tbuckley/cabot-search huggingface dataset:
Abstract 481: QKI, a direct target of miRNA-200, inhibits epithelial-to-mesenchymal transition
Authors: Eun Ju KIM, Der Sheng Sun, Hye Sung Won, Yoon Ho Ko, Young-Ho Ahn
Journal: Cancer Research (2018)

Abstract MicroRNA (miR)-200 family members are well-known regulators of epithelial-to-mesenchymal transition (EMT) in epithelial tumors. To identify novel miR-200 targets, we analyzed TargetScan and TCGA data sets. Among 20 candidate genes, we selected QKI gene and studied its role during EMT process in human head and neck squamous cell carcinoma (HNSCC) and non-small cell lung carcinoma (NSCLC) cells. The expression of QKI was proved to negatively correlate with those of miR-200 members in TCGA data sets. miR-200 suppressed QKI expression directly, which was confirmed by 3'-UTR reporter assays. Interestingly, shRNA-mediated knockdown of QKI promoted migration, invasion, and EMT in cancer cells and increased tumor growth in a xenograft mouse model. These results indicate that QKI inhibits EMT and tumorigenesis in HNSCC and NSCLC cells. Even though further studies are necessary to elucidate the underlying mechanism, we suggest that QKI and miR-200 form a feedback loop to maintain homeostatic responses to EMT-inducing signals. Citation Format: Eun Ju KIM, Der Sheng Sun, Hye Sung Won, Yoon Ho Ko, Young-Ho Ahn. QKI, a direct target of miRNA-200, inhibits epithelial-to-mesenchymal transition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 481.
Abstract 15862: Million Hearts—Estimating the Number of Events Prevented During 2012-2016
Authors: Matthew D Ritchey, Fleetwood Loustalot, Hilary Wall, Claudia Steiner, Cathleen Gillespie, Mary George, Janet Wright
Journal: Circulation (2016)

Introduction: Increased cardiovascular disease (CVD) prevalence and a slowing or reversal in previously declining CVD event rates have been forecast. The Million Hearts initiative was launched to c...
Whole-exome sequencing exploration of acquired uniparental disomies in B-cell precursor acute lymphoblastic leukemia
Authors: Kristina B. Lundin-Ström, Andrea Biloglav, Henrik Lilljebjörn, Marianne Rissler, Thoas Fioretos, Markus Hansson, Mikael Behrendtz, Anders Castor, Linda Olsson, Bertil Johansson
Journal: Leukemia (2018)
Potential Underuse of the Sentinel Lymph Node Biopsy for High-Risk Squamous Cell Carcinoma of the Skin
Authors: Alex M. Glazer, Delaney Stratton, Clara Curiel-Lewandrowski
Journal: JAMA Dermatology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Multi-center phase II trial of bortezomib and rituximab maintenance combination therapy in patients with mantle cell lymphoma after consolidative autologous stem cell transplantation
Authors: Robert W. Chen, Joycelynne M. Palmer, Sarah Tomassetti, Leslie L. Popplewell, Jessica Alluin, Pritsana Chomchan, Auayporn P. Nademanee, Tanya Siddiqi, Ni-Chun Tsai, Lu Chen, Fay Zuo, Rosemarie Abary, Ji-lian Cai, Alex F. Herrera, John J. Rossi, Steven T. Rosen, Stephen J. Forman, Larry W. Kwak, Leona A. Holmberg
Journal: Journal of Hematology & Oncology (2018)

Mantle cell lymphoma (MCL) is an aggressive and incurable lymphoma. Standard of care for younger patients with MCL is induction chemotherapy followed by autologous stem cell transplantation (auto-HCT). Rituximab maintenance after auto-HCT has been shown to improve progression-free survival (PFS) and overall survival (OS) in MCL. Bortezomib maintenance therapy has also been shown to be tolerable and feasible in this setting. However, the combination of bortezomib and rituximab as maintenance therapy post-auto-HCT has not been studied. We conducted a multicenter, phase II trial of bortezomib given in combination with rituximab as maintenance in MCL patients after consolidative auto-HCT. Enrolled patients (n = 23) received bortezomib 1.3 mg/m2 subcutaneously weekly for 4 weeks every 3 months (up to 24 months) and rituximab 375 mg/m2 intravenously weekly for 4 weeks every 6 months (up to 24 months) for a total duration of 2 years. The primary study endpoint was disease-free survival (DFS). With a median follow-up of 35.9 months, the 2-year DFS probability was 90.2% (95% CI 66–97), and 2-year OS was 94.7% (95% CI 68–99). The most frequent grade 3/4 toxic events were neutropenia (in 74% of patients) and lymphopenia (in 35%). The incidence of peripheral neuropathy was 48% for grade 1, 9% for grade 2, and 0% for grade 3/4. We also examined the role of quantitative cyclin D1 (CCND1) mRNA in monitoring minimal residual disease. Combined bortezomib and rituximab as maintenance therapy in MCL patients following auto-HCT is an active and well-tolerated regimen. ClinicalTrials.gov NCT01267812 , registered Dec 29, 2010.
Different response to EGFR inhibitors in non-small cell lung cancer cell lines with del 746-750 mutation
Authors: Yun Jung Choi, Jin Kyung Rho, Seok-Il Hong, Jin Kyung Lee, Jae Soo Koh, Cheol Hyeon Kim, Jae Cheol Lee
Journal: Cancer Research (2008)

1489   EGFR mutations are closely related with the response to the EGFR-tyrosine kinas inhibitors. Among more than 20 EGFR mutations described until now, the del 746-750 mutation on exon 19 has been reported to be a better predictor of the response than others. We investigated the response to EGFR inhibitors and the expression of EGFR-related signaling molecules in HCC827, PC-9 and H1650, non-small cell lung cancer cell lines with del 746-750 mutation. Gefitinib, erlotinib, Cl-387,785, ZD6474 and cetuximab were used for the inhibition of EGFR signals. HCC827 was sensitive to all EGFR inhibitors while H1650 did not respond well. PC-9 cells were also sensitive to all of them except cetuximab. Gefitinib inhibited EGFR phosphorylation and strongly reduced EGF-mediated downstream signals (p-Erk and p-Akt) in HCC827 and PC-9 cells. Moreover, cell death was induced in them after G1 arrest in presence of gefitinib. In contrast, the level of Akt phosphorylation was persisted in H1650 cells, although gefitinib completely inhibited EGFR phosphorylation. Treatment of H1650 cells with gefitinib led to G1 arrest, but did not induce cell death. In summary, three non-small cell lung cancer cell lines with same del 746-750 mutation show different response to EGFR inhibitors suggesting that additional contributing factors may be required to determine the sensitivity.
Onychomadesis Following a Fish Pedicure
Authors: Shari R. Lipner
Journal: JAMA Dermatology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Abstract 5420: Nuclear PTEN directly regulates androgen receptor activity in prostate cancer
Authors: Yen T. Nguyen, Jose A. Rodriguez-Nieves, Qi Yang, David VanderWeele
Journal: Cancer Research (2018)

Abstract The deletion of PTEN, a negative regulator of the PI3K pathway, is among the most frequent genomic alterations in prostate cancer. Attempts to target this alteration using PI3K pathway inhibitors, however, have yielded little clinical benefit for patients, and the function of PTEN loss in prostate cancer progression is not fully understood. Prostate cancers lacking PTEN are less responsive to therapy targeting the Androgen Receptor (AR), a dominant driver of prostate cancer growth, but how PTEN function interacts with AR activity is not clear. We used immunoblotting, immunoprecipitation, proximity ligation assay, chromatin immunoprecipitation, and transcriptome sequencing in cells with endogenous PTEN or PTEN knocked down to evaluate the interactions between these major factors in prostate cancer progression. We demonstrate that PTEN interacts with the Androgen Receptor in the nucleus, and PTEN can bind chromatin at known Androgen Response Elements. Stimulation of cells with androgen and other media components leads to accumulation of phosphorylated (inactive) PTEN, loss of nuclear PTEN, and decreased PTEN-AR interaction. Transcriptome analysis of cells with PTEN knocked down demonstrates increased expression of AR pathway genes, even in the absence of androgen stimulation. These results suggest nuclear PTEN may play a direct role in negative regulation of the Androgen Receptor, with implications for management of PTEN-negative prostate cancers. Citation Format: Yen T. Nguyen, Jose A. Rodriguez-Nieves, Qi Yang, David VanderWeele. Nuclear PTEN directly regulates androgen receptor activity in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5420.
Percutaneous Ablation Versus Partial and Radical Nephrectomy for T1a Renal Cancer
Authors: Adam D. Talenfeld, Renee L. Gennarelli, Elena B. Elkin, Coral L. Atoria, Jeremy C. Durack, William C. Huang, Sharon W. Kwan
Journal: Annals of Internal Medicine (2018)

Stage T1a renal cell carcinoma (RCC) (tumors <4 cm) is usually curable. Nephron-sparing partial nephrectomy (PN) has replaced radical nephrectomy (RN) as the standard of care for these tumors. Radical nephrectomy remains the first alternative treatment option, whereas percutaneous ablation (PA), a newer, nonsurgical treatment, is recommended less strongly because of the relative paucity of comparative PA data.
Abstract 2414: Interrogating cellular metabolism reveals mTORC2 as a new biomarker to stratify epidermal growth factor receptor-mutant non-small cell lung cancer
Authors: Chun-Te Chiang, Nolan Ung, Alexandra N. Demetriou, Chi-Li Chiu, Niha Choudhury, Cosimo Arnesano, Scott E. Fraser, David B. Agus, Naim Matasci, Dan L. Ruderman, Shannon M. Mumenthaler
Journal: Cancer Research (2018)

Abstract Most non-small cell lung cancer (NSCLC) patients with epidermal growth factor (EGFR) mutations initially respond to EGFR tyrosine-kinase inhibitors (TKIs), but these inhibitors are only effective for approximately one year, thus limiting the benefits to patients' survival. Stratification of patients with EGFR-mutant NSCLC would help physicians personalize and optimize patient treatment plans. To this end, we hypothesized that factors residing in the tumor microenvironment play a pivotal role in the evolutionary dynamics of therapeutic response to anti-EGFR therapies. We used the Operetta® High Content Imaging System to track cell dynamics over time under different microenvironmental stresses, and we found that the growth of TKI-resistant cells is more sensitive to glucose starvation than TKI-sensitive cells. To further interrogate cellular metabolism in TKI-sensitive and resistant cells, we utilized both seahorse metabolic assays and fluorescence lifetime imaging microscopy to monitor the changes in glycolysis and oxidative phosphorylation of living cells. We found TKI-resistant cells have higher glycolysis and lower oxidative phosphorylation rates compared to TKI-sensitive cells. Such metabolic reprogramming rendered TKI-resistant cells with lower metabolic plasticity to cope with metabolic stress. Using both genetic and pharmacologic approaches, we then demonstrated that mTORC2 activation contributes to the different metabolic phenotypes between TKI-sensitive and resistant cells. Furthermore, gene set enrichment analysis showed that the oxidative phosphorylation gene set is significantly enriched in patients with low mTORC2 activation, and the glycolysis gene set is upregulated in patients with high mTORC2 activation, which is correlated with shorter progression-free and overall survival time in patients. Overall, these data suggest that TKI-resistant cells use and require distinct metabolic programs that can be employed to stratify EGFR-mutant NSCLC patients for treatment with EGFR-TKIs. Citation Format: Chun-Te Chiang, Nolan Ung, Alexandra N. Demetriou, Chi-Li Chiu, Niha Choudhury, Cosimo Arnesano, Scott E. Fraser, David B. Agus, Naim Matasci, Dan L. Ruderman, Shannon M. Mumenthaler. Interrogating cellular metabolism reveals mTORC2 as a new biomarker to stratify epidermal growth factor receptor-mutant non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2414.
ATR kinase inhibitor AZD6738 potentiates CD8+ T cell–dependent antitumor activity following radiation
Authors: Frank P. Vendetti, Pooja Karukonda, David A. Clump, Troy Teo, Ronald Lalonde, Katriana Nugent, Matthew Ballew, Brian F. Kiesel, Jan H. Beumer, Saumendra N. Sarkar, Thomas P. Conrads, Mark J. O’Connor, Robert L. Ferris, Phuoc T. Tran, Greg M. Delgoffe, Christopher J. Bakkenist
Journal: Journal of Clinical Investigation (2018)

DNA-damaging chemotherapy and radiation therapy are integrated into the treatment paradigm of the majority of cancer patients. Recently, immunotherapy that targets the immunosuppressive interaction between programmed death 1 (PD-1) and its ligand PD-L1 has been approved for malignancies including non–small cell lung cancer, melanoma, and head and neck squamous cell carcinoma. ATR is a DNA damage–signaling kinase activated at damaged replication forks, and ATR kinase inhibitors potentiate the cytotoxicity of DNA-damaging chemotherapies. We show here that the ATR kinase inhibitor AZD6738 combines with conformal radiation therapy to attenuate radiation-induced CD8+ T cell exhaustion and potentiate CD8+ T cell activity in mouse models of Kras-mutant cancer. Mechanistically, AZD6738 blocks radiation-induced PD-L1 upregulation on tumor cells and dramatically decreases the number of tumor-infiltrating Tregs. Remarkably, AZD6738 combines with conformal radiation therapy to generate immunologic memory in complete responder mice. Our work raises the possibility that a single pharmacologic agent may enhance the cytotoxic effects of radiation while concurrently potentiating radiation-induced antitumor immune responses.
Impact of curcumin with and without (+/-) piperine on tamoxifen exposure.
Authors: Gerardus Hussaarts, Daan Hurkmans, Esther Oomen De Hoop, Leonie J. van Harten, Stan Berghuis, Robbert J. van Alphen, Leontine E.A. Spierings, Quirine C. van Rossum, Mijntje B. Vastbinder, Ron H.N. van Schaik, Teun van Gelder, A. Jager, Roelof W.F. van Leeuwen, Ron H.J. Mathijssen
Journal: Journal of Clinical Oncology (2018)

2572 Background: Tamoxifen is extensively used as endocrine therapy for breast cancer. It is a prodrug that is primarily metabolized by CYP2D6 and CYP3A4, particular into endoxifen. In daily practice, the herb curcumin is widely used among patients (pts) because of its presumed anti-tumor effects. Preclinical studies show effects of curcumin on phase I and II drug metabolism, leading to altered plasma levels. We hypothesized that curcumin increases endoxifen exposure by affecting phase II metabolism. Therefore, we performed a randomized, 3-phase, cross-over study to compare tamoxifen exposure in breast cancer pts +/- curcumin, and with the addition of the bioenhancer piperine. Methods: Pharmacokinetic sampling (PK) was performed in 15 pts at the 28th, 56th and 84th day of the trial. In the 28 days prior to PK, tamoxifen (20 mg qd) was either given alone, or combined with curcumin (1,200 mg TID), or with curcumin + piperine (10mg TID) in this order or vice versa. Genotyping was performed to determine CYP2D6 and CYP3A4 phenotypes. Primary endpoint was difference in geometric means for AUC0-24h. A linear mixed model was used to analyze log-transformed area under the curve (AUC). For multiple testing a Bonferroni correction was applied. Results: Tamoxifen AUC0-24h decreased with 7.3 % (95% CI: -0.5,-13.6%; p = .04) with curcumin and 13.0% (95% CI: -5.6,-19.9%; p = .002) with curcumin and piperine, compared to tamoxifen alone. Endoxifen AUC0-24h decreased with 8.9% (95% CI: -0.9,-16.3%; p = .029) and 13.5% (95% CI: -2.8,-23.0%; p = .015), respectively. CYP2D6-screening resulted in 6 intermediate metabolizers (IM), and 6 extensive metabolizers (EM). Interestingly, for pts with a EM phenotype, effects of curcumin with piperine on drug exposure (AUC0-24h) seem to be higher than for IM phenotype pts (a decrease of 21.8% vs 4.8% for tamoxifen, and 22.6% vs 10.2% for endoxifen, respectively). No severe toxicity resulting from co-treatment was observed. Conclusions: In contrast to our hypothesis, the exposure of tamoxifen and endoxifen significantly decreased by concomitant use of curcumin +/- piperine. Although limited effects in most pts, co-treatment with these herbs could drop endoxifen levels below the threshold for efficacy, especially for EM phenotype pts. Clinical trial information: NTR6149.
Abstract 3473: Investigating RAS and RTK signaling in MPNST progression and drug resistance
Authors: Candace N. King, Carrie Graveel, Matthew Steensma
Journal: Cancer Research (2018)

Abstract Neurofibromatosis, type 1 (NF1) is a tumor predisposition syndrome affecting about 1 in 2,500 live births in the United States. The protein product of the NF1 gene, neurofibromin, loses its function as a negative regulator of the RAS protein, leading to the development of painful and disfiguring benign tumors known as a neurofibromas. Eight to thirteen percent of these neurofibromas will transform into malignant peripheral nerve sheath tumors (MPNSTs). MPNSTs are aggressive soft tissue sarcomas that do not respond to the standard sarcoma treatment of chemotherapy and surgical resection. There is a critical need for efficacious targeted therapy to increase the average life span of these patients. Current targeted therapy efforts have shown modest efficacy clinically due to the establishment of compensatory feedback mechanisms that propagate tumor progression and recurrence. These feedback mechanisms are not completely understood in MPNSTs. In lung cancer, inhibition of MEK in the RAS pathway has been shown to activate upstream receptor tyrosine kinases (RTK). Genomic studies of MPNST samples have shown that 30% of tumors have amplification of the RTKs MET and EGFR. Furthermore, in a study of the genomic progression of a NF1 patient pre- and post-treatment, we found amplification of MET and EGFR that increased following treatment. In a study on triple-negative breast cancer cells, it has been shown that MET and EGFR crosstalk may be responsible for the reactivation of the inhibited cancer pathways and drug resistance. Therefore, we hypothesize that coordinated deregulated RAS signaling and MEK inhibition leads to MET and EGFR amplification, expression, activation, and crosstalk, which drives MPNST progression, drug resistance, and tumor recurrence. To test our hypothesis, we will use both in vitro and in vivo experimental methods to pursue the following specific aims: (1) determine the effect of MEK inhibition on establishing compensatory feedback loops that increase RTK activation and downstream signaling, (2) determine the role of MET-EGFR crosstalk signaling in MPNST tumor progression and resistance to kinase inhibition, and (3) determine the efficacy of combination RTK and MEK inhibition in vivo. Citation Format: Candace N. King, Carrie Graveel, Matthew Steensma. Investigating RAS and RTK signaling in MPNST progression and drug resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3473.
Adaptation and conservation insights from the koala genome
Authors: Rebecca N. Johnson, Denis O’Meally, Zhiliang Chen, Graham J. Etherington, Simon Y. W. Ho, Will J. Nash, Catherine E. Grueber, Yuanyuan Cheng, Camilla M. Whittington, Siobhan Dennison, Emma Peel, Wilfried Haerty, Rachel J. O’Neill, Don Colgan, Tonia L. Russell, David E. Alquezar-Planas, Val Attenbrow, Jason G. Bragg, Parice A. Brandies, Amanda Yoon-Yee Chong, Janine E. Deakin, Federica Di Palma, Zachary Duda, Mark D. B. Eldridge, Kyle M. Ewart, Carolyn J. Hogg, Greta J. Frankham, Arthur Georges, Amber K. Gillett, Merran Govendir, Alex D. Greenwood, Takashi Hayakawa, Kristofer M. Helgen, Matthew Hobbs, Clare E. Holleley, Thomas N. Heider, Elizabeth A. Jones, Andrew King, Danielle Madden, Jennifer A. Marshall Graves, Katrina M. Morris, Linda E. Neaves, Hardip R. Patel, Adam Polkinghorne, Marilyn B. Renfree, Charles Robin, Ryan Salinas, Kyriakos Tsangaras, Paul D. Waters, Shafagh A. Waters, Belinda Wright, Marc R. Wilkins, Peter Timms, Katherine Belov
Journal: Nature Genetics (2018)

The koala, the only extant species of the marsupial family Phascolarctidae, is classified as 'vulnerable' due to habitat loss and widespread disease. We sequenced the koala genome, producing a complete and contiguous marsupial reference genome, including centromeres. We reveal that the koala's ability to detoxify eucalypt foliage may be due to expansions within a cytochrome P450 gene family, and its ability to smell, taste and moderate ingestion of plant secondary metabolites may be due to expansions in the vomeronasal and taste receptors. We characterized novel lactation proteins that protect young in the pouch and annotated immune genes important for response to chlamydial disease. Historical demography showed a substantial population crash coincident with the decline of Australian megafauna, while contemporary populations had biogeographic boundaries and increased inbreeding in populations affected by historic translocations. We identified genetically diverse populations that require habitat corridors and instituting of translocation programs to aid the koala's survival in the wild.
A comparison of skin cancer screening and treatment costs at a Massachusetts cancer center, 2008 versus 2013
Authors: Frederick C. Morgan, Juanita Duran, Belen Fraile, Pritesh S. Karia, Jennifer Y. Lin, Patrick A. Ott, Emily Stamell Ruiz, David M. Wang, Yichen Zhang, Chrysalyne D. Schmults
Journal: Journal of the American Academy of Dermatology (2018)