1.Research Progress of Lung Cancer Vaccines.
Hao FAN ; Xiangwei GE ; Xin ZHOU ; Yao LI ; An WANG ; Yi HU
Chinese Journal of Lung Cancer 2023;26(9):692-700
With the development of medical technology, tumor vaccines as a novel precise immunotherapy approach have gradually received attention in clinical applications. Against the backdrop of the global corona virus disease 2019 (COVID-19) outbreak, vaccine technology has further advanced. Depending on the types of antigens, tumor vaccines can be divided into whole-cell vaccines, peptide vaccines, messenger ribonucleic acid (mRNA) vaccines, recombinant virus vaccines, etc. Although some tumor vaccines have been marketed and achieved certain therapeutic effects, the results of tumor vaccines in clinical trials have been unsatisfactory in the past period. With the maturation of next-generation sequencing (NGS) technology and the continuous development of bioinformatics, dynamic monitoring of the entire process of tumor subpopulation development has become a reality, which has laid a solid foundation for personalized, neoantigen-centered therapeutic tumor vaccines. This article reviews the recent developments of tumor vaccines of different types, starts with lung cancer and summarizes the achievements of tumor vaccines in clinical applications, and provides an outlook for the future development of antigen-centered tumor vaccines.
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Humans
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Cancer Vaccines/therapeutic use*
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Antigens, Neoplasm
;
Lung Neoplasms/drug therapy*
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Neoplasms/genetics*
;
Computational Biology
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Immunotherapy/methods*
;
Lung
2.Recent Progress of Nano-drug Combined with Chimeric Antigen Receptor T Cell Therapy in the Treatment of Soild Tumors.
Yi LIU ; Ning LI ; Wenyang JIANG ; Qing GENG
Chinese Journal of Lung Cancer 2023;26(1):59-65
Chimeric antigen receptor T cell (CAR-T) therapy has shown remarkable success in treating hematological malignancies. However, CAR-T therapy for solid tumors is still limited due to the unique solid-tumor microenvironment and heterogeneous target antigen expression, which leads to an urgent need of combining other therapies. At present, nano delivery system has become one of the most promising directions for the development of anti-tumor drugs. Based on the background of CAR-T and tumor treatment, we focus on the research progress of nanomedicine combined with CAR-T therapy, and systematically review the strategies and examples in recent years in the aspects of in vivo delivery of mRNA, regulation of tumor microenvironment, combination with photothermal therapy. And we also look forward to the future direction of this filed.
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Humans
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Receptors, Chimeric Antigen/therapeutic use*
;
Pharmaceutical Preparations/metabolism*
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Antigens, Neoplasm/metabolism*
;
Lung Neoplasms/metabolism*
;
Neoplasms/metabolism*
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T-Lymphocytes
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Tumor Microenvironment
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Nanoparticles/therapeutic use*
3.Clinical features and prognosis of childhood B-lineage acute lymphoblastic leukemia expressing the PRAME gene.
Feng ZHANG ; Ai-Dong LU ; Ying-Xi ZUO ; Ming-Ming DING ; Yue-Ping JIA ; Le-Ping ZHANG
Chinese Journal of Contemporary Pediatrics 2022;24(5):543-549
OBJECTIVES:
To study the clinical and prognostic significance of the preferentially expressed antigen of melanoma (PRAME) gene in the absence of specific fusion gene expression in children with B-lineage acute lymphoblastic leukemia (B-ALL).
METHODS:
A total of 167 children newly diagnosed with B-ALL were enrolled, among whom 70 were positive for the PRAME gene and 97 were negative. None of the children were positive for MLL-r, BCR/ABL, E2A/PBX1, or ETV6/RUNX1. The PRAME positive and negative groups were analyzed in terms of clinical features, prognosis, and related prognostic factors.
RESULTS:
Compared with the PRAME negative group, the PRAME positive group had a significantly higher proportion of children with the liver extending >6 cm below the costal margin (P<0.05). There was a significant reduction in the PRAME copy number after induction chemotherapy (P<0.05). In the minimal residual disease (MRD) positive group after induction chemotherapy, the PRAME copy number was not correlated with the MRD level (P>0.05). In the MRD negative group, there was also no correlation between them (P>0.05). The PRAME positive group had a significantly higher 4-year event-free survival rate than the PRAME negative group (87.5%±4.6% vs 73.5%±4.6%, P<0.05), while there was no significant difference between the two groups in the 4-year overall survival rate (88.0%±4.4% vs 85.3%±3.8%, P>0.05). The Cox proportional-hazards regression model analysis showed that positive PRAME expression was a protective factor for event-free survival rate in children with B-ALL (P<0.05).
CONCLUSIONS
Although the PRAME gene cannot be monitored as MRD, overexpression of PRAME suggests a good prognosis in B-ALL.
Acute Disease
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Antigens, Neoplasm/therapeutic use*
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Child
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Humans
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Neoplasm, Residual/diagnosis*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
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Prognosis
4.Mechanism of Linderae Radix against gastric cancer based on network pharmacology and in vitro experimental validation.
Xiao LIANG ; Jun-Hao ZHANG ; Hao-Tian BAI ; Ya-Lan LI ; Shu-Hui SUN ; Qian-Qian ZHANG ; Jing YANG ; Rui WANG
China Journal of Chinese Materia Medica 2022;47(18):5008-5021
The present study explored the main active ingredients and the underlying mechanism of Linderae Radix the treatment of gastric cancer by network pharmacology, molecular docking, and in vitro cell experiments. TCMSP, OMIM and GeneCards database were used to obtain the active ingredients of Linderae Radix to predict the related targets of both Linderae Radix and gastric cancer. After screening the common potential action targets, the STRING database was used to construct the PPI network for protein interaction of the two common targets. Enrichment analysis of GO and KEGG by DAVID database. Based on STRING and DAVID platform data, Cytoscape software was used to construct an "active ingredient-target" network and an "active ingredient-target-pathway" network. Molecular docking was performed using the AutoDock Vina to predict the binding of the active components to the key action targets, and finally the key targets and pathways were verified in vitro. According to the prediction results, there were 9 active components, 179 related targets of Radix Linderae, 107 common targets of Linderae Radix and gastric cancer, 693 biological processes, 57 cell compositions, and 129 molecular functions involved in the targets, and 161 signaling pathways involved in tumor antigen p53, hypoxia-indu-cible factor 1, etc. Molecular docking results showed that the core component, jimadone, had high binding activity with TP53. Finally, in an in vitro experiment, the screened radix linderae active ingredient gemmadone is used for preliminarily verifying the core targets and pathways of the human gastric cancer cell SGC-7901, The results showed that germacrone could significantly inhibit the proliferation of gastric cancer cells and induce the apoptosis of SGC-7901 by regulating the expression of p53, Bax, Bcl-2 and other key proteins. In summary, Radix Linderae can control the occurrence and development of gastric cancer through multi-components, multi-targets and multi-pathways, which will provide theoretical basis for further clinical discussion on the mechanism of Radix Linderae in treating gastric cancer.
Antigens, Neoplasm
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Drugs, Chinese Herbal/therapeutic use*
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Humans
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Lindera/chemistry*
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Medicine, Chinese Traditional
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Molecular Docking Simulation
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Network Pharmacology
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Stomach Neoplasms/drug therapy*
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Tumor Suppressor Protein p53
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bcl-2-Associated X Protein
5.Effectiveness and Mechanism of Decitabine Maintenance Therapy in Patients with Medium and Low-risk Acute Myeloid Leukemia.
Yi DONG ; Jia WANG ; Qian-Shan TAO ; Yuan-Yuan SHEN ; Zhi-Min ZHAI
Journal of Experimental Hematology 2022;30(5):1369-1375
OBJECTIVE:
To investigate the efficacy and mechanism of decitabine maintenance therapy in patients with medium and low-risk acute myeloid leukemia(AML).
METHODS:
The newly diagnosed medium- and low-risk AML patients in the Second Affiliated Hospital of Anhui Medical University from December 2016 to December 2020 were retrospectively analyzed. Seventy-eight AML patients who were still in remission after consolidation treatment were divided into maintenance treatment group (31 cases) and control group (47 cases). The maintenance treatment patients received decitabine at 20 mg/m2 IV daily for 5 days, every three months for 6 cycles, the control group was only observed and tested regularly. Follow-up was completed by telephone or by viewing outpatient or inpatient medical records. Primary indicators were overall survival (OS), and secondary indicators include relapse-free survival (RFS), tolerance, cellular immune function and analysis of risk factors related to survival.
RESULTS:
Median RFS in maintenance theatment and control groups was 30.1(26.2-33.8) months and 24.3(21.7-30.3) months (P=0.011), median OS 34.7(29.8-39.7) months and 27.7(24.1-31.3) months respectively(P=0.024), with a statistically significant difference. For the univariate and multivariate Cox regression analysis, only the minimal residual disease (HR=25.185, P<0.001) and the treatment methods (HR=0.124, P<0.001) affected the PFS and OS of patients. In the maintenance treatment group, CD3+T cells, CD8+T cells and NK cells increased significantly after decitabine maintenance treatment, and the regulatory T cells decreased significantly (P<0.05). Patients had a low incidence of grade 3-4 adverse events, hematological adverse events were mainly neutropenia and thrombocytopenia, non-hematological adverse events were mainly digestive tract symptoms, and the patient was well tolerated.
CONCLUSION
Maintenance treatment with decitabine provided benefit survival in patients with medium- and low-risk AML and is well tolerated. The mechanism may be inhibition the proliferation of regulatory T cells, induce and enhance the cytotoxic effect of CD8+ T cells on tumor antigens.
Antigens, Neoplasm
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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CD8-Positive T-Lymphocytes
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Decitabine/therapeutic use*
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Humans
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Leukemia, Myeloid, Acute/drug therapy*
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Retrospective Studies
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Treatment Outcome
6.Anti-CD19 CART (C-CAR011) Therapy for Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma.
Lu ZHANG ; Yan ZHANG ; Dao-Bin ZHOU
Journal of Experimental Hematology 2021;29(4):1141-1147
OBJECTIVE:
To evaluate the safety and efficacy of C-CAR011 in the treatment of relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) patients.
METHODS:
B-NHL patients treated with C-CAR011 infusion following lympho-depletion were enrolled. All the patients were followed up for 1 year after C-CAR011 treatment(5.0×10
RESULTS:
The ratio of the male and female of 6 patients was 1∶1, and the patients were treated with C-CAR011 at a dose of 5.0×10
CONCLUSION
C-CAR011 is a safe treatment option for R/R B-NHL; some patients could achieve long-term sustained responses after C-CAR011 infusion(ClinicalTiral.gov number, NCT03483688).
Antigens, CD19/therapeutic use*
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Antineoplastic Combined Chemotherapy Protocols
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B-Lymphocytes
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Female
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Humans
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Lymphoma, Follicular
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Lymphoma, Large B-Cell, Diffuse
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Male
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Middle Aged
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Neoplasm Recurrence, Local/drug therapy*
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Treatment Outcome
7.Bortezomib improves progression-free survival in multiple myeloma patients overexpressing preferentially expressed antigen of melanoma.
Yazhen QIN ; Jin LU ; Li BAO ; Honghu ZHU ; Jinlan LI ; Lingdi LI ; Yueyun LAI ; Hongxia SHI ; Yazhe WANG ; Yanrong LIU ; Bin JIANG ; Xiaojun HUANG ;
Chinese Medical Journal 2014;127(9):1666-1671
BACKGROUNDSignificant efforts have been made to identify factors that differentiate patients treated with novel therapies, such as bortezomib in multiple myeloma (MM). The exact expression pattern and prognostic value of the cancer/testis antigen preferentially expressed antigen of melanoma (PRAME) in MM are unknown and were explored in this study.
METHODSThe transcript level of PRAME was detected in bone marrow specimens from 100 newly diagnosed MM patients using real-time quantitative polymerase chain reaction, and the prognostic value of PRAME was determined through retrospective survival analysis. PRAME expression higher than the upper limit of normal bone marrow was defined as PRAME overexpression or PRAME (+).
RESULTSSixty-two patients (62.0%) overexpressed PRAME. PRAME overexpression showed no prognostic significance to either overall survival (n = 100) or progression-free survival (PFS, n = 96, all P > 0.05) of patients. The patients were also categorized according to regimens with or without bortezomib. PRAME overexpression tended to be associated with a lower two-year PFS rate in patients treated with non-bortezomib-containing regimens (53.5% vs. 76.9%, P = 0.071). By contrast, it was not associated with the two-year PFS rate in patients with bortezomib-containing regimens (77.5% vs. 63.9%, P > 0.05). When the patients were categorized into PRAME (+) and PRAME (-) groups, treatment with bortezomibcontaining regimens predicted a higher two-year PFS rate in PRAME (+) patients (77.5% vs. 53.5%, P = 0.027) but showed no significant effect on two-year PFS rate in PRAME (-) patients (63.9% vs. 76.9%, P > 0.05).
CONCLUSIONPRAME overexpression might be an adverse prognostic factor of PFS in MM patients treated with non-bortezomib-containing regimens. Bortezomib improves PFS in patients overexpressing PRAME.
Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm ; metabolism ; Boronic Acids ; therapeutic use ; Bortezomib ; Disease-Free Survival ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; metabolism ; mortality ; Pyrazines ; therapeutic use ; Real-Time Polymerase Chain Reaction ; Young Adult
8.Advances in immunotherapy for pediatric cancer.
Xiaojun XU ; Haizhao ZHAO ; Yongmin TANG
Chinese Journal of Pediatrics 2014;52(3):231-234
Adolescent
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Antibodies, Monoclonal
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therapeutic use
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Antigens, Neoplasm
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immunology
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Cancer Vaccines
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immunology
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Child
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Child, Preschool
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Humans
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Immunotherapy
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methods
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Infant
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Killer Cells, Natural
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immunology
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Lymphocyte Transfusion
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Neoplasms
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immunology
;
therapy
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Pediatrics
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Stem Cell Transplantation
9.Prognostic impact of epithelial cell adhesion molecule in ovarian cancer patients.
Journal of Gynecologic Oncology 2014;25(4):352-354
No abstract available.
Antigens, Neoplasm/*metabolism
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Antineoplastic Agents/*therapeutic use
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Cell Adhesion Molecules/*metabolism
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Female
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Humans
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Neoplasms, Glandular and Epithelial/*diagnosis
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Organoplatinum Compounds/*therapeutic use
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Ovarian Neoplasms/*diagnosis
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Tumor Markers, Biological/*metabolism
10.Overexpression of the epithelial cell adhesion molecule is associated with a more favorable prognosis and response to platinum-based chemotherapy in ovarian cancer.
Hannah WOOPEN ; Klaus PIETZNER ; Rolf RICHTER ; Christina FOTOPOULOU ; Thomas JOENS ; Elena Ioana BRAICU ; Hakan MELLSTEDT ; Sven MAHNER ; Horst LINDHOFER ; Silvia DARB-ESFAHANI ; Carsten DENKERT ; Jalid SEHOULI
Journal of Gynecologic Oncology 2014;25(3):221-228
OBJECTIVE: Epithelial cell adhesion molecule (EpCAM) has experienced a renaissance lately as a binding site for targeted therapy as well as a prognostic marker in epithelial malignancies. Aim of this study was to study EpCAM as a potential prognostic marker in epithelial ovarian cancer (EOC). METHODS: EpCAM expression was assessed by immunohistochemistry on paraffin-embedded primary EOC-tissue samples. EpCAM overexpression was defined as an expression of EpCAM of 76% to 100%. Tissue samples and clinical data were systematically collected within the international and multicenter "Tumorbank Ovarian Cancer" network. RESULTS: Seventy-four patients, diagnosed with EOC between 1994 and 2009, were included in the study (median age, 56 years; range, 31 to 86 years). The majority of the patients (81.1%) presented with an advanced stage International Federation of Gynecology and Obstetrics (FIGO) III/IV disease. Histology was of the serous type in 41 patients (55.4%), endometrioid in 19 (25.6%), and mucinous in 14 (19%). EpCAM was overexpressed in 87.7%. Serous tumors overexpressed EpCAM significantly more often than mucinous tumors (87.8% vs. 78.6%, p=0.045); while no significant difference was noted between the other histological subgroups. EpCAM overexpression was significantly associated with a better progression free survival and higher response rates to platinum based chemotherapy (p=0.040 and p=0.048, respectively). EpCAM was identified as an independent prognostic marker for overall survival (p=0.022). CONCLUSION: Our data indicate a significant association of EpCAM overexpression with a more favorable survival in EOC-patients. Serous cancers showed a significant EpCAM overexpression compared to mucinous types. Larger multicenter analyses are warranted to confirm these findings.
Adult
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Aged
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Aged, 80 and over
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Antigens, Neoplasm/*metabolism
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Antineoplastic Agents/*therapeutic use
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Carboplatin/therapeutic use
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Cell Adhesion Molecules/*metabolism
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Female
;
Humans
;
Kaplan-Meier Estimate
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Middle Aged
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Neoplasm Proteins/metabolism
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Neoplasm Staging
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Neoplasms, Glandular and Epithelial/*diagnosis/drug therapy/pathology
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Organoplatinum Compounds/*therapeutic use
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Ovarian Neoplasms/*diagnosis/drug therapy/pathology
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Paclitaxel/therapeutic use
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Prognosis
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Tissue Banks
;
Treatment Outcome
;
Tumor Markers, Biological/*metabolism

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