International review of cell and molecular biology最新文献

{"title":"Inflammatory breast cancer: An overview about the histo-pathological aspect and diagnosis.","authors":"Ghada Sahraoui, Nabil Rahoui, Maha Driss, Karima Mrad","doi":"10.1016/bs.ircmb.2024.02.001","DOIUrl":"https://doi.org/10.1016/bs.ircmb.2024.02.001","url":null,"abstract":"<p><p>Inflammatory Breast Cancer (IBC) is a rare and aggressive form of locally advanced breast cancer, classified as stage T4d according to the tumor-node-metastasis staging criteria. This subtype of breast cancer is known for its rapid progression and significantly lower survival rates compared to other forms of breast cancer. Despite its distinctive clinical features outlined by the World Health Organization, the histopathological characteristics of IBC remain not fully elucidated, presenting challenges in its diagnosis and treatment. Histologically, IBC tumors often exhibit a ductal phenotype, characterized by emboli composed of pleomorphic cells with a high nuclear grade. These emboli are predominantly found in the papillary and reticular dermis of the skin overlaying the breast, suggesting a primary involvement of the lymphatic vessels. The tumor microenvironment in IBC is a complex network involving various cells such as macrophages, monocytes, and predominantly T CD8+ lymphocytes, and elements including blood vessels and extracellular matrix molecules, which play a pivotal role in the aggressive nature of IBC. A significant aspect of IBC is the frequent loss of expression of hormone receptors like estrogen and progesterone receptors, a phenomenon that is still under active investigation. Moreover, the overexpression of ERBB2/HER2 and TP53 in IBC cases is a topic of ongoing debate, with studies indicating a higher prevalence in IBC compared to non-inflammatory breast cancer. This overview seeks to provide a comprehensive understanding of the histopathological features and diagnostic approaches to IBC, emphasizing the critical areas that require further research.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"384 ","pages":"47-61"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor microenvironment induced switch to mitochondrial metabolism promotes suppressive functions in immune cells.","authors":"Sanjay Pandey, Vandana Anang, Michelle M Schumacher","doi":"10.1016/bs.ircmb.2024.07.003","DOIUrl":"https://doi.org/10.1016/bs.ircmb.2024.07.003","url":null,"abstract":"<p><p>Understanding the intricacies of the metabolic phenotype in immune cells and its plasticity within the tumor microenvironment is pivotal in understanding the pathology and prognosis of cancer. Unfavorable conditions and cellular stress in the tumor microenvironment (TME) exert a profound impact on cellular functions in immune cells, thereby influencing both tumor progression and immune responses. Elevated AMP:ATP ratio, a consequence of limited glucose levels, activate AMP-activated protein kinase (AMPK) while concurrently repressing the activity of mechanistic target of rapamycin (mTOR) and hypoxia-inducible factor 1-alpha (HIF-1α). The intricate balance between AMPK, mTOR, and HIF-1α activities defines the metabolic phenotype of immune cells in the TME. These Changes in metabolic phenotype are strongly associated with immune cell functions and play a crucial role in creating a milieu conducive to tumor progression. Insufficiency of nutrient and oxygen supply leads to a metabolic shift in immune cells characterized by a decrease in glycolysis and an increase in oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) rates. In most cases, this shift in metabolism is accompanied by a compromise in the effector functions of these immune cells. This metabolic adaptation prompts immune cells to turn down their effector functions, entering a quiescent or immunosuppressive state that may support tumor growth. This article discusses how tumor microenvironment alters the metabolism in immune cells leading to their tolerance and tumor progression, with emphasis on mitochondrial metabolism (OXPHOS and FAO).</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"389 ","pages":"67-103"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting KRAS and SHP2 signaling pathways for immunomodulation and improving treatment outcomes in solid tumors.","authors":"Priyanka Sahu, Ankita Mitra, Anirban Ganguly","doi":"10.1016/bs.ircmb.2024.01.005","DOIUrl":"10.1016/bs.ircmb.2024.01.005","url":null,"abstract":"<p><p>Historically, KRAS has been considered 'undruggable' inspite of being one of the most frequently altered oncogenic proteins in solid tumors, primarily due to the paucity of pharmacologically 'druggable' pockets within the mutant isoforms. However, pioneering developments in drug design capable of targeting the mutant KRAS isoforms especially KRAS^G12C-mutant cancers, have opened the doors for emergence of combination therapies comprising of a plethora of inhibitors targeting different signaling pathways. SHP2 signaling pathway, primarily known for activation of intracellular signaling pathways such as KRAS has come up as a potential target for such combination therapies as it emerged to be the signaling protein connecting KRAS and the immune signaling pathways and providing the link for understanding the overlapping regions of RAS/ERK/MAPK signaling cascade. Thus, SHP2 inhibitors having potent tumoricidal activity as well as role in immunomodulation have generated keen interest in researchers to explore its potential as combination therapy in KRAS mutant solid tumors. However, the excitement with these combination therapies need to overcome challenges thrown up by drug resistance and enhanced toxicity. In this review, we will discuss KRAS and SHP2 signaling pathways and their roles in immunomodulation and regulation of tumor microenvironment and also analyze the positive effects and drawbacks of the different combination therapies targeted at these signaling pathways along with their present and future potential to treat solid tumors.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"386 ","pages":"167-222"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The crosstalk between miRNAs and signaling pathways in human cancers: Potential therapeutic implications.","authors":"Ritu Shekhar, Sujata Kumari, Satyam Vergish, Prajna Tripathi","doi":"10.1016/bs.ircmb.2023.12.001","DOIUrl":"10.1016/bs.ircmb.2023.12.001","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are increasingly recognized as central players in the regulation of eukaryotic physiological processes. These small double stranded RNA molecules have emerged as pivotal regulators in the intricate network of cellular signaling pathways, playing significant roles in the development and progression of human cancers. The central theme in miRNA-mediated regulation of signaling pathways involves their ability to target and modulate the expression of pathway components. Aberrant expression of miRNAs can either promote or suppress key signaling events, influencing critical cellular processes such as proliferation, apoptosis, angiogenesis, and metastasis. For example, oncogenic miRNAs often promote cancer progression by targeting tumor suppressors or negative regulators of signaling pathways, thereby enhancing pathway activity. Conversely, tumor-suppressive miRNAs frequently inhibit oncogenic signaling by targeting key components within these pathways. This complex regulatory crosstalk underscores the significance of miRNAs as central players in shaping the signaling landscape of cancer cells. Furthermore, the therapeutic implications of targeting miRNAs in cancer are substantial. miRNAs can be manipulated to restore normal signaling pathway activity, offering a potential avenue for precision medicine. The development of miRNA-based therapeutics, including synthetic miRNA mimics and miRNA inhibitors, has shown promise in preclinical and clinical studies. These strategies aim to either enhance the activity of tumor-suppressive miRNAs or inhibit the function of oncogenic miRNAs, thereby restoring balanced signaling and impeding cancer progression. In conclusion, the crosstalk between miRNAs and signaling pathways in human cancers is a dynamic and influential aspect of cancer biology. Understanding this interplay provides valuable insights into cancer development and progression. Harnessing the therapeutic potential of miRNAs as regulators of signaling pathways opens up exciting opportunities for the development of innovative cancer treatments with the potential to improve patient outcomes. In this chapter, we provide an overview of the crosstalk between miRNAs and signaling pathways in the context of cancer and highlight the potential therapeutic implications of targeting this regulatory interplay.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"386 ","pages":"133-165"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune checkpoints targeting dendritic cells for antibody-based modulation in cancer.","authors":"Xin Lei, Yizhi Wang, Chayenne Broens, Jannie Borst, Yanling Xiao","doi":"10.1016/bs.ircmb.2023.07.006","DOIUrl":"10.1016/bs.ircmb.2023.07.006","url":null,"abstract":"<p><p>Dendritic cells (DC) are professional antigen-presenting cells which link innate to adaptive immunity. DC play a central role in regulating antitumor T-cell responses in both tumor-draining lymph nodes (TDLN) and the tumor microenvironment (TME). They modulate effector T-cell responses via immune checkpoint proteins (ICPs) that can be either stimulatory or inhibitory. Functions of DC are often impaired by the suppressive TME leading to tumor immune escape. Therefore, better understanding of the mechanisms of action of ICPs expressed by (tumor-infiltrating) DC will lead to potential new treatment strategies. Genetic manipulation and high-dimensional analyses have provided insight in the interactions between DC and T-cells in TDLN and the TME upon ICP targeting. In this review, we discuss (tumor-infiltrating) DC lineage cells and tumor tissue specific \"mature\" DC states and their gene signatures in relation to anti-tumor immunity. We also review a number of ICPs expressed by DC regarding their functions in phagocytosis, DC activation, or inhibition and outline position in, or promise for clinical trials in cancer immunotherapy. Collectively, we highlight the critical role of DC and their exact status in the TME for the induction and propagation of T-cell immunity to cancer.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"382 ","pages":"145-179"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory breast cancer: Epidemiologic data and therapeutic results.","authors":"Hamouda Boussen, Yosra Berrazaga, Sherif Kullab, Maroua Manai, Narjess Berrada, Nesrine Mejri, Ismail Siala, Paul H Levine, Massimo Cristofanilli","doi":"10.1016/bs.ircmb.2023.10.003","DOIUrl":"https://doi.org/10.1016/bs.ircmb.2023.10.003","url":null,"abstract":"<p><p>Since the early description more than a century ago, inflammatory breast cancer (IBC) remains an aggressive disease, with a different geographic repartition, with the highest ones incidence reported in the North of Africa (Tunisia, Algeria, Morocco, and Egypt), and the lowest incidence in Western countries (USA, Europe…). In this study, we reviewed the literature using the Surveillance, Epidemiology, and End Results (SEER) database compared to other published series. We observed that in the high incidence areas (North of Africa) when compared to \"classical\" breast cancer, IBC was associated to younger age (less than 50 years) with rapid evolution of signs and symptoms (in less than 3 up to 6 months), and more aggressive clinical and histopathological-molecular parameters, due to the predominance of triple-negative and HER2+ subtypes in around 60% of cases. An epidemiologic trend was observed in both high and low incidence areas since the eighties are towards reduction of IBC prevalence. Concerning Tunisia, in comparison with the historical series of the 1980s, the incidence decreased in part by applying more stringent diagnostic criteria but also probably due to a slight improvement of the socio-economic level (SEL). This trend was also observed in the US, due to the efforts of collaborative IBC groups from MD Anderson Cancer Center (MDACC), Duke and IBC patient advocacy groups. Therapeutic results are slightly better due to the standardization of a multidisciplinary approach and the use of combined primary chemotherapy and/or targeted therapies (especially in HER2 positive patients), followed by mastectomy plus radiotherapy. The 5-year overall and disease-free survival is at more than 60%, related to an IBC mortality decrease observed in the cohorts of patients treated in the last decade.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"384 ","pages":"1-23"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular signaling in glioblastoma: A molecular and clinical perspective.","authors":"Debarati Ghosh, Brett Pryor, Nancy Jiang","doi":"10.1016/bs.ircmb.2024.01.007","DOIUrl":"10.1016/bs.ircmb.2024.01.007","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is the most aggressive brain tumor with an average life expectancy of less than 15 months. Such high patient mortality in GBM is pertaining to the presence of clinical and molecular heterogeneity attributed to various genetic and epigenetic alterations. Such alterations in critically important signaling pathways are attributed to aberrant gene signaling. Different subclasses of GBM show predominance of different genetic alterations and therefore, understanding the complex signaling pathways and their key molecular components in different subclasses of GBM is extremely important with respect to clinical management. In this book chapter, we summarize the common and important signaling pathways that play a significant role in different subclasses and discuss their therapeutic targeting approaches in terms of preclinical studies and clinical trials.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"386 ","pages":"1-47"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemokine receptors in COVID-19 infection.","authors":"Claudia Gutierrez-Chavez, Shalom Aperrigue-Lira, Brando Ortiz-Saavedra, Irmia Paz","doi":"10.1016/bs.ircmb.2024.05.002","DOIUrl":"https://doi.org/10.1016/bs.ircmb.2024.05.002","url":null,"abstract":"<p><p>Chemokine receptors play diverse roles in the immune response against pathogens by recruiting innate and adaptive immune cells to sites of infection. However, their involvement could also be detrimental, causing tissue damage and exacerbating respiratory diseases by triggering histological alterations such as fibrosis and remodeling. This chapter reviews the role of chemokine receptors in the immune defense against SARS-CoV-2 infection. In COVID-19, CXCR3 is expressed mainly in T cells, and its upregulation is related to an increase in SARS-CoV-2-specific antibodies but also to COVID-19 severity. CCR5 is a key player in T-cell recruitment, and its suppression leads to reduced inflammation and viremia levels. Conversely, CXCR6 is implicated in the aberrant migration of memory T cells within airways. On the other hand, increased CCR4+ cells in the blood and decreased CCR4+ cells in lung cells are associated with severe COVID-19. Additionally, CCR2 is associated with an increase in macrophage recruitment to lung tissues. Elevated levels of CXCR1 and CXCR2, which are predominantly expressed in neutrophils, are associated with the severity of the disease, and finally, the expression of CX3CR1 in cytotoxic T lymphocytes affects the retention of these cells in lung tissues, thereby impacting the severity of COVID-19. Despite the efforts of many clinical trials to find effective therapies for COVID-19 using chemokine receptor inhibitors, no conclusive results have been found due to the small number of patients, redundancy, and co-expression of chemokine receptors by immune cells, which explains the difficulty in finding a single therapeutic target or effective treatment.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"388 ","pages":"53-94"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preface.","authors":"Maroua Manai, Hamouda Boussen, Massimo Cristofanilli","doi":"10.1016/S1937-6448(24)00060-1","DOIUrl":"https://doi.org/10.1016/S1937-6448(24)00060-1","url":null,"abstract":"","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"384 ","pages":"xiii-xiv"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drugging the undruggable: Advances in targeting KRAS signaling in solid tumors.","authors":"Prajna Tripathi, Rajni Kumari, Rajiv Pathak","doi":"10.1016/bs.ircmb.2023.11.004","DOIUrl":"10.1016/bs.ircmb.2023.11.004","url":null,"abstract":"<p><p>Cancer remains the leading cause of global mortality, prompting a paradigm shift in its treatment and outcomes with the advent of targeted therapies. Among the most prevalent mutations in RAS-driven cancers, Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations account for approximately 86% of cases worldwide, particularly in lung, pancreatic, and colon cancers, contributing to poor prognosis and reduced overall survival. Despite numerous efforts to understand the biology of KRAS mutants and their pivotal role in cancer development, the lack of well-defined drug-binding pockets has deemed KRAS an \"undruggable\" therapeutic target, presenting significant challenges for researchers and clinicians alike. Through significant biochemical and technological advances, the last decade has witnessed promising breakthroughs in targeted therapies for KRAS-mutated lung, colon, and pancreatic cancers, marking a critical turning point in the field. In this chapter, we provide an overview of the characteristics of KRAS mutations across various solid tumors, highlighting ongoing cutting-edge research on the immune microenvironment, the development of KRAS-driven mice models, and the recent progress in the exploration of specific KRAS mutant-targeted therapeutic approaches. By comprehensive understanding of the intricacies of KRAS signaling in solid tumors and the latest therapeutic developments, this chapter will shed light on the potential for novel therapeutic strategies to combat KRAS-driven tumors and improve patient outcomes.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"385 ","pages":"1-39"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}