tbuckley/cabot-search huggingface dataset:
Multicenter Phase I-II Trial of Docetaxel, Cisplatin, and Fluorouracil Induction Chemotherapy for Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck
Authors: Marshall R. Posner, Bonnie Glisson, Gary Frenette, Muhyi Al-Sarraf, A. Dimitrios Colevas, Charles M. Norris, Jeffery D. Seroskie, Dong M. Shin, Robert Olivares, Carlos A. Garay
Journal: Journal of Clinical Oncology (2001)

PURPOSE: We conducted a phase I-II, multi-institutional trial to determine the maximum-tolerated dose (MTD) of cisplatin in an induction chemotherapy regimen of docetaxel, cisplatin, and fluorouracil for squamous cell cancer of the head and neck (SCCHN) and to determine the safety, tolerability, and efficacy of the regimen at MTD. PATIENTS AND METHODS: A total of 43 patients with previously untreated, locally advanced, curable SCCHN were entered. Overall, 29 patients (67%) had N2 or N3 nodal disease and nine (21%) had T4 primary tumors. All patients received docetaxel 75 mg/m 2 on day 1; cisplatin at 75 (level I) or 100 (level II) mg/m 2 on day 1; and a continuous fluorouracil infusion at 1,000 mg/m 2 /d on days 1 through 4. Patients were treated with prophylactic antibiotics on days 5 through 15. Cycles were repeated every 21 days for a total of three cycles. Patients then received definitive therapy based on institutional preferences. RESULTS: Thirteen patients were treated at level I, and 30 patients were treated at level II. All 43 patients were assessable for toxicity. There were no major differences in toxicity between level I and level II. Cisplatin-associated grade 3 or 4 hypomagnesemia or hypocalcemia occurred in 13 (30%) and hearing loss in two patients (5%). Grade 3 or 4 neutropenia was observed in 41 patients (95%) and febrile neutropenia occurred in eight (19%). There was one serious infection (2%). There were 17 (40% [95% confidence interval [CI], 25% to 56%]) clinical complete responders (CR), 23 (54% [95% CI, 39% to 69%]) partial responders (PR), one (2%) with no change, and two (5%) unassessable patients. Major responses (CR, PR) were observed in 40 (93% [95% CI, 81% to 99%]) patients. Primary site CR was documented in 24 (54%) of patients. Postchemotherapy primary site biopsies were performed in 25 patients (58%) and pathologically negative biopsy was obtained in 11 (92%) of 12 primary site clinical CRs and seven (54%) of 13 with PR or no change. Overall, negative biopsies were obtained in 18 patients (72%). CONCLUSION: TPF induction chemotherapy can be delivered safely with a cisplatin dose of 100 mg/m 2 in previously untreated patients with SCCHN. The regimen is associated with a high rate of primary site clinical and pathologic CRs. Phase III comparison with cisplatinum and fluorouracil chemotherapy is warranted.
Abstract 5280: Positron Emission Tomography (PET) for <i>In Vivo</i> Quantification and Optimization of Acute Cell Retention after Intramyocardial Cardiac-Derived Stem Cell Delivery
Authors: John Terrovitis, Riikka Lautamäki, Michael Bonios, James Fox, James M Engles, Jianhua Yu, Michelle K Leppo, Martin Pomper, Richard L Wahl, Benjamin M Tsui, Frank M Bengel, M. Roselle Abraham, Eduardo Marbán
Journal: Circulation (2008)

Success of stem cell transplantation for cardiac regeneration is partially limited by low retention/engraftment of the delivered cells. A clinically applicable method for accurate quantification of cell retention would enable optimization of cell delivery. To quantify acute myocardial retention and identify strategies that improve retention following intramyocardial injection of cardiac-derived stem cells (CDCs). Two million CDCs derived from syngeneic, male Wistar Kyoto (WK) rats were labeled with 18 FDG (2μCi/mL) and injected intramyocardially into the ischemic region of female WK rats (n=43) immediately following permanent left coronary artery ligation. The effects of fibrin glue, local 2,3-butanedione-2-monoxime (BDM, an excitation-contraction uncoupler), bradycardia (adenosine) and cardiac arrest were examined. 18 FDG PET images were coregistered with myocardial perfusion 13 NH 3 images for myocardial delineation, and with chest CT images for attenuation correction. Quantitative PCR for the male-specific SRY gene was performed in 6 control animals to validate the PET results. Myocardial cell retention 1 hr after cell delivery in control animals was 17.6±11.5% (n=6) by quantitative PCR, and 17.8±7.3% (n=7) by PET. When CDCs were injected immediately following induction of cardiac arrest (n=4), retention was greatly increased to 75.6±18.6% ( P &lt;0.001), suggesting a role for cardiac contraction, heart rate and/or coronary flow on CDC retention. Adenosine slowed the ventricular rate and doubled CDC retention (35.4±5.3%, n=4, P &lt;0.05). A similar increase in CDC retention was observed following epicardial application of fibrin glue at the injection site (37.5±8.2%; n=8, P &lt;0.01). The combination of fibrin glue and adenosine further improved CDC retention to 39.0±11.6% (n=8, P &lt;0.001). Local BDM treatment transiently suppressed contractility at the injection site (by visual inspection), but did not affect CDC retention (14.9 ±6.9%, P =ns). In vivo PET permits accurate measurement of CDC retention early after intramyocardial delivery. Sealing injection sites with fibrin glue may be a clinically translatable method for improving stem cell engraftment in a beating heart.
Double-blind, multicenter, randomized trial to compare the effect of two doses of adrenocorticotropic hormone versus placebo in controlling delayed emesis after high-dose cisplatin in adult patients with cancer.
Authors: R Passalacqua, G Cocconi, C Caminiti, V Silingardi, M A Bella, E Bichisao, M Michiara, V Malavasi, D Donati, F Di Costanzo, A Rocca, S Di Sarra, F Scaglione, F Fraschini
Journal: Journal of Clinical Oncology (1997)

PURPOSE To compare, in a double-blind, placebo-controlled, randomized trial, the efficacy of two different doses of the depot formulation of adrenocorticotropic hormone (ACTH) in controlling delayed emesis after cisplatin. PATIENTS AND METHODS One hundred fifty-two patients were enrolled onto the study. On day 1, all patients received cisplatin (60 to 120 mg/m2) and a combination of dexamethasone 20 mg plus ondansetron or metoclopramide to prevent acute emesis. On day 2 (24 hours after cisplatin administration), patients were randomized to receive placebo, or ACTH 1 mg intramuscularly (I.M.), or ACTH 2 mg I.M. plus one additional dose of 1 mg on day 4. Details of vomiting, nausea, and adverse effects were recorded daily for every 24-hour period from day 2 to day 6. In a subset of patients, serum cortisol levels were measured between 20 and 72 hours after cisplatin administration. RESULTS One hundred fifty patients were assessable. Over the 5 days of the study, delayed vomiting occurred less frequently in the patients treated with ACTH 2 mg plus 1 mg than in those treated with ACTH 1 mg or placebo (28%, 38%, and 65%, respectively; P = .001). The greatest observed differences were seen on days 2 (24 to 48 hours; P = .01) and 3 (48 to 72 hours; P = .01). On days 4, 5, and 6 (96 to 144 hours), no significant differences were observed among the three arms. The severity of delayed emesis expressed as the mean number of emetic episodes per day was 0.48, 0.70, and 0.80, respectively (P = .002). Patients treated with the higher dose of ACTH had the least nausea on day 3 (P = .02) and day 4 (P = .03). Adrenal cortisol secretion rapidly increased after ACTH injection, but was suppressed for approximately 44 hours in the placebo group. Toxicity was mild and transient in all groups. CONCLUSION ACTH reduces the incidence and severity of delayed vomiting and nausea after cisplatin. A dose of 2 mg 24 hours after cisplatin is better than one of 1 mg. Whether the activity of ACTH is mediated only by adrenal corticosteroids needs to be verified.
Malignant mesothelioma diagnosed at medical thoracoscopy - A service review
Authors: Shehnoor Tarique, Emma Watkins, Amila Premawardhana, Sam Williams, Ian Williamson, Alina Ionescu
Journal: European Respiratory Journal (2013)

The incidence of malignant mesothelioma (MM) is predicted to rise. Poor prognosis means a timely diagnosis is a priority.  The aim of this service assessment was to review the effectiveness of thoracoscopy in terms of diagnostic yield, agreement between pathologists, failed pleurodesis and the need for tunnelled indwelling pleural catheter (TIPC) insertion.  Methods: cases of MM were identified from the cancer and the thoracoscopy databases. Data was collected prospectively for the previous 3 years.  Results: 50 cases were included, 8 female, mean age 60.5 years. Awake sedation thoracoscopy (AST) was performed in 31 cases and a histological diagnosis obtained in 29. Eleven had surgical video assisted thoracoscopy (VATS), 2 were diagnosed by cell block, 2 clinico-radiological, 4 by CT guided biopsy, 1 peritoneal mesothelioma by laparotomy, 1 complex case diagnosed at post mortem. In two cases biopsies at AST were non conclusive;VATS confirmed diagnosis. Length of hospital stay after AST was less than 4 days in 70%; no serious complications occurred. The pathologists9 opinion (peer review) was concordant in 100% of cases for AST biopsies. Time from initial review to diagnostic procedure was less than half for AST than VATS.  Ten cases had lung entrapment and TIPC was inserted (8 AST). TIPC was in situ for a mean 5 months, 50% of patients had TIPC in situ when died. Active treatment was given in 62% of cases (2 had debulking and chemotherapy, the others chemotherapy only).  In conclusion AST is a safe and effective method to obtain reliable biopsies in mesothelioma without the risk of surgery and general anaesthetic. Consideration needs to be given to TIPC insertion at thoracoscopy in cases of lung entrapment.
Lung cancer patients in TB hospital: Factors associated with diagnostic delay
Authors: Zhanna Laushkina, Pavel Filiimonov, Elena Pushkareva
Journal: European Respiratory Journal (2012)

The delay of diagnostics worsens prognosis of disease.   The purpose.  To define factors, associated with a delay of lung cancer diagnostics.   Materials and methods.  An analysis of waiting times for 31 patients with lung cancer was undertaken. Males 65 %, villagers 61 %, mean age 55 ± 14 yrs. Clinical, radiological, laboratory data of all admitted patients were collected. The period from the disease manifestation up to making a hospital diagnosis was 106 ± 68 days, patient delay - 25 ± 30 days. 39 % of patients were previously treated of an assumed pneumonia before hospitalization in TB hospital. All patients have been hospitalized with wrong diagnosis pulmonary TB, a principal cause - misinterpretation of chest radiogram. 48 % of patients up to making a hospital diagnosis received antituberculous treatment. 55 % of patients - smokers.   Results.  Factors associated with increase of diagnostic delay: acute disease beginning (OR 0,34, p=0,03), absence of hematological changes (OR 0,23, p=0,01), nonspecific microbial growth in sputum (OR 0,1, p=0,003). Factors, associated with decrease of a diagnostic delay – old age (OR 2,7, p=0,034), low body weight (OR 2,4, p=0,038), lost of appetite (OR 3,7, p=0,006), dyspnea (OR 3,4, p=0,002), leukocytosis (OR 2,5, p=0,03), ESR acceleration (OR 3,3, p=0,007), lymphopenia (OR 2,5, p=0,043), eosinophilia (OR 3,3, p=0,01), spherical opacity patterns on chest radiogram (OR 5,9, p=0,000), pleural exudates (OR 11,7, p=0,000), presence of atypical cells in sputum (OR 46, p=0,000), biopsy performed (OR 10,5, p=0,000).   Conclusion.  The results would allow to optimize the diagnostic approaches to such a patients.
Changes in Plasma Solutes after Food
Authors: G V Gill, P H Baylis, C T G Flear, J Y Lawson
Journal: Journal of the Royal Society of Medicine (1985)

In experiments on 8 healthy young male volunteers, the ingestion of a large meal was found to cause plasma osmolality to rise from 288.8 +/- 0.8 (mean +/- s.e. mean) to 295.6 +/- 0.9 mmol/kg at 4 hours (P less than 0.001). There was an accompanying rise in plasma sodium (Na) from 141.9 +/- 0.8 to 144.6 +/- 0.8 mmol/l, also at 4 hours (P less than 0.01), but little change in other plasma electrolytes. Serum total amino acids rose slightly, non-esterified fatty acid fell minimally and changes in blood glucose concentrations were unremarkable. Thirst was experienced at plasma osmolality of 294.8 +/- 0.7 mmol/kg. Repeating the experiment either without food, or with the salt content of the meal only, was without effect on plasma Na, other solutes or osmolality. Postprandial hypersomolality and hypernatraemia is probably due to movement of water from the vascular compartment to the gut, or into cells. Plasma osmolality is best measured in the fasting state.
Interferon and Murine Leukemia. V. Effect of Interferon Preparations on the Evolution of Rauscher Disease in Mice
Authors: I Gresser, L Berman, G De Thé, D Brouty-Boyé, J Coppey, E Falcoff
Journal: JNCI Journal of the National Cancer Institute (1968)

The continued administration of concentrated interferon preparations prolonged the mean survival time of BALB/c mice infected with Rauscher virus. The evolution of various manifestations of Rauscher disease—hepatosplenomegaly, leulcocytosis, and anemia—was also delayed in interferon-treated mice as was the development of sequential pathologic changes in the spleen. Less infectious virus was present in the spleens of several interferon-treated mice than in the spleens of controls, as determined by biologic assay and electron microscopy. It is suggested that continued interferon treatment delays the progression of Rauscher disease by a continued inhibition of the multiplication of Rauscher virus.
Downregulation of Estrogen and Progesterone Receptors in the Abnormal Smooth Muscle Cells in Pulmonary Lymphangioleiomyomatosis Following Therapy
Authors: KAZUHIRO MATSUI, KAZUYO TAKEDA, ZU-XI YU, JULIO VALENCIA, WILLIAM D. TRAVIS, JOEL MOSS, VICTOR J. FERRANS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Immunohistochemical and confocal microscopic studies were made on lung tissue from 10 women with lymphangioleiomyomatosis (LAM) to evaluate the distribution of estrogen receptors (ER) and progesterone receptors (PR) in the abnormal smooth muscle cells (LAM cells) that characterize this disorder. PR and ER were localized mainly in the nuclei of large, epithelioid LAM cells, in five patients in whom tissues were obtained before treatment. However, the reaction for PR and ER was essentially negative in similarly processed tissues from five patients studied after receiving hormonal therapy (progesterone and tamoxifen). In the untreated group, staining for ER and PR colocalized with that for HMB-45, but not with that for membrane type-1 matrix metalloproteinase (MT-1-MMP), which we have shown to be localized in proliferating LAM cells. These observations demonstrate that PR and ER are selectively expressed in a subpopulation of LAM cells that are larger in size, have a limited ability to proliferate, and do not produce MT-1-MMP, the enzyme that activates MMP-2 (which is secreted by LAM cells and is capable of lysing elastin and collagens). ER and PR in LAM cells appear to be downregulated by hormonal therapy. Matsui K, Takeda K, Yu Z-X, Valencia J, Travis WD, Moss J, Ferrans VJ. Downregulation of estrogen and progesterone receptors in the abnormal smooth muscle cells in pulmonary lymphangioleiomyomatosis following therapy: an immunohistochemical study.
Cystoid macular edema associated with latanoprost therapy in a case series of patients with glaucoma and ocular hypertension11Sayoko E. Moroi, MD, PhD, has no proprietary interest in any materials in this study but has received support from Pharmacia and Upjohn as a speaker and for clinical pharmacology trials and from Alcon Laboratories, Inc., for basic research. The other authors have no proprietary interests in any aspect of this study.
Authors: Sayoko E Moroi, Maria S Gottfredsdottir, Miriam T Schteingart, Susan G Elner, Carol M Lee, Robert M Schertzer, Gary W Abrams, Mark W Johnson
Journal: Ophthalmology (1999)
Down-Regulation of Overexpressed Sp1 Protein in Human Fibrosarcoma Cell Lines Inhibits Tumor Formation
Authors: Zhenjun Lou, Sandra O'Reilly, Hongyan Liang, Veronica M. Maher, Stuart D. Sleight, J. Justin McCormick
Journal: Cancer Research (2005)

Sp1 is a transcription factor for many genes, including genes involved in tumorigenesis. We found that human fibroblast cells malignantly transformed in culture by a carcinogen or by stable transfection of an oncogene express Sp1 at 8-fold to 18-fold higher levels than their parental cells. These cell lines form fibrosarcomas in athymic mice with a very short latency, and the cells from the tumors express the same high levels of Sp1. Similar high levels of Sp1 were found in the patient-derived fibrosarcoma cell lines tested, and in the tumors formed in athymic mice by these cell lines. To investigate the role of overexpression of Sp1 in malignant transformation of human fibroblasts, we transfected an Sp1 U1snRNA/Ribozyme into two human cell lines, malignantly transformed in culture by a carcinogen or overexpression of an oncogene, and into a patient-derived fibrosarcoma cell line. The level of expression of Sp1 in these transfected cell lines was reduced to near normal. The cells regained the spindle-shaped morphology and exhibited increased apoptosis and decreased expression of several genes linked to cancer, i.e., epithelial growth factor receptor, urokinase plasminogen activator, urokinase plasminogen activator receptor, and vascular endothelial growth factor. When injected into athymic mice, these cell lines with near normal levels of Sp1 failed to form tumors or did so only at a greatly reduced frequency and with a much longer latency. These data indicate that overexpression of Sp1 plays a causal role in malignant transformation of human fibroblasts and suggest that for cancers in which it is overexpressed, Sp1 constitutes a target for therapy.
Prognostic factors and treatment results for supratentorial primitive neuroectodermal tumors in children using radiation and chemotherapy: a Childrens Cancer Group randomized trial.
Authors: B H Cohen, P M Zeltzer, J M Boyett, J R Geyer, J C Allen, J L Finlay, P McGuire-Cullen, J M Milstein, L B Rorke, P Stanley
Journal: Journal of Clinical Oncology (1995)

PURPOSE To determine clinical characteristics and response to treatment for children with supratentorial primitive neuroectodermal tumors (S-PNETs). PATIENTS AND METHODS After surgery and staging, 55 patients aged 1.5 to 19.3 years with S-PNETs were randomized to receive craniospinal radiotherapy (RT) followed by eight cycles of 1-(2-chloro-ethyl)-3-cyclohexylnitrosourea (CCNU), vincristine (VCR), and prednisone (standard treatment) or two cycles of 8-in-1 chemotherapy followed by RT and then eight additional cycles of 8-in-1. RESULTS Three-year Kaplan-Meier estimates (estimate +/- SE) of survival and progression-free survival (PFS) rates for patients with confirmed diagnoses of S-PNET were 57% +/- 8% and 45% +/- 8%, respectively; survival and PFS rates for children with PNETs located in the pineal region were 73% +/- 12% and 61% +/- 13%, respectively, and were significantly different from the other S-PNETs (P &lt; .03). The 8-in-1 arm had greater toxicity than the standard-treatment arm. Distributions of PFS between the two treatment groups were not significantly different (P &gt; .5). Other univariate prognostic factors that influenced PFS included metastasis (M) stage (P &lt; .03: M0 50% +/- 9% v M1-4 0%) and age (P &lt; .02: 1.5 to 2 years 25% +/- 13% v &gt; or = 3 years 53% +/- 9%). CONCLUSION In this first randomized treatment trial for S-PNETs in children, no significant differences were detected between the two treatment groups. M0 and pineal site of involvement were independent predictors of a better outcome. However, survival was better than previously reported.
Prenatal Anti‐Ro Antibody Exposure, Congenital Complete Atrioventricular Heart Block, and High‐Dose Steroid Therapy: Impact on Neurocognitive Outcome in School‐Age Children
Authors: E. N. Kelly, R. Sananes, C. Chiu‐Man, E. D. Silverman, E. Jaeggi
Journal: Arthritis & Rheumatology (2014)

Objective To determine the impact of prenatal exposure to maternal anti‐Ro antibodies, slow fetal heart rate, and/or prolonged dexamethasone therapy for immune‐mediated congenital atrioventricular heart block (CAVB) on the cognitive and academic performance of these children at school age. Methods We performed a prospective, blinded assessment of the cognitive functioning of 3 cohorts of children ages 6–16 years with in utero exposure to maternal anti‐Ro antibodies in the following groups: no CAVB and no prenatal dexamethasone treatment (n = 14), CAVB without prenatal treatment (n = 10), and CAVB with prenatal dexamethasone treatment (n = 16). Domains assessed included intelligence, visual perceptual and visual motor skills, auditory and visual attention, verbal learning and memory, visual memory, executive function, and behavior. Results All cohorts scored within the normal range and were not significantly different in terms of intelligence scores, verbal comprehension, perceptional reasoning, working memory, and processing speed. For children with CAVB who were treated prenatally, there were no significant associations between the neurocognitive function scores, the minimal fetal heart rate (range 47–80 beats per minute), and either the duration (range 2–15 weeks) or dosage (range 56–824 mg) of dexamethasone therapy. Conclusion CAVB and transplacental treatment with dexamethasone was not associated with neurocognitive impairment in school‐age children. Larger numbers of children are needed to validate our observation, and assessment of other cognitive abilities is warranted.
Surgical Palliation for Pancreatic Cancer: Will Biliary Bypass Alone Suffice?
Authors: A G Holbrook, J F Chester, D C Britton
Journal: Journal of the Royal Society of Medicine (1990)

Because a number of options are available to relieve the obstructed bile duct, stomach or both in patients with irresectable carcinoma of the pancreatic head, palliative surgery for this condition was reviewed retrospectively between 1971 and 1981 at the Royal United Hospital, Bath. One hundred and sixty-five patients underwent a biliary bypass procedure with (n = 37), or without (n = 128) gastric drainage. Thirty patients had a prophylactic gastroenterostomy to avoid gastric outlet obstruction: tumour encroachment made gastroenterostomy essential in seven others. After biliary bypass alone, operative mortality was 14%. After a concomitant gastroenterostomy, mortality was 27% (P less than 0.04). Within a year of biliary bypass alone, there was a 9% incidence of gastric outlet obstruction requiring gastric drainage, with an associated mortality rate of 18%. Survival after biliary bypass or biliary bypass with gastroenterostomy was equal (7-8 months). Except where gastric outlet obstruction is imminent, palliation for irresectable pancreatic head carcinomas should be by biliary bypass alone, because the addition of a gastroenterostomy almost doubles the mortality without any advantage in survival time.