Zhaoyun Liu , Hao Wang , Hui Liu , Kai Ding , Hongli Shen , Xianghong Zhao , Rong Fu
{"title":"Targeting NKG2D/NKG2DL axis in multiple myeloma therapy","authors":"Zhaoyun Liu , Hao Wang , Hui Liu , Kai Ding , Hongli Shen , Xianghong Zhao , Rong Fu","doi":"10.1016/j.cytogfr.2024.02.001","DOIUrl":"10.1016/j.cytogfr.2024.02.001","url":null,"abstract":"<div><p>Immune effector cells in patients with multiple myeloma (MM) are at the forefront of many immunotherapy treatments, and several methods have been developed to fully utilise the antitumour potential of immune cells. T and NK cell-derived immune lymphocytes both expressed activating NK receptor group 2 member D(NKG2D). This receptor can identify eight distinct NKG2D ligands (NKG2DL), including major histocompatibility complex class I (MHC) chain-related protein A and B (MICA and MICB). Their binding to NKG2D triggers effector roles in T and NK cells. NKG2DL is polymorphic in MM cells. The decreased expression of NKG2DL on the cell surface is explained by multiple mechanisms of tumour immune escape. In this review, we discuss the mechanisms by which the NKG2D/NKG2DL axis regulates immune effector cells and strategies for promoting NKG2DL expression and inhibiting its release in multiple myeloma and propose therapeutic strategies that increase the expression of NKG2DL in MM cells while enhancing the activation and killing function of NK cells.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"76 ","pages":"Pages 1-11"},"PeriodicalIF":13.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S135961012400011X/pdfft?md5=a54857b555d6f936945598982ff17d91&pid=1-s2.0-S135961012400011X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139878342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dimitra P. Anastasiadou , Agathe Quesnel , Camille L. Duran , Panagiota S. Filippou , George S. Karagiannis
{"title":"An emerging paradigm of CXCL12 involvement in the metastatic cascade","authors":"Dimitra P. Anastasiadou , Agathe Quesnel , Camille L. Duran , Panagiota S. Filippou , George S. Karagiannis","doi":"10.1016/j.cytogfr.2023.10.003","DOIUrl":"10.1016/j.cytogfr.2023.10.003","url":null,"abstract":"<div><p>The chemokine CXCL12, also known as stromal cell-derived factor 1 (SDF1), has emerged as a pivotal regulator in the intricate molecular networks driving cancer progression. As an influential factor in the tumor microenvironment, CXCL12 plays a multifaceted role that spans beyond its traditional role as a chemokine inducing invasion and metastasis. Indeed, CXCL12 has been assigned functions related to epithelial-to-mesenchymal transition, cancer cell stemness, angiogenesis, and immunosuppression, all of which are currently viewed as specialized biological programs contributing to the “metastatic cascade” among other cancer hallmarks. Its interaction with its cognate receptor, CXCR4, initiates a cascade of events that not only shapes the metastatic potential of tumor cells but also defines the niches within the secondary organs that support metastatic colonization. Given the profound implications of CXCL12 in the metastatic cascade, understanding its mechanistic underpinnings is of paramount importance for the targeted elimination of rate-limiting steps in the metastatic process. This review aims to provide a comprehensive overview of the current knowledge surrounding the role of CXCL12 in cancer metastasis, especially its molecular interactions rationalizing its potential as a therapeutic target.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"75 ","pages":"Pages 12-30"},"PeriodicalIF":13.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359610123000771/pdfft?md5=a9c26f438d02bad3bc02b25c430593f8&pid=1-s2.0-S1359610123000771-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72208738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bioengineering strategies to enhance the interleukin-18 bioactivity in the modern toolbox of cancer immunotherapy","authors":"Mojtaba Taheri , Hossein Abdul Tehrani , Fatemeh Daliri , Mona Alibolandi , Masoud Soleimani , Alireza Shoari , Ehsan Arefian , Mohammad Ramezani","doi":"10.1016/j.cytogfr.2023.09.005","DOIUrl":"10.1016/j.cytogfr.2023.09.005","url":null,"abstract":"<div><p>Cytokines are the first modern immunotherapeutic agents used for activation immunotherapy. Interleukin-18 (IL-18) has emerged as a potent anticancer immunostimulatory cytokine over the past three decades. IL-18, structurally is a stable protein with very low toxicity at biological doses. IL-18 promotes the process of antigen presentation and also enhances innate and acquired immune responses. It can induce the production of proinflammatory cytokines and increase tumor infiltration of effector immune cells to revert the immunosuppressive milieu of tumors. Furthermore, IL-18 can reduce tumorigenesis, suppress tumor angiogenesis, and induce tumor cell apoptosis. These characteristics present IL-18 as a promising option for cancer immunotherapy. Although several preclinical studies have reported the immunotherapeutic potential of IL-18, clinical trials using it as a monotherapy agent have reported disappointing results. These results may be due to some biological characteristics of IL-18. Several bioengineering approaches have been successfully used to correct its defects as a bioadjuvant. Currently, the challenge with this anticancer immunotherapeutic agent is mainly how to use its capabilities in a rational combinatorial therapy for clinical applications. The present study discussed the strengths and weaknesses of IL-18 as an immunotherapeutic agent, followed by comprehensive review of various promising bioengineering approaches that have been used to overcome its disadvantages. Finally, this study highlights the promising application of IL-18 in modern combinatorial therapies, such as chemotherapy, immune checkpoint blockade therapy, cell-based immunotherapy and cancer vaccines to guide future studies, circumventing the barriers to administration of IL-18 for clinical applications, and bring it to fruition as a potent immunotherapy agent in cancer treatment.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"75 ","pages":"Pages 65-80"},"PeriodicalIF":13.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41182204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting interleukin-17 in radiation-induced toxicity and cancer progression","authors":"Piyush Baindara","doi":"10.1016/j.cytogfr.2024.01.001","DOIUrl":"10.1016/j.cytogfr.2024.01.001","url":null,"abstract":"<div><p>Recent strategies to combine chemoradiation with immunotherapy to treat locally advanced lung cancer have improved five-year survival outcomes. However, collateral toxicity to healthy lungs, esophagus, cardiac, and vascular tissue continues to limit the effectiveness of curative-intent thoracic radiation (tRT). It is necessary to gain a deeper comprehension of the fundamental mechanisms underlying inflammation-mediated radiation-induced damage to normal cells. Several cells have been linked in published studies to the release of cytokines and chemokines after radiation therapy. Several inflammatory mediators, such as IL-1, IL-6, TNF-α, and TGF-β, also cause the production of Interleukin-17 (IL-17), a cytokine that is essential for maintaining immunological homeostasis and plays a role in the toxicity caused by radiation therapy. However, currently, the role of IL-17 in RT-induced toxicity in conjunction with cancer progression remains poorly understood. This review provides an overview of the most recent data from the literature implicating IL-17 in radiation-mediated tissue injuries and the efficacy of tRT in lung cancer, as well as its potential as a therapeutic target for interventions to reduce the side effects of tRT with curative intent and to boost an anti-tumor immune response to improve treatment outcomes. IL-17 may also act as a biomarker for predicting the effectiveness of a given treatment as well as the toxicity caused by tRT.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"75 ","pages":"Pages 31-39"},"PeriodicalIF":13.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139458439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Demi Wekking , Vera Piera Leoni , Matteo Lambertini , Mariele Dessì , Andrea Pretta , Andrea Cadoni , Luigi Atzori , Mario Scartozzi , Cinzia Solinas
{"title":"CDK4/6 inhibition in hormone receptor-positive/HER2-negative breast cancer: Biological and clinical aspects","authors":"Demi Wekking , Vera Piera Leoni , Matteo Lambertini , Mariele Dessì , Andrea Pretta , Andrea Cadoni , Luigi Atzori , Mario Scartozzi , Cinzia Solinas","doi":"10.1016/j.cytogfr.2023.10.001","DOIUrl":"10.1016/j.cytogfr.2023.10.001","url":null,"abstract":"<div><p>A dysregulated cell division, one of the key hallmarks of cancer, results in uncontrolled cellular proliferation. This aberrant process, mediated by a dysregulated cell-cycle machinery and overactivation of cyclin-dependent kinase (CDK) 4 and 6, can potentially promote tumorigenesis. The clinical application of CDK 4/6 inhibitors, developed to inhibit cell-cycle progression, in the treatment regimens of breast cancer (BC) patients is expanding. Currently, three agents, ribociclib, palbociclib, and abemaciclib, are approved for treating patients with hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic BC. In addition, abemaciclib is FDA and EMA-approved for patients with hormone receptor-positive HER2-negative, node-positive, early BC at high risk of recurrence. Emerging data suggest potential anti-tumor effects beyond cell cycle arrest, providing novel insights into the agent’s mechanisms of action. As a result, a broader application of the CDK4/6 inhibitors in patients with cancer is achieved, contributing to enhanced optimized treatment in the adjuvant and neoadjuvant settings. Herein, the immunomodulatory activities of CDK4/6 inhibitors, their impact on the cell’s metabolic state, and the effect on the decision of the cell to undergo quiescence or senescence are discussed. Moreover, this review provides an update on clinical trial outcomes and the differences in the underlying mechanisms between the distinct CDK4/6 inhibitors.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"75 ","pages":"Pages 57-64"},"PeriodicalIF":13.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359610123000758/pdfft?md5=82544afa8e0d73ab216a2708d880b682&pid=1-s2.0-S1359610123000758-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41194408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic implications of the interplay between interferons and ER in breast cancer","authors":"Nataša Todorović-Raković , Jonathan R. Whitfield","doi":"10.1016/j.cytogfr.2024.01.002","DOIUrl":"10.1016/j.cytogfr.2024.01.002","url":null,"abstract":"<div><p>The involvement of interferons (IFNs) in various diseases, including breast cancer, has sparked controversy due to their diverse roles in immunity and significant impact on pathological mechanisms. In the context of breast cancer, the heightened expression of endogenous IFNs has been linked to anti-tumor activity and a favorable prognosis for patients. Within the tumor tissue and microenvironment, IFNs initiate a cascade of molecular events involving numerous factors, which can lead to either cooperative or repressive interactions. The specific functions of IFNs in breast cancer vary depending on the two major disease phenotypes: hormone dependent (or responsive) and hormone independent (or unresponsive) breast cancer. Hormone dependence is determined by the presence of estrogen receptors (ERs). The interplay between the IFN and ER signaling pathways, and the involvement of intermediate factors such as NFκB, are areas that have been somewhat under-researched, but that hold potential importance for the understanding and treatment of breast cancer. This review aims to provide a comprehensive overview of the actions of IFNs in breast cancer, particularly in relation to the different breast cancer phenotypes and the significance of comprehending the underlying mechanisms. Furthermore, the use of IFN-based therapies in cancer treatment remains a topic of debate and has not yet gained widespread acceptance. However, emerging discoveries may redirect focus towards the potential of IFN-based therapies.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"75 ","pages":"Pages 119-125"},"PeriodicalIF":13.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139103636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mojtaba Taheri , Hossein Abdul Tehrani , Sadegh Dehghani , Alireza Rajabzadeh , Mona Alibolandi , Nina Zamani , Ehsan Arefian , Mohammad Ramezani
{"title":"Signaling crosstalk between mesenchymal stem cells and tumor cells: Implications for tumor suppression or progression","authors":"Mojtaba Taheri , Hossein Abdul Tehrani , Sadegh Dehghani , Alireza Rajabzadeh , Mona Alibolandi , Nina Zamani , Ehsan Arefian , Mohammad Ramezani","doi":"10.1016/j.cytogfr.2024.01.004","DOIUrl":"10.1016/j.cytogfr.2024.01.004","url":null,"abstract":"<div><p>Mesenchymal stem cells (MSCs) have been extensively used in various therapeutic applications over the last two decades, particularly in regenerative medicine and cancer treatment. MSCs have the ability to differentiate into mesodermal and non-mesodermal lineages, which makes them a popular choice in tissue engineering and regenerative medicine. Studies have shown that MSCs have inherent tumor-suppressive properties and can affect the behavior of multiple cells contributing to tumor development. Additionally, MSCs possess a tumor tropism property and have a hypoimmune nature. The intrinsic features of MSCs along with their potential to undergo genetic manipulation and be loaded with various anticancer therapeutics have motivated researchers to use them in different cancer therapy approaches without considering their complex dynamic biological aspects. However, despite their desirable features, several reports have shown that MSCs possess tumor-supportive properties. These contradictory results signify the sophisticated nature of MSCs and warn against the potential therapeutic applications of MSCs. Therefore, researchers should meticulously consider the biological properties of MSCs in preclinical and clinical studies to avoid any undesirable outcomes. This manuscript reviews preclinical studies on MSCs and cancer from the last two decades, discusses how MSC properties affect tumor progression and explains the mechanisms behind tumor suppressive and supportive functions. It also highlights critical cellular pathways that could be targeted in future studies to improve the safety and effectiveness of MSC-based therapies for cancer treatment. The insights obtained from this study will pave the way for further clinical research on MSCs and development of more effective cancer treatments.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"76 ","pages":"Pages 30-47"},"PeriodicalIF":13.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chen Sun , Qi Pan , Mingyang Du , Jiahe Zheng , Ming Bai , Wei Sun
{"title":"Decoding the roles of heat shock proteins in liver cancer","authors":"Chen Sun , Qi Pan , Mingyang Du , Jiahe Zheng , Ming Bai , Wei Sun","doi":"10.1016/j.cytogfr.2023.12.003","DOIUrl":"10.1016/j.cytogfr.2023.12.003","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) is one of the most common gastrointestinal malignancies, characterized by insidious onset and high propensity for metastasis and recurrence. Apart from surgical resection, there are no effective curative methods for HCC in recent years, due to resistance to radiotherapy and chemotherapy. Heat shock proteins (HSP) play a crucial role in maintaining cellular homeostasis and normal organism development as molecular chaperones for intracellular proteins. Both basic research and clinical data have shown that HSPs are crucial participants in the HCC microenvironment, as well as the occurrence, development, metastasis, and resistance to radiotherapy and chemotherapy in various malignancies, particularly liver cancer. This review aims to discuss the molecular mechanisms and potential clinical value of HSPs in HCC, which may provide new insights for HSP-based therapeutic interventions for HCC.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"75 ","pages":"Pages 81-92"},"PeriodicalIF":13.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139053320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Demi Wekking , Thilini H. Senevirathne , Josie L. Pearce , Marco Aiello , Mario Scartozzi , Matteo Lambertini , Pushpamali De Silva , Cinzia Solinas
{"title":"The impact of COVID-19 on cancer patients","authors":"Demi Wekking , Thilini H. Senevirathne , Josie L. Pearce , Marco Aiello , Mario Scartozzi , Matteo Lambertini , Pushpamali De Silva , Cinzia Solinas","doi":"10.1016/j.cytogfr.2023.11.004","DOIUrl":"10.1016/j.cytogfr.2023.11.004","url":null,"abstract":"<div><p>The COVID-19 pandemic poses a significant challenge for individuals with compromised immune systems, such as patients with cancer, as they face a heightened susceptibility to severe infections compared to the general population. Such severe infections substantially increase the risk of morbidity and mortality among these patients. Notable risk factors for mortality include advanced age (> 70 years), current or past smoking history, advanced disease stage, the use of cytotoxic chemotherapy, and an Eastern Cooperative Oncology Group (ECOG) score of 2 or higher. Multiple types of vaccines have been developed and implemented, demonstrating remarkable efficacy in preventing infections. However, there have been observable reductions in their ability to elicit an immune response, particularly among individuals with hematological malignancies. The situation becomes more challenging due to the emergence of viral variants of concern (VOCs). Despite the increase in neutralizing antibody levels after vaccination, they remain lower in response to these evolving variants. The need for booster vaccinations has become apparent, particularly for this vulnerable population, due to the suboptimal immune response and waning of immunity post-vaccination. Examining and comprehending how the immune system reacts to various vaccination regimens for SARS-CoV-2 and its VOCs in cancer patients is crucial for designing clinical and public health strategies. This review aims to provide an updated overview of the effectiveness of COVID-19 vaccines in cancer patients, including those undergoing treatments such as hematopoietic stem cell transplantation (HCT) or chimeric antigen receptor (CAR) T cell therapy, by exploring the extent of both humoral and cellular immune responses to COVID-19 vaccination. Furthermore, it outlines risk factors and potential biomarkers that are associated with severe SARS-CoV-2 infection and vaccine responses, and offers suggestions for improving SARS-CoV-2 protection in cancer patients.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"75 ","pages":"Pages 110-118"},"PeriodicalIF":13.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138526218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Harnessing the potential of CD40 agonism in cancer therapy","authors":"Yang Zhou , Ann Richmond , Chi Yan","doi":"10.1016/j.cytogfr.2023.11.002","DOIUrl":"10.1016/j.cytogfr.2023.11.002","url":null,"abstract":"<div><p>CD40 is a member of the tumor necrosis factor (TNF) receptor superfamily of receptors expressed on a variety of cell types. The CD40–CD40L interaction gives rise to many immune events, including the licensing of dendritic cells to activate CD8<sup>+</sup> effector T cells, as well as the facilitation of B cell activation, proliferation, and differentiation. In malignant cells, the expression of CD40 varies among cancer types, mediating cellular proliferation, apoptosis, survival and the secretion of cytokines and chemokines. Agonistic human anti-CD40 antibodies are emerging as an option for cancer treatment, and early-phase clinical trials explored its monotherapy or combination with radiotherapy, chemotherapy, immune checkpoint blockade, and other immunomodulatory approaches. In this review, we present the current understanding of the mechanism of action for CD40, along with results from the clinical development of agonistic human CD40 antibodies in cancer treatment (selicrelumab, CDX-1140, APX005M, mitazalimab, 2141-V11, SEA-CD40, LVGN7409, and bispecific antibodies). This review also examines the safety profile of CD40 agonists in both preclinical and clinical settings, highlighting optimized dosage levels, potential adverse effects, and strategies to mitigate them.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"75 ","pages":"Pages 40-56"},"PeriodicalIF":13.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359610123000795/pdfft?md5=e2336dcb3765155f17297d0ef320fa9c&pid=1-s2.0-S1359610123000795-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138526205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}