1.MUC16: The Novel Target for Tumor Therapy.
Ruyun GAO ; Ning LOU ; Xiaohong HAN ; Yuankai SHI
Chinese Journal of Lung Cancer 2022;25(7):452-459
Mucin16 (MUC16), also known as carbohydrate antigen 125 (CA125), is a glycoprotein antigen that can be recognized by the monoclonal antibody OC125 detected from epithelial ovarian carcinoma antigen by Bast et al in 1981. CA125 is not present in normal ovarian tissue but is usually elevated in the serum of epithelial ovarian carcinoma patients. CA125 is the most commonly used serologic biomarker for the diagnosis and recurrence monitoring of epithelial ovarian carcinoma. MUC16 is highly expressed in varieties of tumors. MUC16 can interact with galectin-1/3, mesothelin, sialic acid-binding immunoglobulin-type lectins-9 (Siglec-9), and other ligands. MUC16 plays an important role in tumor genesis, proliferation, migration, invasion, and tumor immunity through various signaling pathways. Besides, therapies targeting MUC16 have some significant achievements. Related preclinical studies and clinical trials are in progress. MUC16 may be a potential novel target for tumor therapy. This article will review the mechanism of MUC16 in tumor genesis and progression, and focus on the research actuality of MUC16 in tumor therapy. This article also provides references for subsequent tumor therapy studies targeting MUC16.
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CA-125 Antigen/metabolism*
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Carcinoma, Ovarian Epithelial
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Female
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Humans
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Lung Neoplasms
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Membrane Proteins/metabolism*
;
Ovarian Neoplasms/pathology*
2.Interpretation for Evidence-based Practice Guideline of Medication Therapy of High-dose Methotrexate in China
Zaiwei SONG ; Shuang LIU ; Rongsheng ZHAO ; Suodi ZHAI ; Xianglin ZHANG ; Youping LI ; Guanhua DU ; Yuankai SHI ; Liyan MIAO ; Lingli ZHANG ; Hongmei JING
China Pharmacy 2022;33(16):2032-2039
Evidence-based Practice Guideline of Medication Therapy of High-dose Methotrexate in China was published in the British Journal of Clinical Pharmacology in February 2022. The guideline followed the latest definition of clinical practice guideline and the methodology specification for the guideline development of WHO. The Grading of Recommendations Assessment , Development,and Evaluation (GRADE)approach was applied to rate the quality of evidence and determine the strength of recommendations. Finally ,this guideline presents 28 recommendations covering the whole process of clinical medication of high-dose methotrexate ,involving evaluation prior to administration (liver and renal function ,pleural effusion and ascites , comedication,genetic testing ),pre-treatment and routine dosing regimen (pretreatment of hydration and alkalization ,urine alkalization,routine dosing regimen ),therapeutic drug monitoring (necessity,method,timing,target concentration ),leucovorin rescue(rescue timing ,rescue regimen ,rescue dose optimization ),and management of toxicities (liver and kidney function monitoring,supportive treatment ,blood purification treatment ). This article aims to summarize and interpret the recommendations of this guideline ,so as to promote the better promotion and implementation of this guideline and provide comprehensive technical support and suggestions for whole-course individualized administration of high-dose methotrexate in China.
3.Efficacy and safety of obinutuzumab for the first-line treatment of follicular lymphoma: a subgroup analysis of Chinese patients enrolled in the phase III GALLIUM study
Xiaonan HONG ; Yuqin SONG ; Yuankai SHI ; Qingyuan ZHANG ; Wei GUO ; Gang WU ; Junmin LI ; Jifeng FENG ; Anastasiia KINKOLYKH ; Andrea KNAPP ; Tongyu LIN
Chinese Medical Journal 2022;135(4):433-440
Backgrounds::GALLIUM is a global phase III study that demonstrated significant improvements in progression-free survival (PFS) for obinutuzumab plus chemotherapy (G-chemo) vs. rituximab plus chemotherapy (R-chemo) in previously untreated patients with follicular lymphoma (FL). This study aimed to report the results of a subgroup of patients in China. Methods::Patients were randomized to G-chemo or R-chemo. Responders received maintenance therapy for 2 years or until disease progression. The primary endpoint was investigator (INV)-assessed PFS. Secondary endpoints included the overall response rate (ORR) and complete response rate (CRR) at the end of induction chemotherapy, overall survival (OS), and safety.Results::Overall, 58 patients with FL were randomized to the G-chemo ( n = 25) and R-chemo arms ( n = 33). The INV-assessed PFS rate at 3 years was 81.8% in the G-chemo arm, vs. 70.2% in the R-chemo arm (hazard ratio 0.35; 95% confidence interval: 0.09-1.34; P = 0.1120). The INV-assessed CRRs (without positron emission tomography [PET]) in these arms were 24.0% and 21.2%, respectively, whereas the ORRs were 80.0% and 90.9%, respectively. INV-assessed CRR-PET was 52.6% in the G-chemo, vs. 60.9% in the R-chemo. Median OS was not reached in either arm. Grade 3 to 5 adverse events were more frequent in the R-chemo arm (97.0% vs. 88.0%). Conclusions::The results of this subgroup analysis were consistent with those of the global population, and they suggest that G-chemo has a positive benefit-risk profile in patients from China with FL.Trial registration::ClinicalTrials.gov, No. NCT01332968.
4.Progress of prognostic factors for Hodgkin lymphoma
Journal of Leukemia & Lymphoma 2021;30(3):185-189
Hodgkin lymphoma (HL) is a type of curable tumor. The treatment strategy of HL is based on staging and risk of recurrence. With the continuous optimization of combined treatment mode, the prognosis of HL has been greatly improved. The predictive value of the prognostic models widely used in HL is lower than before. Therefore, exploring new prognostic factors and enriching existing prognostic models to provide patients with precise and individualized treatment is an important research direction for HL. This article reviews the progress of prognostic factors for HL in recent years.
5.Tumor autoantibodies in the diagnosis and prognosis of prostate cancer
Ning LOU ; Yuankai SHI ; Xiaohong HAN
Chinese Journal of Laboratory Medicine 2021;44(3):260-264
Detection of prostate specific antigen (PSA) is the most commonly used screening method for prostate cancer. However, many studies have found that the false positive rate and false negative rate of PSA detection for prostate cancer screening are very high, which easily leads to the overuse of PSA detection. Autoantibodies appear at the early stage of cancer, accompany the occurrence and development of prostate cancer. Autoantibodies have a long half-life and are easy to detect. Existing studies have found that autoantibodies can be used in the diagnosis of prostate cancer, and correlated with some prognostic indicators such as Gleason grade and overall survival (OS) of prostate cancer patients. This paper summarized 8 studies on the role of single autoantibody in the diagnosis and prognosis of prostate cancer. Most of the reported single autoantibodies have better diagnostic performance than PSA, and combined application could improve the diagnostic performance. Some autoantibodies are related to a poor prognosis of prostate cancer.
6.Response of Lung Adenocarcinoma Harbouring Sensitizing EGFR Mutation to the Fourth-line Combination Treatment of Pembrolizumab and Anlotinib.
Liling HUANG ; Yan QIN ; Fengyi ZHAO ; Shengyu ZHOU ; Yuankai SHI
Chinese Journal of Lung Cancer 2021;24(10):739-742
45.7% of Chinese patients with advanced lung adenocarcinoma were reported to harbour sensitizing epidermal growth factor receptor (EGFR) mutations. Limited therapeutic options are left for non-small cell lung cancer (NSCLC) harbouring sensitizing EGFR mutations after failure of EGFR-tyrosine kinase inhibitor (TKI) therapy and chemotherapy, finding effective options for them is an unmet clinic need. Herein we reported a case that till January 12, 2021, an 82-year-old female with sensitizing EGFR-mutant advanced lung adenocarcinoma received a surprising progression-free survival (PFS) benefit of over 21 months from the combination therapy of pembrolizumab and anlotinib after her failure of treatments of osimertinib, chemotherapy and anlotinib-monotherapy.
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Adenocarcinoma of Lung/genetics*
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Aged, 80 and over
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Antibodies, Monoclonal, Humanized
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Antineoplastic Combined Chemotherapy Protocols
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Carcinoma, Non-Small-Cell Lung/genetics*
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ErbB Receptors/genetics*
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Female
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Humans
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Indoles
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Lung Neoplasms/genetics*
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Mutation
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Quinolines
7.The development and main achievements of clinical trials for anti-cancer investigational new drug in the past 60 years in China (1960—2020)
Chinese Journal of Oncology 2021;43(6):696-706
Medical oncology is a subject characterized by drug therapy. Continuous research and development (R&D) of high-efficiency and low-toxic anti-cancer drugs is the premise of the development of medical oncology. Clinical trials play an indispensable role in the process from drug R&D to application, which determines the success or failure of a new drug. The clinical trials for anti-cancer investigational new drug (IND) in China began in 1960, and have developed rapidly since 2008. With the guidance and support of national policies, as well as involved by all aspects of the society, the R&D of anti-cancer drugs in China has changed from imitation to innovation. China innovative anti-cancer drugs have been widely recognized in the world, and more and more new domestic anti-cancer drugs have been used in clinical practice, bringing benefit to Chinese cancer patients. This article reviews the development of the clinical trials for anti-cancer IND in China from 1960 to 2020, and the main achievements having been made in the past 60 years. A thorough understanding of this history will help us keep in mind the mission and grasp the direction, as to make more achievements when implementing the strategy of "Healthy China" .
8.Immune evasion mechanism and its clinical application value in Hodgkin′s lymphoma
Chinese Journal of Oncology 2021;43(9):917-923
Hodgkin′s lymphoma (HL) is a unique malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are scattered in the inflammatory cell rich microenvironment. This extensive but ineffective inflammatory cell infiltrate indicates that HRS cells have developed mechanisms to evade immune surveillance. The immune escape mechanisms of HL provide prognostic biomarkers and opportunities to develop new drugs. The immune evasion mechanisms in Hodgkin lymphoma include a reduction of human leukocyte antigen (HLA) to affect first signal which is essential for T cell activation; an upregulation of negative co-stimulatory molecules to inhibit T cell activation; resistance to apoptosis or killing by expressing some molecules on HRS cells membrane; an immunosuppressive network formed by HRS cells regulating the microenvironment immune cells. Immune escape mechanisms of HRS cells provide new targets for the development of new drug and the new drug development strategies include drugs on HRS cells and drugs on microenvironment.
9.Venous thromboembolism risk and prophylaxis status of cancer inpatient
Ruihua XU ; Yuankai SHI ; Yuan GAO ; Weimin LI ; Xinyu QIN ; Jieming QU ; Zhenguo ZHAI ; Chen WANG
Chinese Journal of Oncology 2021;43(10):1100-1104
Objective:To determine the risk profile of venous thromboembolism (VTE) and evaluate VTE prophylaxis implementation of the hospitalized cancer patients in the DissolVE 2 study.Methods:The data of hospitalized cancer patients in the DissolVE 2 study were analyzed. The risk distribution of VTE, preventive measures and in-hospital VTE events of hospitalized patients with tumors were described by percentage and 95% confident interval (CI).Results:A total of 1 535 cancer patients were included. According to the Padua score, 826 (53.8%) patients were at low risk of VTE, while 709 (46.2%) patients were at high VTE risk. VTE events occurred in 4 low-risk patients (0.5%; 95% CI: 0.1%, 1.2%) and 5 high-risk patients (0.7%; 95% CI: 0.2%, 1.6%). The overall incidence was 0.6% (9/1 535, 95% CI: 0.3%, 1.1%). Among patients with high VTE risk, 666 (93.9%) did not receive any VTE prophylaxis, and only 11 (1.6%) patients received appropriate VTE prophylaxis. Among patients who received VTE prevention, no VTE event was observed. Conclusions:Nearly half of the hospitalized cancer patients are at high risk of VTE, but most of them don′t receive VTE prophylaxis. The results reflect the insufficient management of VTE risk for hospitalized cancer patients in China, and improvement of awareness and practice of VTE prophylaxis is urgently needed.
10.The value of autoantibodies in the diagnosis and prognosis of liver cancer
Rongrong LUO ; Yuankai SHI ; Xiaohong HAN
Chinese Journal of Oncology 2021;43(11):1143-1147
Liver cancer is one of the malignant tumors with the highest fatality rate in China and the 5-years survival rate is only 12.5%. Early detection to undertake early treatment can improve the survival rate of patients with liver cancer. Nowadays, the unsatisfactory performance of serum Alpha-fetoprotein (AFP) test, and the problems of insensitive to small lesions for ultrasound and exposure to nuclear radiation for CT, necessitate the urgency to explore novel diagnostic biomarkers of liver cancer. It has been demonstrated the presence of autoantibodies targeting tumor-associated antigens prior to clinic symptoms implied underlying early diagnostic value of malignancies. High specificity but low sensitivity of single autoantibodies such as the most reported anti-p53, anti-insulin like growth factor-Ⅱ mRNA binding protein, and anti-glucose regulated protein can be solved by combining different autoantibodies. However, the autoantibodies of different combinations vary in studies. Simultaneously, autoantibodies in combination with AFP facilitate further improving the detection rate of liver cancer. Nevertheless, the autoantibodies related to prognosis of liver cancer needs to be more studied in the near future.

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