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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

含铂化疗期间卵巢癌循环肿瘤细胞的可塑性

卷 21, 期 11, 2021

发表于: 20 July, 2021

页: [965 - 974] 页: 10

弟呕挨: 10.2174/1568009621666210720141229

价格: $65

摘要

背景：循环肿瘤细胞 (CTC) 是转移和复发的潜在来源。关于卵巢癌 (OC) CTC 分子特征的数据有限。 目的：本研究旨在评估化疗（CT）前后两个OC CTC亚群中TGFβ、CXCL2、VEGFA和ERCC1的表达，以及它们与临床特征的关系。 方法：在治疗前和 3 个周期的含铂 CT 后，使用免疫磁分离富集两个 CTC 亚群（EpCAM+CK18+E-cadherin+；EpCAM+CK18+Vimentin+）。使用 RT-qPCR 评估 mRNA 的表达。 结果：该研究包括 31 名 I-IV 期 OC 患者。在 CT 期间，与初始水平相比，两个部分的 TGFβ 水平都有所增加（p=0.054）。新辅助期间 E-cadherin+ CTC 中 ERCC1 的表达高于辅助 CT (p=0.004)。与初始相比，新辅助 CT 期间 E-cadherin+ CTC 中的 CXCL2 水平增加（p=0.038）。 CT 期间波形蛋白 + CTC 中 TGF-β 的表达与疾病阶段呈负相关（p=0.003）。 CT前的主成分分析显示一个成分结合了VEGFA、TGFβ、CXCL2，一个成分结合了ERCC1和VEGFA；在 CT 期间，组分 1 包含 ERCC1 和 VEGFA，组分 2 - TGFβ 和 CXCL2 在两个部分中。 CT 期间 E-cadherin+ CTC 中 ERCC1 表达增加与多变量分析中的无进展生存期 (PFS) 降低相关 (HR 1.11 (95% CI 1.03-1.21, p=0.009)。 结论：EpCAM+ OC CTC 具有表型异质性，这可能反映了其转移潜能的变异性。 CT 改变了 CTC 的分子特征。 CT 期间 EpCAM+ CTC 中 TGFβ 的表达增加。 CT 期间 EpCAM+CK18+E-cadherin+ CTC 中的高 ERCC1 表达与 OC 中 PFS 降低有关。

关键词: 卵巢癌、循环肿瘤细胞、ERCC1、CXCL2、TGFbeta、VEGFA、EpCAM、上皮-间质转化。

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[1]
Cooke, S.L.; Brenton, J.D. Evolution of platinum resistance in high-grade serous ovarian cancer. Lancet Oncol., 2011, 12(12), 1169-1174.
[http://dx.doi.org/10.1016/S1470-2045(11)70123-1] [PMID: 21742554]
[2]
Ledermann, J.A.; Raja, F.A.; Fotopoulou, C.; Gonzalez-Martin, A.; Colombo, N.; Sessa, C. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol., 2013, 24(Suppl. 6), vi24-vi32.
[http://dx.doi.org/10.1093/annonc/mdt333] [PMID: 24078660]
[3]
Beachler, D.C.; Lamy, F-X.; Russo, L.; Taylor, D.H.; Dinh, J.; Yin, R.; Jamal-Allial, A.; Dychter, S.; Lanes, S.; Verpillat, P. A real-world study on characteristics, treatments and outcomes in US patients with advanced stage ovarian cancer. J. Ovarian Res., 2020, 13(1), 101.
[http://dx.doi.org/10.1186/s13048-020-00691-y] [PMID: 32867806]
[4]
Kiss, I.; Kolostova, K.; Pawlak, I.; Bobek, V. Circulating tumor cells in gynaecological malignancies. J BUON., 2020, 25(1), 40-50.
[5]
Liu, T.; Ma, Q.; Zhang, Y.; Wang, X.; Xu, K.; Yan, K.; Dong, W.; Fan, Q.; Zhang, Y.; Qiu, X. Self-seeding circulating tumor cells promote the proliferation and metastasis of human osteosarcoma by upregulating interleukin-8. Cell Death Dis., 2019, 10(8), 575.
[http://dx.doi.org/10.1038/s41419-019-1795-7] [PMID: 31366916]
[6]
Yang, C.; Zou, K.; Zheng, L.; Xiong, B. Prognostic and clinicopathological significance of circulating tumor cells detected by RT-PCR in non-metastatic colorectal cancer: A meta-analysis and systematic review. BMC Cancer, 2017, 17(1), 725.
[http://dx.doi.org/10.1186/s12885-017-3704-8] [PMID: 29115932]
[7]
Wang, J.; Wang, K.; Xu, J.; Huang, J.; Zhang, T. Prognostic significance of circulating tumor cells in non-small-cell lung cancer patients: A meta-analysis. PLoS One, 2013, 8(11), e78070.
[http://dx.doi.org/10.1371/journal.pone.0078070] [PMID: 24223761]
[8]
Ramirez, J-M.; Fehm, T.; Orsini, M.; Cayrefourcq, L.; Maudelonde, T.; Pantel, K.; Alix-Panabières, C. Prognostic relevance of viable circulating tumor cells detected by EPISPOT in metastatic breast cancer patients. Clin. Chem., 2014, 60(1), 214-221.
[http://dx.doi.org/10.1373/clinchem.2013.215079] [PMID: 24255082]
[9]
Habli, Z.; AlChamaa, W.; Saab, R.; Kadara, H.; Khraiche, M.L. Circulating tumor cell detection technologies and clinical utility: Challenges and opportunities. Cancers (Basel), 2020, 12(7), E1930.
[http://dx.doi.org/10.3390/cancers12071930] [PMID: 32708837]
[10]
Mentis, A.A.; Grivas, P.D.; Dardiotis, E.; Romas, N.A.; Papavassiliou, A.G. Circulating tumor cells as trojan horse for understanding, preventing, and treating cancer: A critical appraisal. Cell. Mol. Life Sci., 2020, 77(18), 3671-3690.
[http://dx.doi.org/10.1007/s00018-020-03529-4] [PMID: 32333084]
[11]
Lowes, L. E.; Allan, A. L. Circulating tumor cells and implications of the epithelial-to-mesenchymal transition. 2018, 83, 121-181.
[http://dx.doi.org/10.1016/bs.acc.2017.10.004]
[12]
Tada, H.; Takahashi, H.; Ida, S.; Nagata, Y.; Chikamatsu, K. Epithelial–mesenchymal transition status of circulating tumor cells is associated with tumor relapse in head and neck squamous cell carcinoma. Anticancer Res., 2020, 40(6), 3559-3564.
[http://dx.doi.org/10.21873/anticanres.14345]
[13]
Banys-Paluchowski, M.; Fehm, T.; Neubauer, H.; Paluchowski, P.; Krawczyk, N.; Meier-Stiegen, F.; Wallach, C.; Kaczerowsky, A.; Gebauer, G. Clinical relevance of circulating tumor cells in ovarian, fallopian tube and peritoneal cancer. Arch. Gynecol. Obstet., 2020, 301(4), 1027-1035.
[http://dx.doi.org/10.1007/s00404-020-05477-7] [PMID: 32144573]
[14]
Kim, M.; Suh, D.H.; Choi, J.Y.; Bu, J.; Kang, Y-T.; Kim, K.; No, J.H.; Kim, Y.B.; Cho, Y-H. Post-debulking circulating tumor cell as a poor prognostic marker in advanced stage ovarian cancer: A prospective observational study. Medicine (Baltimore), 2019, 98(20), e15354.
[http://dx.doi.org/10.1097/MD.0000000000015354] [PMID: 31096435]
[15]
Zhou, Y.; Bian, B.; Yuan, X.; Xie, G.; Ma, Y.; Shen, L. Prognostic value of circulating tumor cells in ovarian cancer: A meta-analysis. PLoS One, 2015, 10(6), e0130873.
[http://dx.doi.org/10.1371/journal.pone.0130873] [PMID: 26098665]
[16]
Obermayr, E.; Castillo-Tong, D.C.; Pils, D.; Speiser, P.; Braicu, I.; Van Gorp, T.; Mahner, S.; Sehouli, J.; Vergote, I.; Zeillinger, R. Molecular characterization of circulating tumor cells in patients with ovarian cancer improves their prognostic significance - a study of the OVCAD consortium. Gynecol. Oncol., 2013, 128(1), 15-21.
[http://dx.doi.org/10.1016/j.ygyno.2012.09.021] [PMID: 23017820]
[17]
Guffanti, F.; Alvisi, M.F.; Caiola, E.; Ricci, F.; De Maglie, M.; Soldati, S.; Ganzinelli, M.; Decio, A.; Giavazzi, R.; Rulli, E.; Damia, G. Impact of ercc1, xpf and dna polymerase β expression on platinum response in patient-derived ovarian cancer xenografts. Cancers (Basel), 2020, 12(9), E2398.
[http://dx.doi.org/10.3390/cancers12092398] [PMID: 32847049]
[18]
Ntellas, P.; Mavroeidis, L.; Gkoura, S.; Gazouli, I.; Amylidi, A-L.; Papadaki, A.; Zarkavelis, G.; Mauri, D.; Karpathiou, G.; Kolettas, E.; Batistatou, A.; Pentheroudakis, G. Old player-new tricks: Non angiogenic effects of the vegf/vegfr pathway in cancer. Cancers (Basel), 2020, 12(11), E3145.
[http://dx.doi.org/10.3390/cancers12113145] [PMID: 33121034]
[19]
Lamouille, S.; Xu, J.; Derynck, R. Molecular mechanisms of epithelial-mesenchymal transition. Nat. Rev. Mol. Cell Biol., 2014, 15(3), 178-196.
[http://dx.doi.org/10.1038/nrm3758] [PMID: 24556840]
[20]
Zhang, Z.; Tan, X.; Luo, J.; Cui, B.; Lei, S.; Si, Z.; Shen, L.; Yao, H. GNA13 promotes tumor growth and angiogenesis by upregulating CXC chemokines via the NF-κB signaling pathway in colorectal cancer cells. Cancer Med., 2018, 7(11), 5611-5620.
[http://dx.doi.org/10.1002/cam4.1783] [PMID: 30267476]
[21]
Zhang, C.; Gao, S.; Hou, J. ERCC1 expression and platinum chemosensitivity in patients with ovarian cancer: A meta-analysis. Int. J. Biol. Markers, 2020, 35(4), 12-19.
[http://dx.doi.org/10.1177/1724600820963396] [PMID: 33126828]
[22]
Yu, L.; Deng, L.; Li, J.; Zhang, Y.; Hu, L. The prognostic value of vascular endothelial growth factor in ovarian cancer: A systematic review and meta-analysis. Gynecol. Oncol., 2013, 128(2), 391-396.
[http://dx.doi.org/10.1016/j.ygyno.2012.11.002] [PMID: 23142075]
[23]
Coosemans, A.; Decoene, J.; Baert, T.; Laenen, A.; Kasran, A.; Verschuere, T.; Seys, S.; Vergote, I. Immunosuppressive parameters in serum of ovarian cancer patients change during the disease course. OncoImmunology, 2015, 5(4), e1111505.
[http://dx.doi.org/10.1080/2162402X.2015.1111505] [PMID: 27141394]
[24]
Roane, B.M.; Arend, R.C.; Birrer, M.J. Review: Targeting the transforming growth factor-beta pathway in ovarian cancer. Cancers (Basel), 2019, 11(5), E668.
[http://dx.doi.org/10.3390/cancers11050668] [PMID: 31091744]
[25]
Zhou, J.; Jiang, W.; Huang, W.; Ye, M.; Zhu, X. Prognostic values of transforming growth factor-beta subtypes in ovarian cancer. BioMed Res. Int., 2020, 2020, 2170606.
[http://dx.doi.org/10.1155/2020/2170606] [PMID: 32351985]
[26]
Ye, Q.; Zhai, X.; Wang, W.; Zhang, S.; Zhu, H.; Wang, D.; Wang, C. Overexpression of growth-related oncogene-β is associated with tumorigenesis, metastasis, and poor prognosis in ovarian cancer. Dis. Markers, 2015, 2015, 387382.
[http://dx.doi.org/10.1155/2015/387382] [PMID: 26063953]
[27]
Takeyama, Y.; Kato, M.; Tamada, S.; Azuma, Y.; Shimizu, Y.; Iguchi, T.; Yamasaki, T.; Gi, M.; Wanibuchi, H.; Nakatani, T. Myeloid-derived suppressor cells are essential partners for immune checkpoint inhibitors in the treatment of cisplatin-resistant bladder cancer. Cancer Lett., 2020, 479, 89-99.
[http://dx.doi.org/10.1016/j.canlet.2020.03.013] [PMID: 32200039]
[28]
Friedlander, M.; Trimble, E.; Tinker, A.; Alberts, D.; Avall-Lundqvist, E.; Brady, M.; Harter, P.; Pignata, S.; Pujade-Lauraine, E.; Sehouli, J.; Vergote, I.; Beale, P.; Bekkers, R.; Calvert, P.; Copeland, L.; Glasspool, R.; Gonzalez-Martin, A.; Katsaros, D.; Kim, J.W.; Miller, B.; Provencher, D.; Rubinstein, L.; Atri, M.; Zeimet, A.; Bacon, M.; Kitchener, H.; Stuart, G.C. Clinical trials in recurrent ovarian cancer. Int. J. Gynecol. Cancer, 2011, 21(4), 771-775.
[http://dx.doi.org/10.1097/IGC.0b013e31821bb8aa] [PMID: 21543939]
[29]
Zubtsov, D.A.; Zubtsova, Z.I.; Legchenko, E.V.; Lavrov, A.V.; Goldstein, D.V. Comprehensive method for determining circulating tumor cells in the blood of breast cancer patients. 2014, 2522923.
[30]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Δ Δ C(T)) Method. Methods, 2001, 25(4), 402-408.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[31]
Hoppenot, C.; Eckert, M.A.; Tienda, S.M.; Lengyel, E. Who are the long-term survivors of high grade serous ovarian cancer? Gynecol. Oncol., 2018, 148(1), 204-212.
[http://dx.doi.org/10.1016/j.ygyno.2017.10.032] [PMID: 29128106]
[32]
Klymenko, Y.; Johnson, J.; Bos, B.; Lombard, R.; Campbell, L.; Loughran, E.; Stack, M.S. Heterogeneous cadherin expression and multicellular aggregate dynamics in ovarian cancer dissemination. Neoplasia, 2017, 19(7), 549-563.
[http://dx.doi.org/10.1016/j.neo.2017.04.002] [PMID: 28601643]
[33]
Blassl, C.; Kuhlmann, J.D.; Webers, A.; Wimberger, P.; Fehm, T.; Neubauer, H. Gene expression profiling of single circulating tumor cells in ovarian cancer - establishment of a multi-marker gene panel. Mol. Oncol., 2016, 10(7), 1030-1042.
[http://dx.doi.org/10.1016/j.molonc.2016.04.002] [PMID: 27157930]
[34]
Huang, R.Y-J.; Wong, M.K.; Tan, T.Z.; Kuay, K.T.; Ng, A.H.C.; Chung, V.Y.; Chu, Y-S.; Matsumura, N.; Lai, H-C.; Lee, Y.F.; Sim, W-J.; Chai, C.; Pietschmann, E.; Mori, S.; Low, J.J.H.; Choolani, M.; Thiery, J.P. An EMT spectrum defines an anoikis-resistant and spheroidogenic intermediate mesenchymal state that is sensitive to e-cadherin restoration by a src-kinase inhibitor, saracatinib (AZD0530). Cell Death Dis., 2013, 4(11), e915.
[http://dx.doi.org/10.1038/cddis.2013.442] [PMID: 24201814]
[35]
Quan, Q.; Wang, X.; Lu, C.; Ma, W.; Wang, Y.; Xia, G.; Wang, C.; Yang, G. Cancer stem-like cells with hybrid epithelial/mesenchymal phenotype leading the collective invasion. Cancer Sci., 2020, 111(2), 467-476.
[http://dx.doi.org/10.1111/cas.14285] [PMID: 31845453]
[36]
Mehdi, S.; Macdonald, E.; Galpin, K.; Landry, D.A.; Rodriguez, G.; Vanderhyden, B.; Bachvarov, D. LY75 suppression in mesenchymal epithelial ovarian cancer cells generates a stable hybrid eoc cellular phenotype, associated with enhanced tumor initiation, spreading and resistance to treatment in orthotopic xenograft mouse model. Int. J. Mol. Sci., 2020, 21(14), E4992.
[http://dx.doi.org/10.3390/ijms21144992] [PMID: 32679765]
[37]
Abreu, M.; Cabezas-Sainz, P.; Alonso-Alconada, L.; Ferreirós, A.; Mondelo-Macía, P.; Lago-Lestón, R.M.; Abalo, A.; Díaz, E.; Palacios-Zambrano, S.; Rojo-Sebastian, A.; López-López, R.; Sánchez, L.; Moreno-Bueno, G.; Muinelo-Romay, L. Circulating tumor cells characterization revealed timp1 as a potential therapeutic target in ovarian cancer. Cells, 2020, 9(5), E1218.
[http://dx.doi.org/10.3390/cells9051218] [PMID: 32423054]
[38]
Fabregat, A.; Jupe, S.; Matthews, L.; Sidiropoulos, K.; Gillespie, M.; Garapati, P.; Haw, R.; Jassal, B.; Korninger, F.; May, B.; Milacic, M.; Roca, C.D.; Rothfels, K.; Sevilla, C.; Shamovsky, V.; Shorser, S.; Varusai, T.; Viteri, G.; Weiser, J.; Wu, G.; Stein, L.; Hermjakob, H.; D’Eustachio, P. The reactome pathway knowledgebase. Nucleic Acids Res., 2018, 46(D1), D649-D655.
[http://dx.doi.org/10.1093/nar/gkx1132] [PMID: 29145629]
[39]
Hatzikirou, H.; Basanta, D.; Simon, M.; Schaller, K.; Deutsch, A. ‘Go or grow’: The key to the emergence of invasion in tumour progression? Math. Med. Biol., 2012, 29(1), 49-65.
[http://dx.doi.org/10.1093/imammb/dqq011] [PMID: 20610469]
[40]
Roque, R.; Costa Sousa, F.; Figueiredo-Dias, M. Epithelial-mesenchymal interconversions in ovarian cancer: The levels and functions of E-cadherin in intraabdominal dissemination. Oncol. Rev., 2020, 14(2), 475.
[http://dx.doi.org/10.4081/oncol.2020.475] [PMID: 32676171]
[41]
Taki, M.; Abiko, K.; Baba, T.; Hamanishi, J.; Yamaguchi, K.; Murakami, R.; Yamanoi, K.; Horikawa, N.; Hosoe, Y.; Nakamura, E.; Sugiyama, A.; Mandai, M.; Konishi, I.; Matsumura, N. Snail promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation. Nat. Commun., 2018, 9(1), 1685.
[http://dx.doi.org/10.1038/s41467-018-03966-7] [PMID: 29703902]
[42]
Kavandi, L.; Collier, M.A.; Nguyen, H.; Syed, V. Progesterone and calcitriol attenuate inflammatory cytokines CXCL1 and CXCL2 in ovarian and endometrial cancer cells. J. Cell. Biochem., 2012, 113(10), 3143-3152.
[http://dx.doi.org/10.1002/jcb.24191] [PMID: 22615136]
[43]
Jang, K.; Kim, M.; Gilbert, C.A.; Simpkins, F.; Ince, T.A.; Slingerland, J.M. VEGFA activates an epigenetic pathway upregulating ovarian cancer-initiating cells. EMBO Mol. Med., 2017, 9(3), 304-318.
[http://dx.doi.org/10.15252/emmm.201606840] [PMID: 28179359]
[44]
Yousefi, M.; Dehghani, S.; Nosrati, R.; Ghanei, M.; Salmaninejad, A.; Rajaie, S.; Hasanzadeh, M.; Pasdar, A. Current insights into the metastasis of epithelial ovarian cancer - hopes and hurdles. Cell Oncol. (Dordr.), 2020, 43(4), 515-538.
[http://dx.doi.org/10.1007/s13402-020-00513-9] [PMID: 32418122]
[45]
Sarkar, S.; Peng, C-C.; Tung, Y-C. Comparison of VEGF-A secretion from tumor cells under cellular stresses in conventional monolayer culture and microfluidic three-dimensional spheroid models. PLoS One, 2020, 15(11), e0240833.
[http://dx.doi.org/10.1371/journal.pone.0240833] [PMID: 33175874]
[46]
Prunier, C.; Baker, D.; Ten Dijke, P.; Ritsma, L. TGF-β family signaling pathways in cellular dormancy. Trends Cancer, 2019, 5(1), 66-78.
[http://dx.doi.org/10.1016/j.trecan.2018.10.010] [PMID: 30616757]
[47]
Desbois, M.; Udyavar, A.R.; Ryner, L.; Kozlowski, C.; Guan, Y.; Dürrbaum, M.; Lu, S.; Fortin, J-P.; Koeppen, H.; Ziai, J.; Chang, C-W.; Keerthivasan, S.; Plante, M.; Bourgon, R.; Bais, C.; Hegde, P.; Daemen, A.; Turley, S.; Wang, Y. Integrated digital pathology and transcriptome analysis identifies molecular mediators of T- cell exclusion in ovarian cancer. Nat. Commun., 2020, 11(1), 5583.
[http://dx.doi.org/10.1038/s41467-020-19408-2] [PMID: 33149148]
[48]
Kuhlmann, J.D.; Wimberger, P.; Bankfalvi, A.; Keller, T.; Schöler, S.; Aktas, B.; Buderath, P.; Hauch, S.; Otterbach, F.; Kimmig, R.; Kasimir-Bauer, S. ERCC1-positive circulating tumor cells in the blood of ovarian cancer patients as a predictive biomarker for platinum resistance. Clin. Chem., 2014, 60(10), 1282-1289.
[http://dx.doi.org/10.1373/clinchem.2014.224808] [PMID: 25015375]
[49]
Chebouti, I.; Kuhlmann, J.D.; Buderath, P.; Weber, S.; Wimberger, P.; Bokeloh, Y.; Hauch, S.; Kimmig, R.; Kasimir-Bauer, S. ERCC1-expressing circulating tumor cells as a potential diagnostic tool for monitoring response to platinum-based chemotherapy and for predicting post-therapeutic outcome of ovarian cancer. Oncotarget, 2017, 8(15), 24303-24313.
[http://dx.doi.org/10.18632/oncotarget.13286] [PMID: 28388557]
[50]
Gershkovitz, M.; Fainsod-Levi, T.; Zelter, T.; Sionov, R.V.; Granot, Z. TRPM2 modulates neutrophil attraction to murine tumor cells by regulating CXCL2 expression. Cancer Immunol. Immunother., 2019, 68(1), 33-43.
[http://dx.doi.org/10.1007/s00262-018-2249-2] [PMID: 30251149]
[51]
Micheli, D.C.; Jammal, M.P.; Martins-Filho, A.; Côrtes, J.R.X.M.; Souza, C.N.; Nomelini, R.S.; Murta, E.F.C.; Tavares- Murta, B.M. Serum cytokines and CXCR2: Potential tumour markers in ovarian neoplasms. Biomarkers, 2020, 25(6), 474-482.
[http://dx.doi.org/10.1080/1354750X.2020.1783574] [PMID: 32544350]
[52]
Saini, M.; Szczerba, B.M.; Aceto, N. Circulating tumor cell-neutrophil tango along the metastatic process. Cancer Res., 2019, 79(24), 6067-6073.
[http://dx.doi.org/10.1158/0008-5472.CAN-19-1972] [PMID: 31527091]
[53]
Mao, W.; Peters, H.L.; Sutton, M.N.; Orozco, A.F.; Pang, L.; Yang, H.; Lu, Z.; Bast, R.C., Jr The role of vascular endothelial growth factor, interleukin 8, and insulinlike growth factor in sustaining autophagic DIRAS3-induced dormant ovarian cancer xenografts. Cancer, 2019, 125(8), 1267-1280.
[http://dx.doi.org/10.1002/cncr.31935] [PMID: 30620384]
[54]
Li, X.; Hu, Z.; Shi, H.; Wang, C.; Lei, J.; Cheng, Y. Inhibition of vegfa increases the sensitivity of ovarian cancer cells to chemotherapy by suppressing vegfa-mediated autophagy. OncoTargets Ther., 2020, 13, 8161-8171.
[http://dx.doi.org/10.2147/OTT.S250392] [PMID: 32884298]

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