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https://www.readbyqxmd.com/read/29778888/rapid-phenotyping-of-cancer-stem-cells-using-multichannel-nanosensor-arrays
#1
Yingying Geng, Hira L Goel, Ngoc B Le, Tatsuyuki Yoshii, Rubul Mout, Gulen Y Tonga, John J Amante, Arthur M Mercurio, Vincent M Rotello
Cancer stem cells (CSCs) contribute to multidrug resistance, tumor recurrence and metastasis, making them prime therapeutic targets. Their ability to differentiate and lose stem cell properties makes them challenging to study. Currently, there is no simple assay that can capture and trace the dynamic phenotypic changes on the CSC surface. Here, we report rapid discrimination of breast CSCs from non-CSCs using a nanoparticle-fluorescent-protein based sensor. This nanosensor was employed to discriminate CSCs from non-CSCs, as well CSCs that had differentiated in vitro in two breast cancer models...
May 17, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29769644/translational-models-of-prostate-cancer-bone-metastasis
#2
REVIEW
Richard B Berish, Aymon N Ali, Patrick G Telmer, John A Ronald, Hon S Leong
Metastatic disease is the principal cause of prostate-cancer-related mortality. Our ability to accurately recapitulate the spread of prostate cancer to bone - the most common site of metastasis - is critical to the development of novel metastasis-directed therapies. Several translational models of prostate cancer bone metastasis have been developed, including animal models, cell line injection models, 3D in vitro models, bone implant models, and patient-derived xenograft models. The use of these models has led to numerous advances in elucidating the molecular mechanisms of metastasis and innovations in targeted therapy...
May 16, 2018: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29769196/an-in-vivo-screen-identifies-pygo2-as-a-driver-for-metastatic-prostate-cancer
#3
Xin Lu, Xiaolu Pan, Chang-Jiun Wu, Di Zhao, Shan Feng, Yong Zang, Rumi Lee, Sunada Khadka, Samirkumar B Amin, Eun-Jung Jin, Xiaoying Shang, Pingna Deng, Yanting Luo, William R Morgenlander, Jacqueline Weinrich, Xuemin Lu, Shan Jiang, Qing Chang, Nora M Navone, Patricia Troncoso, Ronald A DePinho, Y Alan Wang
Advanced prostate cancer displays conspicuous chromosomal instability and rampant copy number aberrations, yet the identity of functional drivers resident in many amplicons remain elusive. Here, we implemented a functional genomics approach to identify new oncogenes involved in prostate cancer progression. Through integrated analyses of focal amplicons in large prostate cancer genomic and transcriptomic datasets as well as genes upregulated in metastasis, 276 putative oncogenes were enlisted into an in vivo gain-of-function tumorigenesis screen...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29757368/the-long-noncoding-rna-landscape-of-neuroendocrine-prostate-cancer-and-its-clinical-implications
#4
Varune Rohan Ramnarine, Mohammed Alshalalfa, Fan Mo, Noushin Nabavi, Nicholas Erho, Mandeep Takhar, Robert Shukin, Sonal Brahmbhatt, Alexander Gawronski, Maxim Kobelev, Mannan Nouri, Dong Lin, Harrison Tsai, Tamara L Lotan, R Jefferey Karnes, Mark A Rubin, Amina Zoubeidi, Martin E Gleave, Cenk Sahinalp, Alexander W Wyatt, Stanislav V Volik, Himisha Beltran, Elai Davicioni, Yuzhuo Wang, Colin C Collins
Background: Treatment induced neuroendocrine prostate cancer (tNEPC) is an aggressive variant of late-stage metastatic castrate resistant (mCRPC) prostate cancer that commonly arises through neuroendocrine transdifferentiation (NEtD). Treatment options are limited, ineffective, and for most patients, results in death in less than a year. We previously developed a first-in-field patient-derived xenograft (PDX) model of NEtD. Longitudinal deep transcriptome profiling of this model enabled monitoring of dynamic transcriptional changes during NEtD and in the context of androgen deprivation...
May 10, 2018: GigaScience
https://www.readbyqxmd.com/read/29752717/tumor-progression-and-metastatic-dissemination-in-ovarian-cancer-after-dose-dense-or-conventional-paclitaxel-and-cisplatin-plus-bevacizumab
#5
Francesca Bizzaro, Francesca Falcetta, Elisa D'Agostini, Alessandra Decio, Lucia Minoli, Eugenio Erba, Fedro Alessandro Peccatori, Eugenio Scanziani, Nicoletta Colombo, Massimo Zucchetti, MariaRosa Bani, Paolo Ubezio, Raffaella Giavazzi
The efficacy of therapeutic regimens incorporating weekly or every-3-weeks paclitaxel (PTX) for ovarian cancer is debated. We investigated the addition of bevacizumab in regimens of chemotherapy with different PTX doses and schedules in preclinical models. Treatments were cisplatin (DDP) with weekly PTX (conventional), or dose-dense-equi (every other day to the conventional cumulative dose), or dose-dense-high (total dose 1.5 times higher), with or without bevacizumab. Treatment efficacy was evaluated analyzing tumor growth in different time-windows in two patient-derived ovarian cancer xenografts with different sensitivity to cisplatin...
May 11, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29750896/migration-inducing-gene-7-independently-predicts-poor-prognosis-of-human-osteosarcoma-and-is-associated-with-vasculogenic-mimicry
#6
Ke Ren, Jian Zhang, Xiaojie Gu, Sujia Wu, Xin Shi, Yicheng Ni, Yong Chen, Jun Lu, Zengxin Gao, Chen Wang, Nan Yao
Vasculogenic mimicry (VM) is a special type of vascular channel formed by tumor cells without endothelial cell participation. Migration-inducing gene 7 (MIG-7) plays an important role in regulating VM. In this study, immunohistochemical staining was used to detect MIG-7 in tissue specimens from 141 primary osteosarcoma patients, and the relationship between MIG-7 and VM was examined. Survival analysis were performed to evaluate the prognoses. MIG-7 knockdown osteosarcoma cells were used for cell proliferation, apoptosis, migration, invasiveness and VM formation assays...
May 8, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29721203/patient-derived-xenografts-pdx-predict-an-effective-heparanase-based-therapy-for-lung-cancer
#7
Amit Katz, Uri Barash, Ilanit Boyango, Sari Feld, Yaniv Zohar, Edward Hammond, Neta Ilan, Ran Kremer, Israel Vlodavsky
Heparanase, the sole heparan sulfate (HS) degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, metastasis, angiogenesis, and inflammation. Heparanase accomplishes this by degrading HS and thereby facilitating cell invasion and regulating the bioavailability of heparin-binding proteins. HS mimicking compounds that inhibit heparanase enzymatic activity were examined in numerous preclinical cancer models. While these studies utilized established tumor cell lines, the current study utilized, for the first time, patient-derived xenografts (PDX) which better resemble the behavior and drug responsiveness of a given cancer patient...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29721073/ovol2-links-stemness-and-metastasis-via-fine-tuning-epithelial-mesenchymal-transition-in-nasopharyngeal-carcinoma
#8
Xue-Kang Qi, Hui-Qiong Han, Hao-Jiong Zhang, Miao Xu, Lili Li, Lin Chen, Tong Xiang, Qi-Sheng Feng, Tiebang Kang, Chao-Nan Qian, Mu-Yan Cai, Qian Tao, Yi-Xin Zeng, Lin Feng
Rationale: Metastasis is the leading cause of disease-related death among patients with nasopharyngeal carcinoma (NPC). Mounting evidence suggest that epithelial-mesenchymal transition (EMT) is crucial for cancer cells to acquire metastatic ability. In this study, we aim to clarify the extent to which EMT is involved in various cancer properties and identify novel markers for predicting the prognosis of NPC patients. Methods: Two cellular models derived from the same NPC cell line with distinct metastasis ability were used for microarray analysis to identify key transcriptional factors that drive metastasis...
2018: Theranostics
https://www.readbyqxmd.com/read/29719259/the-receptor-tyrosine-kinase-axl-is-required-at-multiple-steps-of-the-metastatic-cascade-during-her2-positive-breast-cancer-progression
#9
Marie-Anne Goyette, Stéphanie Duhamel, Léo Aubert, Ariane Pelletier, Paul Savage, Marie-Pier Thibault, Radia Marie Johnson, Peter Carmeliet, Mark Basik, Louis Gaboury, William J Muller, Morag Park, Philippe P Roux, Jean-Philippe Gratton, Jean-François Côté
AXL is activated by its ligand GAS6 and is expressed in triple-negative breast cancer cells. In the current study, we report AXL expression in HER2-positive (HER2+ ) breast cancers where it correlates with poor patient survival. Using murine models of HER2+ breast cancer, Axl, but not its ligand Gas6, was found to be essential for metastasis. We determined that AXL is required for intravasation, extravasation, and growth at the metastatic site. We found that AXL is expressed in HER2+ cancers displaying epithelial-to-mesenchymal transition (EMT) signatures where it contributes to sustain EMT...
May 1, 2018: Cell Reports
https://www.readbyqxmd.com/read/29684420/novel-cancer-gene-variants-and-gene-fusions-of-triple-negative-breast-cancers-tnbcs-reveal-their-molecular-diversity-conserved-in-the-patient-derived-xenograft-pdx-model
#10
Jaeyun Jung, Kiwon Jang, Jung Min Ju, Eunji Lee, Jong Won Lee, Hee Jung Kim, Jisun Kim, Sae Byul Lee, Beom Seok Ko, Byung Ho Son, Hee Jin Lee, Gyungyup Gong, Sei Yeon Ahn, Jung Kyoon Choi, Shree Ram Singh, Suhwan Chang
Despite the improved 5-year survival rate of breast cancer, triple-negative breast cancer (TNBC) remains a challenge due to lack of effective targeted therapy and higher recurrence and metastasis than other subtypes. To identify novel druggable targets and to understand its unique biology, we tried to implement 24 patient-derived xenografts (PDXs) of TNBC. The overall success rate of PDX implantation was 45%, much higher than estrogen receptor (ER)-positive cases. Immunohistochemical analysis revealed conserved ER/PR/Her2 negativity (with two exceptions) between the original and PDX tumors...
April 20, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29675102/synergistic-antitumor-effects-of-cmet-inhibitor-in-combination-with-anti-vegf-in-colorectal-cancer-patient-derived-xenograft-models
#11
Xiangheng Chen, Zhonghai Guan, Jun Lu, Haohao Wang, Zhongkun Zuo, Fei Ye, Jiangsheng Huang, Lisong Teng
cMet signaling pathway is involved in the resistance to anti-VEGF therapy and cMet overexpression is associated with tumor progression and poor prognosis. In this study, the expression of cMet in 146 Chinese colorectal cancer (CRC) patients was examined by immunohistochemistry staining. Our data demonstrated that cMet overexpression rate was 42.5% (62/146) and cMet overexpression was closely correlated with distant metastasis of CRC. Using CRC patient-derived xenograft (PDX) mouse models we investigated antitumor activity of a novel selective cMet inhibitor volitinib alone or in combination with anti-VEGF inhibitor apatinib in vivo ...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29653142/characterization-of-a-conjunctival-melanoma-cell-line-cm-as16-newly-established-from-a-metastatic-han-chinese-patient
#12
Yongyun Li, Qingfeng Shang, Peng Li, Jinfeng Cao, Liqi Zhu, Martine J Jager, Xianqun Fan, Shengfang Ge, Renbing Jia
Conjunctival melanoma (CM) is associated with metastases formation, can be fatal, and occurs in all different races. While cell lines are essential for experimental research, all available CM cell lines are derived from Caucasian patients. Furthermore, they are not derived from metastases. We aimed to establish a new CM cell line from a parotid metastasis in a Han Chinese patient and to depict its characteristics. The novel cell line, CM-AS16, was obtained from a surgical parotid sample and determined as a unique one with short tandem repeat (STR) analysis...
April 10, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29599301/visualizing-the-tumor-microenvironment-by-color-coded-imaging-in-orthotopic-mouse-models-of-cancer
#13
REVIEW
Atsushi Suetsugu, Masahito Shimizu, Shigetoyo Saji, Hisataka Moriwaki, Robert M Hoffman
The tumor microenvironment (TME) contains stromal cells in a complex interaction with cancer cells. This relationship has become better understood with the use of fluorescent proteins for in vivo imaging, originally developed by our laboratories. Spectrally-distinct fluorescent proteins can used for color-coded imaging of the complex interaction of the tumor microenvironment in the living state using cancer cells expressing a fluorescent protein of one color and host mice expressing another-color fluorescent protein...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29568399/ctbp1-and-metabolic-syndrome-induce-an-mrna-and-mirna-expression-profile-critical-for-breast-cancer-progression-and-metastasis
#14
Paula L Farré, Georgina D Scalise, Rocío B Duca, Guillermo N Dalton, Cintia Massillo, Juliana Porretti, Karen Graña, Kevin Gardner, Paola De Luca, Adriana De Siervi
Metastatic breast cancer (BrCa) is still one of the main causes of cancer death in women. Metabolic syndrome (MeS), a risk factor for BrCa, is associated to high grade tumors, increased metastasis and recurrence of this disease. C-terminal binding protein 1 (CTBP1) is a co-repressor of tumor suppressor genes that is activated by low NAD+ /NADH ratio. Previously, we demonstrated that CTBP1 hyperactivation by MeS increased tumor growth in MDA-MB-231-derived xenografts regulating several genes and miRNAs. In this work, our aim was to elucidate the role of CTBP1 and MeS in BrCa metastasis...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29535842/selenium-targets-resistance-biomarkers-enhancing-efficacy-while-reducing-toxicity-of-anti-cancer-drugs-preclinical-and-clinical-development
#15
REVIEW
Yousef Zakharia, Arup Bhattacharya, Youcef M Rustum
Selenium (Se)-containing molecules exert antioxidant properties and modulate targets associated with tumor growth, metastasis, angiogenesis, and drug resistance. Prevention clinical trials with low-dose supplementation of different types of Se molecules have yielded conflicting results. Utilizing several xenograft models, we earlier reported that the enhanced antitumor activity of various chemotherapeutic agents by selenomethione and Se-methylselenocysteine in several human tumor xenografts is highly dose- and schedule-dependent...
February 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29487690/temozolomide-combined-with-irinotecan-regresses-a-cisplatinum-resistant-relapsed-osteosarcoma-in-a-patient-derived-orthotopic-xenograft-pdox-precision-oncology-mouse-model
#16
Kentaro Igarashi, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Miyake, Masuyo Miyake, Yunfeng Li, Scott D Nelson, Sarah M Dry, Arun S Singh, Irmina A Elliott, Tara A Russell, Mark A Eckardt, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Hiroyuki Tsuchiya, Fritz C Eilber, Robert M Hoffman
Relapsed osteosarcoma is a recalcitrant tumor. A patient's cisplatinum (CDDP)-resistant relapsed osteosarcoma lung metastasis was previously established orthotopically in the distal femur of mice to establish a patient-derived orthotopic xenograft (PDOX) model. In the present study, the PDOX models were randomized into the following groups when tumor volume reached 100 mm3 : G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal (i.p.) injection, weekly, for 2 weeks); gemcitabine (GEM) (100 mg/kg, i...
January 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29481803/tumor-targeting-salmonella-typhimurium-a1-r-is-a-highly-effective-general-therapeutic-for-undifferentiated-soft-tissue-sarcoma-patient-derived-orthotopic-xenograft-nude-mouse-models
#17
Kentaro Igarashi, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Miyake, Masuyo Miyake, Arun S Singh, Mark A Eckardt, Scott D Nelson, Tara A Russell, Sarah M Dry, Yunfeng Li, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Hiroyuki Tsuchiya, Shree Ram Singh, Fritz C Eilber, Robert M Hoffman
Undifferentiated soft tissue sarcoma (USTS) is a recalcitrant and heterogeneous subgroup of soft tissue sarcoma with high risk of metastasis and recurrence. Due to heterogeneity of USTS, there is no reliably effective first-line therapy. We have generated tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R), which previously showed strong efficacy on single patient-derived orthotopic xenograft (PDOX) models of Ewing's sarcoma and follicular dendritic cell sarcoma. In the present study, tumor resected from 4 patients with a biopsy-proven USTS (2 undifferentiated pleomorphic sarcoma [UPS], 1 undifferentiated sarcoma not otherwise specified [NOS] and 1 undifferentiated spindle cell sarcoma [USS]) were grown orthotopically in the biceps femoris muscle of mice to establish PDOX models...
March 18, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29459852/%C3%AE-hpv-infection-correlates-with-early-stages-of-carcinogenesis-in-skin-tumors-and-patient-derived-xenografts-from-a-kidney-transplant-recipient-cohort
#18
Cinzia Borgogna, Carlotta Olivero, Simone Lanfredini, Federica Calati, Marco De Andrea, Elisa Zavattaro, Paola Savoia, Elena Trisolini, Renzo Boldorini, Girish K Patel, Marisa Gariglio
Many malignancies that occur in high excess in kidney transplant recipients (KTRs) are due to viruses that thrive in the setting of immunosuppression. Keratinocyte carcinoma (KC), the most frequently occurring cancer type in KTR, has been associated with skin infection by human papillomavirus (HPV) from the beta genus. In this report, we extend our previous investigation aimed at identifying the presence of active β-HPV infection in skin tumors from KTRs through detection of viral protein expression. Using a combination of antibodies raised against the E4 and L1 proteins of the β-genotypes, we were able to visualize infection in five tumors [one keratoacanthoma (KA), three actinic keratoses (AKs), and one seborrheic keratoses (SKs)] that were all removed from two patients who had been both transplanted twice, had developed multiple KCs, and presented with a long history of immunosuppression (>30 years)...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29453314/ar-expression-in-breast-cancer-ctcs-associates-with-bone-metastases
#19
Nicola Aceto, Aditya Bardia, Ben S Wittner, Maria C Donaldson, Ryan O'Keefe, Amanda Engstrom, Francesca Bersani, Yu Zheng, Valentine Comaills, Kira Niederhoffer, Huili Zhu, Olivia Mackenzie, Toshi Shioda, Dennis Sgroi, Ravi Kapur, David T Ting, Beverly Moy, Sridhar Ramaswamy, Mehmet Toner, Daniel A Haber, Shyamala Maheswaran
Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing was performed of circulating tumor cells (CTC) isolated from blood samples of women with metastatic estrogen receptor (ER)+ breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splice variant AR-v7...
April 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29445127/cripto-1-contributes-to-stemness-in-hepatocellular-carcinoma-by-stabilizing-dishevelled-3-and-activating-wnt-%C3%AE-catenin-pathway
#20
Regina Cheuk-Lam Lo, Carmen Oi-Ning Leung, Kristy Kwan-Shuen Chan, Daniel Wai-Hung Ho, Chun-Ming Wong, Terence Kin-Wah Lee, Irene Oi-Lin Ng
Identification and characterization of functional molecular targets conferring stemness properties in hepatocellular carcinoma (HCC) offers crucial insights to overcome the major hurdles of tumor recurrence, metastasis and chemoresistance in clinical management. In the current study, we investigated the significance of Cripto-1 in contributing to HCC stemness. Cripto-1 was upregulated in the sorafenib-resistant clones derived from HCC cell lines and patient-derived xenograft that we previously developed, suggesting an association between Cripto-1 and stemness...
February 14, 2018: Cell Death and Differentiation
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