Publications by authors named "Mahsa Keshavarz-Fathi"

23 Publications

  • Page 1 of 1

Current and Future Perspectives of PD-1/PDL-1 Blockade in Cancer Immunotherapy.

J Immunol Res 2021 22;2021:6661406. Epub 2021 Feb 22.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Cancer immunotherapy, which reactivates weakened immune cells of cancer patients, has yielded great success in recent years. Among immunotherapeutic agents, immune checkpoint inhibitors have been of particular interest and have gained approval by the FDA for treatment of cancers. Immune checkpoint blockade through targeting programmed cell death protein-1 (PD-1) has demonstrated promising antitumor effects in cancer immunotherapy of many different solid and hematologic malignancies. However, despite promising results, a favorable response is observed only in a fraction of patients, and there is still lack of a single therapy modality with curative ability. In this paper, we review the current and future perspectives of PD-1/L1 blockade in cancer immunotherapy, with a particular focus on predictive biomarkers of response to therapy. We also discuss the adverse events associated with PD-1/L1/2 inhibitors, ranging from severe life-threatening conditions such as autoimmune myocarditis to mild and moderate reactions such as skin rashes, and explore the potential strategies for improving the efficacy of immunotherapy with PD-1/L1 checkpoint inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6661406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925068PMC
February 2021

Cancer Immunoprevention: Current Status and Future Directions.

Arch Immunol Ther Exp (Warsz) 2021 Feb 27;69(1). Epub 2021 Feb 27.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Dr. Qarib St, Keshavarz Blvd, 14194, Tehran, Iran.

Cancer is one of the most serious diseases affecting health and the second leading cause of death worldwide. Despite the development of various therapeutic modalities to deal with cancer, limited improvement in overall survival of patients has been yielded. Since there is no certain cure for cancer, detection of premalignant lesions, and prevention of their progression are vital to the decline of high morbidity and mortality of cancer. Among approaches to cancer prevention, immunoprevention has gained further attention in recent years. Deep understanding of the tumor/immune system interplay and successful prevention of virally-induced malignancies by vaccines have paved the way toward broadening cancer immunoprevention application. The identification of tumor antigens in premalignant lesions was the turning point in cancer immunoprevention that led to designing preventive vaccines for various malignancies including multiple myeloma, colorectal, and breast cancer. In addition to vaccines, immune checkpoint inhibitors are also being tested for the prevention of oral squamous cell carcinoma (SCC), and imiquimod which is an established drug for the prevention of skin SCC, is a non-specific immunomodulator. Herein, to provide a bench-to-bedside understanding of cancer immunoprevention, we will review the role of the immune system in suppression and promotion of tumors, immunoprevention of virally-induced cancers, identification of tumor antigens in premalignant lesions, and clinical advances of cancer immunoprevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00005-021-00604-xDOI Listing
February 2021

Recent progress in immunotherapy of breast cancer targeting the human epidermal growth factor receptor 2 (HER2).

J Oncol Pharm Pract 2021 Feb 2:1078155221991636. Epub 2021 Feb 2.

Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran.

Objective: Breast cancer is responsible for most of the cancer-induced deaths in women around the world. The current review will discuss different approaches of targeting HER2, an epidermal growth factor overexpressed in 30% of breast cancer cases.

Data Sources: We conducted a search on Pubmed and Scopus databases to find studies relevant to HER2+ breast cancers and targeting HER2 as means of immunotherapy. Out of 1043 articles, 105 studies were included in this review.

Data Summary: As well as the introduction of HER2 and breast cancer subtypes, we discussed various aspects of HER2-targeting immunotherapy including monoclonal antibodies, Antibody-drug conjugates (ADCs), Chimeric Antigen Receptor (CAR) T-cells and vaccines.

Conclusions: Despite several ways of controlling breast cancer, the need to investigate new drugs and approaches seems to be much significant as this cancer still has a heavy burden on people's health and survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1078155221991636DOI Listing
February 2021

Chimeric antigen receptor T-cell therapy for melanoma.

Expert Rev Clin Immunol 2021 Mar 31;17(3):209-223. Epub 2021 Jan 31.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: In recent years, chimeric antigen receptor (CAR) T cell therapy has emerged as a cancer treatment. After initial therapeutic success for hematologic malignancies, this approach has been extended for the treatment of solid tumors including melanoma.

Areas Covered: T cells need to be reprogramed to recognize specific antigens expressed only in tumor cells, a difficult problem since cancer cells are simply transformed normal cells. Tumor antigens, namely, CSPG4, CD70, and GD2 have been targeted by CAR-T cells for melanoma. Moreover, different co-stimulatory signaling domains need to be selected to direct T cell fate. In this review, various approaches for the treatment of melanoma and their effectiveness are comprehensively reviewed and the current status, challenges, and future perspective of CAR-T cell therapy for melanoma are discussed. Literature search was accomplished in three databases (PubMed, Google scholar, and Clinicaltrials.gov). Published papers and clinical trials were screened and relevant documents were included by checking pre-defined eligibility criteria.

Expert Opinion: Despite obstacles and the risk of adverse events, CAR T cell therapy could be used for patients with treatment-resistant cancer. Clinical trials are underway to determine the efficacy of this approach for the treatment of melanoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/1744666X.2021.1880895DOI Listing
March 2021

Extensive Deep Tissue Involvement in Nicolau Syndrome and Below-Knee Amputation: A Case Report and Literature Review.

Int J Low Extrem Wounds 2020 Aug 17:1534734620948768. Epub 2020 Aug 17.

Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Nicolau syndrome (NS) is a rare cutaneous drug reaction in response to injections administered via any route. Based on the available studies in the medical literature, NS presents as skin and subcutaneous fat necrosis, and typically, it does not cause severe complications such as acute limb ischemia or death. In this study, we report the case of a 6-year-old boy who received an intramuscular injection of benzathine penicillin G for the treatment of bacterial pharyngitis, and subsequently developed a severe case of NS, which eventually led to below-knee amputation of the right lower limb. Although a few approaches have been suggested for the management of NS, they might not be effective under certain circumstances. Early detection, close monitoring, and consistent interventions, such as surgical fasciotomy and debridement procedures, might be necessary in severe cases of NS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1534734620948768DOI Listing
August 2020

Pro-tumorigenic functions of macrophages at the primary, invasive and metastatic tumor site.

Cancer Immunol Immunother 2020 Sep 4;69(9):1673-1697. Epub 2020 Jun 4.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Dr Qarib St, Keshavarz Blvd, 14194, Tehran, Iran.

The tumor microenvironment (TME) not only facilitates cancer progression from the early formation to distant metastasis, but also it differs itself from time to time alongside the tumor evolution. Tumor-associated macrophages (TAMs), whether as pre-existing tissue-resident macrophages or recruited monocytes, are an inseparable part of this microenvironment. As their parents are broadly classified into a dichotomic, simplistic M1 and M2 subtypes, TAMs also exert paradoxical and diverse phenotypes as they are settled in different regions of TME and receive different microenvironmental signals. Briefly, M1 macrophages induce an inflammatory precancerous niche and flame the early oncogenic mutations, whereas their M2 counterparts are reprogrammed to release various growth factors and providing an immunosuppressive state in TME as long as abetting hypoxic cancer cells to set up a new vasculature. Further, they mediate stromal micro-invasion and co-migrate with invasive cancer cells to invade the vascular wall and neural sheath, while another subtype of TAMs prepares suitable niches much earlier than metastatic cells arrive at the target tissues. Accordingly, at the neoplastic transformation, during the benign-to-malignant transition and through the metastatic cascade, macrophages are involved in shaping the primary, micro-invasive and pre-metastatic TMEs. Whether their behavioral plasticity is derived from distinct genotypes or is fueled by microenvironmental cues, it could define these cells as remarkably interesting therapeutic targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00262-020-02616-6DOI Listing
September 2020

DNA Methylation of CD70 Promoter in Juvenile Systemic Lupus Erythematosus.

Fetal Pediatr Pathol 2020 May 19:1-10. Epub 2020 May 19.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: Epigenetic alterations in pathogenesis of systemic lupus erythematosus (SLE) have gained more attention recently in adults. We assessed the methylation of CD70 promoter, a costimulatory molecule on T cells, in juvenile SLE (JSLE), and compared this to that found in controls and the literature of adult SLE patients.

Methods: DNA methylation status was evaluated on peripheral blood from JSLE patients and healthy controls.

Results: Twenty-five patients with JSLE and 24 healthy controls were compared. JSLE patients had lower unmethylated CpG islands compared to the control group (mean ± SD; 0.78 ± 0.42 vs 10503.80 ± 39796.95). However, the difference was not significant (P-value; 0.22).

Conclusion: Despite hypomethylation of CD70 gene promoter in CD4+ T-cells from adult patients with SLE, no statistically significant differences observed in patients with JSLE compared with healthy controls. This may suggest a mechanism different in JSLE patients than in adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15513815.2020.1764681DOI Listing
May 2020

Effects of lead and cadmium on the immune system and cancer progression.

J Environ Health Sci Eng 2020 Jun 17;18(1):335-343. Epub 2020 Feb 17.

5Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

In our daily life, we are surrounded by harmful pollutants, including heavy metals that are not visible in the macroscopic view easily. Heavy metals can disrupt different aspects of human health, such as the immune system which has gained a lot of attention in recent decades. This had led to its rapid progression and new insights into its alterations in different diseases especially cancer. Heavy metals are non-biodegradable materials that exist in different parts of the food cycle, such as fruits and vegetables as commonly consumed foods and also unexpected sources such as street dust, that exists in the streets that we pass every day, soil, air, and water. These heavy metals can enter the human body through respiratory, cutaneous, and gastrointestinal pathways and then accumulate in different organs, leading to their encountering with various parts of the body. These sources and natural characteristics of heavy metals facilitate their interaction with the immune system. In this review, we investigated the effect of lead and cadmium, as pollutants that exist in many different parts of the human environment, on the immune system which is known to have a key role in the pathophysiology of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40201-020-00455-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203386PMC
June 2020

Delivery of genome editing tools: A promising strategy for HPV-related cervical malignancy therapy.

Expert Opin Drug Deliv 2020 06 13;17(6):753-766. Epub 2020 Apr 13.

Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences , Tehran, Iran.

Introduction: Persistent high-risk human papillomavirus infection is the main cause of various types of cancer especially cervical cancer. The E6 and E7 oncoproteins of HPV play critical roles in promoting carcinogenesis and cancer cell growth. As a result, E6 and E7 oncogenes are considered as promising therapeutic targets for cervical cancer. Recently, the development of genome-editing technologies including transcription activator-like effector nucleases (TALEN), meganucleases (MNs), zinc finger nucleases (ZFN), and more importantly clustered regularly interspaced short palindromic repeat-CRISPR-associated protein (CRISPR-Cas) has sparked a revolution in the cervical cancer-targeted therapy. However, due to immunogenicity, off-target effect, renal clearance, guide RNA (gRNA) nuclease degradation, and difficult direct transportation into the cytoplasm and nucleus, the safe and effective delivery is considered as the Achilles' heel of this robust strategy.

Areas Covered: In this review, we discuss cutting-edge available strategies for delivery of genome-editing technologies for HPV-induced cervical cancer therapy. Moreover, the combination of genome-editing tools and other therapies has been fully discussed.

Expert Opinion: The combination of nanoparticle-based delivery systems and genome-editing tools is a promising powerful strategy for cervical cancer therapy. The most significant limitations of this strategy that need to be focused on are low efficiency and off-target events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17425247.2020.1747429DOI Listing
June 2020

Importance of TNF-alpha and its alterations in the development of cancers.

Cytokine 2020 Mar 21;130:155066. Epub 2020 Mar 21.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Sheffield, UK. Electronic address:

TNF-alpha is involved in many physiologic and pathologic cellular pathways, including cellular proliferation, differentiation, and death, regulation of immunologic reactions to different cells and molecules, local and vascular invasion of neoplasms, and destruction of tumor vasculature. It is obvious that because of integrated functions of TNF-alpha inside different physiologic systems, it cannot be used as a single-agent therapy for neoplasms; however, long-term investigation of its different cellular pathways has led to recognition of a variety of subsequent molecules with more specific interactions, and therefore, might be suitable as prognostic and therapeutic factors for neoplasms. Here, we will review different aspects of the TNF-alpha as a cytokine involved in both physiologic functions of cells and pathologic abnormalities, most importantly, cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cyto.2020.155066DOI Listing
March 2020

The NLRP3 inflammasome: a therapeutic target for inflammation-associated cancers.

Expert Rev Clin Immunol 2020 02 22;16(2):175-187. Epub 2020 Jan 22.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

: Inflammasomes are large multimeric intracellular complexes that are capable of maturation and secretion of pro-inflammatory cytokines, IL-1β and IL-18, in response to danger signal molecules. As a member of the inflammasome family, the NLRP3 inflammasome has recently been under intense investigation revealing its possible role in several human diseases especially cancers.: In this review, we will discuss the biology and mechanism of NLRP3 inflammasome activation, its role in specific types of tumors and the novel therapeutic modalities targeting this complex.: The NLRP3 inflammasome and its components including the adapter apoptosis-associated speck-like (ASC) protein and caspase-1 impose different and sometimes contrasting effects in tumorigenesis depending on various contexts. Considering the novel role of this complex in the initiation and progression of neoplasia, the NLRP3 inflammasome and its pathways provide desirable therapeutic targets for prevention, treatment, and prognosis of certain types of cancer. To date, several agents have been introduced for this purpose, some of which have shown promising results in the clinic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/1744666X.2020.1713755DOI Listing
February 2020

Natural killer cells and cancer therapy, what we know and where we are going.

Immunotherapy 2019 10 19;11(14):1231-1251. Epub 2019 Aug 19.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, 1419733151, Iran.

Natural killer (NK) cells are among the significant components of innate immune system and they have come to the first line of defense against tumor cells developing inside the body. CD56lo/CD16 NK cells are highly cytotoxic and CD56hi NK cells can produce cytokines and perform a regulatory function. Specific features of NK cells have made them a unique choice for cancer immunotherapy. Simple interventions like cytokine-injection to boost the internal NK cells were the first trials to target these cells. Nowadays, many other types of intervention are under investigation, such as adoptive NK cell immunotherapy. In this paper, we will discuss the biology and function of NK cells in cancer immunosurveillance and therapeutic approaches against cancer via using NK cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/imt-2019-0040DOI Listing
October 2019

Nanoparticle-siRNA: a potential strategy for ovarian cancer therapy?

Nanomedicine (Lond) 2019 08 1;14(15):2083-2100. Epub 2019 Aug 1.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, 1419733151, Iran.

Ovarian cancer is one of the most common causes of mortality throughout the world. Unfortunately, chemotherapy has failed to cure advanced cancers developing multidrug resistance (MDR). Moreover, it has critical side effects because of nonspecific toxicity. Thanks to specific silencing of oncogenes and MDR-associated genes, nano-siRNA drugs can be a great help address the limitations of chemotherapy. Here, we review the current advances in nanoparticle-mediated siRNA delivery strategies such as polymeric- and lipid-based systems, rigid nanoparticles and nanoparticles coupled to specific ligand systems. Nanoparticle-based codelivery of anticancer drugs and siRNA targeting various mechanisms of MDR is a cutting-edge strategy for ovarian cancer therapy, which is completely discussed in this review.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/nnm-2018-0379DOI Listing
August 2019

IL-17 and colorectal cancer: From carcinogenesis to treatment.

Cytokine 2019 04 23;116:7-12. Epub 2019 Jan 23.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Sheffield, UK. Electronic address:

Colorectal cancer (CRC) is one of the most common types of cancer in the world. Several factors contribute to the development of this cancer. Tumor formation in colon triggers immune responses such as immune cells proliferation, phenotype alteration, cytokine synthesis and release, which lead to IL-17 producing T cells, the differentiated CD4+ T cells i.e. T helper 17. IL-17 is a pro-inflammatory cytokine, which its level is up regulated in serum and tissues of CRC patients. Several studies have shown that IL-17 has an important role in metastasis and prognosis of CRC. The aim of this review is to summarize the role of this cytokine in tumorigenesis, angiogenesis and metastasis of CRC and discuss its value in diagnosis, prognosis and treatment of CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cyto.2018.12.021DOI Listing
April 2019

The promising role of monoclonal antibodies for gastric cancer treatment.

Immunotherapy 2019 03;11(4):347-364

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Gastric cancer (GC) is the second leading cause of cancer-related death world-wide. Despite improvements in prevention, early detection and various therapeutic options, the prognosis is still poor. GC is often diagnosed at an advanced stage with survivals less than 1 year. Chemotherapy as the mainstay of treatment in advanced stage is not of notable advantages, underlining the need for novel more effective therapeutic options. Based on current knowledge of molecular and cellular mechanisms, a number of novel biologic approaches such as monoclonal antibodies have been recently introduced for cancer treatment that mainly affect the immune system or target signaling pathways playing role in cancer and metastasis development. In this review, various monoclonal antibodies for GC therapy were explained.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/imt-2018-0093DOI Listing
March 2019

Roles of Myeloid-Derived Suppressor Cells in Cancer Metastasis: Immunosuppression and Beyond.

Arch Immunol Ther Exp (Warsz) 2019 Apr 2;67(2):89-102. Epub 2018 Nov 2.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Dr Qarib St, Keshavarz Blvd, Tehran, 14194, Iran.

Metastasis is the direst face of cancer, and it is not a feature solely dependent on cancer cells; however, a complex interaction between cancer cells and host causes this process. Investigating the mechanisms of metastasis can lead to its control. Myeloid-derived suppressor cells (MDSCs) are key components of tumor microenvironment that favor cancer progression. These cells result from altered myelopoiesis in response to the presence of tumor. The most recognized function of MDSCs is suppressing anti-tumor immune responses. Strikingly, these cells are among important players in cancer dissemination and metastasis. They can exert their effect on metastatic process by affecting anti-cancer immunity, epithelial-mesenchymal transition, cancer stem cell formation, angiogenesis, establishing premetastatic niche, and supporting cancer cell survival and growth in metastatic sites. In this article, we review and discuss the mechanisms by which MDSCs contribute to cancer metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00005-018-0531-9DOI Listing
April 2019

Passive-specific immunotherapy with monoclonal antibodies for prostate cancer: A systematic review.

J Oncol Pharm Pract 2019 Jun 22;25(4):903-917. Epub 2018 Oct 22.

4 Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: Treatment of metastatic castration-resistant prostate cancer with conventional therapies is still not successful. Therefore, application of novel biological approaches such as immunotherapy, which appears to be more effective and less toxic, is necessary. Monoclonal antibodies against cancer specific antigens are a kind of immunotherapy that have been approved for specific types of cancer and are being investigated for prostate cancer as well. The aim of this review was to assess the effectiveness and safety of monoclonal antibodies for treatment of advanced prostate cancer.

Method: According to the search strategy stated in our systematic review protocol, Scopus, Medline, TRIP, CENTRAL, ProQuest, DART and OpenGrey databases were searched. Data collection and quality assessment were done independently by two authors and any disagreements between the collected data were resolved by a third author. A meta-analysis was not feasible as there was a considerable statistical heterogeneity among the trials. Hence, this review was limited to a narrative analysis of the included studies.

Results: We found 9756 references by applying search strategy in 4 databases of journal articles and 3 databases of grey literature. We then discarded 3957 duplicate citations using Endnote software and 5143 articles due to obvious irrelevancy of their topics in primary screening. In secondary screening of 656 fulltexts, we excluded 538 articles, and finally included 12 trials in this systematic review, updated on 23 June 2017. The overall quality of the studies was fair. In general, results of this systematic review show promising advances in the treatment of prostate cancer patients with monoclonal antibodies against prostate-specific antigens with regard to PSA/disease response. Some of the studies reported pain relief after treatment as well.

Conclusion: Currently, the role of immunotherapy in the treatment of advanced prostate cancer still remains debated. Although passive specific immunotherapy could be offered as a novel therapeutic option in the coming years, patients should be informed about the risks and benefits of this therapy. One of the obstacles in this review was the lack of adequate assessment of survival-related endpoints reported in the included studies. Our study provides support for further research in this field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1078155218808080DOI Listing
June 2019

Cancer cachexia: Diagnosis, assessment, and treatment.

Crit Rev Oncol Hematol 2018 Jul 31;127:91-104. Epub 2018 May 31.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Sheffield, UK. Electronic address:

Cancer cachexia is a multi-factorial syndrome, which negatively affects quality of life, responsiveness to chemotherapy, and survival in advanced cancer patients. Our understanding of cachexia has grown greatly in recent years and the roles of many tumor-derived and host-derived compounds have been elucidated as mediators of cancer cachexia. However, cancer cachexia remains an unmet medical need and attempts towards a standard treatment guideline have been unsuccessful. This review covers the diagnosis, assessment, and treatment of cancer cachexia; the elements impeding the formulation of a standard management guideline; and future directions of research for the improvement and standardization of current treatment procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.critrevonc.2018.05.006DOI Listing
July 2018

The role of inflammatory cytokines and tumor associated macrophages (TAMs) in microenvironment of pancreatic cancer.

Cytokine Growth Factor Rev 2018 02 12;39:46-61. Epub 2018 Jan 12.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Sheffield, UK. Electronic address:

Pancreatic cancer is considered as one of the most lethal types of cancer due to its poor prognosis and lack of effective therapeutic approaches. Although many studies have been done on pancreatic cancer, the current treatment methods did not exhibit successful results. Hence, novel strategies are needed for treatment of pancreatic cancer. The microenvironment of pancreatic cancer contains many factors such as inflammatory cytokines and tumor associated macrophages (TAMs), which influence the tumor's status. These factors can be upregulated and consequently lead to exacerbation of tumor progression. Understanding the role of pro- and anti-inflammatory cytokines and the function of TAMs in the pancreatic cancer microenvironment might lead to development and improvement of novel strategies in the diagnosis and treatment of pancreatic cancer and may result in promising treatments for this type of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cytogfr.2018.01.007DOI Listing
February 2018

Basic understanding and therapeutic approaches to target toll-like receptors in cancerous microenvironment and metastasis.

Med Res Rev 2018 09 28;38(5):1469-1484. Epub 2017 Dec 28.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Toll-like receptors (TLRs) are transmembrane components that sense danger signals, like damage- and pathogen-associated molecular pattern molecules, as receptors, and maintain homeostasis in tissues. They are mainly involved in immune system activation through a variety of mediators, which either carry out (1) elimination of pathogenic threats and redressing homeostatic imbalances or (2) contribution to the initiation and worsening of pathological conditions, including cancers. Under physiological conditions, TLRs coordinate the innate and adaptive immunity, and inhibit autoimmune disorders. In pathological conditions, such as cancer, they can present both tumor and receptor-specific roles. Although the roles of individual TLRs in various cancers have been described, the effects of targeting TLRs to treat cancer and prevent metastasis are still controversial. A growing body of literature has suggested contribution of both activators and inhibitors of TLR signaling pathway for cancer treatment, dependent on several context-specific factors. In short, TLRs can play dual roles with contradictory outcomes in neoplastic conditions. This hampers the development of TLR-based therapeutic interventions. A better understanding of the interwoven TLR pathways in cancerous microenvironment is necessary to design TLR-based therapies. In this review, we consider the molecular mechanisms of TLRs signaling and their involvement in tumor progression. Therapeutic modalities targeting TLRs for cancer treatment are discussed as well.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/med.21480DOI Listing
September 2018

The promising role of monoclonal antibodies for immunotherapy of the HIV-associated cancer, non-Hodgkin lymphoma.

Int Rev Immunol 2018 05 19;37(3):165-173. Epub 2017 Dec 19.

c Research Center for Immunodeficiencies , Children's Medical Center, Tehran University of Medical Sciences , Tehran , Iran.

Association between HIV/AIDS and some of the cancers such as lymphomais is well known. Relative risk for developing non-Hodgkin lymphoma (NHL) increases 60-200 folds in HIV-infected individuals. Diffuse large B cell lymphoma (DLBCL), primary effusion lymphoma (PEL), Burkitt's lymphoma (BL) and Plasmablastic Lymphoma (PBL) are among the most frequent subtypes. During the last century, scientists found that the immune system could potentially detect and destroy cancer cells. Therefore, they started a new field of study, which is named immunotherapy. There are different immunotherapeutic methods, among which therapeutic antibodies, such as Brentuximabvedotin (Adcetris), Ibritumomabtiuxetan (Zevalin) and rituximab (Rituxan), used for treatment of NHLs showed promising results. In this article, we will review the immunotherapeutic option, monoclonal antibodies, for treatment of HIV-associated NHLs as well as their recent clinical status. We will also discuss the selective monoclonal antibody for each subtype of NHLs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08830185.2017.1405396DOI Listing
May 2018

Immunotherapy of cancers comes of age.

Expert Rev Clin Immunol 2017 10 23;13(10):1001-1015. Epub 2017 Aug 23.

a Research Center for Immunodeficiencies, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.

Introduction: Cancer immunotherapy has evolved and is aimed at generating the efficacious therapeutic modality to enhance the specificity and power of the immune system to combat tumors. Areas covered: Current efforts in cancer immunotherapy fall into three main approaches. One approach is through the blockade of immune checkpoints, another approach is through adoptive cellular therapy, and the last approach is through vaccination. The goal of this review is to summarize the current understanding and status of cancer immunotherapy in these three categories. Expert commentary: We foresee the development of therapeutic protocols combining these approaches with each other or conventional therapies to achieve the most appropriate guideline for management of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/1744666X.2017.1366315DOI Listing
October 2017

Survival benefits of dexmedetomidine used for sedating septic patients in intensive care setting: A systematic review.

J Crit Care 2016 Apr 23;32:93-100. Epub 2015 Nov 23.

University of Buffalo, Buffalo, NY. Electronic address:

Purpose: The aim of this systematic review was to evaluate the effectiveness and safety of dexmedetomidine used for sedation of patients with sepsis.

Methods: We searched Medline, Scopus, TRIP and CENTRAL, DART, OpenGrey, and ProQuest without applying any language filter up to July 15, 2015. Two of the authors independently reviewed search results for irrelevant and duplicate studies and extracted data and assessed methodological quality of the studies. We used tabulation to synthesize the findings of the studies and transformed data into a common rubric and calculated a weighted treatment effect across studies using Review Manager.

Results: We found 124 references in 7 databases, and after exclusion of irrelevant and duplicate studies, 6 studies with total number of 242 patients with sepsis were included. The risk ratio for 28-day mortality was 0.49 (95% confidence interval, 0.24-0.99; P = .05) for the dexmedetomidine group vs the control group. The weighted mean difference for the length of stay in the intensive care unit was 1.54 (95% confidence interval, -1.73 to 4.81; P = .36). No adverse effect including hypertensive, hypotensive, or bradycardia response was reported in any studies.

Conclusion: In a small group of studies of patients with sepsis, dexmedetomidine improved short-term mortality compared with other sedatives without affecting the intensive care unit length of stay. Further studies are warranted to confirm whether using this particular agent improves sepsis outcomes in comparison to other commonly used sedating agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcrc.2015.11.013DOI Listing
April 2016