Publications by authors named "Omid Kooshkaki"

10 Publications

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

Front Oncol 2020 29;10:572329. Epub 2020 Oct 29.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19) in China, which spread to the rest of the world, led the World Health Organization to classify it as a global pandemic. COVID-19 belongs to the genus of the family, and it 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 such as respiratory system diseases, immune deficiency, diabetes, cardiovascular disease, and cancer are prone to adverse events (admission to the intensive care unit requiring invasive ventilation or even death). The current focus has been on the development of novel therapeutics, including antivirals, monoclonal antibodies, and vaccines. However, although there is undoubtedly an urgent need to identify effective treatment options against infection with COVID-19, it is equally important to clarify management protocols for the other significant diseases from which these patients may suffer, including cancer. This review summarizes the current evidence regarding 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.
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http://dx.doi.org/10.3389/fonc.2020.572329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658542PMC
October 2020

Immune Checkpoints and CAR-T Cells: The Pioneers in Future Cancer Therapies?

Int J Mol Sci 2020 Nov 5;21(21). Epub 2020 Nov 5.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran.

Although the ever-increasing number of cancer patients pose substantial challenges worldwide, finding a treatment with the highest response rate and the lowest number of side effects is still undergoing research. Compared to chemotherapy, the relatively low side effects of cancer immunotherapy have provided ample opportunity for immunotherapy to become a promising approach for patients with malignancy. However, the clinical translation of immune-based therapies requires robust anti-tumoral immune responses. Immune checkpoints have substantial roles in the induction of an immunosuppressive tumor microenvironment and tolerance against tumor antigens. Identifying and targeting these inhibitory axes, which can be established between tumor cells and tumor-infiltrating lymphocytes, can facilitate the development of anti-tumoral immune responses. Bispecific T-cell engagers, which can attract lymphocytes to the tumor microenvironment, have also paved the road for immunological-based tumor elimination. The development of CAR-T cells and their gene editing have brought ample opportunity to recognize tumor antigens, independent from immune checkpoints and the major histocompatibility complex (MHC). Indeed, there have been remarkable advances in developing various CAR-T cells to target tumoral cells. Knockout of immune checkpoints via gene editing in CAR-T cells might be designated for a breakthrough for patients with malignancy. In the midst of this fast progress in cancer immunotherapies, there is a need to provide up-to-date information regarding immune checkpoints, bispecific T-cell engagers, and CAR-T cells. Therefore, this review aims to provide recent findings of immune checkpoints, bispecific T-cell engagers, and CAR-T cells in cancer immunotherapy and discuss the pertained clinical trials.
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http://dx.doi.org/10.3390/ijms21218305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663909PMC
November 2020

Hydro-alcoholic Extract of C. Koch Reduces the Expression of Cell Death-Associated Genes while Inducing DNA Damage in HeLa Cervical Cancer Cells.

Iran J Med Sci 2020 Sep;45(5):359-367

Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran.

Background: C. Koch hydroalcoholic extract (AWHE) is proven to induce cell death. Previous studies suggested that AWHE is an effective inhibitor against the proliferation of prostate cancer cells. The present study aimed to evaluate possible alterations of cell death-associated genes and determine the growth inhibitory activity of AWHE on HeLa cervical cancer cells.

Methods: The antiproliferative activity of AWHE was tested using the tetrazolium dye-based colorimetric assay (MTT assay). The mRNA levels of Vascular endothelial growth factor (), , and Breast Cancer Susceptibility gene 1 () were measured using the real-time Polymerase Chain Reaction method. The in-cell levels of phosphorylated H2AX were determined using the in-cell ELISA method. The data were analyzed using the non-parametric ANOVA and . P<0.05 was considered statistically significant.

Results: Based on the MTT assay, The half-maximal inhibitory concentration and 81.99 µg/mL, respectively. The mRNA levels of increased after 12 and 24 hours of treatment (P<0.001), while the mRNA levels of significantly decreased after 12 hours (P=0.003) and 24 hours (P=0.001). expression was increased in the HeLa cells after 6 and 12 hours (P<0.001) whereas γ-H2AX levels significantly increased after 24 and 48 hours of treatment (P<0.001).

Conclusion: AWHE possesses growth inhibitory activity by altering the expression of cell death-associated genes. Using extracts from herbal plants may provide alternative strategies to be deployed in the fight against cancer.
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http://dx.doi.org/10.30476/ijms.2020.72657.0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519407PMC
September 2020

The Latest Findings of PD-1/PD-L1 Inhibitor Application in Gynecologic Cancers.

Int J Mol Sci 2020 Jul 16;21(14). Epub 2020 Jul 16.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran.

Gynecologic cancers account for approximately 11% of the newly diagnosed cancers in women in the United States and for 18% globally. The presence of tumor-infiltrating lymphocytes (TILs) influences the clinical outcome of cancer patients and immune checkpoint inhibitors (ICIs), including anti programmed cell death protein-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), and anticytotoxic T-lymphocyte antigen 4 (anti-CTLA-4), which have been approved for treating different types of malignancies. Antibodies targeting the PD-1/PD-L1 checkpoint have shown dynamic and durable tumor regressions, suggesting a rebalancing of the host-tumor interaction. There are several the US food and drug administration (FDA)-approved ICIs targeting PD-1, including pembrolizumab and nivolumab, as well as those targeting PD-L1, including avelumab, atezolizumab, and durvalumab for melanoma, renal cell cancer, colorectal cancer, head and neck cancer, cervix cancer, urothelial cancer, and lung cancer. Current pre-clinical and clinical studies assessing PD-1/PD-L1 inhibitors in several gynecologic cancers have reported significant antitumor activity. In this review, we investigate pre-clinical and clinical studies that describe the safety and efficacy of anti-PD-1/PD-L1 antibodies, with a particular focus on ongoing clinical trials, analyzing the oncological outcome and adverse effects of ICIs in gynecologic cancers.
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http://dx.doi.org/10.3390/ijms21145034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404077PMC
July 2020

Combination of Ipilimumab and Nivolumab in Cancers: From Clinical Practice to Ongoing Clinical Trials.

Int J Mol Sci 2020 Jun 22;21(12). Epub 2020 Jun 22.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran.

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are inhibitory checkpoints that are commonly seen on activated T cells and have been offered as promising targets for the treatment of cancers. Immune checkpoint inhibitors (ICIs)targeting PD-1, including pembrolizumab and nivolumab, and those targeting its ligand PD-L1, including avelumab, atezolizumab, and durvalumab, and two drugs targeting CTLA-4, including ipilimumab and tremelimumab have been approved for the treatment of several cancers and many others are under investigating in advanced trial phases. ICIs increased antitumor T cells' responses and showed a key role in reducing the acquired immune system tolerance which is overexpressed by cancer and tumor microenvironment. However, 50% of patients could not benefit from ICIs monotherapy. To overcome this, a combination of ipilimumab and nivolumab is frequently investigated as an approach to improve oncological outcomes. Despite promising results for the combination of ipilimumab and nivolumab, safety concerns slowed down the development of such strategies. Herein, we review data concerning the clinical activity and the adverse events of ipilimumab and nivolumab combination therapy, assessing ongoing clinical trials to identify clinical outlines that may support combination therapy as an effective treatment. To the best of our knowledge, this paper is one of the first studies to evaluate the efficacy and safety of ipilimumab and nivolumab combination therapy in several cancers.
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http://dx.doi.org/10.3390/ijms21124427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352976PMC
June 2020

MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers.

Int J Mol Sci 2020 Apr 8;21(7). Epub 2020 Apr 8.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran.

MicroRNAs (miRNAs) are small and non-coding RNAs that display aberrant expression in the tissue and plasma of cancer patients when tested in comparison to healthy individuals. In past decades, research data proposed that miRNAs could be diagnostic and prognostic biomarkers in cancer patients. It has been confirmed that miRNAs can act either as oncogenes by silencing tumor inhibitors or as tumor suppressors by targeting oncoproteins. MiR-144s are located in the chromosomal region 17q11.2, which is subject to significant damage in many types of cancers. In this review, we assess the involvement of miR-144s in several cancer types by illustrating the possible target genes that are related to each cancer, and we also briefly describe the clinical applications of miR-144s as a diagnostic and prognostic tool in cancers.
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http://dx.doi.org/10.3390/ijms21072578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177921PMC
April 2020

The Association of Major Depressive Disorder with Activation of NLRP3 Inflammasome, Lipid Peroxidation, and Total Antioxidant Capacity.

J Mol Neurosci 2020 Jan 12;70(1):65-70. Epub 2019 Sep 12.

Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.

Increasing number of studies indicates that chronic inflammation and oxidative stress play an essential role in pathophysiology and some symptoms of major depressive disorder (MDD). In the present study, the inflammasome activity and oxidative stress status in untreated and antidepressant-treated MDD patients were compared to the healthy group. Blood samples were taken from 20 MDD patients receiving treatment, 20 first-episode MDD patients not receiving treatment, and 20 healthy controls. The expression level of NLRP3 and caspase-1 was measured by real-time PCR and the serum TAC and MDA were examined in the patients and the control groups. The results showed that the mRNA level of NLRP3 and caspase-1 genes was significantly elevated in MDD groups compared with that in the healthy volunteers (P < 0.005). The expression level of NLRP3 and caspase-1 has slightly decreased in the treated group compared with that in the untreated one, but it was not a meaningful decrease. Moreover, the serum MDA was significantly higher and TAC statistically was lower in untreated MDD patients compared with those in the healthy control group (P = 0.001, P = 0.001). It can be concluded that NLRP3 inflammasome is upregulated in MDD patients. Statistically significant reduction in the level of TAC along with increased lipid peroxidation was detectable in MDD patient's plasma. In contrast, there was no significant difference between the treated and non-treated groups in terms of oxidative stress (P = 0.6, P = 0.1). Our results suggested that inflammasome signaling pathway is a therapeutic potential for MDD.
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http://dx.doi.org/10.1007/s12031-019-01401-0DOI Listing
January 2020

Mild antagonistic effect of Valproic acid in combination with AZD2461 in MCF-7 breast cancer cells.

Med J Islam Repub Iran 2019 10;33:29. Epub 2019 Apr 10.

Student Research committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Breast cancer (BC) is a complex disease, but current treatments are not efficient enough considering increased relapse and decreased survival rate among patients. Poly (ADP-ribose) polymerase inhibitors are recently developed anticancer agents which target cells with defects in homologous recombination (HR) pathway. This study wishes to assess whether the combination of AZD2461 as a newly developed PARP1 inhibitor and valproic acid (VPA), a histone deacetylase inhibitor could effectively reduce the growth of MCF-7 cells with no fundamental DNA repair defect. Both trypan blue dye exclusion assay and MTT viability test were used to evaluate cell death. γ-H2AX levels, as a marker of DNA repair, were measured using in cell ELISA method. The Student's t-test and non-parametric analysis of variance (ANOVA) were applied for our data analyses where p-value <0.05 was considered statistically significant. As calculated by CompuSyn software, IC50 values for VPA and AZD2461 were 4.89 mM and 42.83 µM respectively following 48 hours treatment. Also, the trypan blue exclusion assay results showed a concentration- and time-dependent decrease when MCF-7 cells were treated with both agents (p<0.05). Combination analysis showed a mild antagonism (CI>1.1) while γ-H2AX levels found not to be significantly increased in MCF-7 cells co-treated with VPA+AZD2461 compared to each agent alone (p=0.29). Our findings revealed that the combination of VPA and AZD2461 could decrease cell viability of MCF-7 cells, but it was not able to significantly increase unrepaired DNA damage sites. The mechanism responsible for drugs combination was not of synergism or addition. Determining the type of involved cell death mechanisms might be followed in further studies.
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http://dx.doi.org/10.34171/mjiri.33.29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662678PMC
April 2019

The Association Between Knee Osteoarthritis and HLA-DRB1*0101 in the East of Iran.

Curr Rheumatol Rev 2020 ;16(2):134-138

Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.

Background: Osteoarthritis (OA) is a painful social problem, which breaks down the articular cartilage, causes the failure of synovial joints and subchondral bone sclerosis. OA etiology is not completely understood, but joint trauma, infection, obesity, and diseases are the most important risk factors for OA developing. Recent studies suggested inflammatory factors and genetic components can be involved in the pathogenesis of OA. Experimental evidences suggest a linkage between Human Leukocyte Antigen (HLA) genetic diversity and OA. But a few studies have been conducted in this subject.

Objective: To investigate the association between HLA-DRB1*0101 and OA in Iranian patients.

Methods: Thirty patients with knee osteoarthritis and 30 healthy people as the control group were included in the study. Sex, weight, age, Body mass index (BMI) and height of all participants were recorded. HLA-DRB1*0101 was typed by PCR using the sequence-specific primer.

Results: Our results showed 80% of knee osteoarthritis patients were positively HLA-DRB1*0101 (n=24), while only 26.7% of controls were positive (n=8) (P= 0.015).

Conclusion: These findings proposed that there is a significant association between HLADRB1* 0101 and susceptibility to knee osteoarthritis.
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http://dx.doi.org/10.2174/1573397115666190716114738DOI Listing
March 2021

Investigation of the association between C677T polymorphism of the MTHFR gene and plasma homocysteine level in recurrent fetal miscarriage.

J Obstet Gynaecol Res 2019 Aug 7;45(8):1442-1447. Epub 2019 Jun 7.

Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.

Aim: The aim of this study is to determine the association between C677T polymorphism in MTHFR gene and plasma homocysteine concentration in recurrent fetal miscarriages.

Methods: Overall, 100 women were included in the research, the case group comprised of 50 women who had a history of spontaneously recurrent miscarriage with unspecified cause, and 50 of whom had experienced at least two successful pregnancy, as controls. Methods used in the study included PCR-RFLP with limited effective HinfI enzyme in order to investigate MTHFR polymorphism and enzyme-linked immunosorbent assay analysis to investigate plasma homocysteine concentration.

Results: There was a significant increase in the prevalence of mutant TT genotype among women with miscarriage history. Also, the mean homocysteine level in the case group was significantly higher than that in the control group (P = 0.002) and higher level of homocysteine was found in the carriers of T allele.

Conclusion: Our data suggest that C677TT genotype may be a risk factor for miscarriage and CC wild type genotype supposed to have protective effect on hyperhomocysteinemia.
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http://dx.doi.org/10.1111/jog.13989DOI Listing
August 2019