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patient derived xenograft metastasis

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
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
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...
February 23, 2018: Biochemical and Biophysical Research Communications
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
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 (RNA-seq) was performed of circulating tumor cells (CTCs) 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...
February 16, 2018: Molecular Cancer Research: MCR
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
Chi Fang, Chen-Yun Dai, Zhu Mei, Ming-Jie Jiang, Dian-Na Gu, Qian Huang, Ling Tian
BACKGROUND: Pancreatic cancer characterizes high recurrence and poor prognosis. In clinical practice, radiotherapy is widely used for pancreatic cancer treatment. However, the outcome remains undesirable due to tumor repopulation and following recurrence and metastasis after radiation. So, it is highly needed to explore the underlying molecular mechanisms and accordingly develop therapeutic strategies. Our previous studies revealed that dying cells from chemoradiation could stimulate repopulation of surviving pancreatic cancer cells...
February 13, 2018: Journal of Experimental & Clinical Cancer Research: CR
Mengqi Jia, Yanxia Guo, Deyu Zhu, Nianzhao Zhang, Lin Li, Jin Jiang, Yiwen Dong, Qingqing Xu, Xiulei Zhang, Meijuan Wang, Haina Yu, Fang Wang, Keli Tian, Jinsan Zhang, Charles Y F Young, Hongxiang Lou, Huiqing Yuan
Anterior gradient 2 (AGR2), an endoplasmic reticulum (ER)-resident protein-disulfide isomerase (PDI), is associated with cancer development and malignant progression. Here, we show that high level of AGR2 promotes the aggressive phenotype of prostate cancer (PCa) mouse models developed by either patient-derived xenografts or surgical intra-prostate implantation of PCa cells, associated with enrichment of the blood vessel network in tumor tissues. Angiogenesis markers VEGFR2 and CD34, accompanied with the invasive marker Vimentin, were predominantly stained in metastatic liver tissues...
February 1, 2018: Biochimica et Biophysica Acta
Geun Taek Lee, Seok Joo Kwon, Jongmyung Kim, Young Suk Kwon, Nara Lee, Jeong Hee Hong, Christina Jamieson, Wun-Jae Kim, Isaac Yi Kim
BACKGROUND: Although the standard treatment for the patients with recurrent and metastatic prostate cancer (CaP) is androgen deprivation therapy, castration-resistant prostate cancer (CRPC) eventually emerges. Our previous report indicated that bone morphogenetic protein 6 (BMP6) induced CRPC via tumour-infiltrating macrophages. In a separate line of study, we have observed that the WNT5A/BMP6 loop in CaP bone metastasis mediates resistance to androgen deprivation in tissue culture. Simultaneously, we have reported that BMP6 induced castration resistance in CaP cells via tumour-infiltrating macrophages...
January 30, 2018: British Journal of Cancer
Sifeng Qu, Xinpei Ci, Hui Xue, Xin Dong, Jun Hao, Dong Lin, Pier-Luc Clermont, Rebecca Wu, Colin C Collins, Peter W Gout, Yuzhuo Wang
BACKGROUND: Docetaxel used for first-line treatment of advanced prostate cancer (PCa) is only marginally effective. We previously showed, using the LTL-313H subrenal capsule patient-derived metastatic PCa xenograft model, that docetaxel combined with Aneustat (OMN54), a multivalent plant-derived therapeutic, led to marked synergistic tumour growth inhibition. Here, we investigated the effect of docetaxel+Aneustat on metastasis. METHODS: C4-2 cells were incubated with docetaxel, Aneustat and docetaxel+Aneustat to assess effects on cell migration...
January 30, 2018: British Journal of Cancer
Kentaro Igarashi, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Miyake, Masuyo Miyake, Shukuan Li, Qinghong Han, Yuying Tan, Ming Zhao, 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
In the present study, a patient-derived orthotopic xenograft (PDOX) model of recurrent cisplatinum (CDDP)-resistant metastatic osteosarcoma was treated with Salmonella typhimurium A1-R (S. typhimurium A1-R), which decoys chemoresistant quiescent cells to cycle, and recombinant methioninase (rMETase), which selectively traps cancer cells in late S/G2, and chemotherapy. The PDOX models were randomized into the following groups 14 days after implantation: G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal (i...
January 29, 2018: Cell Cycle
Shan Zeng, Adrian M Seifert, Jennifer Q Zhang, Teresa S Kim, Timothy G Bowler, Michael J Cavnar, Benjamin D Medina, Gerardo A Vitiello, Ferdinand Rossi, Jennifer K Loo, Nesteene J Param, Ronald P DeMatteo
Gastrointestinal stromal tumor (GIST) is the most common sarcoma, often resulting from a KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutation. The lineage transcription factor ETV1 is expressed similarly in GISTs regardless of malignant potential. Although the related transcription factor ETV4 has been associated with metastasis and tumor progression in other cancers, its role in GIST is unknown. In this study, we found that ETV4 levels were high in a subset of human GISTs and correlated with high mitotic rate...
December 26, 2017: Oncotarget
Katja Kiseljak-Vassiliades, Yu Zhang, Stacey Bagby, Adwitiya Kar, Nikita Pozdeyev, Mei Xu, Katherine Gowan, Vibha Sharma, Christopher D Raeburn, Maria Albuja-Cruz, Kenneth L Jones, Lauren Fishbein, Rebecca Schweppe, Hilary L Somerset, Todd M Pitts, Stephen Leong, Margaret Wierman
Adrenocortical cancer (ACC) is an orphan malignancy that results in heterogeneous clinical phenotypes and molecular genotypes. There are no curative treatments for this deadly cancer with 35% survival at five years. Our understanding of the underlying pathobiology and our ability to test novel therapeutic targets has been limited due to the lack of preclinical models. Here, we report the establishment of two new ACC cell lines and corresponding patient derived xenograft (PDX) models. CU-ACC1 cell line and PDX were derived from a perinephric metastasis in a patient whose primary tumor secreted aldosterone...
January 25, 2018: Endocrine-related Cancer
Jason A Hanna, Matthew R Garcia, Alicia Lardennois, Patrick J Leavey, Dino Maglic, Alexandre Fagnan, Jonathan C Go, Jordan Roach, Yong-Dong Wang, David Finkelstein, Mark E Hatley
Rhabdomyosarcoma is the most common soft-tissue sarcoma in childhood and histologically resembles developing skeletal muscle. Alveolar rhabdomyosarcoma (ARMS) is an aggressive subtype with a higher rate of metastasis and poorer prognosis. The majority of ARMS tumors (80%) harbor a PAX3-FOXO1 or less commonly a PAX7-FOXO1 fusion gene. The presence of either the PAX3-FOXO1 or PAX7-FOXO1 fusion gene foretells a poorer prognosis resulting in clinical re-classification as either fusion-positive (FP-RMS) or fusion-negative RMS (FN-RMS)...
January 25, 2018: Oncogene
Jessica Wagner, C Leah Kline, Lanlan Zhou, Vladimir Khazak, Wafik S El-Deiry
BACKGROUND: Small molecule ONC201 is an investigational anti-tumor agent that upregulates intra-tumoral TRAIL expression and the integrated stress response pathway. A Phase I clinical trial using ONC201 therapy in advanced cancer patients has been completed and the drug has progressed into Phase II trials in several cancer types. Colorectal cancer (CRC) remains one of the leading causes of cancer worldwide and metastatic disease has a poor prognosis. Clinical trials in CRC and other tumor types have demonstrated that therapeutics targeting the vascular endothelial growth factor (VEGF) pathway, such as bevacizumab, are effective in combination with certain chemotherapeutic agents...
January 22, 2018: Journal of Experimental & Clinical Cancer Research: CR
Hak-Min Lee, Eunmyong Lee, So-Young Yeo, Sang Shin, Hyun-Kyu Park, Do-Hyun Nam, Seok-Hyung Kim
Cancer associated fibroblasts (CAFs) are the most abundant components of cancer-microenvironment. They play important roles in cancer initiation, progression, and metastasis. In addition, CAFs can confer drug-resistance to cancer cells. Considering their pro-tumorigenic roles, it is recommended to remove CAFs to prevent cancer recurrence after chemotherapy. Despite their clinical significance, few anti-CAF drugs have been developed. The objective of this study was to find a drug that could suppress the viability of patient-derived CAFs through repurposed screening of 51 drugs that were in clinical trials or received FDA approval...
January 18, 2018: Investigational New Drugs
Elizabeth Magnotti, Wayne A Marasco
Epithelial ovarian cancer is a heterogeneous disease classified into five subtypes, each with a different molecular profile. Most cases of ovarian cancer are diagnosed after metastasis of the primary tumor and are resistant to traditional platinum-based chemotherapeutics. Mouse models of ovarian cancer have been utilized to discern ovarian cancer tumorigenesis and the tumor's response to therapeutics. Areas covered: The authors provide a review of mouse models currently employed to understand ovarian cancer...
January 17, 2018: Expert Opinion on Drug Discovery
Tsuyoshi Hasegawa, Garrison Glavich, Mary Pahuski, Aleena M Short, Oliver John Semmes, Lifang Yang, Vitold Galkin, Richard R Drake, Aurora Esquela-Kerscher
Prostate cancer afflicts 1 in 7 men and is the second leading cause of male cancer-related deaths in the United States. MicroRNAs (miRNAs), an extensive class of ~22 nucleotide non-coding RNAs, are often aberrantly expressed in tissues and fluids from prostate cancer patients but the mechanism of how specific miRNAs regulate prostate tumorigenesis and metastasis are poorly understood. Here, miR-888 was identified as a novel prostate factor that promotes proliferation and migration. miR-888 resides within a genomic cluster of 7 miRNA genes (mir-892c, mir-890, mir-888, mir-892a, mir-892b, mir-891b, mir-891a) on human chromosome Xq27...
January 12, 2018: Molecular Cancer Research: MCR
Christopher D Suarez, Junmin Wu, Sunil S Badve, Joseph A Sparano, William Kaliney, Laurie E Littlepage
We previously identified the transcription factor ZNF217 (human) / Zfp217 (mouse) as an oncogene and prognostic indicator of reduced survival, increased metastasis, and reduced response to therapy in breast cancer patients. Here we investigated the role of Zfp217 in chemotherapy resistance. Preclinical animal models of Zfp217 overexpression were treated with a combination therapy of the microtubule inhibitor epothilone B, doxorubicin (Adriamycin), and cyclophosphamide (EAC). Tumors overexpressing Zfp217 increased their tumor burden compared to control tumors after treatment and accumulated a mammary gland progenitor cell population (K8+K14+)...
December 12, 2017: Oncotarget
Francesca Cirillo, Michele Pellegrino, Rocco Malivindi, Vittoria Rago, Silvia Avino, Luigina Muto, Vincenza Dolce, Adele Vivacqua, Damiano Cosimo Rigiracciolo, Paola De Marco, Anna Sebastiani, Sergio Abonante, Miki Nakajima, Rosamaria Lappano, Marcello Maggiolini
The cytochrome P450 1B1 (CYP1B1) is a heme-thiolate monooxygenase involved in both estrogen biosynthesis and metabolism. For instance, CYP1B1 catalyzes the hydroxylation of E2 leading to the production of 4-hydroxyestradiol that may act as a potent carcinogenic agent. In addition, CYP1B1 is overexpressed in different tumors including breast cancer. In this scenario, it is worth mentioning that CYP1B1 expression is triggered by estrogens through the estrogen receptor (ER)α in breast cancer cells. In the present study, we evaluated whether the G protein estrogen receptor namely GPER may provide an alternate route toward the expression and function of CYP1B1 in ER-negative breast cancer cells, in main players of the tumor microenvironment as cancer associated fibroblasts (CAFs) that were obtained from breast cancer patients, in CAFs derived from a cutaneous metastasis of an invasive mammary ductal carcinoma and in breast tumor xenografts...
December 5, 2017: Oncotarget
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