tbuckley/cabot-search huggingface dataset:
The analysis of EGFR expression and <i>EGFR</i> mutations in advanced pancreatic cancer
Authors: M. Ueno, S. Ohkawa, Y. Sakamoto, K. Miyakawa, Y. Miyagi
Journal: Journal of Clinical Oncology (2009)

e15629 Background: The standard chemotherapy of advanced pancreatic cancer is still gemcitabine and recently gemcitabine + EGFR tyrosine kinase inhibitor (TKI)is noted to be positive on Phase III study. In lung cancer, EGFR mutations (the deletion of exon 19, the point mutation of exon 18, 21) have been reported to be correlated with the effect of EGFR TKI. On the other hand, such EGFR mutations were not reported to be recognized by the direct sequencing method in pancreatic cancer. This time we examined EGFR expressions and EGFR mutations in advanced pancreatic cancer. Methods: We examined EGFR expressions immunohistochemically and EGFR mutations by Loop-Hybrid Mobility Shift Assay (LH-MSA) which is more sensitive than the direct sequencing method in the tissue obtained from percutaneous biopsies in advanced pancreatic cancer patients. In addition we examined the correlation between EGFR expressions and survivals by the log-rank test. Results: The subjects were 31 inoperable pancreatic cancer patients. Patients received chemotherapy (gemcitabine: 10, S-1: 8, gemcitabine+S-1: 12, no treatment: 1).The UICC stages were as follows:stage II; 2, stage III; 6, stage IV; 23. The tissues were obtaind from liver; 12, pancreas; 19. EGFR expressions were positive; 15, negative; 16. EGFR expressions were not correlated with survival (p=0.386). Although LH-MSA were performed successfully in all patients, the same EGFR mutations as lung cancer were not detected. Conclusions: EGFR expressions were not correlated with survivals and the same EGFR mutations as lung cancer were not detected in inoperable advanced pancreatic cancer. No significant financial relationships to disclose.
A Comparative Study of Penicillins X and G and Crystalline Penicillin G
Authors: Georgine Rotman-Kavka, Harold L. Hirsh, Harry F. Dowling
Journal: New England Journal of Medicine (1947)

FOUR different fractions obtained from the mold Penicillium notatum have been identified. These have been named penicillins F, G, K and X.1 The two that have received the greatest attention are the G and X fractions. Many commercial preparations containing varying percentages of these two fractions have been employed clinically with little attention to the actual composition of each product. This practice seems to be justified if studies of these two fractions reveal no significant differences in their properties, but is not justified if either is found to be superior. Accordingly, a study comparing the absorption, excretion, therapeutic . . .
Use of a New Compound, UML-491 (1-Methyl-D-Lysergic Acid Butanolamide), in the Prevention of Various Types of Headache
Authors: John R. Graham
Journal: New England Journal of Medicine (1960)

IN 1937 Wolff and Graham1 demonstrated that the pain of the migraine attack was associated with dilatation of branches of the cranial vasculature. Ergotamine tartrate was found to be effective in controlling this pain by virtue of its capacity to cause significant and prolonged constriction of the affected blood vessels. In 1957 Ostfeld et al.,2 in a series of ingenious experiments, indicated that vasodilatation per se was not the sole cause of headache but that it must be accompanied by the presence locally of a "noxious agent" that lowered the pain threshold. The elucidation of the exact chemical nature of . . .
Case 12-1992
Authors: N.T. Zervas, J. Pile-Spellman
Journal: New England Journal of Medicine (1992)

Presentation of CaseA 64-year-old woman was admitted to the hospital because of slowly progressive paraparesis and pain in the buttocks.The patient was in a stable state of health until 10 months earlier, when she began to experience a "heavy" feeling in her legs after a short walk, with improvement on resting. Her symptoms gradually worsened, and two months before admission she found that she was unable to stand during a lengthy ceremony and had to sit down; she also began to have occasional falls because her legs "gave out." She experienced aching in the lower back and buttocks, . . .
Noninvasive Tests in Patients with Stable Coronary Artery Disease
Authors: Thomas H. Lee, Charles A. Boucher
Journal: New England Journal of Medicine (2001)

This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations.A 58-year-old woman presents with chest discomfort while walking that is suggestive of coronary disease. She first noted the discomfort after beginning an exercise program three weeks earlier. The pain occurs within a few minutes after the beginning of exercise and resolves with rest. The physical examination and electrocardiogram are unremarkable. How should this patient be evaluated?The Clinical ProblemIn patients with known or suspected coronary artery disease, diagnosis and risk stratification can be aided by noninvasive tests for myocardial ischemia. The most commonly used tests are exercise electrocardiography, myocardial perfusion imaging, and stress echocardiography. Guidelines for choosing . . .
Enteric Viruses and Diarrhea in HIV-Infected Patients
Authors: Gary S. Grohmann, Roger I. Glass, Helio G. Pereira, Stephan S. Monroe, Allen W. Hightower, Rainer Weber, Ralph T. Bryan
Journal: New England Journal of Medicine (1993)

Diarrhea occurs frequently among persons with the acquired immunodeficiency syndrome, but the cause often remains unknown. We used a group of diagnostic assays to determine which viruses were etiologic agents of diarrhea in a group of persons infected with the human immunodeficiency virus (HIV).
Advanced stage, elevated LDH, primary sites, but not adolescent (A) age (≥ 15 years) as risk factors for disease progression in childhood (C) and adolescent (A) mature B-NHL: Report of the FAB/LMB 96 international trial
Authors: M. S. Cairo, R. Sposto, M. Gerrard, I. Waxman, S. Goldman, A. Auperin, R. Pinkerton, M. Raphael, K. McCarthy, S. L. Perkins, C. Patte
Journal: Journal of Clinical Oncology (2009)

10032 Background: We recently reported the results in C &amp; A with low risk (group A), intermediate risk (group B) and high risk (group C) mature B-NHL treated on FAB/LMB 96 (Gerrard et al, Br J Haematol, 2008; Patte et al, Blood, 2007; Cairo et al, Blood, 2007, respectively). Adolescent age (15–21 yrs) has historically been considered to be an independent risk factor for poor outcome in subsets of mature B-NHL (Hochberg/Cairo et al, Br J Haematol, 2008; Burkhardt et al, Br J Haematol 2005; Cairo et al, Br J Haematol, 2003). Methods: We analyzed the EFS of all pts treated on FAB/LMB 96 and the following risk factors were significant in a univariate and Cox multivariate analysis: age (&lt;15 vs ≥15 yrs), stage I/II vs III/IV, primary sites, LDH &lt;2 vs ≥2 NL and histology (DLBCL vs BL/BLL). Results: 1111 pts (15%, 15–21 years) were treated with group A (N = 132), group B (N = 744), and group C (N = 235) therapy. Five year EFS (CI95) for all, A, B, C pts was 86% (84%,88%), 98% (93%, 100%), 87%% (84%, 89%), and 79%% (73%,84%), respectively. Age (≥15 yrs), LDH ≥2NL, stage III/IV, and BM+/CNS+ and histology were significant univariate risk factors for decreased EFS (P&lt;0.045, &lt;0.0001, &lt;0.0001, &lt;0.0001, and &lt;0.0001 respectively). Multivariate analysis demonstrated age ≥15 yrs and DLBCL histology were no longer independent significant risk factors (p = .82 and 0.08, respectively), but LDH (RR 2.0, p = .001), stage III/IV (RR 3.8, p&lt;0.001), and primary sites including PMBL (RR 4.0, p&lt;.001) and BM+/CNS+ (RR 2.8, p&lt;0.001) were independent significant risk factors for poorer outcome. Conclusions: With the use of modern short but intense FAB-LMB 96 therapy, adolescent age is no longer a poor risk factor in children with mature B-NHL. The independent risk factors identified in this study (stage, LDH, primary site) for decreased EFS in C &amp; A mature B-NHL will form the basis of the next risk adapted international pediatric mature B-NHL trial. No significant financial relationships to disclose.
Use of Radioactive Potassium (K42) in the Study of Benign and Malignant Breast Tumors
Authors: William H. Baker, Ira T. Nathanson, Bertram Selverstone
Journal: New England Journal of Medicine (1955)

RADIOACTIVE phosphorus (P32) has been used for the study of human breast tumors by Low-Beer et al.,1 2 3 who first reported in 1946 that ulcerating carcinoma of the breast, counted externally in vivo after administration of radioactive phosphate intravenously, showed a significant increase in radioactivity when compared with the normal breast. Benign inflammatory lesions also caused a considerable increase in uptake of P32. Lesions deeper than 0.5 cm. from the surface and mucoid carcinomas at any depth produced no increase in counting rate. The method was therefore limited by a huge uptake of P32 in inflamed tissues and by . . .
Case 46-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, M.C. Veidenheimer, C.C. Compton
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 63-year-old woman was admitted to the hospital because of fever, a bullous lesion on the right buttock, and subcutaneous emphysema.The patient was well until one month earlier, when there was the onset of intermittent constipation and diarrhea, with occasional fecal incontinence. Four days before admission she experienced weakness and an increase in pain due to long-standing arthritis of the knees. At one point she slipped to the floor, and her husband was unable to raise her. She was taken to another hospital.There was a long history of arthritis of both knees, which was thought . . .
Maternal and Fetal Deaths after Gastric Bypass Surgery for Morbid Obesity
Authors: Kimberly A. Moore, David W. Ouyang, Edward E. Whang
Journal: New England Journal of Medicine (2004)

To the Editor: Antiobesity operations, particularly the Roux-en-Y gastric bypass, are increasingly common. In the United States, 103,000 such operations were performed in 2003.1 We report a complic...
The use of 5-fluorouracil and oxaliplatin (FOLFOX) for colorectal cancer is associated with the development of splenomegaly and thrombocytopenia
Authors: S. Politano, P. Pathak, P. M. Hoff, C. Charnsangavej, M. J. Overman, E. Loyer, J. Vauthey, M. J. Wallace, R. A. Wolff, S. Kopetz
Journal: Journal of Clinical Oncology (2008)

4102 Background: FOLFOX is associated with hepatic sinusoidal obstructive syndrome (SOS), characterized by sinusoidal congestion, dilation, and disruption of sinusoidal membranes. In a previous study, 19% of pts who underwent hepatic metastasectomy after FOLFOX had SOS. This may result in elevated portal pressures, ultimately leading to splenomegaly and thrombocytopenia. This study was therefore designed to evaluate the association of FOLFOX with splenomegaly and thrombocytopenia. Methods: Retrospective study of consecutive pts initiated on FOLFOX for stage II and III colorectal cancer at MD Anderson Cancer Center from 6/03 to 12/06. Eligible pts had CT scans before and after adjuvant treatment, no known cirrhosis, and more than 3 months of adjuvant therapy. Splenic index, a previously validated measure of splenic volume, was determined radiographically. Results: 97 pts met the inclusion criteria. Eighty six percent of pts had an increase in their spleen volume after completing adjuvant therapy, with a median change of 22%. Splenic size increased by more than 50% and 100% in 24% and 6% of pts, respectively. Change in spleen size was statistically associated with the number of FOLFOX cycles delivered (p=0.04, by Pearson Correlation). Pts with splenic enlargement greater than 50% had lower average platelet counts for the first year after treatment (72% of baseline count vs 81%, p=0.04) and higher rates of thrombocytopenia (27% vs 5%, p=0.003) compared to patients with less than a 50% splenic enlargement. In these pts, thrombocytopenia persisted up to 12 months after completion of therapy (28%, 17%, 13%, at 3, 6, and 12 months, respectively). Platelet counts did not return to baseline during the three-year follow-up, with an average platelet count at 1, 2, and 3 years of 79%, 81%, and 84% of baseline, respectively (p<0.001 for all, compared to baseline). Conclusion: Adjuvant FOLFOX therapy is associated with splenic enlargement and thrombocytopenia in a cumulative dose-dependent manner, with modest long-term reduction in platelet counts. Further studies are needed to confirm the association of SOS, elevated portal pressures, hypersplenism, and thrombocytopenia. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis
Determinants of Survival in Patients with Ventricular Tachyarrhythmias
Authors: Charles D. Swerdlow, Roger A. Winkle, Jay W. Mason
Journal: New England Journal of Medicine (1983)

We analyzed data from 239 patients with sustained ventricular tachycardia or ventricular fibrillation to determine prognosis, predictors of survival, and the prognostic value of inducing arrhythmia and assessing therapy at the time of electrophysiologic study. Therapy predicted to be effective on the basis of electrophysiologic study was administered over a sustained period. There were 71 cardiac deaths, including 44 sudden deaths, during a mean (±S.D.) follow-up period of 14.8±13.9 months (range, one day to 67 months). At one, two, and three years, the actuarial incidence of sudden death was 17±3, 25±4, and 34±6 per cent, and that of cardiac death was 28±3, 37±4, and 50±6 per cent. Multivariate regression analyses demonstrated that the two strongest predictors of both sudden death and cardiac death were a higher New York Heart Association functional class (P<0.0001 for sudden death and P<0.0001 for cardiac death) and the failure of any therapy to be identified as potentially effective on the basis of electrophysiologic study (P = 0.0019 and P = 0.0003). The majority of deaths in patients with ventricular tachyarrhythmias were sudden, but the severity of heart failure was the strongest independent predictor of mortality. Response to therapy during electrophysiologic study was also an independent predictor of survival. (N Engl J Med 1983; 308: 1436–42.)
Case 36-1998
Authors: Jonathan Rhodes, Mary Etta King, H. Thomas Aretz
Journal: New England Journal of Medicine (1998)

Presentation of CaseAn 11-year-old girl was admitted to the hospital because of fever, hypotension, and azotemia.The patient had been in excellent health until four days earlier, when fever, headache, sore throat, stiffness of the neck, abdominal pain, and an abdominal rash developed. The results of laboratory tests performed three days before admission and subsequently are presented in Table 1 and Table 2. A rapid test for streptococcal antigens was negative. Two days before admission, amoxicillin and diphenhydramine were administered. A throat culture yielded non–group A, β-hemolytic streptococci. The symptoms persisted, the urinary output was low, and menses began. One day before . . .
Abstract LB-144: Derivation of a model of cancer stem cell from human induced pluripotent stem cells
Authors: Tomonari Kasai, Kenta Hoshikawa, Shuto Takejiri, Masashi Ikeda, Kazuki Kumon, Anna Sanchez Calle, Arun Vaidyanath, Akifumi Mizutani, Chen Ling, Masaharu Seno
Journal: Cancer Research (2015)

Abstract The existence of cancer stem cell (CSC) has been considered as one of the important reason as to why patients have a poor prognosis. However, heterotopic transplantation of embryonic stem cells and induced pluripotent stem cells has been shown to form teratoma, but not malignant teratoma. Since the microenvironment niche is playing a significant role for the proper differentiation of stem cells, the cancerous niche should drive stem cells into malignant cells in vivo. According to this hypothesis, we tried to generate cancer cells from human induced pluripotent stem (hiPS) cells. For the conversion into CSC, the conditioned medium from different human cancer cell lines was collected from confluent dishes and filtered using 0.22 micrometer filter. Then, hiPS cells, without MEF feeder cells, were maintained in the conditioned medium (CM) in the ratio of 1:1. The medium was changed every day with CM for 4 weeks. hiPS cells with the complete medium were used as control. For transplantation studies, 10^4 cells were suspended in HBSS and were xenotransplantated into NOD-SCID mice. After 3 months, tumors were excised and fixed in 10% neutral formalin buffer solution, or subjected to primary culture. The converted cells and primary cultured cells formed spheroids in suspension culture, and had tumorigenicity in vivo. The stemness of living cells was checked under fluorescent microscopy observation with rBC2LCN-FITC staining. The RNAs were extracted from converted cells and microarray analysis was perfomed. The RNA expression patterns of cell lines were visualized by sphered self-organizing map (sSOM) analysis. The sSOM analysis perfomed based upon various parameters shows the converted CSCs can be characterized into various cell types. Utilizing this method, we successfully established two different hiPS-CSC lines using CM from A172 and RERF-LC-KJ. The comprehensive understanding of cancer could be realized as the heterogeneity of cancer tissues is clarified and their component cells are identified. This study will lead to the development of the true personalized therapy of cancer in the future. Citation Format: Tomonari Kasai, Kenta Hoshikawa, Shuto Takejiri, Masashi Ikeda, Kazuki Kumon, Anna Sanchez Calle, Arun Vaidyanath, Akifumi Mizutani, Chen Ling, Masaharu Seno. Derivation of a model of cancer stem cell from human induced pluripotent stem cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-144. doi:10.1158/1538-7445.AM2015-LB-144
Transplantation of Bone Marrow as Compared with Peripheral-Blood Cells from HLA-Identical Relatives in Patients with Hematologic Cancers
Authors: William I. Bensinger, Paul J. Martin, Barry Storer, Reginald Clift, Steven J. Forman, Robert Negrin, Ashwin Kashyap, Mary E.D. Flowers, Kathy Lilleby, Thomas R. Chauncey, Rainer Storb, Karl Blume, Shelly Heimfeld, Scott Rowley, Frederick R. Appelbaum
Journal: New England Journal of Medicine (2001)

In recipients of allogeneic hematopoietic-cell transplants, peripheral-blood cells mobilized with the use of filgrastim (recombinant granulocyte colony-stimulating factor) engraft more rapidly than bone marrow. However, the relative effects of these techniques on the rates of acute and chronic graft-versus-host disease, overall survival, and disease-free survival have not been determined in randomized studies.
Diagnostic and Therapeutic Problems in Benign Mediastinal Tumors
Authors: Gustaf E. Lindskog, Harvey W. Kausel
Journal: New England Journal of Medicine (1951)

RAPID developments in thoracic surgery and increased use of mass roentgen surveys during the past decade have revealed a greater incidence of mediastinal lesions than heretofore suspected, have shown the necessity of efforts at more careful and exact diagnoses, and have brought about a profound change in the general attitude toward their treatment.For the numerous benign lesions which occur in the mediastinum, various classifications have been employed. All discrete and well circumscribed lesions have by usage been classified as benign tumors, although various types of cysts encountered are, in the strictest sense, not true neoplasms. In general, mediastinal tumefactions . . .
The Ciba Foundation and Sir Gordon Wolstenholme
Authors: George W. Pickering
Journal: New England Journal of Medicine (1979)

Some 30 years ago, in gratitude for legal advice from a British barrister, Raymond Needham, the Ciba company of Basel decided to establish in London a foundation that would foster international co-operation between scientists. London was chosen, first because it had been the center for resistance to Nazism, because it was a midpoint between war-battered Europe and the United States, because the English language was becoming the international language of science and, finally, because its trust laws ensured that the foundation would function independently of the founder. Last month (December, 1978) the Ciba Foundation celebrated its 200th Symposium on Brain . . .
MNGO-08MENINGIOMA GROWTH INHIBITION AND RADIOSENSITIZATION BY THE SMALL MOLECULE YAP INHIBITOR VERTEPORFIN
Authors: Juan Carlos Martinez-Gutierrez, Alejandro Ruiz-Valls, Sagar R. Shah, Gregory J. Riggins, Alfredo Quinones-Hinojosa
Journal: Neuro-Oncology (2015)

Meningiomas frequently harbor inactivating mutations in the tumor suppressor protein Merlin (NF2), an upstream activator of the Hippo signaling pathway. This aberration drives tumor growth and aggressiveness through inactivation of this pathway and unchecked activation of its downstream effector, Yes-associated protein (YAP). The transcriptional coactivator YAP has been previously implicated in driving meningioma growth and malignant transformation of non-neoplastic arachnoid cells. YAP exerts its effect by direct binding to the TEAD family of transcription factors and transactivation of growth-related genes. However, the efficacy of pharmacologic modulation of this pathway in meningioma has yet to be explored. Verteporfin is a small molecule inhibitor of the porphyrin family, recently implicated as a direct inhibitor of YAP. Here, we report that Verteporfin modulates growth and radiation resistance in NF2 driven meningiomas through inhibition of the YAP-TEAD interaction. In particular, our data demonstrates that Verteporfin treatment in the NF2 mutant KT21MG1 human malignant meningioma cell line, results in a decreased activity of oncogenic YAP, resulting in decreased mRNA expression of YAP downstream targets (CTGF, Mcl-1 and ANKRD1) (p ≤ 0.05). Moreover, Verteporfin inhibits meningioma cell growth and proliferation in a dose dependent manner (MTT reduction and viable cell number) (p ≤ 0.05). Interestingly, pretreatment with Verteporfin results in increased sensitivity to irradiation in vitro (p ≤ 0.05). In addition, we explore the in vivo efficacy of Verteporfin treatment in a murine skull base xenograft model of human meningioma. Taken together, our results show that Verteporfin is a potent inhibitor of meningioma cell growth and radioresistance, making it an attractive drug candidate for treatment of this disease. Hence, this targeted therapy towards the NF2-YAP axis holds promising alternatives to current standard of care.
Deoxyribosides of the Blood and Urine of Rats
Authors: Jean Rotherham, Pietro M. Gullino, Walter C. Schneider
Journal: JNCI Journal of the National Cancer Institute (1965)

The total amount of deoxyribosyl compounds excreted in the urine of rats was lower when the animals were fed a synthetic diet containing no preformed source of these compounds than when animals were fed laboratory chow. At least a part of these endogenously formed compounds was probably not derived from in vivo degradation of deoxyribonucleic acid. The concentration of deoxyribosides in the interstitial fluid of two different tumors was lower than in the circulating blood and the concentrations in the interstitial fluid of a third type of tumor and in normal subcutaneous tissue were the same as the blood concentrations.