guided fourth-generation CAR-T cells can cover patient-derived neoantigens expressed in various subpopulations of tumoral cells and inhibit related inhibitory immune checkpoint molecules. The proposed approach can improve anti-tumoral immune responses, decrease the risk of immune-related adverse events, reduce the risk of glioma relapse, and address the vast inter-and intra-heterogeneity of gliomas.

10.3389/fimmu.2021.788211

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Citations (13)

Covid-19: Perspectives on Innate Immune Evasion

Frontiers in Immunology (2020)

Nima Taefehshokr Sina Taefehshokr Nima Hemmat Bryan Heit

The ongoing outbreak of COVID-19 infection achieved pandemic status on 11th March 2020. As of 8th September 2020 it has caused over 890,000 mortalities world-wide. Coronaviral infections are enabled by potent immunoevasory mechanisms that target multiple aspects of innate immunity, with SARS-CoV-2 able to induce a cytokine storm, impair interferon responses, and suppress antigen presentation on both MHC class I and class II. Understanding the immune responses to SARS-CoV-2 and its immunoevasion approaches will improve our understanding of pathogenesis, virus clearance, and contribute towards vaccine and immunotherepeutic design and evaluation. This review discusses the known host innate immune response and immune evasion mechanisms driving SARS-CoV-2 infection and pathophysiology.

Evasion (ethics)

2019-20 coronavirus outbreak

Pandemic

10.3389/fimmu.2020.580641

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Citations (147)

Boosting Immunotherapy Efficacy: Empowering the Potency of Dendritic Cells Loaded with Breast Cancer Lysates through CTLA-4 Suppression

Heliyon (2024)

Mohammad Bakhshivand Javad Masoumi Farid Ghorbaninezhad Leili Aghebati‐Maleki Dariush Shanebandi

Boosting

Cancer Immunotherapy

CTLA-4

10.1016/j.heliyon.2024.e37699

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Citations (0)

The Combination of PD-L1 and CTLA-4 Suppression Significantly Decreased the Expression Levels of Cancer Stem Cell Factors in the Pancreatic Cancer Cell Line

ImmunoAnalysis (2023)

Nazila Alizadeh Tohid Kazemi Nima Hemmat Mahdi Jafarlou Behzad Baradaran

Background: It is thought that a limited number of aberrant cancer stem cells (CSCs), which encourage carcinogenesis, tumor metastasis, and treatment resistance, are the cause of pancreatic cancer, a disease with a high mortality rate. Increasing evidence shows that CSCs use immunosuppressive properties to avoid immune system identification. In Pancreatic cancer, the therapeutic consequences of the relationship between the expression of immune checkpoints such as programmed death receptor ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the presence of CSCs are poorly known. As a result, in the present investigation, we examined how the expression levels of CSCs were affected by PD-L1 and CTLA-4 knockdown using specific siRNA. Methods: Independently and together, PD-L1 and CTLA-4 siRNA were transfected into MIA PaCa-2 cells. RNA extraction and cDNA synthesis were then performed. Finally, using qRT-PCR, the gene expression levels of CSCs markers, including Nanog, CD133, CD44, and Oct-4, in transfected groups were measured. Results: In the MIA PaCa-2 cell line, siRNA-mediated inhibition of PD-L1 and CTLA-4 decreased the expression of CSC factors. Moreover, combined suppression of these two stemness-related immune checkpoints significantly decreased Nanog, CD133, CD44, and Oct-4 expression compared to inhibition of PD-L1 and CTLA-4 separately. Conclusion: Considering that the combination of PD-L1 and CTLA-4 suppression using siRNA significantly decreased the expression levels of CSCs factors, this approach may be regarded as an effective therapy for this cancer.

Homeobox protein NANOG

CTLA-4

10.34172/ia.2023.06

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Citations (4)