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08 February 2024, Volume 51 Issue 2 Previous Issue    Next Issue

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The mechanism of extract of ginkgo biloba inducing mitochondrial autophagy in breast cancer cells MCF-7 Shao Jianqiang, Wang Peng, Bai Jie, Li Huixin, Wang Zunyi, Xu Zhihong 2024, 51 (2):  65-72.  doi: 10.3760/cma.j.cn371439-20230901-00009 Abstract ( 75 )   HTML ( 19 )   PDF (1507KB) ( 31 )   Save Objective To investigate the mechanism of extract of ginkgo biloba （EGB）on mitochondrial autophagy in breast cancer cells MCF-7. Methods Breast cancer MCF-7 cells were divided into four groups. EGB with mass concentrations of 40，80，120 mg/L was used to incubate breast cancer MCF-7 cells for 24 h or 48 h，as a low concentration group of EGB，a medium concentration group of EGB，and a high concentration group of EGB. Breast cancer MCF-7 cells without intervention were taken as control group. Cell proliferation was measured using MTT assay； Flow cytometry was used to detect cell apoptosis； Immunofluorescence assay was used to determine the contents of prostacyclin （P62），microtubule-associated protein light chain 3Ⅱ （LC3Ⅱ），and caspase-3； The levels of multidrug resistance-associated protein 1 （MRP1），multidrug resistance gene 1 （MDR1）and breast cancer resistance protein （BCRP）were identified by PCR； Western blotting was used to detect the expression of extracellular signal-regulated kinase （ERK），mitogen-activated protein kinase （MAPK），p-ERK，and p-MAPK proteins in cells. Results The results of MTT assay for cell proliferation showed that cell proliferation at 24 h in control group，EGB low，medium and high concentration groups were 0.95±0.14，0.65±0.09，0.51±0.07，0.37±0.04，respectively，with a statistically significant difference （F=43.13，P<0.001），cell proliferation at 48 h were 1.32±0.19，0.54±0.08，0.32±0.05，0.15±0.02，respectively，with a statistically significant difference （F=141.30，P<0.001）. Compared with 24 h，cell proliferation was decreased in EGB low，medium and high concentration groups at 48 h （all P<0.05）. Pairwise comparison showed that EGB treatment significantly decreased MCF-7 cell viability and cell proliferation was decreased in turn at 24 and 48 h in control group，low，medium，high EGB groups （all P<0.05）. Flow cytometry analysis revealed that the apoptosis rates of MCF-7 cells in control group，EGB low，medium and high concentration groups were 2.12%±0.23%，9.28%±0.45%，15.17%±1.28% and 22.21%±2.32%，respectively，with a statistically significant difference （F=128.80，P<0.001）. Pairwise comparison showed that the apoptosis rate of control group，EGB low，medium and high concentration groups were increased in turn （all P<0.05）. The results of immunofluorescence assay showed that the protein relative expression levels of P62 protein in MCF-7 cells of control group，EGB low，medium and high concentration groups were 3.34±0.52，2.85±0.47，2.02±0.18 and 1.08±0.21，respectively，with a statistically significant difference （F=41.55，P<0.001）. LC3Ⅱ protein relative expression levels were 0.24±0.05，1.02±0.14，1.47±0.26，1.95±0.21，respectively，with a statistically significant difference （F=94.82，P<0.001）. The relative expression levels of caspase-3 protein were 0.25±0.03，0.68±0.21，1.12±0.17 and 1.65±0.23，respectively，with a statistically significant difference （F=68.09， P<0.001）. Pairwise comparison showed that LC3Ⅱ and caspase-3 protein expression levels were increased in turn in control group，EGB low，medium and high concentration groups，while P62 protein expression levels were decreased in turn （all P<0.05）. The PCR experiment results showed that the MRP1 mRNA level of MCF-7 cells in control group， EGB low，medium and high concentration groups were 1.06±0.14， 0.83±0.18， 0.71±0.11， 0.52±0.08， respectively，with a statistically significant difference （F=17.41，P<0.001）. The mRNA levels of MDR1 were 1.14±0.17， 0.75±0.13， 0.60±0.09， 0.48±0.06，respectively，with a statistically significant difference （F=34.40，P<0.001）. BCRP mRNA levels were 1.09±0.11， 0.88±0.13， 0.69±0.07， 0.57±0.05，respectively，with a statistically significant difference （F=34.13，P<0.001）. Pairwise comparison showed that the levels of MRP1，MDR1 and BCRP mRNA were decreased in turn in control group，EGB low，medium and high concentration groups （all P<0.05）. The results of Western blotting showed that the expression of ERK in MCF-7 cells in control group，EGB low，medium and high concentration groups were 2.54±0.38， 1.89±0.25， 1.55±0.21， 1.12±0.16， respectively，with a statistically significant difference （F=31.18，P<0.001）. MAPK expression were 2.47±0.34， 1.96±0.29， 1.63±0.27， 1.20±0.24， respectively，with a statistically significant difference （F=20.90，P<0.001）. p-ERK expression were 2.03±0.29， 1.74±0.21， 1.45±0.11， 1.18±0.24， respectively，with a statistically significant difference （F=16.31，P<0.001）. p-MAPK expression were 2.26±0.47， 1.90±0.41， 1.61±0.33， 1.35±0.16， respectively，with a statistically significant difference （F=7.01，P=0.002）. Pairwise comparison showed that the expressions of ERK，MAPK，p-ERK and p-MAPK in control group，EGB low，medium and high concentration groups were decreased in turn （all P<0.05）. Conclusion EGB can inhibit the proliferation of breast cancer MCF-7 cells，promote the apoptosis of MCF-7 cells，decrease the expression of P62 protein，increase the expression of LC3Ⅱ and caspase-3 protein，induce mitochondrial autophagy. Figures and Tables | References | Related Articles | Metrics

Role of serum cholinesterase and inflammatory markers in the prognosis of stage ⅠA -ⅢA breast cancer Chen Boguang, Wang Sugui, Zhang Yongjie 2024, 51 (2):  73-82.  doi: 10.3760/cma.j.cn371439-20231008-00010 Abstract ( 74 )   HTML ( 13 )   PDF (1745KB) ( 33 )   Save Objective To analyze the preoperative and postoperative serum cholinesterase （CHE）levels in patients with stage ⅠA-ⅢA breast cancer who underwent surgical treatment， and to explore the roles of them and peripheral blood inflammatory markers in the prognostic prediction of stage ⅠA-ⅢA breast cancer. Methods The relevant blood indicators of 152 patients with stage ⅠA-ⅢA breast cancer who underwent surgery and postoperative adjuvant therapy from January 2012 to December 2017 at Affiliated Huai'an Hospital of Xuzhou Medical University were retrospectively studied. The optimal cut-off values of serum CHE levels and peripheral blood inflammatory markers [systemic immune-inflammation index （SII）and systemic inflammatory response index （SIRI）] were calculated using X-tile 3.6.1 software. Patients were categorized into low and high value groups based on the optimal cutoff values. Kaplan-Meier curves and Cox regression analysis were used to assess the correlation between CHE and peripheral blood inflammation indexes and disease-free survival （DFS）. Spearman correlation coefficient and Wilcoxon test were used to assess the correlation and changes of CHE and inflammation indexes before and after treatment. In addition to this， a nomogram prediction model was conscturcted based on independent prognostic factors by R software， which was validated by Bootstrap method. Results The CHE levels of patients before and after treatment was 8 645.0 （7 251.3， 10 229.3）and 9 309.0 （7 801.0， 10 835.3）U/L， respectively， with a statistically significant difference （Z=2.73， P=0.006）.The optimal cut-off values for postoperative CHE （Post-CHE）， postoperative SII （Post-SII）， and postoperative SIRI （Post-SIRI）associated with patients' DFS， being 7 773 U/L， 741， and 0.9， respectively. Univariate analysis showed that tumor size （≤2 cm vs.>2 cm and ≤5 cm：HR=2.55， 95%CI：1.30-4.99， P=0.006； ≤2 cm vs. >5 cm：HR=8.95， 95%CI：4.15-19.32， P<0.001）， number of positive lymph nodes （HR=3.84， 95%CI：2.24-6.58， P<0.001）， clinical stage （stage Ⅰ vs. stage Ⅱ：HR=1.52， 95%CI：0.68-3.39， P=0.309， stage Ⅰ vs. stage Ⅲ：HR=8.12， 95%CI：3.76-17.55， P<0.001）， Ki-67 expression （HR=2.19， 95%CI：1.24-3.84， P=0.007）， whether radiotherapy （HR=2.05， 95%CI：1.19-3.53， P=0.010）， Post-CHE （HR=6.81， 95%CI：3.94-11.76， P<0.001）， Pre-neutrophil to lymphocyte ratio （NLR）（HR=1.11， 95%CI：1.02-1.21， P=0.014）， Post-NLR （HR=5.23， 95%CI：2.78-9.85， P<0.001）， Pre-platelet to lymphocyte ratio （PLR）（HR=2.08， 95%CI：1.01-4.26， P=0.046）， Post-PLR （HR=7.11， 95%CI：3.78-13.37， P<0.001）， Pre-lymphocyte to monocyte ratio （LMR）（HR=0.37， 95%CI：0.20-0.66， P<0.001）， Post-LMR （HR=0.23， 95%CI：0.13-0.41， P<0.001）， Pre-SII （HR=1.81， 95%CI：1.05-3.12， P=0.033）， Post-SII （HR=6.12， 95%CI：3.48-10.76， P<0.001）， Pre-SIRI （HR=2.12， 95%CI：1.24-3.63， P=0.006）， and Post-SIRI （HR=4.93， 95%CI：2.87-8.48， P<0.001）were associated with DFS in patients with stage ⅠA-ⅢA breast cancer. Multivariate analysis showed that tumor size （≤2 cm vs. >2 cm and ≤5 cm：HR=2.86， 95%CI：1.41-5.78， P=0.003； ≤2 cm vs. >5 cm：HR=3.72， 95%CI：1.50-9.26， P=0.005）， number of positive lymph nodes （HR=4.66， 95%CI：2.28-9.54， P<0.001）， Ki-67 expression （HR=2.13， 95%CI：1.15-3.94， P=0.016）， Post-CHE （HR=0.18， 95%CI：0.10-0.33， P<0.001）， Post-SII （HR=2.71， 95%CI：1.39-5.29， P=0.004）， and Post-SIRI （HR=3.77， 95%CI：1.93-7.36， P<0.001）were independent influencing factors for DFS in patients with stage ⅠA-ⅢA breast cancer. Kaplan-Meier survival curve analysis showed that the median DFS of patients in the Ki-67<30% group was not reached， and the median DFS of patients in the Ki-67≥30% group was 89.0 months， and the 3- and 5-year DFS rates were 84.9% vs. 75.9% and 80.8% vs. 64.3%， respectively， with a statistically significant difference （χ2=7.65， P=0.006）； the median DFS of patients in the tumor size≤2 cm group was not reached， the median DFS of the 2 cm<tumor size≤5 cm group was 93.5 months， and the median DFS of the tumor size>5 cm group was 26.3 months， and the 3- and 5-year DFS rates were 95.5% vs. 74.6% vs. 42.1%， 86.3% vs. 68.6% vs. 25.3%， with a statistically significant difference （χ2=40.46， P<0.001）； the median DFS of patients in the group with the number of positive lymph nodes<4 was not reached， and the median DFS of the group with the number of positive lymph nodes≥4 was 30.7 months， and the 3- and 5-year DFS rates were 87.9% vs. 46.4% and 81.4% vs. 28.6%， respectively， with a statistically significant difference （χ2= 47.34， P<0.001）； the median DFS of patients in the Post-CHE<7 773 U/L group was 47.3 months， and the median DFS of patients in the Post-CHE≥7 773 U/L group was not reached， and the 3- and 5-year DFS rates were 52.8 % vs. 88.6% and 27.8% vs. 81.2%， respectively， with a statistically significant difference （χ2=62.17， P<0.001）； the median DFS was not achieved in patients in the Post-SII<741 group， and the median DFS was 30.5 months in the Post-SII≥741 group， with 3- and 5-year DFS rates of 88.1% vs. 38.5% and 80.1% vs. 30.8%， respectively， with a statistically significant difference （χ2=50.78， P<0.001）； the median DFS of patients in Post-SIRI<0.9 group was not reached， the median DFS of Post-SIRI≥0.9 group was 33.3 months， and the 3- and 5-year DFS rates were 93.5% vs. 46.7% and 84.9% vs. 39.9%， respectively， with a statistically significant difference （χ2=40.67， P<0.001）. Spearman correlation analysis revealed that Post-CHE was not correlated with Post-SII （r=-0.111， P=0.175）， and Post-CHE was negatively correlated with Post-SIRI （r=-0.228， P=0.005）. Post-treatment CHE was elevated compared to preoperative and the median DFS was not reached in patients with elevated CHE group and 61.8 months in patients with reduced CHE group after treatment， with a statistically significant difference （χ2=25.67， P<0.001）. The nomogram based on independent prognostic factors had good predictive performance， with a C-index of 0.893. Conclusion The serum CHE level exhibited a significant increase following treatment. Postoperative serum CHE combined with SII and SIRI can effectively predict DFS in patients with stage ⅠA-ⅢA breast cancer， and the prognosis of patients with elevated CHE after treatment is better. The nomogram constructed based on independent prognostic factors has good predictive performance for DFS in breast cancer patients. 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Clinical value of serum miR-19b and miR-744-5p levels in the diagnosis of non-small cell lung cancer Li Dan, Li Ruiyao, Li Yinghan, Yu Xiuyan, Wu Xuefeng 2024, 51 (2):  83-88.  doi: 10.3760/cma.j.cn371439-20230308-00011 Abstract ( 51 )   HTML ( 8 )   PDF (1147KB) ( 28 )   Save Objective To investigate the serum levels of miR-19b and miR-744-5p in patients with non-small cell lung cancer （NSCLC），and to analyze the clinical value of miR-19b and miR-744-5p in the diagnosis of NSCLC. Methods A total of 226 NSCLC patients （NSCLC group）and 100 healthy people （control group）admitted to Jilin Cancer Hospital from August 2019 to August 2022 were selected as research objects. Quantitative real-time PCR was used to measure and compare the serum levels of miR-19b and miR-744-5p between the NSCLC group and the control group，and the relationships between the two indicators and different clinical and pathological characteristics of NSCLC patients were analyzed. The receiver operating characteristic curve was used to analyze the clinical value of miR-19b，miR-744-5p and their joint detection in the diagnosis of NSCLC. Results Compared with the control group，the serum miR-19b level （3.86±1.25 vs. 1.06±0.41）in the NSCLC group significantly increased （t=21.87，P<0.001），while the miR-744-5p level （1.80±0.48 vs. 5.75±1.69）significantly decreased （t=32.36，P<0.001）. The serum miR-19b levels in NSCLC patients with pathological types of adenocarcinoma，maximum tumor diameter ≥3 cm，medium to low differentiation，stage Ⅲ-Ⅳ，and with lymph node metastasis were higher than those in squamous cell carcinoma （t=5.94，P<0.001），maximum tumor diameter <3 cm （t=2.65，P=0.009），well differentiation （t=4.33，P<0.001），stageⅠ-Ⅱ （t=12.32，P<0.001），patients without lymph node metastasis （t=8.13，P<0.001），while miR-744-5p levels were lower than those in squamous cell carcinoma （t=8.27，P<0.001），tumor maximum diameter <3 cm （t=5.34，P<0.001），well differentiation （t=6.95，P<0.001），stageⅠ-Ⅱ （t=11.40，P<0.001），patients without lymph node metastasis （t=10.36，P<0.001）. The area under the curve （AUC）of serum miR-19b combined with miR-744-5p in the diagnosis of NSCLC was 0.914 （95%CI：0.841-0.959），with sensitivity and specificity of 90.9% and 84.0%，respectively. AUC was significantly than that of the single indicator detection of miR-19b （AUC=0.824，95%CI：0.770-0.869）and miR-744-5p （AUC=0.783，95%CI：0.709-0.838）（Z=2.28，P=0.021； Z=2.36，P=0.017）. Conclusion Serum miR-19b level of NSCLC patients is increased，miR-744-5p levels is decreased，and joint detection of serum miR-19b and miR-744-5p has high clinical value in the diagnosis of NSCLC. Figures and Tables | References | Related Articles | Metrics

Impact of pembrolizumab combined with chemotherapy on angiogenesis and circulating endothelial cells in patients with advanced non-small cell lung cancer Jiang Xi, Wu Yongcun, Liang Yan, Chu Li, Duan Yingxin, Wang Lijun, Huo Junjie 2024, 51 (2):  89-94.  doi: 10.3760/cma.j.cn371439-20231016-00012 Abstract ( 44 )   HTML ( 6 )   PDF (758KB) ( 26 )   Save Objective To explore the impact of pembrolizumab combined with chemotherapy on angiogenesis and circulating endothelial cells in patients with advanced non-small cell lung cancer （NSCLC）. Methods The retrospective analysis of clinical data from 121 patients diagnosed with advanced NSCLC who were admitted to the Second Affiliated Hospital of Xingtai Medical College from August 2021 to January 2023 was conducted. These patients were divided into a control group （n=57）and an observation group （n=64）based on the designated treatment protocol. Specifically，individuals in the control group received standard chemotherapy（cisplatin+paclitaxel），while those in the observation group underwent penpilimab therapy in conjunction with conventional chemotherapy. The comparative assessment encompassed short-term clinical efficacy，quality of life，immune function parameters，angiogenic factors [including endostatin，insulin-like growth factor 1 （IGF-1），and vascular endothelial growth factor （VEGF）]，circulating endothelial cells，and adverse reactions within the two groups. Results After 6 courses of treatment，the objective response rate [67.19% （43/64）vs. 49.12% （28/57）] and disease control rate [87.50% （56/64）vs. 70.18% （40/57）] in observation group were higher than those in control group，with statistically significant differences （χ2=4.06，P=0.044； χ2=5.52，P=0.019）. The quality of life score of observation group [（56.77±6.81）points] was significantly higher than that of control group [（47.73±8.23）points]，with a statistically significant difference （t=6.61，P<0.001）； The T cell subgroup CD3+ levels [（63.59±9.00）% vs. （53.06±8.80%），t=6.49，P<0.001]，CD4+ levels [（46.54±8.20）% vs. （30.74±7.32）%，t=11.13，P<0.001] and CD4+/CD8+ ratio （1.90±0.36 vs. 1.21±0.28，t=11.66，P<0.001）in observation group were significantly higher than those in control group，with statistically significant differences； Endostatin in observation group [（48.99±3.43）μmol/L] was significantly higher than that in control group [（31.35±3.87）μmol/L]，with a statistically significant difference （t=26.58，P<0.001），IGF-1 [（102.31±20.35）μg/L vs. （134.98±19.02）μg/L] and VEGF [（31.70±4.32）pg/ml vs. （58.71±5.99）pg/ml] were significantly lower in observation group than those in control group，with statistically significant differences （t=18.73，P<0.001； t=28.14，P<0.001）. The number of circulating endothelial cells in observation group [（58.77±10.03）/ml] was significantly lower than that in control group [（87.01±8.01）/ml]，with a statistically significant difference （t=17.20，P<0.001）. During treatment，there were no statistically significant differences in the incidence of gastrointestinal reaction （χ2=0.01，P=0.908），leukopenia （χ2=0.64，P=0.424），thrombocytopenia （χ2=0.28，P=0.597），anemia （χ2=1.66，P=0.197），nephrotoxicity （χ2=0.64，P=0.424），skin rash （χ2=1.33，P=0.249）between the two groups. Conclusion The combination therapy of pembrolizumab and chemotherapy for the treatment of advanced NSCLC has demonstrated noteworthy effectiveness. This regimen has the potential to enhance patients' immune functionality，ameliorate their overall quality of life，suppress angiogenesis，and exhibits a commendable profile of safety and reliability. Figures and Tables | References | Related Articles | Metrics

Reviews

Progress of KRASG12C mutations in non-small cell lung cancer Ma Zhenghong, Jiang Chao 2024, 51 (2):  95-98.  doi: 10.3760/cma.j.cn371439-20231008-00013 Abstract ( 83 )   HTML ( 6 )   PDF (704KB) ( 47 )   Save With the continuous in-depth research on the mechanism of KRASG12C mutations in targeted therapy of non-small cell lung cancer，KRASG12C has evolved from non producible to an important targeted therapy site. The KRASG12C mutation inhibitor has achieved dual progress in efficiency and survival in targeted therapy of non-small cell lung cancer. Although drug resistance is inevitable with treatment，research on drug resistance mechanisms has found that combination medication is one of the ways to overcome or reduce drug resistance. References | Related Articles | Metrics

Research progress on the role of MTAP in malignant mesothelioma Jin Xudong, Chen Zhongjian, Mao Weimin 2024, 51 (2):  99-104.  doi: 10.3760/cma.j.cn371439-20231109-00014 Abstract ( 76 )   HTML ( 7 )   PDF (740KB) ( 28 )   Save Methylthioadenosine phosphorylase （MTAP）is a rate-limiting enzyme in the methionine and purine salvage pathway，and is closely related to polyamine metabolism，adenine metabolism and methionine metabolism. MTAP is frequently deleted in malignant mesothelioma （MM）and plays an important role in the diagnosis and differential diagnosis of MM. At the same time，metabolic reprogramming caused by MTAP deletion creates new therapeutic strategies for MM. Besides，MTAP gene is also associated with the prognosis of MM，therefore MTAP is a significant biomarker for the diagnosis，treatment and prognosis of MM. Figures and Tables | References | Related Articles | Metrics

Research progress of liquid biopsy technology in esophageal squamous cell carcinoma Liu Bohan, Huang Junxing 2024, 51 (2):  105-108.  doi: 10.3760/cma.j.cn371439-20230621-00015 Abstract ( 54 )   HTML ( 7 )   PDF (696KB) ( 12 )   Save In recent years，with the continuous development of biotechnology，liquid biopsy techno-logy has gradually become a research hotspot in the field of tumor research. As a non-invasive diagnostic method，liquid biopsy has great advantages compared with traditional methods. The liquid biopsy technology is precise，convenient，non-invasive and safe，and has an increasingly important clinical significance in the early diagnosis，treatment and prognosis assessment of esophageal squamous cell carcinoma. References | Related Articles | Metrics

Differentiation therapies in human cancers Yue Hongyun, Zhang Baihong 2024, 51 (2):  109-113.  doi: 10.3760/cma.j.cn371439-20231013-00016 Abstract ( 59 )   HTML ( 3 )   PDF (711KB) ( 19 )   Save Cancer phenotypic plasticity includes dedifferentiation，blocked differentiation and trans- differentiation，and differentiation therapy targeting tumor cell plasticity is becoming a new therapeutic model for human cancers. The application of inducing differentiation，initiating differentiation and regulating differentiation in tumor differentiation therapy will promote the directed differentiation of tumor cells into mature cells and the remodeling of phenotypes，thus to achieve the purpose of cancer treatment. Figures and Tables | References | Related Articles | Metrics

Research progress on the histopathological growth patterns of colorectal liver metastasis Sun Guobao, Yang Qian, Zhuang Qingchun, Gao Binbin, Sun Xiaogang, Song Wei, Sha Dan 2024, 51 (2):  114-118.  doi: 10.3760/cma.j.cn371439-20231016-00017 Abstract ( 66 )   HTML ( 2 )   PDF (714KB) ( 17 )   Save The histopathological growth patterns （HGPs）of colorectal cancer （CRC）liver metastasis reflect the complicated and varied interactions between tumor cells and host microenvironment. Exploring the tumor vascular and immunological features of HGPs，the relationship between HGPs and anti-tumor treatment efficacy，and HGPs prediction methods may have potential clinical aplication value for making optimal treatment strategies，evaluating patients' prognosis，and monitoring disease progression. References | Related Articles | Metrics

Progress of MCL-1 and its inhibitors in hematologic malignancies Teng Yuan, Li Lijuan, Zhang Liansheng 2024, 51 (2):  119-122.  doi: 10.3760/cma.j.cn371439-20230612-00018 Abstract ( 101 )   HTML ( 5 )   PDF (735KB) ( 31 )   Save Myeloid cell leukemia-1 （MCL-1）is an anti-apoptotic protein that plays a key role in promoting cell survival in multiple myeloma，acute myeloid leukemia and non-Hodgkin lymphoma. MCL-1 is highly expressed in a variety of hematological malignancies，which is one of the important factors leading to poor prognosis and chemoresistance in patients with hematological malignancies. Therefore，MCL-1 is an important therapeutic target for hematological malignancies. Several MCL-1 inhibitors have entered clinical trials，including S63845，AZD5991，S64315，AMG-176，and AMG-397. The treatment plans used for hematological malignancies include monotherapy with MCL-1 inhibitors，as well as combination therapy with B cell lymphoma 2 inhibitors or immunomodulatory drugs，all indicating that MCL-1 inhibitors may be a breakthrough point for targeted treatment of hematological malignancies. References | Related Articles | Metrics