tbuckley/cabot-search huggingface dataset:
Quantitative assessment of tumor cell density in rectal cancer following three different preoperative therapies compared to surgery alone.
Authors: N. West, H. Grabsch, D. Treanor, D. Sebag-Montefiore, H. Thorpe, D. Jayne, H. Rutten, H. A. Swellengrebel, I. D. Nagtegaal, P. Quirke
Journal: Journal of Clinical Oncology (2010)

3651 Background: Patients with rectal cancer may be offered preoperative therapy. Regimens differ and include short course radiotherapy (25Gy) or long course chemoradiotherapy (CRT). The response to therapy is usually assessed by the pathologist on the resection specimen using one of several subjective tumor regression grading systems with poor reproducibility. We report here an objective quantitative tumour cell density (TCD) analysis allowing direct comparison of different regimens. Methods: Resection specimens from four rectal cancer series were evaluated: surgery alone (controls, n=45), short course radiotherapy with early resection (25Gy, n=45), 50Gy with capecitabine (50Gy+Cap, n=45), and 45Gy with capecitabine and oxaliplatin (45Gy+Cap/Ox, n=45). The glass slides were digitally scanned at 400x magnification. Using a digital slide viewer, a 9 mm2 area was selected in the region of greatest TCD and a systematic random sample of 300 points was superimposed using virtual graticule software. TCD was expressed as the percentage of points falling on tumour cells out of all the informative points. Results: The running mean TCD showed stabilization after approximately 30 cases (standard error of the mean = 1.55% in the controls). There was a significant reduction in median TCD in all three groups when compared to the controls (see Table). There was a significant difference in TCD between the 50Gy+Cap and the 45Gy+Cap/Ox groups (p=0.043). Conclusions: We have shown that quantitative TCD analysis on virtual slides gives an objective measure of the response to preoperative therapy in rectal cancer. 25Gy results in a significant reduction in the number of tumor cells within a tumor after early resection. Long course CRT with 6 weeks delay leads to a significantly greater reduction. The addition of oxaliplatin appeared to further reduce the TCD when compared to capecitabine alone as radiosensitizer. This method may offer a reproducible quantifiable solution to identifying the effectiveness of different preoperative regimens. Regimen Median TCD (%) IQR (%) P value vs. control Controls 56 50-63 — 25Gy 36 14-46 p<0.0001 50Gy+Cap 14 2-22 p<0.0001 45Gy+Cap/Ox 4 1-13 p<0.0001 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis
Chronic Granulomatous Disease in Females
Authors: B. Holmes, B. H. Park, S. E. Malawista, P. G. Quie, D. L. Nelson, R. A. Good
Journal: New England Journal of Medicine (1970)

Leukocyte glutathione peroxidase activity of two female patients with chronic granulomatous disease was shown to be significantly diminished as compared to the activity of control leukocytes. By contrast, the activity of this enzyme in the leukocytes from male patients with the same disease was within normal limits. The activity of glutathione reductase and glucose-6-phosphate dehydrogenase was normal in the same leukocyte extracts from female patients. The demonstration of a deficiency of leukocyte glutathione peroxidase in females distinguishes their disease from that of male patients with the x-linked defect.
Surgical Treatment of the Lower Esophageal Ring
Authors: Earle W. Wilkins, Marshall K. Bartlett
Journal: New England Journal of Medicine (1963)

THE differential diagnosis of dysphagia must include consideration of the lower esophageal ring. This entity was first described in 1953 by Schatzki and Gary1 and Ingelfinger and Kramer2 as a constant, symmetrical, weblike area of narrowing in the lower esophagus just above the diaphragm. The former subsequently reported3 that the ringlike narrowing occurs at the junction of esophageal and gastric mucosa in association with a small sliding hiatus hernia of the stomach. They stated that dysphagia invariably appears when the diameter of the ring is less than 12 mm. The smaller the lumen, the greater the degree of dysphagia.In . . .
The Toxic Effects of Phenylbutazone (Butazolidin)
Authors: Edgar F. Mauer
Journal: New England Journal of Medicine (1955)

DRUGS employed in the past and at present for the relief of pain in the various forms of arthritis carry with them noxious traits that limit or prevent their use. Cincophen was abandoned because of its adverse effects on the liver. Cortisone has been responsible for serious side reactions, which have been limited by professional and public awareness of this drug's unwanted effects. Toxic reactions from gold have been held within bounds because it cannot be self-administered. Aminopyrine is no longer used because of its disastrous effects on the bone marrow. Today, phenylbutazone (Butazolidin), chemically similar to aminopyrine, is in . . .
Long-term results of a cisplatin-containing combination chemotherapy regimen for the treatment of advanced ovarian carcinoma.
Authors: K G Louie, R F Ozols, C E Myers, Y Ostchega, J Jenkins, D Howser, R C Young
Journal: Journal of Clinical Oncology (1986)

Sixty-two patients with advanced ovarian adenocarcinoma (stages III and IV) and without prior chemotherapy or radiotherapy were treated with a four-drug combination consisting of cyclophosphamide, hexamethylmelamine, 5-fluorouracil (5-FU), and cisplatin (Chex-UP). All patients were evaluable for toxicity and response, and survivors have been observed for a minimum of 48 months. The overall response rate to Chex-UP chemotherapy was 69%, with 12 patients (19%) achieving a pathologically confirmed complete remission (CR) as documented by a negative second-look laparotomy. Seven of the twelve patients (58%) who achieved a surgically confirmed CR were randomized to six cycles of intraperitoneal (IP) 5-FU. There have been seven relapses in patients who had a negative second-look laparotomy, but only four of the patients died from recurrent ovarian cancer. The median duration of remission following a negative second-look laparotomy was 53 months, while the median duration of survival has not been reached and will exceed 7.5 years. Seventeen patients (27%) achieved a clinical CR with chemotherapy but were found to have residual disease at second-look laparotomy. The median survival for these patients was 29 months, which was statistically inferior to that achieved for those patients with a negative second-look laparotomy (P less than .002), and only one patient is alive after 4 years. All patients who either achieved a partial response (PR) to therapy (14 of 62; 23%) or did not respond to therapy (19 of 62; 31%) died of ovarian cancer by 24 months. Thus, prolonged survival is associated with a surgically confirmed CR to induction therapy with Chex-UP. However, only a minority of advanced-stage ovarian cancer patients (15%) are alive 4 years after initiation of treatment with this regimen.
A novel nanopolymer based tumor targeted delivery system for paclitaxel
Authors: A. T. Singh, M. Jaggi, D. Khattar, A. Awasthi, S. K. Mishra, S. Tyagi, A. C. Burman
Journal: Journal of Clinical Oncology (2008)

11095 Background: We have developed a novel cremophor-free paclitaxel formulation-Nanoxel in which the drug is delivered as nanomicelles using a polymeric carrier. Our phase I data has previously shown that Nanoxel™ has linear pharmacokinetics and can be administered without premedication. The phase II data in metastatic breast cancers showed comparable efficacy and better safety profile than cremophor paclitaxel. We report here the putative mechanism of action of nanoxel. Methods: We have designed and synthesized a pH sensitive co-polymer of N-isopropyl acrylamide (NIPAM) and vinylpyrrolidone (VP) monomers. The nanomicelles were characterized for size and morphology by scanning electron microscopy (SEM). The journey of nanomicelles after systemic administration was tracked using chromatographic methods and transmission electron microscopy (TEM). The cellular uptake studies were carried out in target cancers and the tumor uptake was assessed in xenograft models. Release of intracellular Paclitaxel from the nanomicelles in the lysosomal compartment was correlated with the in vitro release of the drug at varying pH conditions. Tubulin polymerization and apoptosis were assessed by standard techniques. Results: Paclitaxel was found to retain the in vitro cytotoxicity in nanomicellar particles. Smooth spherical particles of 80 -100 nm were observed by SEM. Nanoxel™ showed upto three-fold higher uptake in target cancer cells as compared to cremophor paclitaxel. TEM demonstrated that the nanomicelles were endocytosed and entrapped in the acidic endolysosomal compartment. In vitro release of paclitaxel was faster at lower pH conditions. This resulted in an increase in tubulin stabilization & induction of apoptosis. Conclusion: Our data delineates the putative mechanism of action of nanoxel, which may explain its clinical efficacy & improved safety. It also suggests that this nanopolymer is a novel pH sensitive tumor targeting delivery system with potential for application to other hydrophobic drugs. No significant financial relationships to disclose.
Abstract 121: Combinatorial Tailored Polymers Enhanced Maturation of Human iPSC-CMs
Authors: Young Wook Chun, Tromondae K Feaster, Timothy Boire, Calvin C Sheng, Hak-Joon Sung, Charles C Hong
Journal: Circulation Research (2014)

There is a tremendous interest in human cardiomyocytes generated from patient-derived induced pluripotent stem cells (iPSC-CMs) for the study and possible treatment of human heart diseases. Despite their vast potential, a significant impediment to a broader application of iPSC-CMs to study human myocyte biology is the structural and functional immaturity of iPSC-CMs. Growing evidence indicates that synthetic polymers utilized as extracellular substrates can exert significant effects on in vitro tissue generation, although the underlying mechanisms remain largely unknown. Based on the profound impact of the extracellular matrix of developing embryos on in vivo organogenesis, we hypothesize that engineered polymer substrates will likewise influence in vitro maturation of iPSC-CMs. A subset of combinatorial polymers was synthesized by polymerizing poly(ε-caprolacton) (PCL), polyethylene glycol (PEG), and carboxylated PCL (cPCL), abbreviated as x%PEG-y%PCL-z%cPCL (x, y, and z: molar %). We investigated effects of the polymer composition on maturation of iPSC-CMs with respect to the beating behavior, mitochondrial function and molecular profiles after 30 days in culture on polymer scaffolds. Results showed the 4%PEG-96%PCL scaffold promoted the most active beating in iPSC-CMs at 30 days and further, that the mitochondrial function, as assessed by tetramethyl rhodamine methylester (TMRM) was significantly increased in the iPSC-CMs cultured on 4%PEG-96%PCL over other polymers. Molecular profiling analysis indicates 4%PEG-96%PCL scaffolds enhanced the expression of MYL2 (a commonly accepted marker of mature ventricular myocytes) as well as of components of the intermediate filaments linking the plasma membrane to the myofilament. In summary, although the polymers we used here exhibit similar physicochemical properties, they have divergent effects on iPSC-CM differentiation. Thus, specific chemical compositions of synthetic substrates can exert profound influence on in vitro maturation of hiPSC-CMs. Our work exploring the effects of synthetic biomaterials on human stem cell differentiation could pave the way for a successful translation of ongoing advances in tissue engineering to new treatments for human heart diseases.
A sustained release formulation of novel quininib-hyaluronan microneedles inhibits angiogenesis and retinal vascular permeability in vivo
Authors: Orla Galvin, Akshay Srivastava, Oliver Carroll, Rajiv Kulkarni, Steve Dykes, Steven Vickers, Keith Dickinson, Alison L. Reynolds, Claire Kilty, Gareth Redmond, Rob Jones, Sharon Cheetham, Abhay Pandit, Breandán N. Kennedy
Journal: Journal of Controlled Release (2016)
The IASLC Lung Cancer Staging Project: Proposals for Coding T Categories for Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer
Authors: William D. Travis, Hisao Asamura, Alexander A. Bankier, Mary Beth Beasley, Frank Detterbeck, Douglas B. Flieder, Jin Mo Goo, Heber MacMahon, David Naidich, Andrew G. Nicholson, Charles A. Powell, Mathias Prokop, Ramón Rami-Porta, Valerie Rusch, Paul van Schil, Yasushi Yatabe, Peter Goldstraw, Ramón Rami-Porta, Hisao Asamura, David Ball, David Beer, Ricardo Beyruti, Vanessa Bolejack, Kari Chansky, John Crowley, Frank Detterbeck, Wilfried Ernst Erich Eberhardt, John Edwards, Françoise Galateau-Sallé, Dorothy Giroux, Fergus Gleeson, Patti Groome, James Huang, Catherine Kennedy, Jhingook Kim, Young Tae Kim, Laura Kingsbury, Haruhiko Kondo, Mark Krasnik, Kaoru Kubota, Antoon Lerut, Gustavo Lyons, Mirella Marino, Edith M. Marom, Jan van Meerbeeck, Alan Mitchell, Takashi Nakano, Andrew G. Nicholson, Anna Nowak, Michael Peake, Thomas Rice, Kenneth Rosenzweig, Enrico Ruffini, Valerie Rusch, Nagahiro Saijo, Paul Van Schil, Jean-Paul Sculier, Lynn Shemanski, Kelly Stratton, Kenji Suzuki, Yuji Tachimori, Charles F. Thomas, William Travis, Ming S. Tsao, Andrew Turrisi, Johan Vansteenkiste, Hirokazu Watanabe, Yi-Long Wu, Paul Baas, Jeremy Erasmus, Seiki Hasegawa, Kouki Inai, Kemp Kernstine, Hedy Kindler, Lee Krug, Kristiaan Nackaerts, Harvey Pass, David Rice, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Kazuya Kondo, Marco Lucchi, Meinoshin Okumura, Eugene Blackstone
Journal: Journal of Thoracic Oncology (2016)
Hypoventilation in Obstructive Lung Disease
Authors: Richard Mountain, Clifford Zwillich, John Weil
Journal: New England Journal of Medicine (1978)

To determine the role of familial factors in the hypoventilation of chronic obstructive lung disease we measured chemical drives to breathe in normal offspring of two groups of patients with an equal degree of obstruction. One group of five patients had repeatedly normal arterial carbon dioxide tension (PaCO2), whereas PaCO2's were elevated in the other group of six. Two adult offspring of each patient were studied. Drives were measured as the ventilatory response to isocapnic hypoxia, and the slopes of the ventilation/PCO2 relation (the hypercapnic ventilatory response). The mean response to isocapnic hypoxia was lower (P<0.01) in offspring of patients with high PaCO2's than in the offspring of patients with normal levels (71±7.8 [S.E.M.] vs. 113±10.3); one offspring of each patient with high PaCO2 had a response below the range found in offspring of all patients with normal PaCO2. Lower hypercapnic ventilatory responses (P<0.05) were also found in the offspring of patients with high PaCO2. Familial factors in the control of breathing may be an important determinant of ventilation in chronic obstructive lung disease. (N Engl J Med 298:521–525, 1978)
Metabolism of the Pancreatic Carcinogen N-Nitroso-bis(2-oxopropyl)amine After Oral and Intraperitoneal Administration to Syrian Golden Hamsters: Brief Communication23
Authors: Ralph Gingell, Parviz Pour
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Metabolism of the Pancreatic Carcinogen N-Nitroso-bis(2-oxopropyl)amine After Oral and Intraperitoneal Administration to Syrian Golden Hamsters: Brief Communication Get access Ralph Gingell, Ralph Gingell 4Eppley Institute for Research in Cancer, University of Nebraska Medical Center, 42d St. and Dewey Ave., Omaha, Nebr. 68105 Search for other works by this author on: Oxford Academic PubMed Google Scholar Parviz Pour Parviz Pour 4Eppley Institute for Research in Cancer, University of Nebraska Medical Center, 42d St. and Dewey Ave., Omaha, Nebr. 68105 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 4, April 1978, Pages 911–913, https://doi.org/10.1093/jnci/60.4.911 Published: 01 April 1978 Article history Revision received: 08 July 1977 Received: 04 October 1977 Accepted: 31 October 1977 Published: 01 April 1978
In Vitro Effects of Magnesium Ions on Mutant Cells from Patients with the Lesch-Nyhan Syndrome
Authors: Paul J. Benke, Annette Hebert, Norma Herrick
Journal: New England Journal of Medicine (1973)

Addition of nontoxic amounts of magnesium ions to fibroblast cell cultures from patients with the Lesch-Nyhan syndrome increased both the rate of cell growth in limiting medium and the enzymatic activity of the mutant hypoxanthine-guanine phosphoribosyltransferase. Six Lesch-Nyhan strains normally resistant to the purine analogue, 8-azaguanine, became sensitive to growth-inhibitory effects of this antimetabolite when magnesium ions were added to the culture. Assay of fibroblast hypoxanthine-guanine-phosphoribosyltransferase with azaguanine-14C as substrate demonstrated that magnesium ions stimulate conversion of small amounts of the analogue to the toxic ribonucleotide in Lesch-Nyhan cell strains. Average apparent Michaelis constants for magnesium phosphoribosyl-pyrophosphate were 3.1 ± 0.8 X 10–3M and 1.9 ± 0.9 X 10–3M for control and mutant erythrocyte hypoxanthine-guanine-phosphoribosyltransferase respectively (p>0.05). Although the Lesch-Nyhan mutation does not reduce affinity of the enzyme for magnesium ions, increased magnesium levels change some of the biochemical abnormality of Lesch-Nyhan cells in culture. (N Engl J Med 289: 446–450, 1973)
Diagnosis of Clinical and Subclinical Salmonellosis by Means of a Serologic Hemagglutination Test
Authors: Erwin Neter, Anne M. Drislane, Albert H. Harris, Grace T. Jansen
Journal: New England Journal of Medicine (1959)

ALTHOUGH extraordinary advances in sanitation and other control measures of infectious diseases have been made during the present century in many countries, salmonellosis, other than typhoid fever, still contributes substantially to morbidity, particularly in children and debilitated persons. Recently, several authors1 2 3 4 reviewed their experiences with this malady. Saphra and Winter1 analyzed data on 7779 human infections; gastroenteritis was present in 68.3 per cent, and carriers accounted for 15 per cent. Eisenberg et al.2 observed among 75 bacteriologically proved cases of salmonellosis an over-all fatality rate of 20 per cent, and a rate of 5.3 per cent from the infection itself. . . .
Anomalous ABO Phenotype in a Child after an ABO-Incompatible Liver Transplantation
Authors: Raymond L. Comenzo, Marie E. Malachowski, Richard J. Rohrer, Richard B. Freeman, Arthur Rabson, Eugene M. Berkman
Journal: New England Journal of Medicine (1992)

RED-CELL A and B antigens are primarily intrinsic membrane glycoproteins that become attached during erythropoiesis by specific A and B transferase enzymes.1 A and B antigens may also be acquired by red-cell adsorption of A and B substances present in the plasma of secretors.2 The acquisition or loss of ABO antigens has been reported in association with cancers, hematologic disorders, infections, and bone marrow transplantation.3 Except in emergencies, the compatibility of the donor's and the recipient's ABO blood types is ensured in liver transplantation.4 5 6 In this report we describe a successful ABO-incompatible liver transplantation in a child whose blood type . . .
An open-label, phase II study of weekly nab-paclitaxel as first-line therapy for patients (pts) with metastatic breast cancer (MBC): Safety update.
Authors: C. B. Brezden, G. Cantin, J. Younus, L. C. Panasci, P. Klimo, K. E. Laing, N. Raymond, W. Lam, M. E. Trudeau, A. Robidoux
Journal: Journal of Clinical Oncology (2010)

1127 Background: In a phase III study in pts with MBC, nab-paclitaxel (260 mg/m2 every 3 weeks, q3w) produced a favorable safety profile and improved efficacy compared with solvent based paclitaxel (175 mg/m2 q3w), with 23.0 and 16.9 weeks of median time to progression (TTP), respectively. Pts who received nab-paclitaxel as first-line therapy had a median TTP of 24.0 weeks (Gradishar et al., 2005). In a recent phase II study (Gradishar et al., 2009), weekly nab-paclitaxel improved efficacy and safety compared with the q3w schedule. This open- label phase II study was designed to investigate the efficacy and safety of 100 mg/m2 weekly nab-paclitaxel in pts who had received prior taxanes (PT) and pts who had not received prior taxanes (NPT) as part of their neo/adjuvant chemotherapy. Methods: Pts with pathologically confirmed adenocarcinoma of the breast and stage IV disease are enrolling into 2 cohorts: PT and NPT. The primary endpoints are response rate and adverse events. Results: Enrollment is ongoing and at the data cut-off for this presentation (12-04-09), only a safety update is available. Planned sample size is 75/cohort; 23 (31%) pts in the PT cohort and 58 (77%) pts in the NPT cohort have been treated to date. Overall, pt demographics and baseline characteristics were similar between the 2 cohorts. The median age was 55.9 years (range 35-76). Most pts had visceral disease (91% PT; 98% NPT) and ECOG status 0 or 1 (87% PT; 90% NPT) at baseline. All pts in the PT cohort and 52% in the NPT cohort received prior neo/adjuvant chemotherapy. Sixty-one percent of pts in the PT and 67% of pts in the NPT had at least 1 adverse event. Nine percent of pts had grade 3 neutropenia in the PT cohort; 4% of pts had grade 3 and 5% had grade 4 events in the NPT cohort. No febrile neutropenia or hypersensitivity reactions were reported in either cohort. Seventeen percent of pts had sensory neuropathy (grade 1/2) in both cohorts, no grade 3/4 events. Conclusions: Preliminary results indicate that weekly 100 mg/m2 nab-paclitaxel in first-line MBC is well tolerated in both cohorts. The safety profile is similar in pts in the PT and NPT cohorts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abraxis BioScience Abraxis BioScience Abraxis BioScience
Acute Myocardial Infarction Secondary to Ergot Therapy
Authors: Jerome D. Goldfischer
Journal: New England Journal of Medicine (1960)

THE precipitation of an acute myocardial infarction by ergot preparations is unusual. This is due in part to the restricted use of the drugs in patients with obliterative vascular disease (that is, marked arteriosclerosis, coronary-artery disease, thrombophlebitis, syphilitic arteritis and Raynaud's and Buerger's syndromes), disease of the liver or kidney and sepsis.1 All previous reports concern either patients with known contraindications to the use of ergot or those who had received an obvious overdosage. The patient described below had received ergotamine tartrate for many years, had no known contraindications to its continued use and had received what is considered to . . .
Mechanism of Vitamin B<sub>12</sub>Malabsorption in Patients Receiving Colchicine
Authors: Dale I. Webb, Robert B. Chodos, Constance Q. Mahar, William W. Faloon
Journal: New England Journal of Medicine (1968)

Intermittent Schilling tests and daily 57Co-labeled vitamin B12 administration and analyses of urinary and fecal radioactivity revealed that colchicine given by mouth decreased vitamin B12 absorption in all except one normal subject, and this effect was greatest when colchicine was delivered by tube into the ileum. Gastric mucosa was histologically unchanged, and gastric-juice intrinsic-factor activity was undiminished as shown by bioassay in subjects with pernicious anemia and by in vitro assay. Colchicine in vitro did not prevent vitamin B12 binding to intrinsic factor or binding of this combination to guinea-pig ileal mucosa. Intestinal hypermotility induced by cascara for comparison with colchicine did not alter 57Co-labeled vitamin B12 urinary excretion, but did yield increased fecal excretion. Colchicine appears to induce reversible vitamin B12 malabsorption by altering the function of ileal mucosa.