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TROP2

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https://www.readbyqxmd.com/read/28503956/sacituzumab-govitecan-an-antibody-drug-conjugate
#1
Sheena Sahota, Linda T Vahdat
Despite advances in the diagnosis and treatment of patients with cancer, patients with metastatic cancer have limited therapeutic options after initial lines of therapy. Understanding tumor biology has translated into the identification of actionable targets that resulted in therapeutics. Antibody-drug conjugates (ADC) are capitalizing on this explosion of scientific information. ADCs allow an antibody to a unique target to be conjugated via an innovative linker, to a highly toxic drug which is delivered to its target...
May 15, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28448983/intrauterine-growth-restriction-alters-the-postnatal-development-of-the-rat-cerebellum
#2
Annie R A McDougall, Vanny Wiradjaja, Aminath Azhan, Anqi Li, Nadia Hale, Mary E Wlodek, Stuart B Hooper, Megan J Wallace, Mary Tolcos
Intrauterine growth restriction (IUGR) is a major cause of antenatal brain injury. We aimed to characterize cerebellar deficits following IUGR and to investigate the potential underlying cellular and molecular mechanisms. At embryonic day 18, pregnant rats underwent either sham surgery (controls; n = 23) or bilateral uterine vessel ligation to restrict blood flow to fetuses (IUGR; n = 20). Offspring were collected at postnatal day 2 (P2), P7, and P35. Body weights were reduced at P2, P7, and P35 in IUGR offspring (p < 0...
April 28, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28423362/trop2-promotes-proliferation-migration-and-metastasis-of-gallbladder-cancer-cells-by-regulating-pi3k-akt-pathway-and-inducing-emt
#3
Xinxing Li, Shifeng Teng, Yanyan Zhang, Weigang Zhang, Xianwen Zhang, Kai Xu, Houshan Yao, Jun Yao, Haolu Wang, Xiaowen Liang, Zhiqian Hu
The human trophoblast cell surface antigen 2 (TROP2) is overexpressed in many cancers. However, its effect on proliferation, migration and metastasis of gallbladder cancer remains unclear. In this study, we found that TROP2 was highly expressed in gallbladder cancer. Overexpression of TROP2 was associated with poor prognosis. Knockdown of TROP2 in gallbladder cancer cell lines strongly inhibited the cell proliferation, clone formation, invasion and migration in vitro, while TROP2 overexpression had opposite effects...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404926/association-of-tumor-trop2-expression-with-prognosis-varies-among-lung-cancer-subtypes
#4
Kentaro Inamura, Yusuke Yokouchi, Maki Kobayashi, Hironori Ninomiya, Rie Sakakibara, Sophia Subat, Hiroko Nagano, Kimie Nomura, Sakae Okumura, Tomoko Shibutani, Yuichi Ishikawa
TROP2 is a transmembrane glycoprotein that is overexpressed in various cancers. Emerging evidence suggests that TROP2-targeting therapies are efficacious and safe in patients with multiple prior treatments. TROP2 is a promising target for lung cancer treatment; however, little is known regarding the association of TROP2 expression with clinicopathological/molecular features, including prognosis, in lung cancer. We examined consecutive cases of adenocarcinoma, squamous cell carcinoma (SqCC), and high-grade neuroendocrine tumor (HGNET) for the membranous expression of TROP2 using immunohistochemistry...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28386338/pigment-epithelium-derived-factor-pedf-peptide-promotes-the-expansion-of-hepatic-stem-progenitor-cells-via-erk-and-stat3-dependent-signaling
#5
Shou-Chuan Shih, Tsung-Chuan Ho, Show-Li Chen, Yeou-Ping Tsao
Hepatic stem/progenitor cells (HPC) have been considered as a potential cell source of an alternative to liver transplantation. Production of large numbers of autologous HPC from small pieces of live tissue is crucial for the application of HPC-based liver therapy. In this study, we demonstrated that a synthetic 44-amino acid peptide (44-mer) derived from pigment epithelium-derived factor (PEDF) can facilitate the production of a large number of actively dividing HPC from normal adult rat livers in a 35-day culture period...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28345466/tumor-associated-calcium-signal-transducer-2-regulates-neovascularization-of-non-small-cell-lung-cancer-via-activating-erk1-2-signaling-pathway
#6
Xiaobin Guo, Xiaoming Zhu, Limin Zhao, Xiao Li, Dongjun Cheng, Keqing Feng
Lung cancer, especially the non-small-cell lung cancer, is a highly aggressive vascular cancer with excessively activated signaling pathways. Tumor-associated calcium signal transducer 2, also known as trop2, was identified to be correlated with tumor proliferation and invasion of non-small-cell lung cancer; however, the biological role of trop2 in neovascularization of non-small-cell lung cancer remained elusive. In this study, we first verified that trop2 was overexpressed in non-small-cell lung cancer tissues as well as cell lines and that the increased expression of trop2 promoted non-small-cell lung cancer cell proliferation and invasion...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28298147/interrogating-bronchoalveolar-lavage-samples-via-exclusion-based-analyte-extraction
#7
Jacob J Tokar, Jay W Warrick, David J Guckenberger, Jamie M Sperger, Joshua M Lang, J Scott Ferguson, David J Beebe
Although average survival rates for lung cancer have improved, earlier and better diagnosis remains a priority. One promising approach to assisting earlier and safer diagnosis of lung lesions is bronchoalveolar lavage (BAL), which provides a sample of lung tissue as well as proteins and immune cells from the vicinity of the lesion, yet diagnostic sensitivity remains a challenge. Reproducible isolation of lung epithelia and multianalyte extraction have the potential to improve diagnostic sensitivity and provide new information for developing personalized therapeutic approaches...
June 2017: SLAS Technology
https://www.readbyqxmd.com/read/28256068/correlation-between-trop2-and-amphiregulin-coexpression-and-overall-survival-in-gastric-cancer
#8
Wei Zhao, Guipeng Ding, Jinbo Wen, Qi Tang, Hongmei Yong, Huijun Zhu, Shu Zhang, Zhenning Qiu, Zhenqing Feng, Jin Zhu
Gastric cancer (GC) is a multistep and multistage disease and the majority of GC cells could overexpressed one or more oncogenes. Trop2 and amphiregulin (AREG) are both overexpressed in various epithelial cell cancers and have the role in the increases tumor cells division and metastasis. However, little is known about the function and correlation of two oncogenes coexpressed in GC. The expression level of these two genes in 791 cases of GC tissues were tested, the correlations between two genes expression and clinical pathological characteristics and overall survival in GC patients through immunohistochemistry (IHC) were analyzed...
May 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28151644/improved-lysosomal-trafficking-can-modulate-the-potency-of-antibody-drug-conjugates
#9
Rachel M DeVay, Kathy Delaria, Guoyun Zhu, Charles Holz, Davide Foletti, Janette Sutton, Gary Bolton, Russell Dushin, Christine Bee, Jaume Pons, Arvind Rajpal, Hong Liang, David Shelton, Shu-Hui Liu, Pavel Strop
Antibody drug conjugates (ADCs) provide an efficacious and relatively safe means by which chemotherapeutic agents can be specifically targeted to cancer cells. In addition to the selection of antibody targets, ADCs offer a modular design that allows selection of ADC characteristics through the choice of linker chemistries, toxins, and conjugation sites. Many studies have indicated that release of toxins bound to antibodies via noncleavable linker chemistries relies on the internalization and intracellular trafficking of the ADC...
February 13, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28030564/poorly-differentiated-medullary-phenotype-predicts-poor-survival-in-early-lymph-node-negative-gastro-esophageal-adenocarcinomas
#10
Christoph Treese, Pedro Sanchez, Patricia Grabowski, Erika Berg, Hendrik Bläker, Martin Kruschewski, Oliver Haase, Michael Hummel, Severin Daum
BACKGROUND: 5-year survival rate in patients with early adenocarcinoma of the gastro-esophageal junction or stomach (AGE/S) in Caucasian patients is reported to be 60-80%. We aimed to identify prognostic markers for patients with UICC-I without lymph-node involvement (N0). METHODS: Clinical data and tissue specimen from patients with AGE/S stage UICC-I-N0, treated by surgery only, were collected retrospectively. Tumor size, lymphatic vessel or vein invasion, grading, classification systems (WHO, Lauren, Ming), expression of BAX, BCL-2, CDX2, Cyclin E, E-cadherin, Ki-67, TP53, TP21, SHH, Survivin, HIF1A, TROP2 and mismatch repair deficiency were analyzed using tissue microarrays and correlated with overall and tumor related survival...
2016: PloS One
https://www.readbyqxmd.com/read/28009986/conditionally-reprogrammed-normal-and-primary-tumor-prostate-epithelial-cells-a-novel-patient-derived-cell-model-for-studies-of-human-prostate-cancer
#11
Olga A Timofeeva, Nancy Palechor-Ceron, Guanglei Li, Hang Yuan, Ewa Krawczyk, Xiaogang Zhong, Geng Liu, Geeta Upadhyay, Aleksandra Dakic, Songtao Yu, Shuang Fang, Sujata Choudhury, Xueping Zhang, Andrew Ju, Myeong-Seon Lee, Han C Dan, Youngmi Ji, Yong Hou, Yun-Ling Zheng, Chris Albanese, Johng Rhim, Richard Schlegel, Anatoly Dritschilo, Xuefeng Liu
Our previous study demonstrated that conditional reprogramming (CR) allows the establishment of patient-derived normal and tumor epithelial cell cultures from a variety of tissue types including breast, lung, colon and prostate. Using CR, we have established matched normal and tumor cultures, GUMC-29 and GUMC-30 respectively, from a patient's prostatectomy specimen. These CR cells proliferate indefinitely in vitro and retain stable karyotypes. Most importantly, only tumor-derived CR cells (GUMC-30) produced tumors in xenografted SCID mice, demonstrating maintenance of the critical tumor phenotype...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/27887617/increased-expression-of-trop2-in-airway-basal-cells-potentially-contributes-to-airway-remodeling-in-chronic-obstructive-pulmonary-disease
#12
Qixiao Liu, Haijun Li, Qin Wang, Yuke Zhang, Wei Wang, Shuang Dou, Wei Xiao
BACKGROUND: The airway epithelium of chronic obstructive pulmonary disease (COPD) patients undergoes aberrant repair and remodeling after repetitive injury following exposure to environmental factors. Abnormal airway regeneration observed in COPD is thought to originate in the stem/progenitor cells of the airway epithelium, the basal cells (BCs). However, the molecular mechanisms underlying these changes remain unknown. Here, trophoblast cell surface antigen 2 (TROP2), a protein implicated in the regulation of stem cell activity, was examined in lung tissue samples from COPD patients...
November 25, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27793919/cell-surface-antibody-retention-influences-in-vivo-antitumor-activity-mediated-by-antibody-dependent-cellular-cytotoxicity
#13
Masahiro Ikeda, Kazunori Kato, Miki Yamaguchi, Hirofumi Hamada, Kazuyasu Nakamura, Yoshiyuki Sugimoto
BACKGROUND: Multiple factors affect the in vivo antitumor activity of antibody-based therapeutics; however, the influence of cell surface retention on antibody-dependent cellular cytotoxicity (ADCC) is not fully understood. Here we evaluated the importance of cell surface antibody retention in antitumor activity mediated by ADCC in vivo. MATERIALS AND METHODS: Two mAbs against tumor-associated calcium signal transducer 2 (TACSTD2/TROP2), AR47A6.4.2 and Pr1E11, were used...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27645103/impact-of-trop2-expression-on-prognosis-in-solid-tumors-a-systematic-review-and-meta-analysis
#14
Ping Zeng, Min-Bin Chen, Li-Na Zhou, Min Tang, Chao-Ying Liu, Pei-Hua Lu
Over-expression of TROP2 (the trophoblast cell surface antigen 2) was reported to predict poor prognosis in various solid tumors in number of studies. However, the results remained not comprehensive. Therefore, we here carried out this meta-analysis of relevant studies published on this topic to quantitatively evaluate the clinicopathological significance of TROP2 in solid tumors. Relevant articles were identified through searching the PubMed, Web of Science and Embase database. The primary outcomes were overall survival (OS) and disease-free survival (DFS)...
September 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27634768/v-src-oncogene-induces-trop2-proteolytic-activation-via-cyclin-d1
#15
Xiaoming Ju, Xuanmao Jiao, Adam Ertel, Mathew C Casimiro, Gabriele Di Sante, Shengqiong Deng, Zhiping Li, Agnese Di Rocco, Tingting Zhan, Adam Hawkins, Tanya Stoyanova, Sebastiano Andò, Alessandro Fatatis, Michael P Lisanti, Leonard G Gomella, Lucia R Languino, Richard G Pestell
Proteomic analysis of castration-resistant prostate cancer demonstrated the enrichment of Src tyrosine kinase activity in approximately 90% of patients. Src is known to induce cyclin D1, and a cyclin D1-regulated gene expression module predicts poor outcome in human prostate cancer. The tumor-associated calcium signal transducer 2 (TACSTD2/Trop2/M1S1) is enriched in the prostate, promoting prostate stem cell self-renewal upon proteolytic activation via a γ-secretase cleavage complex (PS1, PS2) and TACE (ADAM17), which releases the Trop2 intracellular domain (Trop2 ICD)...
November 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27310709/clinical-value-of-serum-trophoblast-cell-surface-protein-2-trop2-antibody-in-non-small-cell-lung-cancer-patients
#16
Zhuan Zheng, Xue-Jun Dong
OBJECTIVE: This study was to explore the clinical role of serum trophoblast cell surface protein 2 (TROP2) antibody in patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: We collected serum specimens from 117 NSCLC patients, 40 benign lung disease patients, and 60 healthy controls. TROP2 antibody concentrations were measured using enzyme-linked immunosorbent assay. RESULTS: Serum TROP2 antibody levels were higher in the NSCLC group compared to the control group (p < 0...
June 16, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/27283984/high-expression-of-trop2-characterizes-different-cell-subpopulations-in-androgen-sensitive-and-androgen-independent-prostate-cancer-cells
#17
Jinhan Xie, Christina Mølck, Sophie Paquet-Fifield, Lisa Butler, Erica Sloan, Sabatino Ventura, Frédéric Hollande
Progression of castration-resistant tumors is frequent in prostate cancer. Current systemic treatments for castration-resistant prostate cancer only produce modest increases in survival time and self-renewing Tumor-Initiating Cells (TICs) are suspected to play an important role in resistance to these treatments. However it remains unclear whether the same TICs display both chemo-resistance and self-renewing abilities throughout progression from early stage lesions to late, castration resistant tumors. Here, we found that treatment of mice bearing LNCaP-derived xenograft tumors with cytotoxic (docetaxel) and anti-androgen (flutamide) compounds enriched for cells that express TROP2, a putative TIC marker...
July 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27127000/overexpression-of-trophoblast-cell-surface-antigen-2-as-an-independent-marker-for-a-poor-prognosis-and-as-a-potential-therapeutic-target-in-epithelial-ovarian-carcinoma
#18
Ning Xu, Zhihong Zhang, Jin Zhu, Lu Xu, Yuhua Li, Lei Duan, Yuan Mao, Hongxia Li
Most patients with epithelial ovarian cancer (EOC) are diagnosed at an advanced stage, and therapeutic options for these patients are limited. The identification of suitable biomarkers could be helpful for patients with EOC, who might benefit from targeted therapies even in advanced stages of the disease. Trophoblast cell surface antigen 2 (TROP2) is highly expressed in various human malignant tumours; however, this has not been demonstrated clearly in EOC. In this study, we further evaluated whether TROP2 is a promising marker for EOC, and thus also a potential target for EOC immunotherapy...
April 2016: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/27050150/the-tumor-inhibitory-effectiveness-of-a-novel-anti-trop2-fab-conjugate-in-pancreatic-cancer
#19
Yuan Mao, Xiaoying Wang, Feng Zheng, Changjun Wang, Qi Tang, Xiaojun Tang, Ning Xu, Huiling Zhang, Dawei Zhang, Lin Xiong, Jie Liang, Jin Zhu
Human trophoblastic cell surface antigen 2 (Trop2) has been reported to act oncogenically. In this study, one-step quantitative real-time polymerase chain reaction (qPCR) test and immunohistochemistry (IHC) analysis with were employed to evaluate the relationship between Trop2 expression and the clinicopathological features of patients with PC. Then a novel anti-Trop2 Fab antibody was conjugated with Doxorubicin (DOX) to form Trop2Fab-DOX, an antibody-drug conjugate. This Trop2Fab-DOX conjugate was characterized by cell ELISA and immunofluorescence assay...
April 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/26989172/trop2-marks-transient-gastric-fetal-epithelium-and-adult-regenerating-cells-after-epithelial-damage
#20
Valeria Fernandez Vallone, Morgane Leprovots, Sandra Strollo, Gabriela Vasile, Anne Lefort, Frederick Libert, Gilbert Vassart, Marie-Isabelle Garcia
Mouse fetal intestinal progenitors lining the epithelium prior to villogenesis grow as spheroids when cultured ex vivo and express the transmembrane glycoprotein Trop2 as a marker. Here, we report the characterization of Trop2-expressing cells from fetal pre-glandular stomach, growing as immortal undifferentiated spheroids, and their relationship with gastric development and regeneration. Trop2(+) cells generating gastric spheroids differed from adult glandular Lgr5(+) stem cells, but appeared highly related to fetal intestinal spheroids...
May 1, 2016: Development
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