tbuckley/cabot-search huggingface dataset:
Erlotinib as single agent in patients (p) with advanced or metastatic NSCLC: A multivariate analysis in a prospective study
Authors: C. Pallares, L. Paz-Ares, J. López-Picazo, R. Pérez-Carrión, A. Montes, G. López-Vivanco, J. De Castro, M. Cobo, A. García Velasco, P. Regueiro, B. Massutí
Journal: Journal of Clinical Oncology (2006)

7180 Background: Erlotinib is the first orally available selective EGFR tyrosine-kinase inhibitor that improves survival in 2nd and 3rd line therapy for NSCLC. This non-randomised, phase II trial evaluated the efficacy and safety of erlotinib in patients with advanced or metastatic NSCLC. Methods: Patients with previously treated advanced or metastatic NSCLC or patients that were not suitable for first line conventional chemotherapy, stage IIIB/IV, PS 0–2 were enrolled to receive erlotinib 150 mg/day until disease progression or withdrawal. The primary endpoint of the study was time to progression (TTP) in the intent to treat (ITT) population. A multivariate analysis (Cox-model) was performed. Results: 416 patients were enrolled from June 04 to March 05. Demographics: M 78%/F 22%; median age 64 y [range 28–100]; stage IV 91.6%; PS 0/1/≥2: 65 (16%)/227 (55%)/105 (25%); adeno histology 178p (43%), SCC 121p (29%), BAC 3p (0.7%), LLC 2p (20%), other 29p (7%); smoking status: yes 349 p (84%) no 62 p (15%). 1st line: 60p (14.4%); 2nd line 181p (43.5%) and ≥ 3 rd line 175p (42%). 230 patients had measurable disease and were evaluable for response: 1CR, 30 PR (ORR: 13.4%), 98 SD, and 101 PD. Toxicity was predictable (mainly rash, and diarrhoea). In the ITT population the median TTP was 3.2 m [95% CI 2.8–3.6]. For evaluable population median TTP was 4.6 m in 1st line, 3.23 m in 2nd line, and 2.8 m in 3rd line. Exploratory analysis showed that ORR was associated with gender, smoking history, previous treatment and histology. The multivariate analysis for TTP showed that no smoking history (p &lt; 0.005), adeno histology (p &lt; 0.0001), and erlotinib as 1st line treatment (p &lt; 0.02) correlated with better TTP. Conclusions: Erlotinib is an active and very well tolerated treatment in patients with advanced NSCLC untreated or that have previously failed to conventional chemotherapy. Our data suggest that non smoking history, adeno histology and erlotinib as 1st line treatment are associated with better TTP. The study is ongoing. [Table: see text]
The Natural History of Primary First-Degree Atrioventricular Heart Block
Authors: David Mymin, Francis A.L. Mathewson, Robert B. Tate, Jure Manfreda
Journal: New England Journal of Medicine (1986)

The long-term prognosis of first-degree heart block in the absence of organic heart disease has not been clearly defined. We addressed this question in a 30-year longitudinal study of 3983 healthy men. We identified 52 cases that were present on entry into the study and 124 incident cases during follow-up. The incidence rose steadily after age 40 and was 1.13 per 1000 person-years over the entire period. Two thirds of the cases had only moderate prolongation of the PR interval (0.22 to 0.23 second). We compared four age-matched controls with each case for histories of scarlet fever, rheumatic fever, diphtheria, smoking, blood pressure, and body-mass index. No significant differences (P>0.05) were found. Likewise, mortality from all causes did not differ between cases and controls. Although somewhat higher rates of morbidity and mortality from ischemic heart disease were observed in the cases than in the controls, the differences were not significant. Progression to higher grades of heart block occurred in only two cases. In view of the prognostic findings and the rare occurrence of advanced degrees of heart block, we conclude that primary first-degree heart block with moderate PR prolongation is a benign condition. This conclusion may not apply, however, to persons with more marked prolongation of the PR interval, a very rare condition. (N Engl J Med 1986; 315:1183–7.)
Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer–Initiating Cells and Is a Potent Target of Immunotherapy
Authors: Rena Morita, Yoshihiko Hirohashi, Toshihiko Torigoe, Satoko Ito-Inoda, Akari Takahashi, Tasuku Mariya, Hiroko Asanuma, Yasuaki Tamura, Tomohide Tsukahara, Takayuki Kanaseki, Terufumi Kubo, Goro Kutomi, Toru Mizuguchi, Takeshi Terui, Kunihiko Ishitani, Satoshi Hashino, Toru Kondo, Nozomi Minagawa, Norihiko Takahashi, Akinobu Taketomi, Satoru Todo, Masahiro Asaka, Noriyuki Sato
Journal: Clinical Cancer Research (2016)

Cancer-initiating cells (CICs) are thought to be essential for tumor maintenance, recurrence, and distant metastasis, and they are therefore reasonable targets for cancer therapy. Cancer immunotherapy is a novel approach to target cancer. In this study, we aimed to establish novel CIC-targeting immunotherapy.Colorectal cancer (CRC) CICs were isolated as side population (SP) cells. The gene expression profile of CRC CICs was analyzed by cDNA microarray and RT-PCR. Protein expression of olfactory receptor family 7 subfamily C member 1 (OR7C1) were analyzed by Western blot and immunohistochemical staining. The functions of OR7C1 were analyzed by gene overexpression and gene knockdown using siRNAs. OR7C1-positive cells were isolated by a flow cytometer and analyzed. CTLs specific for OR7C1 peptide were generated, and the antitumor effect was addressed by mice adoptive transfer model.OR7C1 has essential roles in the maintenance of colon CICs, and the OR7C1-positive population showed higher tumorigenicity than that of the OR7C1-negative population, indicating that OR7C1 is a novel functional marker for colon CIC. Immunohistochemical staining revealed that OR7C1 high expression was correlated with poorer prognosis in CRC patients. OR7C1-derived antigenic peptide-specific CTLs showed specific cytotoxicity for CICs, and an OR7C1-specific CTL clone showed a greater antitumor effect than did a CTL clone targeting all cancer cells in a CTL adoptive transfer mouse model.OR7C1 is a novel marker for colon CICs and can be a target of potent CIC-targeting immunotherapy. Clin Cancer Res; 22(13); 3298-309. ©2016 AACR.
Extreme Hyperglobulinemia in Subacute Hepatic Necrosis
Authors: H. J. Zimmerman, P. Heller, R. P. Hill
Journal: New England Journal of Medicine (1951)

SERUM protein disturbance has been recognized in liver disease since Jolies,1 in 1902, first described depression of the whole-blood proteins in cirrhosis. Several years later, Gilbert and Chiray2 and Grenet3 observed this to be due to serum protein depression. In 1925 Filinski4 showed that the serum protein abnormality in cirrhosis included not only albumin depression but also globulin elevation. Subsequent observations5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 have shown these findings to be so common in intrinsic liver disease that the opinion has been advanced12 , 22 that the diagnosis of cirrhosis should be held in doubt in the absence of serum globulin elevation. While for prognostic value . . .
The Age Distribution of Poliomyelitis in Massachusetts
Authors: R. J. M. Horton, A. Daniel Rubenstein
Journal: New England Journal of Medicine (1948)

DATA concerning the incidence of poliomyelitis in Massachusetts have been collected by the Department of Public Health since 1907. This material had been studied statistically by Forsbeck and Luther1 in 1930, and it was thought that a review of these older records, combined with the data accumulated during the past fifteen years would yield additional information on this subject.In the present analysis particular attention has been given to the age distribution and the geographical behavior of poliomyelitis in Massachusetts since 1907. This discussion is limited to a consideration of the age distribution. The material on the geographical aspects will . . .
Prostaglindin I2 Receptor (IP) Signaling Increases Regulatory T (Treg) Cell Induction and Function and Renders T Effector (Teff) Cells More Susceptible to Treg-Mediated Suppression
Authors: Melissa H. Bloodworth, Kasia Goleniewska, R. Stokes Peebles
Journal: Journal of Allergy and Clinical Immunology (2016)
Case 38-2003
Authors: H. Shaw Warren, R. Gilberto Gonzalez, Di Tian
Journal: New England Journal of Medicine (2003)

Presentation of CaseA 12-year-old girl was admitted to the hospital because of fever, vomiting, and an abrupt onset of unresponsiveness.She had been well until one week earlier, when a cough, sore throat, and rhinorrhea developed. Laboratory values obtained six days before admission are shown in Table 1 and Table 2. On the evening before admission, her temperature was 39.4°C. At noon on the following day, she began to vomit, and at 6:30 p.m. she was taken to the emergency department of another hospital. The temperature was 39.2°C, the pulse was 121 beats per minute, and the blood pressure was 135/75 mm . . .
A Method for the Study of Calcium Absorption by the Human Gut Using a Standard Dose of Calcium Labeled with Calcium47
Authors: Z. F. Jaworski, E. M. Brown, S. Fedoruk, H. Seitz
Journal: New England Journal of Medicine (1963)

THE process of calcium absorption by the human gut and the factors that affect it in health and in disease are still poorly understood. Workers in this field have been hindered by the lack of convenient methods.1 2 3 4 This aspect of calcium metabolism has been studied chiefly by the metabolic-balance technic, which is not only protracted and difficult but also inherently limited in scope — for example, the net calcium absorption, calculated as a difference between the mean daily ingested and fecal calcium, ignores the part of the fecal calcium contributed by gastrointestinal secretions. Once a suitable isotope such as calcium . . .
Case 25-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, R.K. Goyal, C.C. Compton
Journal: New England Journal of Medicine (1990)

Presentation of Case First admission. A 63-year-old man was admitted to the hospital because of recurrent diarrhea.The patient stated that he became malnourished as a prisoner of war during World War II, with a decrease in his weight from 90 to 74 kg and symptoms of peripheral neuropathy. During the next 41 years he was well except for the passage of loose stools once or twice a week without associated abdominal pain, nausea, or vomiting. The stools were not malodorous and did not contain recognizable blood. Twenty-two months before admission the patient had a 9-kg loss in weight over . . .
Clonal Rearrangements of T-Cell Receptor Genes in Mycosis Fungoides and Dermatopathic Lymphadenopathy
Authors: Lawrence M. Weiss, Eddie Hu, Gary S. Wood, Courtney Moulds, Michael L. Cleary, Roger Warnke, Jeffrey Sklar
Journal: New England Journal of Medicine (1985)

Histologic diagnosis of mycosis fungoides may be difficult, especially in lymph nodes that show changes frequently associated with chronic skin disease. As an alternative approach to diagnosis, we have analyzed the configuration of DNA for the beta T-cell receptor genes in biopsy tissues from 14 patients with mycosis fungoides. Clonal rearrangements of these genes were found in each specimen that contained histologically unambiguous mycosis fungoides. Clonal rearrangements were also found in seven of nine lymph nodes removed from patients with mycosis fungoides and considered histologically to contain only benign lymphadenopathy. Matching rearrangements of beta T-cell receptor genes were detected in benign lymph nodes and histologically involved tissues when paired specimens were available from the same cases. Our findings provide molecular evidence for the clonal T-cell origin of mycosis fungoides and indicate the high incidence of extracutaneous disease in patients with palpable lymphadenopathy. In addition, this study demonstrates that the detection of rearranged T-cell receptor genes can be a sensitive and practical method for the diagnosis and characterization of T-cell neoplasms. (N Engl J Med 1985; 313:539–44.)
Narrow band imaging optical diagnosis of small colorectal polyps in routine clinical practice: the Detect Inspect Characterise Resect and Discard 2 (DISCARD 2) study
Authors: Colin J Rees, Praveen T Rajasekhar, Ana Wilson, Helen Close, Matthew D Rutter, Brian P Saunders, James E East, Rebecca Maier, Morgan Moorghen, Usman Muhammad, Helen Hancock, Anthoor Jayaprakash, Chris MacDonald, Arvind Ramadas, Anjan Dhar, James M Mason
Journal: Gut (2016)

<h3>Background</h3> Accurate optical characterisation and removal of small adenomas (&lt;10 mm) at colonoscopy would allow hyperplastic polyps to be left in situ and surveillance intervals to be determined without the need for histopathology. Although accurate in specialist practice the performance of narrow band imaging (NBI), colonoscopy in routine clinical practice is poorly understood. <h3>Methods</h3> NBI-assisted optical diagnosis was compared with reference standard histopathological findings in a prospective, blinded study, which recruited adults undergoing routine colonoscopy in six general hospitals in the UK. Participating colonoscopists (N=28) were trained using the NBI International Colorectal Endoscopic (NICE) classification (relating to colour, vessel structure and surface pattern). By comparing the optical and histological findings in patients with only small polyps, test sensitivity was determined at the patient level using two thresholds: presence of adenoma and need for surveillance. Accuracy of identifying adenomatous polyps &lt;10 mm was compared at the polyp level using hierarchical models, allowing determinants of accuracy to be explored. <h3>Findings</h3> Of 1688 patients recruited, 722 (42.8%) had polyps &lt;10 mm with 567 (78.5%) having only polyps &lt;10 mm. Test sensitivity (presence of adenoma, N=499 patients) by NBI optical diagnosis was 83.4% (95% CI 79.6% to 86.9%), significantly less than the 95% sensitivity (p&lt;0.001) this study was powered to detect. Test sensitivity (need for surveillance) was 73.0% (95% CI 66.5% to 79.9%). Analysed at the polyp level, test sensitivity (presence of adenoma, N=1620 polyps) was 76.1% (95% CI 72.8% to 79.1%). In fully adjusted analyses, test sensitivity was 99.4% (95% CI 98.2% to 99.8%) if two or more NICE adenoma characteristics were identified. Neither colonoscopist expertise, confidence in diagnosis nor use of high definition colonoscopy independently improved test accuracy. <h3>Interpretation</h3> This large multicentre study demonstrates that NBI optical diagnosis cannot currently be recommended for application in routine clinical practice. Further work is required to evaluate whether variation in test accuracy is related to polyp characteristics or colonoscopist training. <h3>Trial registration number</h3> The study was registered with clinicaltrials.gov (NCT01603927).
Abstract B31: Combined siRNA and small molecule screening identifies Aurora B kinase as an effective target in MYCN-driven neuroblastoma
Authors: Dominik Bogen, Jun S. Wei, David O. Azorsa, Pinar Ormanoglu, Eugen Buehler, Rajarshi Guha, Jonathan M. Keller, Lesley A. Mathews Griner, Marc Ferrer, Young K. Song, Hongling Liao, Arnulfo Mendoza, Berkley E. Gryder, Sivasish Sindri, Jianbin He, Xinyu Wen, Xinyu Wen, Shile Zhang, John F. Shern, Marielle E. Yohe, Sabine Taschner-Mandl, Jason Shohet, Craig J. Thomas, Scott E. Martin, Peter F. Ambros, Javed Khan
Journal: Cancer Research (2016)

Abstract Despite advances in multimodal treatment, neuroblastoma (NB) is often fatal for children with high-risk disease and many survivors need to cope with long-term side effects from high-dose chemotherapy and radiation. To identify new therapeutic targets, we performed a siRNA screen of the druggable genome combined with a small molecule screen of 465 compounds targeting 39 different mechanisms of actions in four NB cell lines. We identified 58 genes as targets, including AURKB, in at least one cell line. In the drug screen, aurora kinase inhibitors (nine molecules) and in particular the AURKB-selective compound, barasertib, were the most discriminatory with regard to sensitivity for MYCN-amplified cell lines. In an expanded panel of NB cell lines, those with MYCN amplification and wild-type TP53 were the most sensitive to low nanomolar concentrations of barasertib. Inhibition of the AURKB kinase activity resulted in decreased phosphorylation of its known target histone H3, and upregulation of p53 pathway in MYCN-amplified NB cells with wild-type TP53. Both wild-type and p53-mutant MYCN-amplified cell lines arrested in G2/M phase upon AURKB inhibition. Additionally, barasertib induced endoreduplication and apoptosis. Treatment of MYCN-amplified/TP53 wild-type neuroblastoma xenografts resulted in profound growth inhibition and tumor regression. Therefore, aurora B kinase inhibition is highly effective in aggressive neuroblastoma and warrants further investigation in clinical trials. Citation Format: Dominik Bogen, Jun S. Wei, David O. Azorsa, Pinar Ormanoglu, Eugen Buehler, Rajarshi Guha, Jonathan M. Keller, Lesley A. Mathews Griner, Marc Ferrer, Young K. Song, Hongling Liao, Arnulfo Mendoza, Berkley E. Gryder, Sivasish Sindri, Jianbin He, Xinyu Wen, Xinyu Wen, Shile Zhang, John F. Shern, Marielle E. Yohe, Sabine Taschner-Mandl, Jason Shohet, Craig J. Thomas, Scott E. Martin, Peter F. Ambros, Javed Khan. Combined siRNA and small molecule screening identifies Aurora B kinase as an effective target in MYCN-driven neuroblastoma. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr B31.
Predictors of response and nonresponse to light treatment for winter depression
Authors: M Terman, L Amira, J S Terman, D C Ross
Journal: American Journal of Psychiatry (1996)

The authors' goal was to determine whether the pattern and severity of depressive symptoms predict response to light treatment for seasonal affective disorder.Subjects with winter depression (N = 103) were given bright light treatment. Seventy-one were classified as responders, 15 as nonresponders, and 17 as partial responders. Using depression rating scale data and correlational and multivariate analysis, the authors sought predictors of response in baseline symptom and scale scores.Responders were characterized by atypical symptoms, especially hypersomnia, afternoon or evening slump, reverse diurnal variation (evenings worse), and carbohydrate craving. By contrast, nonresponders were characterized mainly by melancholic symptoms, retardation, suicidality, depersonalization, typical diurnal variation (mornings worse), anxiety, early and late insomnia, appetite loss, and guilt. The ratio of atypical to classical symptoms of depression, rather than severity per se, best predicted treatment outcome for the group as a whole. Pretreatment expectations were positively correlated with improvement on the Hamilton Depression Rating Scale but not on a supplementary scale of atypical symptoms.Light-responsive seasonal affective disorder is distinguished by a dominant atypical symptom profile closely associated with depressed mood. Nonresponders from a clinically distinct group with melancholic features. The patient's symptom profile, therefore, should be considered when diagnosing seasonal affective disorder and selecting treatment.
Choleretic Action of Cortisone
Authors: Paul R. Patterson, Joseph F. Dingman, Harry Shwachman, George W. Thorn
Journal: New England Journal of Medicine (1954)

ACTH and cortisone have had extensive therapeutic trials in the management of acute and chronic diseases of the liver. Most patients with acute hepatitis treated with ACTH or cortisone, as reported by Colbert et al.,1 Sborov and his colleagues2 and Evans, Sprinz and Nelson,3 showed prompt improvements in appetite and sense of well-being, accompanied by sharp decreases in serum bilirubin levels, which fell to normal in a shorter period than those of untreated groups.2 Clinical remission was significantly hastened. However, the frequency and severity of complications that occurred during administration and the relapses after withdrawal limit the usefulness of these . . .
Abstract PD3-05: Inhibition of fatty-acid oxidation as a therapy for triple-negative breast cancer
Authors: A Goga, R Camarda, AY Zhou, RA Kohnz, S Balakrishnan, B Anderton, C Mahieu, H Eyob, G Krings, DK Nomura
Journal: Cancer Research (2016)

Abstract Expression of the oncogenic transcription factor MYC is disproportionately elevated in triple-negative breast cancer (TNBC) compared to estrogen, progesterone and/or human epidermal growth factor 2 receptor-positive (RP) breast tumors. We and others have shown that MYC alters metabolism during tumorigenesis. However, the role of MYC in TNBC metabolism remains largely unexplored. We hypothesized that pharmacologic inhibition of MYC-driven metabolic pathways may serve as a therapeutic strategy for this clinically challenging subtype of breast cancer. Using an unbiased metabolomics approach, we identified fatty acid oxidation intermediates as dramatically up-regulated in MYC-driven models of TNBC. A lipid metabolism gene signature was identified in patients with TNBC in the TCGA and multiple other clinical datasets, implicating fatty acid oxidation as a deregulated pathway critical for TNBC metabolism. We find that MYC-overexpressing TNBC, including transgenic models and patient-derived xenografts (PDX), display increased bioenergetic reliance upon fatty-acid oxidation (FAO). Pharmacologic inhibition of FAO catastrophically decreases energy metabolism of MYC over-expressing breast cancer, blocks growth of a MYC-driven transgenic TNBC model and MYC-overexpressing patient-derived xenografts. In vivo inhibition of FAO induced proliferation arrest and increased cell death in PDX models of TNBC. Our results demonstrate that inhibition of FAO is a novel therapeutic strategy against TNBCs that over-express MYC. Citation Format: Goga A, Camarda R, Zhou AY, Kohnz RA, Balakrishnan S, Anderton B, Mahieu C, Eyob H, Krings G, Nomura DK. Inhibition of fatty-acid oxidation as a therapy for triple-negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD3-05.
Racial Patterns in Pernicious Anemia
Authors: Ralph Carmel, Cage S. Johnson
Journal: New England Journal of Medicine (1978)

Pernicious anemia affects primarily elderly northern Europeans, but may affect others more often than previously thought. Therefore, we analyzed the data from 156 documented cases: there were 73 patients of "European" origin, 52 black patients and 31 Latin-American patients. The mean age (±1 S.D.) at presentation among black women, 53±16 years, was lower than that of all the others (P<0.001 in most comparisons), and seven of the 33 black women were less than 40 years old. In addition, 23 of the 24 black women tested had circulating antibody to intrinsic factor. A similar though less striking antibody prevalence (85 per cent) and age pattern (60±13 years) in Latin-American women did not reach statistical significance. No other group exceeded the usual 55 to 70 per cent prevalence of antibody. These findings suggest a different form of or a different response to the disease in black women and perhaps in Latin-American women. (N Engl J Med 298:647–650, 1978)