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Cyclooxygenase-2 contributes to mutant epidermal growth factor receptor lung tumorigenesis by promoting an immunosuppressive environment 环氧化酶-2通过促进免疫抑制环境参与突变型表皮生长因子受体肺肿瘤的发生
Pub Date : 2020-04-01 DOI: 10.4103/ctm.ctm_7_20
Mun‐kyoung Kim, A. Iravani, M. Topham
Targeted therapies reduce growth of mutant epidermal growth factor receptor (EGFR) non-small cell lung cancers, but most patients develop drug resistance. This has led to efforts to develop additional therapies. We found abundant activation of the cyclooxygenase-2 (COX-2) axis in a mouse model of mutant EGFR lung cancer. Inhibiting COX-2 in the mice significantly reduced lung tumor growth, and dual targeting of COX-2 and EGFR had more pronounced effects. Collectively, our data and published data have led us to hypothesize that COX-2 contributes to mutant EGFR lung tumorigenesis, in part, by promoting an immunosuppressive environment that facilitates tumor progression.
靶向治疗可减少突变型表皮生长因子受体(EGFR)非小细胞肺癌的生长,但大多数患者会产生耐药性。这促使人们努力开发其他治疗方法。我们在突变型EGFR肺癌小鼠模型中发现环氧化酶-2 (COX-2)轴大量活化。抑制小鼠COX-2可显著降低肺肿瘤生长,且COX-2和EGFR双靶向作用更为显著。总的来说,我们的数据和已发表的数据使我们假设COX-2通过促进促进肿瘤进展的免疫抑制环境,在一定程度上促进了EGFR突变肺肿瘤的发生。
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引用次数: 0
Characteristics and outcome of patients with pheochromocytoma 嗜铬细胞瘤患者的特点及预后
Pub Date : 2020-04-01 DOI: 10.4103/ctm.ctm_5_20
Nadeema Rafiq, Tauseef Nabi, S. Dar, Shahnawaz Rasool
Aim: Pheochromocytomas are rare neuroendocrine tumors with variable clinical presentation, including hypertension, and usually arise from the adrenal medulla. The aim of the current study was to evaluate the clinical characteristics and therapeutic outcomes of patients with pheochromocytoma. Methods: This was a single-center retrospective observational study designed to study the clinical, laboratory, radiological, and surgical outcomes of 14 patients diagnosed with pheochromocytoma. Results: Of 14 patients, 10 were females and 4 males, with a mean age of 38 ± 16 years at diagnosis. Headache (96.6%), palpitation (64.3%), abdominal pain (64.3%), and sweating (57.1%) were the most common presenting symptoms, while triad was present in 42.8%. Hypertension was the predominant clinical finding (92.8%) followed by orthostasis in 35.7% and hyperglycemia in 35.7%. Most pheochromocytomas were sporadic (85.7%), adrenal gland tumors (78.6%), and benign (92.8%); two were familial (each due to neurofibromatosis type and von Hippel–Lindau). Metanephrine and nor-metanephrine secretory pattern was seen in 58.3% of the patients, while metanephrine only was seen in 41.7% of the patients. More than half of the tumors (54.5%) were located on the left side, with 36.4% on the right side, and one patient had bilateral presentation of a tumor. Postsurgical remission of hypertension was found in 35.7% of the hypertensive patients. Biochemical cure was obtained in 85.7% and surgical cure rate in 78.5% of the patients. Patient survival ranged from 2 months to 9 years. Conclusions: The present study confirms that the clinical presentation of pheochromocytoma is variable and nonspecific. Although pheochromocytoma is a rare tumor, proper evaluation, preoperative preparation, and complete surgical excision are important for its management.
目的:嗜铬细胞瘤是一种罕见的神经内分泌肿瘤,临床表现多变,包括高血压,通常起源于肾上腺髓质。本研究的目的是评估嗜铬细胞瘤患者的临床特征和治疗结果。方法:这是一项单中心回顾性观察性研究,旨在研究14例诊断为嗜铬细胞瘤的患者的临床、实验室、放射学和手术结果。结果:14例患者中,女性10例,男性4例,确诊时平均年龄38±16岁。头痛(96.6%)、心悸(64.3%)、腹痛(64.3%)和出汗(57.1%)是最常见的症状,而三联征(42.8%)存在。高血压是主要的临床表现(92.8%),其次是站立不稳(35.7%)和高血糖(35.7%)。嗜铬细胞瘤多为散发性(85.7%)、肾上腺肿瘤(78.6%)和良性(92.8%);2例为家族性(均为神经纤维瘤型和von Hippel-Lindau)。58.3%的患者有肾上腺素和去肾上腺素分泌模式,41.7%的患者有肾上腺素分泌模式。超过一半的肿瘤(54.5%)位于左侧,36.4%位于右侧,1例患者双侧表现为肿瘤。35.7%的高血压患者术后高血压缓解。生化治愈率为85.7%,手术治愈率为78.5%。患者生存时间从2个月到9年不等。结论:本研究证实嗜铬细胞瘤的临床表现是可变的和非特异性的。虽然嗜铬细胞瘤是一种罕见的肿瘤,但正确的评估、术前准备和完全的手术切除对其治疗至关重要。
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引用次数: 0
Comparison of histopathological grading and staging of breast cancer with p53-positive and transforming growth factor-beta receptor 2-negative immunohistochemical marker expression cases p53阳性和转化生长因子-受体2阴性免疫组化标志物表达乳腺癌组织病理学分级和分期的比较
Pub Date : 2020-04-01 DOI: 10.4103/ctm.ctm_4_20
P. Mandal, Anindya Adhikari, Subir Biswas, A. Giri, Arnab Gupta, A. Bhattacharya
Background: Immunohistochemical analysis of biomarkers is essential to understand the nature of breast cancer (BC) and predict its prognosis. A noticeable correlation is found between p53-positive and transforming growth factor-beta receptor 2 (TGFBR-2)-negative immunomarker expression in BC cases. Materials and Methods: Between January 2018 and December 2018, immunohistochemical analysis of p53 and TGFBR-2 biomarkers was done in biopsy samples from 50 BC cases (49 females and 1 male). Results: p53 expression was positive in 24 (48%) and negative in 26 (52%) cases. Similarly, TGFBR-2 expression was positive in 26 (52%) and negative in 24 (48%) cases. Among p53-positive cases, 8 (16%), 15 (30%), and 1 (2%) cases correlated with histologic Grade 1, Grade 2, and Grade 3 cases, respectively. Among TGFBR-2-negative cases, 9 (18%), 13 (26%), and 2 (4%) cases correlated with histologic Grade 1, Grade 2, and Grade 3 cases, respectively. Further, Grade 2 cancer cases were found mostly associated with both p53-positive and TGFBR-2-negative cases. Maximum p53positive cases was in T2N1Mx stage while maximum TGFBR-2-negative cases were in T2N0Mx stage. Conclusion: p53-positive and TGFBR-2-negative cases are mostly associated with Grade 2 and T2 stage of BC.
背景:生物标志物的免疫组织化学分析对于了解乳腺癌(BC)的性质和预测其预后至关重要。在BC病例中,p53阳性和转化生长因子- β受体2 (TGFBR-2)阴性的免疫标志物表达之间存在显著的相关性。材料和方法:2018年1月至2018年12月,对50例BC患者(49例女性和1例男性)的活检样本进行了p53和TGFBR-2生物标志物的免疫组织化学分析。结果:p53阳性24例(48%),阴性26例(52%)。同样,TGFBR-2阳性26例(52%),阴性24例(48%)。在p53阳性的病例中,分别有8例(16%)、15例(30%)和1例(2%)与组织学1级、2级和3级相关。在tgfbr -2阴性病例中,分别有9例(18%)、13例(26%)和2例(4%)与组织学1级、2级和3级相关。此外,发现2级癌症病例大多与p53阳性和tgfbr -2阴性病例相关。p53阳性以T2N1Mx期最多,tgfbr -2阴性以T2N0Mx期最多。结论:p53阳性和tgfbr -2阴性病例多与2级和T2期相关。
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引用次数: 0
Chemical compositions and antiproliferative effect of essential oil of asafoetida on MCF7 human breast cancer cell line and female wistar rats 牛油果挥发油对MCF7人乳腺癌细胞系及雌性wistar大鼠的化学成分及抗增殖作用
Pub Date : 2020-04-01 DOI: 10.4103/ctm.ctm_36_19
S. Bagheri, Davood Javidmehr, M. Ghaffari, Ehsan Ghoderti-Shatori
Background: Breast cancer is a leading cause of cancer-associated mortality in women, and the incidence is on the rise worldwide. Asafoetida has shown a good anti-cancer activity against breast cancer in both in vivo and in vitro studies. Materials and Methods: For the evaluation of the cytotoxic effect of essential oil of asafoetida (EOA), MCF7 cells, a highly invasive variant of human breast cancer cell line, were exposed to different concentrations of EOA (2, 4, 6, 8, and 10 μl/ml) over different periods (24, 48, and 72 h), followed by cell viability analysis using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. For determining thein vivo toxicity of EOA, the oil was administered orally at doses of 0.1, 1, 10, and 100 μl/kg for 28 days in female Wistar rats. After completion of the experiment, hematological and serum biochemical parameters were evaluated and compared to the untreated group. Results: MTT assay results showed that EOA significantly decreased the viability of MCF7 cells in a time- and concentration-dependent manner, demonstrating a strong cytotoxic effect of EOA on breast cancer cells. In chronic toxicity study, the female Wistar rats showed no change in hematological and biochemical parameters at any of the administered dose. Conclusions: The cytotoxic effect of EOA on breast cancer cells, without general toxicity, makes it a promising compound as adjuvant therapy for breast cancer.
背景:乳腺癌是女性癌症相关死亡的主要原因,其发病率在世界范围内呈上升趋势。在体内和体外研究中,asafetida均显示出良好的抗乳腺癌活性。材料与方法:为评价荷叶花精油(EOA)的细胞毒作用,将高侵袭性人乳腺癌细胞系MCF7细胞暴露于不同浓度的EOA(2、4、6、8和10 μl/ml)中不同时间(24、48和72 h),采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)法分析细胞活力。实验采用0.1、1、10、100 μl/kg的剂量给雌性Wistar大鼠口服EOA油28 d,测定其体内毒性。实验结束后,进行血液学和血清生化指标评估,并与未治疗组进行比较。结果:MTT实验结果显示,EOA显著降低MCF7细胞活力,且呈时间和浓度依赖性,表明EOA对乳腺癌细胞具有较强的细胞毒作用。在慢性毒性研究中,雌性Wistar大鼠在任何给药剂量下,血液学和生化参数均未发生变化。结论:EOA对乳腺癌细胞具有细胞毒作用,无一般毒性,是一种很有前景的乳腺癌辅助治疗药物。
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引用次数: 4
Best-match blood transfusion in pediatric patients with mixed autoantibodies 混合自身抗体患儿的最佳配型输血
Pub Date : 2020-01-01 DOI: 10.4103/ctm.ctm_27_19
Debasish Mishra, D. Sahoo, Smita Mahapatra, A. Panigrahi
Finding matched blood in autoimmune hemolytic anemic (AIHA) patients is extremely difficult due to autoantibodies. Generally, these antibodies directed against antigens of high prevalence. It is essential for transfusion purposes to provide blood without alloantibodies. We report three cases of mixed AIHA in children. Mixed AIHA may present with blood group discrepancy, as well as incompatibility may possess difficult situation for transfusion laboratory to provide blood units to patients. The patient must be transfused cautiously with least-incompatible, ABO and Rh/ Kell phenotype-matched packed red blood cells slowly under strict supervision and steroid cover.
由于自身抗体的存在,在自身免疫性溶血性贫血(AIHA)患者中寻找匹配的血液是非常困难的。一般来说,这些抗体针对的是高流行率的抗原。输血时必须提供不含同种异体抗体的血液。我们报告三例儿童混合性AIHA。混合型AIHA可能存在血型差异,以及配型不匹配,输血实验室难以向患者提供血液单位。患者必须在严格的监督和类固醇覆盖下,谨慎地输注最不相容、ABO和Rh/ Kell表型匹配的填充红细胞。
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引用次数: 1
Potential inhibitor for 2019-novel coronaviruses in drug development 2019新型冠状病毒药物开发中的潜在抑制剂
Pub Date : 2020-01-01 DOI: 10.4103/ctm.ctm_3_20
Xiaohui Xu, Zi-long Dang, Lei Zhang, L. Zhuang, Wutang Jing, L. Ji, Guoyu Qiu
The coronavirus disease 2019 (COVID-19), which is first detected in Wuhan, China, is a virus identified as the cause of pneumonia. In the event of epidemic outbreak, a series of actions have been taken by the Chinese government to control the pandemic of the virus, and effective medical methods are in urgent need to prevent COVID-19 infection and cure the disease, especially a drug that can suppress COVID-19 is urgently needed. However, there are no specific drugs and vaccine that can prevent coronavirus infection. Some research works on the transmissibility, severity, and other features associated with this virus are ongoing. Some works about new drug against COVID-19 are carried out; more time is required to develop an effective drug against pneumonia caused by COVID-19. Now, to develop broad-spectrum antiviral agents, there is a quick method to identify drugs with high binding capacity with COVID-19 by virtual screening based on the clinical drug libraries; all these drugs have been widely used in clinical applications with guaranteed safety, which may serve as promising candidates to treat the infection of COVID-19. In this article, we summarize the discovery and clinical application of specific drugs against COVID-19 as potential inhibitors to alleviate the current epidemic.
在中国武汉首次发现的新型冠状病毒病(COVID-19)是一种被确定为肺炎病因的病毒。在疫情爆发的情况下,中国政府已经采取了一系列措施来控制病毒的大流行,迫切需要有效的医学方法来预防COVID-19感染和治愈疾病,特别是迫切需要一种可以抑制COVID-19的药物。然而,目前还没有特定的药物和疫苗可以预防冠状病毒感染。有关该病毒的传播性、严重性和其他相关特征的一些研究工作正在进行中。开展了一些抗COVID-19新药研制工作;需要更多的时间来开发对抗COVID-19引起的肺炎的有效药物。目前,为了开发广谱抗病毒药物,有一种基于临床药物库的虚拟筛选方法,可以快速识别出与COVID-19具有高结合能力的药物;这些药物已广泛应用于临床,安全性有保障,可能成为治疗COVID-19感染的有希望的候选药物。本文就新型冠状病毒肺炎特异性药物的发现和临床应用进行综述。
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引用次数: 4
Clinicopathological association of p16 and its impact on outcome of chemoradiation in head-and-neck squamous cell cancer patients in North-East India p16的临床病理关联及其对印度东北部头颈部鳞状细胞癌患者放化疗结果的影响
Pub Date : 2020-01-01 DOI: 10.4103/ctm.ctm_34_19
S. Mohanty, Y. Devi, Nithinraj Daniel, D. Ponna, M. Devi, L. Singh
Purpose: Human papillomavirus-associated head–and-neck squamous cell cancer (HNSCC) is following an increasing trend in Western countries, which has unique biology and confers better prognosis, whereas there are limited data from Indian studies in this context. Methods: We conducted a prospective cohort study to evaluate the clinicopathological association of p16 in locally advanced HNSCC and its impact on outcome of chemoradiation. The study population was divided into two arms; p16-positive and p16-negative arms. All patients were treated with concurrent chemoradiation using weekly cisplatin. Statistical Analysis Used: SPSS version 21 for Windows was used for statistical analysis. Chi-square test and multivariate analysis were performed to evaluate different association and impact of p16. P <0.05 was considered statistically significant. Results: The present study found p16-positive HNSCC patients to be associated with better performance status (P = 0.010), oropharyngeal primary location (P = 0.034), advanced nodal stage at presentation (P = 0.000), and higher histopathologic grade of tumor (P = 0.021) and was associated with better response (P = 0.005) to concurrent chemoradiation. Subsite analysis revealed p16-positive oropharyngeal squamous cell cancer (OPSCC) to have significantly better response (P = 0.036) to chemoradiation, whereas a trend toward better response to chemoradiation (P = 0.066) was found among p16-positive non-OPSCC. Higher p16 expression score was associated with better (P = 0.000) response to chemoradiation. Multivariate analysis revealed p16 to have an independent positive impact on tumor response to chemoradiation in HNSCC irrespective of tumor subsite. Conclusion: p16 overexpression is a good prognostic factor in both OPSCC and non-OPSCC. Treatment response have a positive correlation with intensity of p16 staining in the tissue biopsy material.
目的:人乳头瘤病毒相关的头颈部鳞状细胞癌(HNSCC)在西方国家呈上升趋势,其具有独特的生物学特性,预后较好,而印度在这方面的研究数据有限。方法:我们进行了一项前瞻性队列研究,以评估p16在局部晚期HNSCC中的临床病理关联及其对放化疗结果的影响。研究人群分为两组;p16阳性臂和p16阴性臂。所有患者均接受每周顺铂同步放化疗。统计分析方法:采用SPSS version 21 for Windows进行统计分析。采用卡方检验和多变量分析评价p16的不同相关性和影响。P <0.05为差异有统计学意义。结果:本研究发现p16阳性HNSCC患者与较好的运动状态(P = 0.010)、口咽原发部位(P = 0.034)、出现时淋巴结分期较晚(P = 0.000)、较高的肿瘤组织病理分级(P = 0.021)相关,并且与同期放化疗的较好反应(P = 0.005)相关。亚位分析显示,p16阳性的口咽鳞状细胞癌(OPSCC)对放化疗有更好的反应(P = 0.036),而p16阳性的非OPSCC对放化疗有更好的反应(P = 0.066)。更高的p16表达评分与更好的放化疗反应相关(P = 0.000)。多因素分析显示,p16对HNSCC中肿瘤对放化疗的反应具有独立的积极影响,与肿瘤亚位点无关。结论:p16过表达在OPSCC和非OPSCC中都是一个良好的预后因素。治疗反应与组织活检材料中p16染色的强度呈正相关。
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引用次数: 1
Protein disulfide isomerase A3: A potential regulatory factor of colon epithelial cells 蛋白二硫异构酶A3:结肠上皮细胞的潜在调节因子
Pub Date : 2020-01-01 DOI: 10.4103/ctm.ctm_33_19
Yang Li, Z. Huang, Hai-ping Jiang
Aim: This study aimed to investigate the effects of protein disulfide isomerase A3 (PDIA3) on the proliferation and apoptosis of colon epithelial cells, so as to explore its possible role in colon compensation of ultra-short bowel syndrome. Methods: The expression of PDIA3 gene in NCM460 colonic epithelial cells was upregulated and silenced by liposome transient transfection technique. The expression of PDIA3 protein was determined by Western blotting, the proliferation rate of NCM460 cells was detected by CCK8, and the apoptosis rate of NCM460 cells was determined by flow cytometry. Results: DNA sequencing and Western blotting results successfully verified that PDIA3 protein expression in NCM460 cells was upregulated and silenced by liposomal transfection. In the PDIA3 overexpression experiment, the proliferation rate of the experimental group was lower than that of the empty carrier group at 24 h, 48 h, and 72 h, and the apoptosis rate of the experimental group was higher than that of the empty carrier group (P < 0.05, the difference was statistically significant). In the PDIA3-silenced experiment, the proliferation rate of the experimental group was higher than that of the empty carrier group at 24 h, 48 h, and 72 h, and the apoptosis rate of the experimental group was lower than that of the empty carrier group (P < 0.05, the difference was statistically significant). Conclusion: PDIA3 inhibits the proliferation of human colonic epithelial cells (NCM460) and promotes their apoptosis, which may not be a key regulatory protein in colon compensation of ultra-short bowel syndrome.
目的:本研究旨在研究蛋白二硫异构酶A3 (PDIA3)对结肠上皮细胞增殖和凋亡的影响,探讨其在超短肠综合征结肠代偿中的可能作用。方法:采用脂质体瞬时转染技术,上调PDIA3基因在NCM460结肠上皮细胞中的表达并使其沉默。Western blot检测PDIA3蛋白的表达,CCK8检测NCM460细胞的增殖率,流式细胞术检测NCM460细胞的凋亡率。结果:DNA测序和Western blotting结果成功验证了脂质体转染后PDIA3蛋白在NCM460细胞中的表达上调和沉默。在PDIA3过表达实验中,实验组在24 h、48 h、72 h的增殖率低于空载体组,凋亡率高于空载体组(P < 0.05,差异有统计学意义)。pdia3沉默实验中,实验组在24 h、48 h、72 h的增殖率均高于空载体组,凋亡率低于空载体组(P < 0.05,差异有统计学意义)。结论:PDIA3抑制人结肠上皮细胞(NCM460)增殖并促进其凋亡,可能不是超短肠综合征结肠代偿的关键调节蛋白。
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引用次数: 0
Supraclavicular lymphadenopathy as the initial manifestation in carcinoma of cervix 锁骨上淋巴结病是子宫颈癌的最初表现
Pub Date : 2019-10-01 DOI: 10.4103/ctm.ctm_23_19
Priyanka Priyaarshini, T. Sahoo
Carcinoma of the cervix has been considered as a preventable disease. However, it continues to be a significant health problem worldwide and is the second most frequent cause of cancer death among women in developing countries. It rarely metastasizes to the supraclavicular group of lymph nodes during the initial presentation, and few cases have been reported in the literature. Here, we report a case of cervical carcinoma in a 40-year-female with unusual manifestation at the time of initial presentation. The patient was diagnosed with squamous cell carcinoma of the cervix with supraclavicular lymph node metastatic FIGO Clinical Stage IVB and treated in the line of concurrent chemoradiotherapy followed by adjuvant chemotherapy. The patient is reported to be disease-free after 1 year of completion of therapy.
宫颈癌一直被认为是一种可预防的疾病。然而,它仍然是世界范围内的一个重大健康问题,是发展中国家妇女癌症死亡的第二大常见原因。在最初的表现中,它很少转移到锁骨上淋巴结群,文献中报道的病例很少。在此,我们报告一个40岁女性宫颈癌的病例,在最初的表现时表现不寻常。诊断为宫颈鳞状细胞癌伴锁骨上淋巴结转移FIGO临床分期IVB期,行同步放化疗伴辅助化疗。据报道,患者在完成治疗1年后无病。
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引用次数: 0
ABO typing error resolution and transfusion support in a case of an acute leukemia patient showing loss of antigen expression ABO分型错误解决和输血支持在一例急性白血病患者显示抗原表达丧失
Pub Date : 2019-10-01 DOI: 10.4103/ctm.ctm_28_19
Debasish Mishra, G. Ray, Smita Mahapatra, Pankaj Parida
ABO and RhD typing is an essential step before the transfusion of blood components to a patient. ABO blood group system is a significant group, which causes hemolytic transfusion reaction destroying donor red blood cells. Hence, ABO typing error should be resolved before transfusion. Especially acute leukemia patients, there is a loss of A, B, and H antigens. In this group of patients, no reaction was seen in Cell typing/forward grouping typing. An adsorption-elution study is required to support the correct blood type. Response with anti-A1, anti-AB, and anti-H in red cell typing and saliva testing is necessary to distinguish between different weak A subgroups. We presented a case of loss of A antigens and transfusion support to a leukemia patient for initiation of chemotherapy.
ABO和RhD分型是向患者输血前的重要步骤。ABO血型系统是一个重要的血型,它引起溶血性输血反应,破坏供者的红细胞。因此,ABO血型错误应在输血前解决。特别是急性白血病患者,存在a、B和H抗原的缺失。在这组患者中,细胞分型/正向分组分型未见反应。需要一项吸附-洗脱研究来支持正确的血型。在红细胞分型和唾液检测中有抗a1、抗ab和抗h反应是区分不同弱A亚群的必要条件。我们提出了一个病例丢失的a抗原和输血支持白血病患者开始化疗。
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引用次数: 0
期刊
Cancer Translational Medicine
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