tbuckley/cabot-search huggingface dataset:
NOTCH1 Signaling Regulates Self-Renewal and Platinum Chemoresistance of Cancer Stem–like Cells in Human Non–Small Cell Lung Cancer
Authors: Yun Zhang, Wei Xu, Huiqin Guo, Yanmei Zhang, Yuexi He, Sau Har Lee, Xin Song, Xiaoyan Li, Yongqing Guo, Yunlong Zhao, Cheng Ding, Fei Ning, Yuanyuan Ma, Qun-Ying Lei, Xiaoyu Hu, Shengnan Li, Wei Guo
Journal: Cancer Research (2017)

Cancer stem-like cells (CSC) are thought to drive tumor initiation, metastasis, relapse, and therapeutic resistance, but their specific pathogenic characters in many cancers, including non-small cell lung cancer (NSCLC), have yet to be well defined. Here, we develop findings that the growth factor HGF promotes CSC sphere formation in NSCLC cell populations. In patient-derived sphere-forming assays (PD-SFA) with HGF, CD49f and CD104 were defined as novel markers of lung CSC (LCSC). In particular, we isolated a subpopulation of CD166+CD49fhiCD104-Lin- LCSC present in all human specimens of NSCLC examined, regardless of their histologic subtypes or genetic driver mutations. This specific cell population was tumorigenic and capable of self-renewal, giving rise to tumor spheres in vitro and orthotopic lung tumors in immune-compromised mice. Mechanistic investigations established that NOTCH1 was preferentially expressed in this cell subpopulation and required for self-renewal via the transcription factor HES1. Through a distinct HES1-independent pathway, NOTCH1 also protected LCSCs from cisplatin-induced cell death. Notably, treatment with a γ-secretase inhibitor that blunts NOTCH1 function ablated self-renewing LCSC activity and restored platinum sensitivity in vitro and in vivo Overall, our results define the pathogenic characters of a cancer stem-like subpopulation in lung cancer, the targeting of which may relieve platinum resistance in this disease. Cancer Res; 77(11); 3082-91. ©2017 AACR.
Adenoma Prevalence in Blacks and Whites Having Equal Adherence To Screening Colonoscopy: The National Colonoscopy Study
Authors: Robin B. Mendelsohn, Sidney J. Winawer, Anjani Jammula, Glenn Mills, Paul Jordan, Michael J. O’Brien, Georgia M. Close, Michael Dorfman, Timothy R. Church, Margaret T. Mandelson, John Allen, Andrew Feld, Noah D. Kauff, Georgia A. Morgan, Julie M.R. Kumar, Victoria Serrano, Sharon Bayuga-Miller, Sara E. Fischer, Deborah Kuk, Ann G. Zauber
Journal: Clinical Gastroenterology and Hepatology (2017)
NRF2 Induction Supporting Breast Cancer Cell Survival Is Enabled by Oxidative Stress–Induced DPP3–KEAP1 Interaction
Authors: Kevin Lu, Allen L. Alcivar, Jianglin Ma, Tzeh Keong Foo, Susan Zywea, Amar Mahdi, Yanying Huo, Thomas W. Kensler, Michael L. Gatza, Bing Xia
Journal: Cancer Research (2017)

Abstract NRF2 is a transcription factor serving as a master regulator of the expression of many genes involved in cellular responses to oxidative and other stresses. In the absence of stress, NRF2 is constantly synthesized but maintained at low levels as it is targeted by KEAP1 for ubiquitination and proteasome-mediated degradation. NRF2 binds KEAP1 mainly through a conserved “ETGE” motif that has also been found in several other proteins, such as DPP3, which has been shown to bind KEAP1 and enhance NRF2 function upon overexpression. Here we demonstrate the interaction between endogenous DPP3 and endogenous KEAP1. We further show that the DPP3–KEAP1 interaction is strongly induced by hydrogen peroxide and that DPP3 is required for timely NRF2 induction and nuclear accumulation in the estrogen receptor (ER)-positive MCF7 breast cancer cells. Moreover, we present evidence that the binding of DPP3 to KEAP1 stabilizes the latter. Finally, we show that DPP3 is overexpressed in breast cancer and that elevated levels of DPP3 mRNA correlate with increased NRF2 downstream gene expression and poor prognosis, particularly for ER-positive breast cancer. Our studies reveal novel insights into the regulation of NRF2 and identify DPP3 and an NRF2 transcriptional signature as potential biomarkers for breast cancer prognosis and treatment. Cancer Res; 77(11); 2881–92. ©2017 AACR.
Food protein–induced enterocolitis syndrome in Australia: A population-based study, 2012-2014
Authors: Sam Mehr, Katie Frith, Elizabeth H. Barnes, Dianne E. Campbell, Katrina Allen, Elizabeth Barnes, Dianne E. Campbell, Katie Frith, Mike Gold, Preeti Joshi, Alyson Kakakios, Richard Loh, Sam Mehr, Jane Peake, Joanne Smart, Peter Smith, Mimi Tang, Brynn Wainstein, Melanie Wong, Yvonne Zurynski
Journal: Journal of Allergy and Clinical Immunology (2017)
Low Tumor Mitochondrial DNA Content Is Associated with Better Outcome in Breast Cancer Patients Receiving Anthracycline-Based Chemotherapy
Authors: Marjolein J.A. Weerts, Antoinette Hollestelle, Anieta M. Sieuwerts, John A. Foekens, Stefan Sleijfer, John W.M. Martens
Journal: Clinical Cancer Research (2017)

Purpose: In this study, we aimed to explore whether low levels of mitochondrial DNA (mtDNA) content in the primary tumor could predict better outcome for breast cancer patients receiving anthracycline-based therapies. We hypothesized that tumor cells with low mtDNA content are more susceptible to mitochondrial damage induced by anthracyclines, and thus are more susceptible to anthracycline treatment.Experimental Design: We measured mtDNA content by a qPCR approach in 295 primary breast tumor specimens originating from two well-defined cohorts: 174 lymph node-positive patients who received adjuvant chemotherapy and 121 patients with advanced disease who received chemotherapy as first-line palliative treatment. The chemotherapy regimens given were either anthracycline-based (FAC/FEC) or methotrexate-based (CMF).Results: In both the adjuvant and advanced settings, we observed increased benefit for patients with low mtDNA content in their primary tumor, but only when treated with FAC/FEC. In multivariable Cox regression analysis for respectively distant metastasis-free survival and progression-free survival, the HR for the FAC/FEC-treated mtDNA low group in the adjuvant setting was 0.46 [95% confidence interval (CI), 0.24-0.89; P = 0.020] and in the advanced setting 0.49 (95% CI, 0.27-0.90; P = 0.022) compared with the FAC/FEC-treated mtDNA high group. We did not observe these associations in the patients treated with CMF.Conclusions: In our two study cohorts, breast cancer patients with low mtDNA content in their primary tumor had better outcome from anthracycline-containing chemotherapy. The frequently observed decrease in mtDNA content in primary breast tumors may be exploited by guiding chemotherapeutic regimen decision making. Clin Cancer Res; 23(16); 4735-43. ©2017 AACR.
Intensive CT scan surveillance for patients who have undergone curative intent treatment for colorectal cancer: The Medstar Washington Hospital Center experience.
Authors: Konstantinos Leventakos, Stanlee Santos Lu, David John Perry
Journal: Journal of Clinical Oncology (2013)

e14675 Background: The current ASCO guideline for surveillance after curative intent treatment of colorectal cancer is yearly CT scan of the chest, abdomen and pelvis with every 3-6 months history and physical exam and serial measurement of Carcinoembryonic antigen (CEA). The benefit of doing more intensive CT scan surveillance has not been adequately substantiated. Methods: Data of patients with resectable stage I-III colorectal cancer treated at Medstar Washington Hospital Center from January 2000-June 2012 were retrospectively reviewed. Epidemiologic, histopathologic , surveillance schedule (CT scan and CEA), and survival data were analyzed. Our institutional standard was to obtain CT scans every 3 months for the first year, every 6 months for the second year and then yearly for years 3-5. Results: Thirty-three patients with adequate documentation were included. The mean age of the patients was 59.6 years at diagnosis, 55% were female and 78% ethnically African American. 6% were in stage I, 37% were in stage II and 57% in stage III. CT scan was used in 100% of the patients done with a median interval of 7 months. At follow up, 28 (85%) patients had recurrence at a median of 21.6 months from surgery. 67% had recurrence in the liver. 96% of these recurrences were diagnosed primarily by CT scan and only 1 patient (3%) was diagnosed with MRI of the liver following an elevated CEA with a negative CT scan. Only 50% of patients with recurrence had an elevated CEA. 54% of patients with recurrence were able to undergo curative treatment (resection and/or chemotherapy). Conclusions: In this single institution, retrospective review, CT scan surveillance was utilized more frequently than specified in current ASCO guidelines. CEA screening alone would have missed 50% of patients with potentially curable recurrent cancer. Our data shows that more intensive CT scan surveillance led to earlier detection of recurrences that allowed patients to undergo curative intent treatment. A prospective study is warranted to further support this finding.
Inhibition of the sterol regulatory element‐binding protein pathway suppresses hepatocellular carcinoma by repressing inflammation in mice
Authors: Na Li, Zhang‐Sen Zhou, Yang Shen, Jie Xu, Hong‐Hua Miao, Ying Xiong, Feng Xu, Bo‐Liang Li, Jie Luo, Bao‐Liang Song
Journal: Hepatology (2016)

Obesity is a critical risk factor for hepatocellular carcinoma (HCC). However, it remains unknown whether inhibition of de novo lipid biosynthesis can suppress HCC. In this study, we blocked the sterol regulatory element‐binding protein (SREBP) pathway, one of the key determinants of lipid homeostasis, by ablating 78‐kDa cell‐surface glycoprotein or SREBP cleavage‐activating protein in hepatocytes, as well as by administering a chemical compound called betulin. We found that either genetically or pharmacologically inhibiting the SREBP pathway dramatically reduced diethylnitrosamine‐induced HCC progression by down‐regulating tumor‐promoting cytokines, including interleukin (IL)‐6, tumor necrosis factor alpha, and IL‐1β. Conclusion: Inhibition of de novo lipid biosynthesis by suppressing the SREBP pathway prevents HCC. This study identifies a previously underappreciated role of the SREBP pathway in HCC and suggests a novel metabolic strategy to control liver cancer. (H epatology 2017;65:1936‐1947).
Predicting the Oncotype DX score: An inexpensive guesstimation.
Authors: Catherine Pesce, Michelle Stempel, Anne Eaton, Sujata Patil, Edi Brogi, Brittany Potz, Clifford Hudis, Mahmoud El-Tamer
Journal: Journal of Clinical Oncology (2012)

557 Background: Oncotype DX Recurrence Score [RS] is used to predict the benefits of chemotherapy added to adjuvant hormone therapy in ER positive early stage breast cancer. It is also prognostic. However, its expense may be a concern in some health care systems and communities. In addition, it is labor intensive, requiring shipment of tissue samples to a single laboratory with an average 10-14 day turnaround time (in the US). A reliable and inexpensive estimator of the Oncotype DX risk score using readily available pathologic variables from tumor specimens could be useful. Methods: We reviewed our prospective database of patients with Oncotype DX results obtained over 2.5 years (1155 specimens with Oncotype DX scores, September 2008 – March 2011) and identified 766 invasive ductal carcinomas with known ER status, PR status, histologic grade, and nuclear grade. Through linear regression analysis, we predicted recurrence score for each tumor using these four parameters. After categorizing according to the same risk classification as in Oncotype DX (low risk: RS&lt;18, intermediate risk: RS 18-30, or high risk: RS&gt;30) we compared our predicted recurrence score to actual Oncotype DX recurrence score. Results: Overall 69.7% of specimens were assigned the same risk category as with the Oncotype DX level. In the predicted low risk group, 1.7% of patients were actually high risk. None of the predicted high risk patients had a low score. Conclusions: We found a strong correlation between scores estimated using our model and actual reported Recurrence Scores. If validated, our model could provide a clinically useful estimation of risk at lower cost. [Table: see text]
Imaging-guided synergetic therapy of orthotopic transplantation tumor by superselectively arterial administration of microwave-induced microcapsules
Authors: Shunsong Tang, Changhui Fu, Longfei Tan, Tianlong Liu, Jingsong Mao, Xiangling Ren, Hongying Su, Dan Long, Qianqian Chai, Zhongbing Huang, Xudong Chen, Jingzhuo Wang, Jun Ren, Xianwei Meng
Journal: Biomaterials (2017)
Linking Subclonal Genetic Diversity with Functional Heterogeneity Identifies Diagnosis Subclones Destined to Relapse
Authors: Stephanie M. Dobson, Esme Waanders, Robert Vanner, Olga I Gan, Jessica McLeod, Ildiko Grandal, Debbie Payne-Turner, Michael Edmonson, Zhaohui Gu, Xiaotu Ma, Yiping Fan, Sagi Abelson, Pankaj Gupta, Michael Rusch, Ying Shao, Lei Shi, Stanley Pounds, Scott Olsen, Geoffrey A. Neale, John Easton, Cynthia J. Guidos, Jayne S. Danska, Jinghui Zhang, Mark D. Minden, Charles G. Mullighan, John E. Dick
Journal: Blood (2016)
Identification of Patients With Documented Pathologic Complete Response in the Breast After Neoadjuvant Chemotherapy for Omission of Axillary Surgery
Authors: Audree B. Tadros, Wei T. Yang, Savitri Krishnamurthy, Gaiane M. Rauch, Benjamin D. Smith, Vicente Valero, Dalliah M. Black, Anthony Lucci, Abigail S. Caudle, Sarah M. DeSnyder, Mediget Teshome, Carlos H. Barcenas, Makesha Miggins, Beatriz E. Adrada, Tanya Moseley, Rosa F. Hwang, Kelly K. Hunt, Henry M. Kuerer
Journal: JAMA Surgery (2017)

<h3>Importance</h3> A pathologic complete response (pCR; no invasive or in situ cancer) occurs in 40% to 50% of patients with<i>HER2</i>-positive (<i>HER2</i>+) and triple-negative (TN) breast cancer. The need for surgery if percutaneous biopsy of the breast after neoadjuvant chemotherapy (NCT) indicates pCR in the breast (hereinafter referred to as breast pCR) has been questioned, and appropriate management of the axilla in such patients is unknown. <h3>Objective</h3> To identify patients among exceptional responders to NCT with a low risk for axillary metastases when breast pCR is documented who may be eligible for an omission of surgery clinical trial design. <h3>Design, Setting, and Participants</h3> This prospective cohort study at a single-institution academic national comprehensive cancer center included 527 consecutive patients with<i>HER2</i>+/TN (T1/T2 and N0/N1) cancer treated with NCT followed by standard breast and nodal surgery from January 1, 2010, through December 31, 2014. <h3>Main Outcomes and Measures</h3> Patients who achieved a breast pCR were compared with patients who did not based on subtype, initial ultrasonographic findings, and documented pathologic nodal status. Incidence of positive findings for nodal disease on final pathologic review was calculated for patients with and without pCR and compared using relative risk ratios with 95% CIs. <h3>Results</h3> The analysis included 527 patients (median age, 51 [range, 23-84] years). Among 290 patients with initial nodal ultrasonography showing N0 disease, 116 (40.4%) had a breast pCR and 100% had no evidence of axillary lymph node metastases after NCT. Among 237 patients with initial biopsy-proved N1 disease, 69 of 77 (89.6%) with and 68 of 160 (42.5%) without a breast pCR had no evidence of residual nodal disease (<i>P</i> &lt; .01). Patients without a breast pCR had a relative risk for positive nodal metastases of 7.4 (95% CI, 3.7-14.8;<i>P</i> &lt; .001) compared with those with a breast pCR. <h3>Conclusions and Relevance</h3> Breast pCR is highly correlated with nodal status after NCT, and the risk for missing nodal metastases without axillary surgery in this cohort is extremely low. These data provide the fundamental basis and rationale for management of the axilla in clinical trials of omission of cancer surgery when image-guided biopsy indicates a breast pCR.
Group B streptococcus and respiratory syncytial virus immunisation during pregnancy: a landscape analysis
Authors: Paul T Heath, Fiona J Culley, Christine E Jones, Beate Kampmann, Kirsty Le Doare, Marta C Nunes, Manish Sadarangani, Zain Chaudhry, Carol J Baker, Peter J M Openshaw
Journal: The Lancet Infectious Diseases (2017)
Cloning and expression of three thaumatin-like protein genes from Polyporus umbellatus
Authors: Mengmeng Liu, Dawei Zhang, Yongmei Xing, Shunxing Guo
Journal: Acta Pharmaceutica Sinica B (2017)

Genes encoding thaumatin-like protein (TLPs) are frequently found in fungal genomes. However, information on TLP genes in Polyporus umbellatus is still limited. In this study, three TLP genes were cloned from P. umbellatus. The full-length coding sequence of PuTLP1, PuTLP2 and PuTLP3 were 768, 759 and 561 bp long, respectively, encoding for 256, 253 and 187 amino acids. Phylogenetic trees showed that P. umbellatus PuTLP1, PuTLP2 and PuTLP3 were clustered with sequences from Gloeophyllum trabeum, Trametes versicolor and Stereum hirsutum, respectively. The expression patterns of the three TLP genes were higher in P. umbellatus with Armillaria mellea infection than in the sclerotia without A. mellea. Furthermore, over-expression of three PuTLPs were carried out in Escherichia coli BL21 (DE3) strain, and high quality proteins were obtained using Ni-NTA resin that can be used for preparation of specific antibodies. These results suggest that PuTLP1, PuTLP2 and PuTLP3 in P. umbellatus may be involved in the defense response to A. mellea infections.
Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors
Authors: Tessa Brabander, Wouter A. van der Zwan, Jaap J.M. Teunissen, Boen L.R. Kam, Richard A. Feelders, Wouter W. de Herder, Casper H.J. van Eijck, Gaston J.H. Franssen, Eric P. Krenning, Dik J. Kwekkeboom
Journal: Clinical Cancer Research (2017)

Purpose: Bronchial and gastroenteropancreatic neuroendocrine tumors (NET) are slow-growing tumors, which frequently express somatostatin receptors on their cell membranes. These receptors are targets for therapy with Lutetium-177-labeled somatostatin analogues. We have treated over 1,200 patients with peptide receptor radionuclide therapy (PRRT) with [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE) since the year 2000 and present the results on efficacy, survival, and toxicity of this therapy.Experimental Design: For safety analysis, 610 patients treated with a cumulative dose of at least 100 mCi (3.7 GBq) 177Lu-DOTATATE were included. A subgroup of 443 Dutch patients who were treated with a cumulative dose of at least 600 mCi (22.2 GBq) 177Lu-DOTATATE before 2013 was further analyzed for efficacy and survival.Results: The objective response rate of the total group of patients was 39%. Stable disease was reached in 43% of patients. Progression-free survival (PFS) and overall survival (OS) for all NET patients were 29 months [95% confidence interval (CI), 26-33 months] and 63 months (95% CI, 55-72 months). Long-term toxicity included acute leukemia in four patients (0.7%) and myelodysplastic syndrome in nine patients (1.5%). No therapy-related long-term renal or hepatic failure occurred.Conclusions: PRRT with 177Lu-DOTATATE is a favorable therapeutic option in patients with metastatic bronchial and gastroenteropancreatic NETs that express somatostatin receptors. PRRT with 177Lu-DOTATATE is safe with few side-effects and shows good response rates with PFS of 29 months and OS of 63 months. Clin Cancer Res; 23(16); 4617-24. ©2017 AACR.
Thyroid Cancer Clinical Practice Guidelines in Oncology
Authors: Steven I Sherman, Peter Angelos, Douglas W Ball, Samuel W Beenken, David Byrd, Orlo H Clark, Gilbert H Daniels, Raza A Dilawari, Hormoz Ehya, William B Farrar, Robert F Gagel, Fouad Kandeel, Richard T Kloos, Peter Kopp, Dominick M Lamonica, Thom R Loree, William M Lydiatt, Judith McCaffrey, John A Olson, John A Ridge, Richard Robbins, Jatin P Shah, James C Sisson, Norman W Thompson
Journal: Journal of the National Comprehensive Cancer Network (2005)

In 2005, approximately 1,490 cancer deaths will occur among persons living with thyroid carcinoma in the United States. Interestingly, although thyroid carcinoma occurs more often in women, mortality rates are higher for men, probably because men are usually older at the time of diagnosis. The incidence of thyroid carcinoma increased almost 240% between 1950 and 2000, but mortality rates decreased more than 44%. Although the causes of these statistically significant changes are uncertain, the increasing incidence may be caused by the increase in radiation-induced thyroid carcinoma. Conversely, the decrease in mortality may be related to earlier diagnosis, when the disease is presumably more amenable to intervention. However, this conclusion is confounded by a possible lead time bias. For the most recent version of the guidelines, please visit NCCN.org
Molecular Profiling of Multiple Primary Merkel Cell Carcinoma to Distinguish Genetically Distinct Tumors From Clonally Related Metastases
Authors: Kelly L. Harms, Lorena Lazo de la Vega, Daniel H. Hovelson, Samantha Rahrig, Andi K. Cani, Chia-Jen Liu, Douglas R. Fullen, Min Wang, Aleodor A. Andea, Christopher K. Bichakjian, Timothy M. Johnson, Scott A. Tomlins, Paul W. Harms
Journal: JAMA Dermatology (2017)

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. In rare cases, the development of an additional cutaneous MCC tumor is clinically consistent with a second primary MCC tumor rather than a cutaneous metastasis, which has important treatment and prognostic implications.To evaluate genetic relatedness in 4 cases with the clinical diagnosis of multiple primary MCCs.In this case series, 7 cases of clinically designated multiple primary MCC were identified; 4 cases met inclusion criteria for next-generation sequencing (NGS) analysis. Mutations, copy number alterations, and Merkel cell polyomavirus (MCPyV) sequence were analyzed and compared between clinically designated multiple primary tumors to characterize genetic relatedness and hence assess clonality. Patients with clinically designated multiple primary MCC were identified from the multidisciplinary MCC Program at the University of Michigan, a tertiary care center.Four cases of clinically designated multiple primary MCC were characterized by tumor sequencing and targeted MCPyV sequencing to distinguish independent primary tumors from related metastases.Overall, 4 patients in their 70s or 80s were included and analyzed. Cases 1 and 4 were verified as genetically distinct primary tumors and did not harbor similar copy number alterations or demonstrate significant mutational overlap. Cases 2 and 3 were designated as clonally related based on overlapping copy number alterations. In clonally related tumors, chromosomal copy number changes were more reliable than mutations for demonstrating clonality. Regardless of clonality, we found that MCPyV status was concordant for all tumor pairs and MCPyV positive tumors harbored predominatly subclonal mutations.Our findings suggest that patients with MCC may develop a second genetically distinct primary tumor; in this case, the subsequent tumor is likely to develop through similar mechanisms of pathogenesis, either MCPyV-mediated or ultraviolet light-mediated. Next-generation sequencing analysis of chromosomal copy number changes and mutations is useful in distinguishing multiple primary MCCs from progression of MCC clinically resembling multiple primaries, allowing appropriate staging of the patient.
Synovial fibroblast-neutrophil interactions promote pathogenic adaptive immunity in rheumatoid arthritis
Authors: Carmelo Carmona-Rivera, Philip M. Carlucci, Erica Moore, Nithya Lingampalli, Hannes Uchtenhagen, Eddie James, Yudong Liu, Kevin L. Bicker, Heidi Wahamaa, Victoria Hoffmann, Anca Irinel Catrina, Paul R. Thompson, Jane H. Buckner, William H. Robinson, David A. Fox, Mariana J. Kaplan
Journal: Science Immunology (2017)

Neutrophil extracellular traps containing citrullinated peptides promote inflammation in synovial fibroblasts.