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Battlegrounds of treatment resistance: decoding the tumor microenvironment

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY 2025年 1-19页

作者： Bayat, Mobina nahand, javid sadri Tabriz Univ Med Sci Mol Med Res Ctr Tabriz Iran Tabriz Univ Med Sci Infect & Trop Dis Res Ctr Tabriz Iran

The tumor microenvironment (TME) emerges as a formidable actor in the cancer treatment landscape, wielding the power to thwart therapeutic efficacy across various modalities, including chemotherapy, radiotherapy, immunotherapy, targeted therapy, and hormonal therapy. This intricate ecosystem comprising diverse cellular constituents, signaling molecules, and the extracellular matrix fosters a dynamic interplay that profoundly influences tumor behavior and treatment outcomes. This review explores the mechanisms through which the TME drives resistance to standard therapies, emphasizing key factors such as hypoxia, immune evasion, and metabolic reprogramming. Furthermore, we illuminate innovative strategies aimed at reprogramming this hostile environment, including the application of therapeutic vaccines, CAR T cell therapy, and combination immunotherapies designed to enhance anti-tumor responses. By advocating for multidimensional approaches that dismantle the TME's barriers to effective treatment, this review calls for a transformative shift in cancer treatment paradigms. By bridging the gap between the TME's complexities and targeted therapeutic strategies, we pave the way for targeted interventions that promise to enhance clinical outcomes and improve patient prognosis in the relentless battle against cancer.

关键词： Treatment resistance Tumor microenvironment Targeted therapy Tumor-immune therapy

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The role of immune cells and inflammasomes in Modulating cytokine responses in HPV-Related cervical cancer

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INTERNATIONAL IMMUNOPHARMACOLOGY 2025年 145卷 113625页

作者： Aghbash, Parisa Shiri Rasizadeh, Reyhaneh nahand, javid sadri Baghi, Hossein Bannazadeh Tabriz Univ Med Sci Infect & Trop Dis Res Ctr Tabriz Iran Tabriz Univ Med Sci Fac Med Dept Virol Tabriz Iran Tabriz Univ Med Sci Immunol Res Ctr Tabriz Iran

One of the most frequent cancers associated with gynecological malignancies is cervical cancer. Nearly 99% of cervical tumor lesions are produced by prolonged infection with hr-HPV and almost 70% of cases are related to HPV-16 and HPV-18. The human immune system has a crucial role in defending against infections caused by HPV infection. As an illustration, elevation in neutrophils reduces T cell antitumor activity, which in turn results in the development of malignancies and subsequently inhibits immune system function. HPV-infected cells, also, express a significant number of genes related to pro-inflammatory mediators including IL-1 beta. Moreover, inflammasomes, which are multi-protein complexes, owing the production of the pro-inflammatory cytokines including IL-1 beta and IL-18 in response to viral infections. In other words, these multi-protein complexes have a crucial role in tumor immunity regulation through the secretion of pro-inflammatory cytokines and induction of antigen presentation and maturation by APCs including dendritic cells. In this study, we attempted to investigate the inflammasome's general role in the initiation and advancement of cervical cancer, as well as a summary of the pathways connected to the possible participation of inflammasomes in the pathological process of cervical carcinoma and immune cell engagement. Novel strategy techniques that target the inflammatory reaction of tumor-related antigens may be created with an understanding of inflammasome-dependent pathways to accomplish tumor immunotherapy and cervical tumor treatment.

关键词： Inflammasomes Cervical cancer Human papillomavirus Immune cells Antigen associated proteins

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Novel strategies in HPV-16-related cervical cancer treatment: An in vitro study of combined siRNA-E5 with oxaliplatin and ifosfamide chemotherapy

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GENE 2025年 932卷 148904页

作者： Rasizadeh, Reyhaneh Aghbash, Parisa Shiri Mokhtarzadeh, Ahad Poortahmasebi, Vahdat Oskouee, Mahin Ahangar nahand, javid sadri Amini, Mohammad Mahdavi, Seyedeh Zahra Bahojb Yari, Amir Hossein Baghi, Hossein Bannazadeh Tabriz Univ Med Sci Infect & Trop Dis Res Ctr Tabriz 516615731 Iran Tabriz Univ Med Sci Immunol Res Ctr Tabriz Iran Tabriz Univ Med Sci Fac Med Dept Virol Tabriz Iran Higher Educ Inst Rab Rashid Dept Genet Tabriz Iran

Background: Cervical cancer, primarily caused by HPV infection, remains a global health concern. Current treatments face challenges including drug resistance and toxicity. This study investigates combining E5-siRNA with chemotherapy drugs, Oxaliplatin and Ifosfamide, to enhance treatment efficacy in HPV-16 positive cervical cancer cells, targeting E5 oncoprotein to overcome limitations of existing therapies. Methods: The CaSki cervical cancer cell line was transfected with E5-siRNA, and subsequently treated with Oxaliplatin/Ifosfamide. Quantitative real-time PCR was employed to assess the expression of related genes including p53, MMP2, Nanog, and Caspases. Cell apoptosis, cell cycle progression, and cell viability were evaluated using Annexin V/PI staining, DAPI staining, and MTT test, respectively. Furthermore, stemness ability was determined through a colony formation assay, and cell motility was assessed by wound healing assay. Results: E5-siRNA transfection significantly reduced E5 mRNA expression in CaSki cells compared to the control group. The MTT assay revealed that monotherapy with E5-siRNA, Oxaliplatin, or Ifosfamide had moderate effects on cell viability. However, combination therapy showed synergistic effects, reducing the IC50 of Oxaliplatin from 11.42 x 10- 8 M (45.36 mu g/ml) to 6.71 x 10- 8 M (26.66 mu g/ml) and Ifosfamide from 12.52 x 10-5 M (32.7 mu g/ ml) to 8.206 x 10-5 M (21.43 mu g/ml). Flow cytometry analysis demonstrated a significant increase in apoptosis for combination treatments, with apoptosis rates rising from 11.02 % (Oxaliplatin alone) and 16.98 % (Ifosfamide alone) to 24.8 % (Oxaliplatin + E5-siRNA) and 34.9 % (Ifosfamide + E5-siRNA). The sub-G1 cell population increased from 15.7 % (Oxaliplatin alone) and 18 % (Ifosfamide alone) to 21.9 % (Oxaliplatin + E5-siRNA) and 27.1 % (Ifosfamide + E5-siRNA), indicating cell cycle arrest. The colony formation assay revealed a substantial decrease in the number of colonies following combinatio

关键词： Cervical cancer Combination therapy E5 oncoprotein Oxaliplatin Ifosfamide siRNA Gene therapy

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To be or not to be: navigating the influence of MicroRNAs on cervical cancer cell death

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CANCER CELL INTERNATIONAL 2025年第1期25卷 1-23页

作者： Taghizadieh, Mohammad Kalantari, Masoumeh Bakhshali, Roksana Kobravi, Sepehr Khalilollah, Shayan Baghi, Hossein Bannazadeh Bayat, Mobina nahand, javid sadri Akhavan-Sigari, Reza Tabriz Univ Med Sci Fac Med Dept Pathol Tabriz Iran Tehran Univ Hlth Sci Dept Biol Tehran Iran Omid Canc Ctr Ahvaz Iran Islamic Azad Univ Fac Dent Dept Oral & Maxillofacial Surg Tehran Med Sci Branch Tehran Iran Islamic Azad Univ Fac Med Dept Neurosurg Tehran Med Sci Tehran Iran Tabriz Univ Med Sci Infect & Trop Dis Res Ctr Tabriz Iran Univ Med Ctr Tuebingen Dept Neurosurg Tubingen Germany Coll Humanum Warsaw Management Univ Dept Hlth Care Management & Clin Res Warsaw Poland

With all diagnostic and therapeutic advances, such as surgery, radiation- and chemo-therapy, cervical cancer (CC) is still ranked fourth among the most frequent cancers in women globally. New biomarkers and therapeutic targets are warranted to be discovered for the early detection, treatment, and prognosis of CC. As component of the non-coding RNA's family, microRNAs (miRNAs) participate in several cellular functions such as cell proliferation, gene expression, many signaling cascades, apoptosis, angiogenesis, etc. MiRNAs can suppress or induce programmed cell death (PCD) pathways by altering their regulatory genes. Besides, abnormal expression of miRNAs weakens or promotes various signaling pathways associated with PCD, resulting in the development of human diseases such as CC. For that reason, understanding the effects that miRNAs exert on the various modes of tumor PCD, and evaluating the potential of miRNAs to serve as targets for induction of cell death and reappearance of chemotherapy. The current study aims to define the effect that miRNAs exert on cell apoptosis, autophagy, pyroptosis, ferroptosis, and anoikis in cervical cancer to investigate possible targets for cervical cancer therapy. Manipulating the PCD pathways by miRNAs could be considered a primary therapeutic strategy for cervical cancer.

关键词： Cervical cancer MicroRNAs Apoptosis Ferroptosis Pyroptosis Autophagy

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Exosomal miRNAs: the tumor's trojan horse in selective metastasis

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MOLECULAR CANCER 2024年第1期23卷 167页

作者： Bayat, Mobina nahand, javid sadri Tabriz Univ Med Sci Infect & Trop Dis Res Ctr Tabriz 15731 Iran

Organs of future metastasis are not passive receivers of circulating tumor cells, but are instead selectively and actively modified by the primary tumor before metastatic spread has even occurred. Tumors orchestrate a pre-metastatic program by conditioning distant organs to create microenvironments that foster the survival and proliferation of tumor cells before their arrival, thereby establishing pre-metastatic niches. Primary tumor-derived exosomes modulate these pre-metastatic niches, generating a permissive environment that facilitates the homing and expansion of tumor cells. Moreover, microRNAs have emerged as a key component of exosomal cargo, serving not only to induce the formation of pre-metastatic niches but also to prime these sites for the arrival and colonization of specific secondary tumor populations. Against this backdrop, this review endeavors to elucidate the impact of tumor-derived exosomal microRNAs on the genesis of their individualized pre-metastatic niches, with a view towards identifying novel means of specifying cancer metastasis and exploiting this phenomenon for cancer immunotherapy.

关键词： Selective Metastasis Pre-metastatic Niche Exosomes MicroRNA

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MicroRNAs and human viral diseases: A focus on the role of microRNA-29

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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 2025年第1期1871卷 167500页

作者： Kesheh, Mina Mobini Bayat, Mobina Kobravi, Sepehr Lotfalizadeh, Mohammad Hassan Heydari, Azhdar Memar, Mohammad Yousef Baghi, Hossein Bannazadeh Kermanshahi, Atefeh Zamani Ravaei, Fatemeh Taghavi, Seyed Pouya Zarepour, Fatemeh nahand, javid sadri Hashemian, Seyed Mohammad Reza Mirzaei, Hamed Iran Univ Med Sci Sch Med Dept Virol Tehran Iran Tabriz Univ Med Sci Infect & Trop Dis Res Ctr Tabriz Iran Tehran Azad Univ Fac Dent Dept Oral & Maxillofacial Surg Tehran Iran North Khorasan Univ Med Sci Sch Dent Bojnurd Iran Kashan Univ Med Sci Physiol Res Ctr Inst Basic Sci Kashan Iran Tabriz Univ Med Sci Fac Med Dept Virol Tabriz Iran Kashan Univ Med Sci Sch Med Kashan Iran Kashan Univ Med Sci Student Res Comm Kashan Iran Shahid Beheshti Univ Med Sci Natl Res Inst TB & Lung Dis NRITLD Chron Resp Dis Res Ctr CRDRC Tehran Iran Kashan Univ Med Sci Res Ctr Biochem & Nutr Metab Dis Inst Basic Sci Kashan Iran Kashan Univ Med Sci Sch Med Dept Physiol & Pharmacol Kashan Iran

The viral replication can impress through cellular miRNAs. Indeed, either the antiviral responses or the viral infection changes through cellular miRNAs resulting in affecting many regulatory signaling pathways. One of the microRNA families that is effective in human cancers, diseases, and viral infections is the miR-29 family. Members of miR-29 family are effective in different viral infections as their roles have appeared in regulation of immunity pathways either in innate immunity including interferon and inflammatory pathways or in adaptive immunity including activation of T-cells and antibodies production. Although miR-29a affects viral replication by suppressing antiviral responses, it can inhibit the expression of viral mRNAs via binding to their 3 ' UTR. In the present work, we discuss the evidence related to miR-29a and viral infection through host immunity regulation. We also review roles of other miR-29 family members by focusing on their role as biomarkers for diagnosing and targets for viral diseases management.

关键词： microRNA miR-29 family members Viral infection Biomarker

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War or peace: Viruses and metastasis

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BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER 2024年第6期1879卷 189179页

作者： Bayat, Mobina Golestani, Shahin Motlaghzadeh, Saeed Baghi, Hossein Bannazadeh Lalehzadeh, Aidin nahand, javid sadri Tabriz Univ Med Sci Infect & Trop Dis Res Ctr Tabriz Iran Shahid Beheshti Univ Med Sci Dept Ophthalmol Tehran Iran Iran Univ Med Sci Fac Med Dept Virol Tehran Iran

Metastasis, the dissemination of malignant cells from a primary tumor to secondary sites, poses a catastrophic burden to cancer treatment and is the predominant cause of mortality in cancer patients. Metastasis as one of the main aspects of cancer progression could be strongly under the influence of viral infections. In fact, viruses have been central to modern cancer research and are associated with a great number of cancer cases. Viral-encoded elements are involved in modulating essential pathways or specific targets that are implicated in different stages of metastasis. Considering the continuous emergence of new viruses and the establishment of their contribution to cancer progression, the warfare between viruses and cancer appears to be endless. Here we aimed to review the critical mechanism and pathways involved in cancer metastasis and the influence of viral machinery and various routes that viruses adopt to manipulate those pathways for their benefit.

关键词： Cancer metastasis Viral infection Signal transduction pathways Oncoviruses

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The interplay between mitochondrial dysfunction and NLRP3 inflammasome in multiple sclerosis: Therapeutic implications and animal model studies

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BIOMEDICINE & PHARMACOTHERAPY 2024年 175卷 116673-116673页

作者： Shadab, Alireza Abbasi-Kolli, Mohammad Saharkhiz, Mansoore Ahadi, Seyed Hamed Shokouhi, Behrooz nahand, javid sadri Iran Univ Med Sci Deputy Hlth Tehran Iran Semnan Univ Med Sci Sch Med Dept Immunol Semnan Iran Tarbiat Modares Univ Fac Med Sci Dept Med Genet Tehran Iran Birjand Univ Med Sci Fac Med Dept Immunol Birjand Iran Birjand Univ Med Sci Cellular & Mol Res Ctr Birjand Iran Tabriz Univ Med Sci Pathol Dept Tabriz 15731 Iran Tabriz Univ Med Sci Infect & Trop Dis Res Ctr Tabriz 15731 Iran

Multiple sclerosis (MS) is a complex autoimmune disorder that impacts the central nervous system (CNS), resulting in inflammation, demyelination, and neurodegeneration. The NOD -like receptor (NLR) family pyrin domain -containing 3 (NLRP3) inflammasome, a multiprotein complex of the innate immune system, serves an essential role in the pathogenesis of MS by regulating the production of pro -inflammatory cytokines (IL-1 beta & IL18) and the induction of pyroptotic cell death. Mitochondrial dysfunction is one of the main potential factors that can trigger NLRP3 inflammasome activation and lead to inflammation and axonal damage in MS. This highlights the importance of understanding how mitochondrial dynamics modulate NLRP3 inflammasome activity and contribute to the inflammatory and neurodegenerative features of MS. The lack of a comprehensive understanding of the pathogenesis of MS and the urge for the introduction of new therapeutic strategies led us to review the therapeutic potential of targeting the interplay between mitochondrial dysfunction and the NLRP3 inflammasome in MS. This paper also evaluates the natural and synthetic compounds that can improve mitochondrial function and/or inhibit the NLRP3 inflammasome, thereby providing neuroprotection. Moreover, it summarizes the evidence from animal models of MS that demonstrate the beneficial effects of these compounds on reducing inflammation, demyelination, and neurodegeneration. Finally, this review advocates for a deeper investigation into the molecular crosstalk between mitochondrial dynamics and the NLRP3 inflammasome as a means to refine therapeutic targets for MS.

关键词： Multiple Sclerosis Mitochondrial dynamics NLRP3 inflammasome Inflammation Neurodegeneration Mitochondrial dysfunctions

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Genetic and epigenetic contribution to astrocytic gliomas pathogenesis

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JOURNAL OF NEUROCHEMISTRY 2019年第2期148卷 188-203页

作者： Khani, Pouria Nasri, Farzad Chamani, Fateme Khani Saeidi, Farzane nahand, javid sadri Tabibkhooei, Alireza Mirzaei, Hamed IUMS Fac Med Dept Med Genet & Mol Biol Tehran Iran Iran Univ Med Sci Student Res Comm Tehran Iran IUMS Fac Med Dept Med Immunol Tehran Iran Shahid Beheshti Univ Med Sci Sch Med Dept Immunol Tehran Iran Tarbiat Modares Univ Sch Med Sci Dept Med Genet Tehran Iran Iran Univ Med Sci Fac Med Dept Virol Tehran Iran Iran Univ Med Sci Dept Neurosurg Tehran Iran Kashan Univ Med Sci Res Ctr Biochem & Nutr Metab Dis Kashan Iran

Astrocytic gliomas are the most common and lethal form of intracranial tumors. These tumors are characterized by a significant heterogeneity in terms of cytopathological, transcriptional, and (epi)genomic features. This heterogeneity has made these cancers one of the most challenging types of cancers to study and treat. To uncover these complexities and to have better understanding of the disease initiation and progression, identification, and characterization of underlying cellular and molecular pathways related to (epi)genetics of astrocytic gliomas is crucial. Here, we discuss and summarize molecular and (epi)genetic mechanisms that provide clues as to the pathogenesis of astrocytic gliomas.

关键词： astrocytic glioma molecular mechanism therapy

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Viruses and thrombocytopenia

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HELIYON 2024年第6期10卷 e27844页

作者： Rasizadeh, Reyhaneh Ebrahimi, Fatemeh Kermanshahi, Atefeh Zamani Sorkhabi, Amin Daei Sarkesh, Aila nahand, javid sadri Baghi, Hossein Bannazadeh Tabriz Univ Med Sci Immunol Res Ctr Tabriz Iran Tabriz Univ Med Sci Fac Med Dept Virol Tabriz Iran Univ Tabriz Fac Nat Sci Dept Anim Biol Tabriz Iran Tabriz Univ Med Sci Student Res Comm Tabriz Iran Tabriz Univ Med Sci Infect & Trop Dis Res Ctr POB *** Tabriz Iran

Thrombocytopenia, characterized by a decrease in platelet count, is a multifaceted clinical manifestation that can arise from various underlying causes. This review delves into the intriguing nexus between viruses and thrombocytopenia, shedding light on intricate pathophysiological mechanisms and highlighting the pivotal role of platelets in viral infections. The review further navigates the landscape of thrombocytopenia in relation to specific viruses, and sheds light on the diverse mechanisms through which hepatitis C virus (HCV), measles virus, parvovirus B19, and other viral agents contribute to platelet depletion. As we gain deeper insights into these interactions, we move closer to elucidating potential therapeutic avenues and preventive strategies for managing thrombocytopenia in the context of viral infections.

关键词： Thrombocytopenia Platelets Coagulation Inflammation Thrombosis

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