{"title":"Radiotherapy of high-grade gliomas: current standards and new concepts, innovations in imaging and radiotherapy, and new therapeutic approaches.","authors":"Frederic Dhermain","doi":"10.5732/cjc.013.10217","DOIUrl":"https://doi.org/10.5732/cjc.013.10217","url":null,"abstract":"<p><p>The current standards in radiotherapy of high-grade gliomas (HGG) are based on anatomic imaging techniques, usually computed tomography (CT) scanning and magnetic resonance imaging (MRI). The guidelines vary depending on whether the HGG is a histological grade 3 anaplastic glioma (AG) or a grade 4 glioblastoma multiforme (GBM). For AG, T2-weighted MRI sequences plus the region of contrast enhancement in T1 are considered for the delineation of the gross tumor volume (GTV), and an isotropic expansion of 15 to 20 mm is recommended for the clinical target volume (CTV). For GBM, the Radiation Therapy Oncology Group favors a two-step technique, with an initial phase (CTV1) including any T2 hyperintensity area (edema) plus a 20 mm margin treated with up to 46 Gy in 23 fractions, followed by a reduction in CTV2 to the contrast enhancement region in T1 with an additional 25 mm margin. The European Organisation of Research and Treatment of Cancer recommends a single-phase technique with a unique GTV, which comprises the T1 contrast enhancement region plus a margin of 20 to 30 mm. A total dose of 60 Gy in 30 fractions is usually delivered for GBM, and a dose of 59.4 Gy in 33 fractions is typically given for AG. As more than 85% of HGGs recur in field, dose-escalation studies have shown that 70 to 75 Gy can be delivered in 6 weeks with relevant toxicities developing in <10% of the patients. However, the only randomized dose-escalation trial, in which the boost dose was guided by conventional MRI, did not show any survival advantage of this treatment over the reference arm. HGGs are amongst the most infiltrative and heterogeneous tumors, and it was hypothesized that the most highly aggressive areas were missed; thus, better visualization of these high-risk regions for radiation boost could decrease the recurrence rate. Innovations in imaging and linear accelerators (LINAC) could help deliver the right doses of radiation to the right subvolumes according to the dose-painting concept. Advanced imaging techniques provide functional information on cellular density (diffusion MRI), angiogenesis (perfusion MRI), metabolic activity and cellular proliferation [positron emission tomography (PET) and magnetic resonance spectroscopy (MRS)]. All of these non-invasive techniques demonstrated good association between the images and histology, with up to 40% of HGGs functionally presenting a high activity within the non-contrast-enhanced areas in T1. New LINAC technologies, such as intensity-modulated and stereotactic radiotherapy, help to deliver a simultaneous integrated boost (SIB) > 60 Gy. Trials delivering a SIB into a biological GTV showed the feasibility of this treatment, but the final results, in terms of clinical benefits for HGG patients, are still pending. Many issues have been identified: the variety of MRI and PET machines (and amino-acid tracers), the heterogeneity of the protocols used for image acquisition and post-treatment, the geometric distortion","PeriodicalId":10034,"journal":{"name":"Chinese Journal of Cancer","volume":"33 1","pages":"16-24"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5732/cjc.013.10217","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31995353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Radiation and concomitant chemotherapy for patients with glioblastoma multiforme.","authors":"Salvador Villà, Carme Balañà, Sílvia Comas","doi":"10.5732/cjc.013.10216","DOIUrl":"10.5732/cjc.013.10216","url":null,"abstract":"<p><p>Postoperative external beam radiotherapy was considered the standard adjuvant treatment for patients with glioblastoma multiforme until the advent of using the drug temozolomide (TMZ) in addition to radiotherapy. High-dose volume should be focal, minimizing whole brain irradiation. Modern imaging, using several magnetic resonance sequences, has improved the planning target volume definition. The total dose delivered should be in the range of 60 Gy in fraction sizes of 1.8-2.0 Gy. Currently, TMZ concomitant and adjuvant to radiotherapy has become the standard of care for glioblastoma multiforme patients. Radiotherapy dose-intensification and radiosensitizer approaches have not improved the outcome. In spite of the lack of high quality evidence, stereotactic radiotherapy can be considered for a selected group of patients. For elderly patients, data suggest that the same survival benefit can be achieved with similar morbidity using a shorter course of radiotherapy (hypofractionation). Elderly patients with tumors that exhibit methylation of the O-6-methylguanine-DNA methyltransferase promoter can benefit from TMZ alone. </p>","PeriodicalId":10034,"journal":{"name":"Chinese Journal of Cancer","volume":"33 1","pages":"25-31"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/92/dc/cjc-33-01-025.PMC3905087.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31944543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"High-grade gliomas: reality and hopes.","authors":"René-Olivier Mirimanoff","doi":"10.5732/cjc.013.10215","DOIUrl":"https://doi.org/10.5732/cjc.013.10215","url":null,"abstract":"<p><p>In this issue of the Chinese Journal of Cancer, European experts review current standards, trends, and future prospects in the difficult domain of high-grade glioma. In all fields covered by the different authors, the progress has been impressive. For example, discoveries at the molecular level have already impacted imaging, surgery, radiotherapy, and systemic therapies, and they are expected to play an increasing role in the management of these cancers. The European Organization for Research and Treatment of Cancer (EORTC) has pioneered new treatment strategies and contributed to new standards. The articles in this issue will cover basic molecular biological principles applicable today, novel surgical approaches, innovations in radiotherapy planning and delivery, evidence-based standards for radiotherapy alone or combined with chemotherapy, current standards and novel approaches for systemic treatments, and the important but often neglected field of health-related quality of life. Despite the advances described in these articles, the overall prognosis of high-grade glioma, especially glioblastoma, remains poor, and more research is needed to address this problem. </p>","PeriodicalId":10034,"journal":{"name":"Chinese Journal of Cancer","volume":"33 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/17/1c/cjc-33-01-001.PMC3905083.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31995349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lifang Hou, Li Yan, Wei Zhang, M. Wang, Shi-Yuan Cheng
{"title":"Four outstanding young Chinese scientists received the 2013 Scholar Award from the US Chinese Anti-Cancer Association and the National Foundation for Cancer Research","authors":"Lifang Hou, Li Yan, Wei Zhang, M. Wang, Shi-Yuan Cheng","doi":"10.5732/cjc.013.10228","DOIUrl":"https://doi.org/10.5732/cjc.013.10228","url":null,"abstract":"To facilitate and strengthen collaborations among cancer researchers and physicians in the United States and China, the US Chinese Anti-Cancer Association (USCACA) and the National Foundation for Cancer Research (NFCR) have established the Scholar Excellence Award for the USCACA-NFCR Scholar Exchange and Fellowship Program in Basic, Translational, and Clinical Studies. Since 2010, 10 young Chinese researchers and physicians have received the award for their outstanding achievements in cancer research accomplished while in the United States, as well as their continuing efforts in eradicating cancer after their return to China. This year, USCACA and NFCR selected 4 young scientists for their excellence in basic or clinical cancer research. Here, we are proud to introduce these 4 winners of the 2013 USCACA-NFCR Scholar Excellence Award: \u0000 \u0000 \u0000 \u0000The ceremony of the fourth USCACA-NFCR Scholar Excellent Award in Guangzhou, China, November 9, 2013. \u0000 \u0000 \u0000 \u0000 \u0000Dr. Yan Sun at the Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin; \u0000 \u0000 \u0000Dr. Weiwei Yang at the Laboratory of Cancer Metabolism, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai; \u0000 \u0000 \u0000Dr. Chenfang Dong at the Department of Pathology, Zhejiang University School of Medicine, Hangzhou; and \u0000 \u0000 \u0000Dr. Haizhong Feng at the Stem Cell Research Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai. \u0000 \u0000 \u0000 \u0000The awards were presented to these 4 awardees at the 3rd International Symposium on Oncology held at Baiyun Conference Center in Guangzhou during November 7-9, 2013. \u0000 \u0000We have invited each of these four awardees to contribute a short essay summarizing their achievements in cancer research. As illustrated in their essays, these outstanding young scholars have received excellent training under their US mentors who are USCACA members. These talented young scientists have not only made impressive discoveries in the mechanisms underlying the causes or progression of human cancers, but also discovered new approaches for improving treatments for cancer patients. Our ultimate goal is to expedite novel cancer drug development by stimulating the translation of laboratory findings into novel cancer therapies, fostering collaborations in clinical cancer drug development, and sharing expert knowledge and medical practices between China and the United States.","PeriodicalId":10034,"journal":{"name":"Chinese Journal of Cancer","volume":"160 1","pages":"631 - 635"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80108228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xi Zhang, Cheng Zhang, Zhongjun Li, Jiangjian Zhong, Leslie P Weiner, Jiang F Zhong
{"title":"Investigating evolutionary perspective of carcinogenesis with single-cell transcriptome analysis.","authors":"Xi Zhang, Cheng Zhang, Zhongjun Li, Jiangjian Zhong, Leslie P Weiner, Jiang F Zhong","doi":"10.5732/cjc.012.10291","DOIUrl":"https://doi.org/10.5732/cjc.012.10291","url":null,"abstract":"<p><p>We developed phase-switch microfluidic devices for molecular profiling of a large number of single cells. Whole genome microarrays and RNA-sequencing are commonly used to determine the expression levels of genes in cell lysates (a physical mix of millions of cells) for inferring gene functions. However, cellular heterogeneity becomes an inherent noise in the measurement of gene expression. The unique molecular characteristics of individual cells, as well as the temporal and quantitative information of gene expression in cells, are lost when averaged among all cells in cell lysates. Our single-cell technology overcomes this limitation and enables us to obtain a large number of single-cell transcriptomes from a population of cells. A collection of single-cell molecular profiles allows us to study carcinogenesis from an evolutionary perspective by treating cancer as a diverse population of cells with abnormal molecular characteristics. Because a cancer cell population contains cells at various stages of development toward drug resistance, clustering similar single-cell molecular profiles could reveal how drug-resistant sub-clones evolve during cancer treatment. Here, we discuss how single-cell transcriptome analysis technology could enable the study of carcinogenesis from an evolutionary perspective and the development of drug-resistance in leukemia. The single-cell transcriptome analysis reported here could have a direct and significant impact on current cancer treatments and future personalized cancer therapies. </p>","PeriodicalId":10034,"journal":{"name":"Chinese Journal of Cancer","volume":"32 12","pages":"636-9"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/38/5a/cjc-32-12-636.PMC3870846.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31456124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Safety of in vitro amplified HLA-haploidentical donor immune cell infusions for childhood malignancies.","authors":"Fei Zhang, Xiao-Fei Sun, Yong-Qiang Li, Zi-Jun Zhen, Hai-Xia Zheng, Jia Zhu, Qi-Jing Wang, Su-Ying Lu, Jia He, Juan Wang, Ke Pan, Rui-Qing Cai, Yan Chen, De-Sheng Weng, Fei-Fei Sun, Jian-Chuan Xia","doi":"10.5732/cjc.012.10298","DOIUrl":"https://doi.org/10.5732/cjc.012.10298","url":null,"abstract":"<p><p>In vitro amplified human leukocyte antigen (HLA)-haploidentical donor immune cell infusion (HDICI) is not commonly used in children. Therefore, our study sought to evaluate its safety for treating childhood malignancies. Between September 2011 and September 2012, 12 patients with childhood malignancies underwent HDICI in Sun Yat-sen University Cancer Center. The median patient age was 5.1 years (range, 1.7-8.4 years). Of the 12 patients, 9 had high-risk neuroblastoma (NB) [7 showed complete response (CR), 1 showed partial response (PR), and 1 had progressive disease (PD) after multi-modal therapies], and 3 had Epstein-Barr virus (EBV)-positive lymphoproliferative disease (EBV-LPD). The 12 patients underwent a total of 92 HDICIs at a mean dose of 1.6×10(8) immune cells/kg body weight: 71 infusions with natural killer (NK) cells, 8 with cytokine-induced killer (CIK) cells, and 13 with cascade primed immune cells (CAPRIs); 83 infusions with immune cells from the mothers, whereas 9 with cells from the fathers. Twenty cases (21.7%) of fever, including 6 cases (6.5%) accompanied with chills and 1 (1.1%) with febrile convulsion, occurred during infusions and were alleviated after symptomatic treatments. Five cases (5.4%) of mild emotion changes were reported. No other adverse events occurred during and after the completion of HDIDIs. Neither acute nor chronic graft versus host disease (GVHD) was observed following HDICIs. After a median of 5.0 months (range, 1.0-11.5 months) of follow-up, the 2 NB patients with PR and PD developed PD during HDICIs. Of the other 7 NB patients in CR, 2 relapsed in the sixth month of HDICIs, and 5 maintained CR with disease-free survival (DFS) ranging from 4.5 to 11.5 months (median, 7.2 months). One EBV-LPD patient achieved PR, whereas 2 had stable disease (SD). Our results show that HDICI is a safe immunotherapy for childhood malignancies, thus warranting further studies. </p>","PeriodicalId":10034,"journal":{"name":"Chinese Journal of Cancer","volume":"32 12","pages":"661-6"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c3/e0/cjc-32-12-661.PMC3870850.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31456125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jia Zhu, Yu Zhang, Zi-Jun Zhen, Yan Chen, Juan Wang, Rui-Qing Cai, Xiao-Fei Sun
{"title":"Lymphoma and cerebral vasculitis in association with X-linked lymphoproliferative disease.","authors":"Jia Zhu, Yu Zhang, Zi-Jun Zhen, Yan Chen, Juan Wang, Rui-Qing Cai, Xiao-Fei Sun","doi":"10.5732/cjc.012.10238","DOIUrl":"https://doi.org/10.5732/cjc.012.10238","url":null,"abstract":"<p><p>Lymphoma is seen in up to 30% of patients with X-linked lymphoproliferative disease (XLP), but cerebral vasculitis related with XLP after cure of Burkitt lymphoma is rarely reported. We describe a case of a 5-year-old boy with XLP who developed cerebral vasculitis two years after cure of Burkitt lymphoma. He had Burkitt lymphoma at the age of 3 years and received chemotherapy (non-Hodgkin's lymphoma-Berlin-Frankfurt-Milan-90 protocol plus rituximab), which induced complete remission over the following two years. At the age of 5 years, the patient first developed headache, vomiting, and then intellectual and motorial retrogression. His condition was not improved after anti-infection, dehydration, or dexamethasone therapy. No tumor cells were found in his cerebrospinal fluid. Magnetic resonance imaging showed multiple non-homogeneous, hypodense masses along the bilateral cortex. Pathology after biopsy revealed hyperplasia of neurogliocytes and vessels, accompanied by lymphocyte infiltration but no tumor cell infiltration. Despite aggressive treatment, his cognition and motor functions deteriorated in response to progressive cerebral changes. The patient is presently in a vegetative state. We present this case to inform clinicians of association between lymphoma and immunodeficiency and explore an optimal treatment for lymphoma patients with compromised immune system. </p>","PeriodicalId":10034,"journal":{"name":"Chinese Journal of Cancer","volume":"32 12","pages":"673-7"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7d/86/cjc-32-12-673.PMC3870852.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31547621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
癌症Pub Date : 2013-12-01Epub Date: 2013-07-02DOI: 10.5732/cjc.012.10283
Yu-Shan Chen, Xiao-Bo Qiu
{"title":"Ubiquitin at the crossroad of cell death and survival.","authors":"Yu-Shan Chen, Xiao-Bo Qiu","doi":"10.5732/cjc.012.10283","DOIUrl":"10.5732/cjc.012.10283","url":null,"abstract":"<p><p>Ubiquitination is crucial for cellular processes, such as protein degradation, apoptosis, autophagy, and cell cycle progression. Dysregulation of the ubiquitination network accounts for the development of numerous diseases, including cancer. Thus, targeting ubiquitination is a promising strategy in cancer therapy. Both apoptosis and autophagy are involved in tumorigenesis and response to cancer therapy. Although both are categorized as types of cell death, autophagy is generally considered to have protective functions, including protecting cells from apoptosis under certain cellular stress conditions. This review highlights recent advances in understanding the regulation of apoptosis and autophagy by ubiquitination. </p>","PeriodicalId":10034,"journal":{"name":"癌症","volume":"32 12","pages":"640-7"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7e/f6/cjc-32-12-640.PMC3870847.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31547024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lin-Ru Zhao, Wei Tian, Guo-Wen Wang, Ke-Xin Chen, Ji-Long Yang
{"title":"The prognostic role of PRUNE2 in leiomyosarcoma.","authors":"Lin-Ru Zhao, Wei Tian, Guo-Wen Wang, Ke-Xin Chen, Ji-Long Yang","doi":"10.5732/cjc.013.10069","DOIUrl":"https://doi.org/10.5732/cjc.013.10069","url":null,"abstract":"<p><p>PRUNE2 plays an important role in regulating tumor cell differentiation, proliferation, and invasiveness in neuroblastoma. Our previous study revealed that PRUNE2/OBSCN two-gene relative expression classifer accurately differentiated leiomyosarcoma from gastrointestinal stromal tumor. However, the association between PRUNE2 expression and prognosis in leiomyosarcoma is poorly understood. In this study, we evaluated the prognostic role of PRUNE2 in leiomyosarcoma. PRUNE2 expression was detected using immunohistochemistry in 30 formalin-fixed, paraffin-embedded leiomyosarcoma tissues from MD Anderson Cancer Center, and high expression was detected in 36.7% (11/30) of the samples. To validate these results, immunohistochemistry was performed on another cohort of 45 formalin-fixed, paraffin-embedded leiomyosarcoma tissues from Tianjin Medical University Cancer Institute & Hospital, and high PRUNE2 protein expression was detected in 37.8% (17/45) of the samples. Moreover, elevated PRUNE2 expression was significantly associated with tumor size (P = 0.03) and hemorrhage/cyst (P = 0.014), and was an independent favorable prognostic factor for overall survival in leiomyosarcoma patients from Tianjin Medical University Cancer Institute & Hospital (P < 0.05). These data suggest that increased PRUNE2 protein expression may serve as a favorable prognostic marker in human leiomyosarcoma. </p>","PeriodicalId":10034,"journal":{"name":"Chinese Journal of Cancer","volume":"32 12","pages":"648-52"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5732/cjc.013.10069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31478085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lian-Jie Mo, Hong-Xing Ye, Ying Mao, Yu Yao, Jian-Min Zhang
{"title":"B7-H4 expression is elevated in human U251 glioma stem-like cells and is inducible in monocytes cultured with U251 stem-like cell conditioned medium.","authors":"Lian-Jie Mo, Hong-Xing Ye, Ying Mao, Yu Yao, Jian-Min Zhang","doi":"10.5732/cjc.012.10228","DOIUrl":"https://doi.org/10.5732/cjc.012.10228","url":null,"abstract":"<p><p>Previous studies indicated that B7-H4, the youngest B7 family, negatively regulates T cell-mediated immunity and is significantly overexpressed in many human tumors. Tumor stem cells are purported to play a role in tumor renewal and resistance to radiation and chemotherapy. However, the link between B7-H4 and tumor stem cells is unclear. In this study, we investigated B7-H4 expression in the medium of human glioma U251 cell cultures. Immunofluorescence results showed that U251 cells cultured in serum-free medium (supplemented with 2% B27, 20 ng/mL epidermal growth factor, 20 ng/mL basic fibroblast growth factor) maintained stem-like cell characteristics, including expression of stem cell marker CD133 and the neural progenitor cell markers nestin and SOX2. In contrast, U251 cells cultured in serum-containing medium highly expressed differentiation marker glial fibrillary acidic protein. Flow cytometry analysis showed serum-free medium-cultured U251 cells expressed higher intracellular B7-H4 than serum-containing medium-cultured U251 cells (24%-35% vs. 8%-11%, P < 0.001). Immunofluorescence in purified monocytes from normal human peripheral blood mononuclear cells revealed moderate expression of B7-H4 after stimulation with conditioned medium from U251 cells cultured in serum-containing medium. Moreover, conditioned medium from U251 stem-like cells had a significant stimulation effect on B7-H4 expression compared with serum-containing conditioned medium (P < 0.01). Negative costimulatory molecule B7-H4 was preferentially expressed in U251 stem-like cells, and conditioned medium from these cells more effectively induced monocytes to express B7-H4 than conditioned medium from U251 cells cultured in the presence of serum. Our results show that U251 stem-like cells may play a more crucial role in tumor immunoloregulation with high expression of B7-H4. </p>","PeriodicalId":10034,"journal":{"name":"Chinese Journal of Cancer","volume":"32 12","pages":"653-60"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a6/05/cjc-32-12-653.PMC3870849.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31168633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}