tbuckley/cabot-search huggingface dataset:
Naturally Arising Tumors of the Inbred WAB/Not Rat Strain. I. Classification, Age and Sex Distribution, and Transplantation Behavior&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: J G Middle, G Robinson, M J Embleton
Journal: JNCI Journal of the National Cancer Institute (1981)

During a 3-year period, 97 naturally arising tumors were collected from an inbred colony of WAB/Not rats. These tumors were largely confined to the breeding groups of approximately 5,300 female and 2,700 male rats retained up to 2 years of age. The tumors included 39 nephroblastomas and 41 mammary tumors (24 of which were histologically benign); the remaining tumors were mainly connective tissue sarcomas and skin tumors with 1 lymphoma and 2 gastrointestinal lesions. With the exception of the incidence of mammary tumors, males and females had similar tumor incidence, although nephroblastomas in female rats had a marked preference for growth in the left kidney. Most tumors occurred in the first year of life, especially the histologically malignant mammary tumors and the nephroblastomas. Of the tumors investigated, 31 were transplantable. Poor correlation between histologic malignancy and transplantation was seen with the mammary tumors. Only 50% of the nephroblastomas were transplantable. Although most transplanted tumors retained histologic characteristics of the primary tumor, 1 mammary tumor, 1 gastrointestinal tumor, and 1 nephroblastoma deviated from this general finding. In the case of this nephroblastoma, separate transplant lines from opposite poles of the primary tumor also showed differences in histology.
HER-2/neu oncogene protein and prognosis in breast cancer.
Authors: A K Tandon, G M Clark, G C Chamness, A Ullrich, W L McGuire
Journal: Journal of Clinical Oncology (1989)

Amplification of the HER-2/neu oncogene was recently reported to predict poor clinical outcome in node-positive breast cancer patients. Since expression of the oncogene as its protein product might be even more closely related than gene amplification to disease progression, we have now examined levels of the HER-2/neu oncogene protein for its prognostic potential in both node-positive and node-negative breast cancer. Using Western blot analysis, levels of this protein were determined in 728 primary human breast tumor specimens. We examined relationships between this protein and other established markers of prognosis, as well as clinical outcome. In node-negative patients (n = 378), the HER-2/neu protein failed to predict disease outcome. However, in node-positive patients (n = 350), those patients with higher HER-2/neu protein had statistically shorter disease-free (P = .0014) and overall survival (P less than .0001) than patients with lower levels of the protein. Higher HER-2/neu protein was found in tumors without estrogen receptor (ER) (P = .02) or progesterone receptor (PgR) (P = .0003), and in patients with more than three positive lymph nodes (P = .04). A significant correlation between levels of the HER-2/neu gene protein and amplification of the gene itself was also found (n = 48, P less than .001). Multivariate analyses in these patients showed that the HER-2/neu protein is a significant independent predictor of both the disease-free and the overall survival in node-positive breast cancer, even when other prognostic factors are considered.
Human B-Cell Antigens in Acute Lymphocytic Leukemia. Correlation With Other Lack of Lymphocyte Surface Markers
Authors: D L Mann, B B Kundsen, G C Yarbro, B G Leventhal
Journal: JNCI Journal of the National Cancer Institute (1979)

Cells from patients with acute lymphocytic leukemia were studied for cell surface markers and B-cel alloantigens. Three cell types were defined. Those spontaneously rosetting with erythrocytes and not prossessing surface immunoglobulin or complement receptors were considered T-cells. Cells not showing rosette formation, surface immunoglobulin, or complement receptors were considered null cells and could be divided into two categories based on their ability to stimulate in mixed lymphocyte reaction. B-cell alloantigens were found randomly distributed on all cell types. The results suggested that genetic information for human B-cell antigens was present in all cell types and that other cell surface markers may reflect a stage of differentiation of the leukemia cell type.
Phase I/II study of the CAPABLE regimen for patients with poorly differentiated carcinoma of the nasopharynx.
Authors: L L Siu, P M Czaykowski, I F Tannock
Journal: Journal of Clinical Oncology (1998)

PURPOSE To evaluate the role of aggressive combination chemotherapy in patients with poorly differentiated carcinoma of the nasopharynx (NPC). PATIENTS AND METHODS In a prospective phase I/II study, 90 chemotherapy-naive patients with NPC (21 with very advanced locoregional disease, 18 with locoregional persistent and/or recurrent disease postradiotherapy, and 51 with metastatic disease) were treated with cyclophosphamide, doxorubicin, cisplatin, methotrexate, and bleomycin (CAPABLE). Two schedules of this regimen were used over a 9-year period, with the second schedule being a modification of the first in an attempt to minimize treatment-related toxicity. RESULTS Of 21 patients with very advanced local disease, one had a complete response (CR) and 17 had partial responses (PRs) (response rate, 86%). Seventeen of these 21 patients had subsequent radiotherapy. Of 17 patients with measurable locoregional disease either persistent and/or recurrent postradiotherapy, there were four CRs and three PRs (response rate, 41%). Of 44 patients with measurable metastatic disease, there were three CRs and 32 PRs (response rate, 80%). The median survival durations for these three groups of patients were 47, 16, and 14 months, respectively. The two chemotherapy schedules had similar received dose-intensities (RDIs) and produced similar response rates and survival. Toxicity was severe with frequent mucositis and myelosuppression. Overall, 37 patients required at least one hospital admission for management of toxic side effects and there were seven drug-related deaths. Three of the deaths were due to fulminant hepatitis, likely from reactivation of hepatitis B. CONCLUSION This aggressive regimen provides a high rate of tumor response, but limited palliation for most patients with recurrent or metastatic NPC. The results with chemotherapy followed by radiotherapy for patients with very advanced local disease are encouraging, but proof of benefit would require evaluation in a randomized trial.
Evolution of plant genome architecture
Authors: Jonathan F. Wendel, Scott A. Jackson, Blake C. Meyers, Rod A. Wing
Journal: Genome biology (2016)

We have witnessed an explosion in our understanding of the evolution and structure of plant genomes in recent years. Here, we highlight three important emergent realizations: (1) that the evolutionary history of all plant genomes contains multiple, cyclical episodes of whole-genome doubling that were followed by myriad fractionation processes; (2) that the vast majority of the variation in genome size reflects the dynamics of proliferation and loss of lineage-specific transposable elements; and (3) that various classes of small RNAs help shape genomic architecture and function. We illustrate ways in which understanding these organism-level and molecular genetic processes can be used for crop plant improvement.
Relationship between the spatial pattern of P300 and performance of a P300-based brain-computer interface in amyotrophic lateral sclerosis
Authors: Hisato Sugata, Masayuki Hirata, Yu Kageyama, Haruhiko Kishima, Jinichi Sawada, Toshiki Yoshimine
Journal: Brain-Computer Interfaces (2016)

The P300-based brain-computer interface (P300-BCI) is expected to provide a new communication tool for patients with amyotrophic lateral sclerosis (ALS). Currently, there is little evidence about the relationship between the neurophysiological profiles of P300 and the performance of the P300-BCI in patients with ALS. In the present study, we investigate this relationship in detail. Patients were asked to input five characters using a traditional row/column speller which consisted of a 7 × 10 matrix. EEGs were recorded using eight electrodes. The on-line P300-BCI performance was then compared with the neurophysiological profiles of P300. We found that patients who had a robust P300 response over the occipital area showed a higher success rate in the P300-BCI compared with patients who had a large P300 response over the fronto-central area. These results suggest that appropriate evaluation of the neurophysiological aspects of P300 may lead to prediction of and improvement in the P300-BCI performance.
Abstract B33: Integration of genome-wide datasets identifies SOX10 as a lineage-specific genetic dependency in melanoma
Authors: Terence C. Wong, Cory M. Johannessen, Levi A. Garraway
Journal: Clinical Cancer Research (2015)

Abstract Melanoma accounts for less than 5% of skin cancers, but a majority of skin cancer deaths. Genomic studies have firmly established the role of recurrent somatic alterations in the pathogenesis of melanoma, including mutations in BRAF, NRAS, TP53, PTEN, and CDKN2A. While the discovery of activating mutations in BRAF in over 60% of melanomas has led to the development of FDA-approved BRAF and MEK inhibitors that induce dramatic responses in BRAF V600-mutant melanomas, the inevitable resistance to BRAF/MEK inhibitors necessitates a greater understanding of melanoma biology and genetics. By integrating genome-wide functional genomic and expression data, we have identified SOX10 as a lineage-specific genetic dependency in melanoma. SOX10 dependency is highly correlated with SOX10 gene expression in melanoma. Subsequent functional in vitro experiments have confirmed the role of SOX10 in the cellular proliferation and growth of melanoma cell lines. The combination of SOX10 depletion with current FDA-approved targeted therapies for melanoma hold promise for the delay or prevention of resistance to these therapeutics and may lead to more durable control of melanoma in human patients. Citation Format: Terence C. Wong, Cory M. Johannessen, Levi A. Garraway. Integration of genome-wide datasets identifies SOX10 as a lineage-specific genetic dependency in melanoma. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr B33.
Genome dynamics of multidrug-resistant Acinetobacter baumannii during infection and treatment
Authors: Meredith S. Wright, Alina Iovleva, Michael R. Jacobs, Robert A. Bonomo, Mark D. Adams
Journal: Genome Medicine (2016)

Limited treatment options are available for patients infected with multidrug (MDR)- or pan-drug (PDR)-resistant bacterial pathogens, resulting in infections that can persist for weeks or months. In order to better understand transmission and evolutionary dynamics of MDR Acinetobacter baumannii (Ab) during long-term infection, we analyzed genomes from a series of isolates from individual patients at isolate-specific, patient-specific, and population levels. Whole genome analysis of longitudinal isolates (range 2-10 isolates per patient spanning 0-829 days) from 40 patients included detection of single-nucleotide variants (SNVs), insertion sequence (IS) mapping, and gene content changes. Phylogenetic analysis revealed that a significant fraction of apparently persistent infections are in fact due to re-infection with new strains. SNVs primarily resulted in protein coding changes, and IS events primarily interrupted genes or were in an orientation such that the adjacent gene would be over-expressed. Mutations acquired during infection were over-represented in transcriptional regulators, notably pmrAB and adeRS, which can mediate resistance to the last line therapies colistin and tigecycline, respectively, as well as transporters, surface structures, and iron acquisition genes. Most SNVs and IS events were isolate-specific indicating these mutations did not become fixed on the time scale investigated, yet over-representation of independent mutations in some genes or functional categories suggests that they are under selective pressure. Genome analysis at the population-level suggests that gene transfer including recombination also contributes to Ab evolutionary dynamics. These findings provide important insight into the transmission dynamics of Ab and the identification of patients with repeat infections has implications for infection control programs targeted to this pathogen.
Effects of Cyanate, Thiocyanate, and Amygdalin on Metabolite Uptake in Normal and Neoplastic Tissues of the Rat&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M A Lea, M R Koch
Journal: JNCI Journal of the National Cancer Institute (1979)

Thiocyanate was found to resemble cyanate in its inhibitory effects on [3H]thymidine incorporation and the uptake of [32P]phosphate and [3H]amino acids in transplanted tumors of the BUF rat. The capacity to inhibit metabolite uptake in hepatomas and a colon tumor under conditions in which uptake was unchanged or increased in host liver was concluded to be a common feature of the action of cyanate and thiocyanate. Inhibition of [32P]phosphate uptake and [3H]thymidine incorporation into DNA of tumors was also observed after treatment of rats with amygdalin. With this drug, however, the action on tumors and livers of host rats was similar.
A characteristic pattern of leukemic cell differentiation without cytoreduction during remission induction in acute promyelocytic leukemia.
Authors: H M Kantarjian, M J Keating, K B McCredie, M Beran, R Walters, W T Dalton, W Hittleman, E J Freireich
Journal: Journal of Clinical Oncology (1985)

While differentiation of leukemic cells in vitro is well established, the role of differentiation in vivo is not defined and is generally attributed to differentiation inducers. In five patients with acute promyelocytic leukemia (APL) an unusual pattern of a slow and progressive decrease of immature blasts with a concomitant increase in mature cellular elements was observed following intensive combination chemotherapy. All patients eventually achieved complete remission, four of them without an intermediate phase of marrow hypoplasia. This morphologic pattern of response suggests that leukemic cellular differentiation rather than cytotoxicity was one mechanism involved in remission induction. Cytogenetic studies of remission revealed disappearance of the cytogenetic marker, the balanced translocation between the long arms of chromosomes 15 and 17. This remission induction process appears to be due to the cellular biologic characteristic rather than the therapy used as it occurs in a substantial proportion of patients with APL. It should be considered for optimal diagnostic and therapeutic decisions.
Depletion of Abundant Sequences by Hybridization (DASH): using Cas9 to remove unwanted high-abundance species in sequencing libraries and molecular counting applications
Authors: W. Gu, E. D. Crawford, B. D. O’Donovan, M. R. Wilson, E. D. Chow, H. Retallack, J. L. DeRisi
Journal: Genome biology (2016)

Next-generation sequencing has generated a need for a broadly applicable method to remove unwanted high-abundance species prior to sequencing. We introduce DASH (Depletion of Abundant Sequences by Hybridization). Sequencing libraries are 'DASHed' with recombinant Cas9 protein complexed with a library of guide RNAs targeting unwanted species for cleavage, thus preventing them from consuming sequencing space. We demonstrate a more than 99 % reduction of mitochondrial rRNA in HeLa cells, and enrichment of pathogen sequences in patient samples. We also demonstrate an application of DASH in cancer. This simple method can be adapted for any sample type and increases sequencing yield without additional cost.
Nature of Early Appearing, Carcinogen-Induced Liver Lesions Resistant to Iron Accumulation 2 3
Authors: Gary M. Williams, Marianne Klaiber, Sally E. Parker, Emmanuel Farber
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Nature of Early Appearing, Carcinogen-Induced Liver Lesions Resistant to Iron Accumulation Get access Gary M. Williams, Gary M. Williams Search for other works by this author on: Oxford Academic PubMed Google Scholar Marianne Klaiber, Marianne Klaiber Search for other works by this author on: Oxford Academic PubMed Google Scholar Sally E. Parker, Sally E. Parker Search for other works by this author on: Oxford Academic PubMed Google Scholar Emmanuel Farber Emmanuel Farber Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 1, July 1976, Pages 157–165, https://doi.org/10.1093/jnci/57.1.157 Published: 01 July 1976 Article history Received: 14 October 1975 Accepted: 10 December 1975 Published: 01 July 1976
Bendamustine (Treanda®)-Based Regimens Are Effective In Mobilizing Peripheral Blood Hematopoietic Stem Cells For Autologous Transplantation
Authors: Damian J. Green, William I. Bensinger, Leona Holmberg, Theodore A. Gooley, Brian G. Till, Lihua Elizabeth Budde, John M. Pagel, Shani L. Frayo, Jennifer E. Roden, Lacey M. Hedin, Malcolm Mack, Oliver W. Press, Ajay K. Gopal
Journal: Blood (2013)
Final results of E2603: A double-blind, randomized phase III trial comparing carboplatin (C)/paclitaxel (P) with or without sorafenib (S) in metastatic melanoma.
Authors: K. T. Flaherty, S. J. Lee, L. M. Schuchter, L. E. Flaherty, J. J. Wright, P. D. Leming, J. M. Kirkwood
Journal: Journal of Clinical Oncology (2010)

8511 Background: Systemic treatment of metastatic melanoma has not advanced for decades, prompting investigation of novel approaches. Sorafenib is a kinase inhibitor active against RAF and VEGFR tyrosine kinases, amongst others. The discovery of BRAF mutations in 60% of melanoma prompted investigation of the combination of S/C/P following promising results in a large, uncontrolled phase II trial in metastatic melanoma. Methods: Our primary objective was to determine whether S/C/P improves overall survival (OS) compared to C/P in chemotherapy- naïve metastatic melanoma pts. Pts were not prescreened for BRAF mutations. All pts received C AUC 6 IV q 21d and P 225 mg/m2 IV q21d with random assignment to S 400 mg BID days 2-19 every 21d or placebo. 800 patients were needed to provide 90% power to detect a 22.5% improvement in hazard ratio (HR) for OS. Interim analyses were conducted preserving the overall type I error rate of 0.05 (two-sided), and monitoring for early stopping in favor of the null hypothesis using Jennison-Turnbull repeated confidence interval. PFS, RR, and toxicity were secondary endpoints. Potential predictive genetic and immunohistologic correlates are under study. Results: 823 pts (411 C/P, 409 S/C/P, 3% ineligible) were accrued over 34 months. After the third interim analysis, 75% of the events required for final analysis had transpired. The study had crossed the futility boundary, and was unblinded. The log-rank test HR, stratifying by AJCC stage, ECOG PS and prior therapy, was 1.0 (p = 0.878). The median OS for the S/C/P group is 11.1 months (95% CI and 10.3-12.3) and for the C/P group is 11.3 mos. (95% CI 9.7-12.3). Median PFS was 4.9 for S/C/P and 4.1 for C/P (p = 0.12). RR was 18% for S/C/P and 16% for C/P (p = 0.48). 78% of patients in C/P arm and 84% in the S/C/P arm had grade 3 or higher toxicities (p = 0.032), with significantly increased rash, hand-foot syndrome, neuropathy, and thrombocytopenia. Conclusions: S/C/P does not improve overall survival in combination with C/P for chemotherapy-naïve pts with metastatic melanoma. This study also establishes RR and PFS for the C/P combination chemotherapy regimen in first-line therapy of metastatic melanoma. No significant financial relationships to disclose.
Targeting MDM2 for Treatment of Adenoid Cystic Carcinoma
Authors: Kristy A. Warner, Felipe Nör, Gerson A. Acasigua, Manoela D. Martins, Zhaocheng Zhang, Scott A. McLean, Matthew E. Spector, Douglas B. Chepeha, Joseph Helman, Michael J. Wick, Christopher A. Moskaluk, Rogerio M. Castilho, Alexander T. Pearson, Shaomeng Wang, Jacques E. Nör
Journal: Clinical Cancer Research (2016)

Abstract Purpose: There are no effective treatment options for patients with advanced adenoid cystic carcinoma (ACC). Here, we evaluated the effect of a new small molecule inhibitor of the MDM2–p53 interaction (MI-773) in preclinical models of ACC. Experimental Design: To evaluate the anti-tumor effect of MI-773, we administered it to mice harboring three different patient-derived xenograft (PDX) models of ACC expressing functional p53. The effect of MI-773 on MDM2, p53, phospho-p53, and p21 was examined by Western blots in 5 low passage primary human ACC cell lines and in MI-773-treated PDX tumors. Results: Single-agent MI-773 caused tumor regression in the 3 PDX models of ACC studied here. For example, we observed a tumor growth inhibition index of 127% in UM-PDX-HACC-5 tumors that was associated with an increase in the fraction of apoptotic cells (P = 0.015). The number of p53-positive cells was increased in MI-773-treated PDX tumors (P &amp;lt; 0.001), with a correspondent shift in p53 localization from the nucleus to the cytoplasm. Western blots demonstrated that MI-773 potently induced expression of p53 and its downstream targets p21, MDM2, and induced phosphorylation of p53 (serine 392) in low passage primary human ACC cells. Notably, MI-773 induced a dose-dependent increase in the fraction of apoptotic ACC cells and in the fraction of cells in the G1 phase of cell cycle (P &amp;lt; 0.05). Conclusions: Collectively, these data demonstrate that therapeutic inhibition of the MDM2–p53 interaction with MI-773 activates downstream effectors of apoptosis and causes robust tumor regression in preclinical models of ACC. Clin Cancer Res; 22(14); 3550–9. ©2016 AACR.
Mgmt Methylation in Tissue and Serum from Unresectable Glioblastoma (Gbm) Patients (P) Included in the Genom 009 Study, a Multicenter Randomized Study By the Geino Group Comparing Temozolomide (Tmz) Versus Tmz-Plus-Bevacizumab (Bev). (Clinicaltrials.Gov Nct01102595)
Authors: C. Balana, C. Sanz, J.L. Ramirez, J.M. Gil, J.M. Sepúlveda, R. De Las Penas, R. Luque, O. Gallego, G. Reynes, C. Carrato, B. Sanchez, A. Herrero, A. Berrocal, P. Perez Segura, A. Garcia Castano, S. Peralta, S. Vazquez, I. Fernández Perez, M. Martinez-Garcia
Journal: Annals of Oncology (2014)