tbuckley/cabot-search huggingface dataset:
A phase I dose-escalating study of combination pemetrexed-based chemotherapy and concomitant radiotherapy for locally advanced or metastatic non-small cell lung or esophageal cancer
Authors: T. Y. Seiwert, P. P. Connell, A. M. Mauer, P. C. Hoffman, C. M. George, L. Szeto, C. Obasaju, D. J. Haraf, R. Salgia, E. E. Vokes
Journal: Journal of Clinical Oncology (2005)

7062 Background: Pemetrexed (pem, Alimta) is a multitargeted antifolate approved for second-line treatment of metastatic non-small cell lung cancer (NSCLC). Treatment failure with chemoradiotherapy (CRT) is frequently due to development of distant metastasis suggesting a potential need for more effective systemic therapy. The primary objective was to determine whether pem based CRT allows administration of systemically active chemotherapy doses. Methods: Patients (pts) with locally advanced or metastatic (dominant local symptoms) NSCLC or esophageal cancer (ca) were enrolled in a phase I dose-escalating study with chemotherapy delivered on day 1, every 21 days for 2 cycles. Schedule 1 was pem (200–600 mg/m2) with concurrent radiotherapy (RT) 40–66Gy (2 Gy/d). Schedule 2 was pem fixed at recommended single-agent dose (500 mg/m2) and escalating carboplatin doses (AUC 4–6) + concomitant RT (40–66Gy). Results: 30 pts (18 locally advanced, 12 metastatic disease) were enrolled. ECOG performance status was 0 (8 pts, 26.7%), 1 (21 pts, 70.0%), and 2 (1 pt, 3.3%). Schedule 1 enrolled 18 pts (15 NSCLC, 3 esophageal ca); all dose levels were tolerable. One DLT (Grade [Gr] 4 esophagitis) was reported. One pt developed Gr 4 pulmonary embolism (PE) at the end of therapy. Gr 3 toxicities were leukopenia (n=3), dysphagia (1), and dehydration (1). Schedule 2 enrolled 12 NSCLC pts; all dose levels were tolerated. One DLT (Gr 4 PE) was reported at 500 mg/m2 + AUC 6. One pt had Gr 4 leukopenia at 500 mg/m2 + AUC 5. Treatment-related grade 3 toxicities were leukopenia (n=3), dehydration (1), and fatigue (1). Overall responses for Schedule 1 were PR (n=5), SD (5), PD (6), and unknown (2); for Schedule 2, pts had CR (1), PR (3), SD (4), PD (1), and unknown (3). Study is on-going. 3 pts had Gr 1/2 radiation pneumonitis (8 d - 8 w) after RT. Several pts underwent curative intent surgery. In-field responses are being assessed. Conclusions: The combination of pemetrexed (500 mg/m2) with carboplatin (AUC 6) day 1 every 21 days for 2 cycles with concurrent radiotherapy is feasible, allows administration of systemically active doses, and warrants examination in a phase II trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly Eli Lilly
PI3K as a Potential Therapeutic Target in Thymic Epithelial Tumors
Authors: Anna Teresa Alberobello, Yisong Wang, Frans Joseph Beerkens, Fabio Conforti, Justine N. McCutcheon, Guanhua Rao, Mark Raffeld, Jing Liu, Raneen Rahhal, Yu-Wen Zhang, Giuseppe Giaccone
Journal: Journal of Thoracic Oncology (2016)
Case 21-2008
Authors: Jason B. Harris, Ian C. Michelow, Sjirk J. Westra, Richard L. Kradin
Journal: New England Journal of Medicine (2008)

An 11-month-old boy was admitted to this hospital after returning from a trip to India, during which fever and pulmonary infiltrates had developed and had recurred despite treatment with broad-spectrum antimicrobial therapy. On admission, the patient had fever and an erythematous nodule on his right forearm. Imaging studies disclosed bilateral nodular pulmonary infiltrates with calcification. Diagnostic tests were performed.
Vaccinating Patients With Autologous Tumor
Authors: Paul B. Chapman
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.20.4139 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12377956 Vaccinating Patients With Autologous Tumor Paul B. ChapmanxPaul B. ChapmanSearch for articles by this author Show More Memorial Sloan-Kettering Cancer Center, New York, NY https://doi.org/10.1200/JCO.2002.20.20.4139 Full Text PDF Figures and Tables "Vaccinating Patients With Autologous Tumor." Journal of Clinical Oncology, 20(20), pp. 4139–4140© 2002 by American Society of Clinical Oncology
Mithramycin Treatment of Intractable Hypercalcemia Due to Parathyroid Carcinoma
Authors: Frederick R. Singer, Robert M. Neer, Timothy M. Murray, Henry T. Keutmann, Leonard J. Deftos, John T. Potts
Journal: New England Journal of Medicine (1970)

MITHRAMYCIN, a cytotoxic antibiotic used mainly in the therapy of embryonal tumors of the testis,1 2 3 4 5 has been stated to lower serum calcium levels even in normocalcemic patients.2 , 6 , 7 Its toxic side effects, particularly excessive bleeding, have restricted its reported use to patients with various cancers,1 2 3 4 5 6 , 8 9 10 11 12 13 14 one patient with hyperparathyroidism14 and short-term studies in two patients with Paget's disease of bone.7 We recently administered this drug† to a patient with metastatic parathyroid carcinoma and severe osteitis fibrosa cystica whose hypercalcemia, bone pain and related symptoms could not be controlled by surgical or intensive medical therapy. The drug acutely lowered plasma calcium to . . .
Enteric Fever, Diarrh a, Diphtheria, and Scarlatina, Originating from Drinking-Water
Authors: N. Kerr
Journal: BMJ (1880)

suffered from a typical attack of enteric fever, with hoemorrhage from the bowels, from which she made a perfect recovery.Diarrhoea had previously never been absent for more than a fortnight at a time from the house.Either the father or the mother, or one or other of the four children, or one of the servants, was the sufferer.Two children had been attacked with scarlatina, of which, and of the other ailments enumerated, there had been no case in the neighbourhood for more than two months pre- viously.Nearly the whole household had also repeatedly suffered from more or less severe sore-throat, one child having diphtheritic patches on the tonsils on one occasion.By the method of exclusion, I arrived at the conviction, after the milk-supply had been changed with no benefit, that all these illnesses, to which the family were so prone, must arise from the water of the well used for drinking purposes.My opinion was not seriously listened to till the typhoid fever set in, when the alarming state of the patient secured me, at last, a favourable hearing.-The water formerly in use was given up, and a new supply brought from another well about fifty yards off.The unhealthy symptoms ceased from the day of the change.So marked was the improvement that, in a month, the farmer and the land-
Metabolic Disturbances and Wasting in the Acquired Immunodeficiency Syndrome
Authors: C Grunfeld, K R Feingold
Journal: New England Journal of Medicine (1992)

THE wasting syndrome is one of the most devastating aspects of the acquired immunodeficiency syndrome (AIDS). Until therapies are developed that eradicate the human immunodeficiency virus (HIV) or halt its replication, wasting will be a major cause of morbidity and mortality in AIDS.1 2 3 This paper will review the metabolic disturbances that occur during AIDS, put them in the context of studies of cachexia with infection and cancer, and attempt to define the role of these disturbances in the pathogenesis of wasting.Weight Loss and Death from InanitionIn the absence of disease, starvation leads to death at 66 percent of . . .
Proliferative Rates of Cloned Malignant Mammary Epithelial Cells as a Measure of Clonal Heterogeneity in Human Breast Carcinomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R Schmidt-Ullrich, P S Lin, R B Mikkelsen, M M Monroe
Journal: JNCI Journal of the National Cancer Institute (1986)

Malignant mammary epithelial cells (MMECs) were isolated from 8 human breast carcinomas and 1 adenoma as single cells or organoids and established in vitro. Depending on the cellularity of the tumor, between 9×104 and 4×106 cells were released per gram of tumor tissue. With the use of conditioned media and growth-promoting agents, a high proportion of cells (ranging from 0.5 to 11.4%) could be established in culture. A high degree of tumor cell heterogeneity in breast carcinomas was suggested by the observation that significantly different proliferative rates were found for 50 mammary epithelial cells cloned from 2 different tumors during the first subpassage in vitro prior to significant expansion of the cell colonies. The computed doubling times of these clones varied between 16 hours and more than 48 hours. The mammary epithelial nature of the cells was confirmed by their surface reactivity with monoclonal antibodies specific for MMECs. Studies on clones from 2 tumors revealed a positive correlation between proliferative rates of MMECs, their lactate production, and specific proteins synthesized as analyzed by two-dimensional macromolecular protein maps.
Abstract 346: Lipophilic Statins Attenuate Human Atrial Fibroblast Viability In Vitro
Authors: Kiranjit K Sran, Yun Li, Saeid Ghavami, Melanie Ngo, Rakesh C Arora, Lorrie Kirshenbaum, Darren Freed
Journal: Circulation Research (2012)

Cardiovascular diseases (CVD) leading to heart failure are associated with myocardial cell loss and cardiac fibrosis. Hydroxymethylglutaryl-Coenzyme-A Reductase (HMGR) inhibitors ("statins") are widely used to limit cardiovascular events in patients with hypercholesterolemia and CVD by altering their lipid profile. HMGR inhibition reduces cholesterol precursor L-mevalonate production, whose depletion induces autophagy, apoptosis, and endoplasmic reticulum stress in various cell types. However it is unclear if this is a class effect or a phenomenon specific to various compounds. We examined the in vitro effect of HMGR inhibition on human atrial fibroblast (hATF) viability with particular reference to hydrophilic vs lipophilic compounds. Hypothesis- Lipophilic statins induce cell death in primary hATF via mevalonate depletion; whereas hydrophilic statins do not have any effect on hATF viability. IRB approval was obtained for collection of hATF from consenting patients undergoing open heart surgery. Cells were treated with atorvastatin, simvastatin or pravastatin (0.1, 1.0 or 10 λM) for 24, 48, 72 or 96 hours. Expression of proteins involved in the regulation of apoptosis and autophagy was assessed using immunoblotting. Cell viability was assessed using MTT assay. Treatment of hATF with 0.1 - 10 λM atorvastatin or simvastatin (lipophilic statins) resulted in progressively reduced cell viability in time and dose-dependent manner. Viability could be rescued by coincubation with mevalonate. Expression of key apoptotic cascade proteins -Bcl2, Bax and cleaved Caspase3 showed a clear induction of apoptosis. Also, there was an increase in Atg5-12 expression at 24h indicating induction of early autophagic response. Pravastatin (hydrophilic statin) did not affect cell viability or autophagy and apoptosis. We conclude that statin-induced cell death is mediated by mevalonate depletion, which activates intrinsic apoptotic pathways in hATF. Lipophilic statins impair the viability of hATFs in vitro, whereas hydrophilic statins have no effect on cell growth and cell viability of hATFs. This may represent an additional pleiotropic effect of statins, and may represent a novel therapeutic option for the prevention and treatment of cardiac fibrosis.
AB0897 Risk Factors for Treatment Failure in Osteoporotic Patients with Rheumatoid Arthritis
Authors: J.-W. Lee, K.-E. Lee, D.-J. Park, S.-S. Lee
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> No available anti-osteoporotic medication has been shown to completely prevent declines in bone mineral density (BMD) and the resulting increased risk of fracture. The objective of this study was to investigate the risk factors associated with treatment failure in osteoporotic patients with rheumatoid arthritis (RA). <h3>Methods</h3> A retrospective cohort study of 103 patients with RA and osteoporosis was conducted. Baseline demographics, clinical characteristics, BMD, laboratory results and treatment-related data were collected from the patients9 chart review. Patients were divided into two groups for comparison: those whose osteoporosis treatment was effective and those whose treatment failed. Risk factors for treatment failure were identified by univariate and multivariate logistic regression using variables that differed significantly between the groups. <h3>Results</h3> Osteoporosis treatment failed in 66 of 103 patients (64.1%). During 14.01 months of (SD: 1.89 months) follow-up, non-adherence to bisphosphonate use (OR =12.997; <i>p</i> =0.006) was the most powerful risk factor for treatment failure. Daily glucocorticoid dosage ≥7.5 mg/day before the first BMD measurement (OR =6.230; <i>p</i> =0.015), immobilization &gt;3 months (OR =4.773; <i>p</i> =0.006), and DAS28 ≥3.2 (OR =4.428; <i>p</i> =0.009) were also significantly related to treatment failure. <h3>Conclusions</h3> Our findings indicate that osteoporosis treatment fails frequently in RA patients and adherence to bisphosphonate use, daily glucocorticoid dosage, immobilization, and DAS28 score should be taken into consideration when treating osteoporotic patients with RA. <h3>Disclosure of Interest</h3> None declared
Prophylaxis against Allergy
Authors: Maurice H. Shulman
Journal: New England Journal of Medicine (1948)

THE pediatrician holds a unique position in the field of allergy. To him falls the opportunity of dealing with the patient before the first manifestations of allergy. Therefore, whatever can be achieved in the way of preventive allergy lies within his sphere.Allergy is defined as an altered reactivity of tissues following the introduction of foreign protein by inhalation, injection or ingestion. The difficulties of taking prophylactic measures in the field of allergy are inherent in its definition. In general, it is only after the occurrence of clinical symptoms that steps are taken to eliminate the offending allergens when possible, . . .
How NCCN Guidelines Can Help Young Adults and Older Adolescents With Cancer and the Professionals Who Care for Them
Authors: Archie Bleyer
Journal: Journal of the National Comprehensive Cancer Network (2012)

From 1975 to 2009, adolescents and young adults with cancer in the United States had less mortality reduction and survival improvement than either children or older adults with cancer. An NCI Progress Review Group (PRG) convened in 2005 issued a variety of recommendations to overcome the lack of progress, including the establishment of care guidelines. The outcome of 15- to 39-year-olds with cancer in the United States in 2009 was ascertained from the SEER registry, and the first guidelines for this age group, presented by NCCN, were reviewed. For the first time, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adolescent and Young Adult Oncology provide specific algorithm-based care recommendations for 15- to 39-year-olds with cancer, who as an age group have the greatest potential patient-years of life to be saved. A special emphasis on psychosocial evaluation and care is included, commensurate with the unique needs of persons in this age group. Although how widely the NCCN Guidelines will be used remains to be seen, they are timely, comprehensive, responsive to the NCI PRG recommendations, and a valuable resource for medical oncologists, hematologists, gynecologic oncologists, oncologic surgeons, and pediatric oncologists who care for patients between 15 and 40 years of age. A patient version will have mutually beneficial effects for families and professionals.
Coagulation markers D-dimer and prothrombin fragment 1.2 compared to disease and treatment status in prostate cancer patients
Authors: B. Y. Wong, L. Fink, J. Symanowski, A. Dincer, D. Adcock, N. Vogelzang
Journal: Journal of Clinical Oncology (2007)

15587 Background: Activation of the coagulation cascade is a hallmark of advanced prostate cancer (PC). In patients (pts) with advanced PC, the D-dimer and prostate specific antigen (PSA) are frequently elevated; neither is an established predictive marker for response to treatment. We hypothesized that chemotherapy refractory (CRefrac) PC is associated with active thrombin generation, and that D- dimer and prothrombin fragment 1.2 (PF1.2) as activation markers of coagulation could be markers of CRefrac PC. Methods: We analyzed PSA, D-dimer and PF1.2 from a cross section of 29 PC pts. PSA values were measured by the Bayer/Centaur method (Bayer Healthcare, Tarrytown, NY). D-dimer assay was performed using quantitative latex-agglutination (Diagnostica Stago, Asnieres, France), and PF 1.2 levels were determined by enzyme-immunoassay (Dade Behring, Marburg, Germany). Values were analyzed with respect to disease and treatment status. Results: The median age was 66. Twenty pts had metastatic PC, while 9 pts had stable or rising PSA but no evidence of metastatic disease. Among the 20 metastatic pts, 10 were CRefrac, 3 were hormone refractory and 7 were responding to or stable on hormone therapy. Median PSA was 36 ng/ml (range 0.1–1170). Median D-dimer was 372 ng/ml [range 110–13,300; normal (&lt;256 ng/ml)]. Median PF 1.2 was 402 ng/ml (range 100–853; normal 87–325 ng/ml). Only 19 pts had sufficient sample for PF1.2 values. Stratification by disease and treatment status showed significantly higher D-dimer values in CRefrac pts compared to all other pts (median 1144 vs 317, p=0.014, rank-transformed analysis). Eight of 11 CRefrac specimens had elevated D-dimer values; 2 of the 3 exceptions were pts receiving warfarin therapy. Only 3 of 20 non-CRefrac specimens had elevated D-dimer values. Five of 8 CRefrac pts and 8 of 12 non-CRefrac pts had elevated PF1.2 values. Conclusions: D-dimer values are substantially elevated in CRefrac PC. However, the clinical significance of these findings and of the apparent suppression of D-dimer by warfarin therapy is unknown. Longitudinal studies of D-dimer and PF1.2 in PC pts undergoing chemotherapy are needed. No significant financial relationships to disclose.
Diuretic Augmentation of 131I Uptake in Inoperable Thyroid Cancer
Authors: Joel I. Hamburger
Journal: New England Journal of Medicine (1969)

Diuretics, plus a low-iodine diet, were employed in 25 patients with inoperable thyroid cancer to produce acute iodide depletion and thus augment 131I uptake by the tumor tissue. Initially, intravenous mannitol was used, but more recently oral ethacrynic acid has proved simpler, and more suitable for outpatients. Twofold to threefold increases in 24-hour 131I uptake were achieved in 16, lesser increases in three and no increase in six patients. This increased iodine uptake seemed to be independent of, and additional to that attributable to TSH (whether endogenous by virtue of hypothyroidism or combined endogenous and exogenous). Furthermore, iodine taken up by thyroid tumor tissue after diuretic preparation is well retained for at least 96 hours. Consideration of diuretic augmentation of 131I uptake is justified whenever 131I therapy is contemplated for inoperable thyroid cancer.
Adrenocortical Responsiveness after Alternate-Day Corticosteroid Therapy
Authors: George L. Ackerman, Charles M. Nolan
Journal: New England Journal of Medicine (1968)

Plasma 17-hydroxycorticosteroid levels were measured after insulin-induced hypoglycemia in a group of 10 adults receiving alternate-day steroid therapy. In these patients, who had either idiopathic nephrotic syndrome or lupus nephritis, prednisone was administered in a single dose at 8 a.m. every 48 hours. All the patients had received alternate-day therapy for at least two months in doses ranging from 25 to 120 mg of prednisone every other day. The mean dose was 75 mg every other day. The findings in this group were compared with those of normal control subjects and with those of patients taking steroids each day in divided doses. The resting level of plasma 17-hydroxycorticosteroids was moderately depressed in the patients taking prednisone on alternate days; however, the rise in plasma 17-hydroxycorticosteroids after hypoglycemia was equal to that of the control group and was significantly greater than that observed in patients who received daily steroid therapy.
Control of Cell Growth. III. Direct Mitogenic Effect of Thyroid Hormones on an Estrogen-Dependent Rat Pituitary Tumor Cell Line2
Authors: Willis L. Kirkland, Joseph M. Sorrentino, David A. Sirbasku
Journal: JNCI Journal of the National Cancer Institute (1976)

A possible direct estrogen requirement for growth of GH3/C14 rat pituitary tumor cells was evaluated in culture medium supplemented with estrogen-depleted serum prepared by a 56° C charcoal extraction procedure, and with serum obtained from ovariectomized sheep and ovariectomized-adrenalectomized sheep. Growth of the GH3/C14 cells in culture medium in which the final estrogen concentration was 2 pg/ml or less was equal to growth in medium with normal serum and equal to growth in the presence of estrogen-depleted serum to which estradiol was added back at concentrations of 10–1,000 pg/ml. Under no conditions could a direct estrogen requirement for growth be demonstrated. The function of thyroid hormones in cell growth was examined in culture medium supplemented with serum from thyroidectomized sheep. In such medium the growth of the GH3/C14 cells was stimulated 3.5-fold by addition of 1.0×10−8m l-thyroxine (T4) or 1.0×10−89 m l-triiodothyronine (T3). Investigation of the possible synergistic effects of estrogens and T4 revealed that combinations of estrogen and T4 or T3 did not stimulate growth over that seen with T4 or T3 alone. These data indicated that estrogens are not direct growth requirements for these cells but instead operate in vivo through secondary or indirect mechanisms; in contrast, thyroid hormones are directly mitogenic in vitro.