tbuckley/cabot-search huggingface dataset:
Comparison of the Dose- and Time-Survival Curves for Normal Hematopoietic and Lymphoma Colony-Forming Cells Exposed to Vinblastine, Vincristine, Arabinosylcytosine, and Amethopterin&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: W. R. Bruce, B. E. Meeker, W. E. Powers, F. A. Valeriote
Journal: JNCI Journal of the National Cancer Institute (1969)

Dose- and time-survival curves for normal hematopoietic and transplanted lymphoma colony-forming cells exposed in vivo to vinblastine, vincristine, amethopterin, and arabinosylcytosine were obtained. The dose-survival curves for all four agents given in 24 or 48 hours decreased with dose but reached saturation levels where further increase in dose produced no further decrease in survival. Dose schedules from the saturation portion of the curves were used to obtain the time-survival curves. Survival of the normal cells exposed to vinblastine, vincristine, and arabinosylcytosine decreased little for 12 hours, then decreased exponentially to about 1% at 48 hours. Survival of the lymphoma cells decreased rapidly to about 0.1 % at 12 hours, then less rapidly to about 0.01 % at 48 hours. The curves for normal cells exposed to amethopterin and the lymphoma cells exposed to vincristine differed from the others. Reasons for the similarities of most of the survival curves, possible explanations for the differences of some of the curves, and implications of the results in the use of the agents in chemotherapy are discussed.
Estrogen and Sex Hormone-Binding Globulin Levels in Nulliparous and Parous Women&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: L Bernstein, M C Pike, R K Ross, H L Judd, J B Brown, B E Henderson
Journal: JNCI Journal of the National Cancer Institute (1985)

The hormone profiles of nulliparous and parous women on day 11 of their menstrual cycle have been studied in an attempt to seek evidence for the hormonal basis of the protective effect of first birth on breast cancer risk. A previous publication reported that there were significantly lower (26%) early morning prolactin levels in parous women as compared to those levels in nulliparous women but that there were no differences in plasma and urinary estrogen levels. The present study shows, however, that parous women had significantly shorter cycle lengths than nulliparous women of the same age, and the data were reevaluated with this difference being taken into account. After adjustment for cycle length (within the range of 24-32 days) and age, estrogen levels were significantly lower (22%) in parous women compared to those in nulliparous women. Two further aspects of estrogen metabolism were measured in the plasma samples of these women: the binding capacity of sex hormone-binding globulin (SHBG) and the percentage of free estradiol (E2). SHBG levels were 12% higher in parous women, but there was no difference in percentage of free E2. In the previous publication it was suggested that the protective effect of first birth on breast cancer risk was mediated in part by permanently lowering prolactin levels. The current findings suggest that changes in estrogen metabolism also are a factor.
Elevated Concentrations of Serum α-Fetoprotein in Rats with Chemically Induced Liver Tumors
Authors: Robert Kroes, James M. Sontag, Stewart Sell, Gary M. Williams, John H. Weisburger
Journal: Cancer Research (1975)

Summary  The study was undertaken to determine whether aflatoxin B1 (AFB1)-induced liver tumors in rats produced α1-fetoprotein (AFP) and whether the age of the animals would influence such an appearance, a finding suggested by data seen in man. Other liver carcinogens (N-hydroxy-N-2-fluorenylacetamide, N-2-fluorenylacetamide, and diethylnitrosamine) were tested for their ability to induce liver tumors producing AFP. The presence of AFP in the serum was determined by double diffusion in agarose and by comparison also by quantitative radioimmunoassay.  Using double diffusion, AFP was detected in the majority of tumor-bearing rats that had received either N-2-fluorenylacetamide or N-hydroxy-N-2-fluorenylacetamide. Sera of diethylnitrosamine-treated rats with liver tumors were all positive, whereas sera of rats bearing AFB1-induced tumors were positive in only a few cases. However, all sera of tumor-bearing rats examined had elevated AFP levels by radioimmunoassay. Nonetheless, the average level of AFP in the sera of rats bearing AFB1-induced tumors was considerably lower, compared to the sera of rats with tumors caused by diethylnitrosamine, N-2-fluorenylacetamide, or N-hydroxy-N-2-fluorenylacetamide. Rats started on AFB1 when 6 weeks old had more mixed liver tumors with neoplastic hepatocytes and bile ducts and higher AFP levels than did rats started at 26 weeks of age. However, the histological grade of differentiation of induced tumors did not seem to influence the AFP level.
Adult Intradural Primary Spinal Cord Tumors
Authors: Kamran Aghayev, Frank Vrionis, Marc C. Chamberlain
Journal: Journal of the National Comprehensive Cancer Network (2011)

Primary spinal cord tumors represent 4.5% of all central nervous system neoplasms. They are either intradural intramedullary or intradural extramedullary. Intramedullary tumors are predominantly intrinsic gliomas (astrocytomas and ependymomas). Spinal ependymomas can usually be completely removed by separating the tumor from the spinal cord and, when complete, no further therapy is required. Astrocytomas, by contrast, infiltrate the myelon, and therefore surgery is frequently incomplete. Intradural extramedullary tumors are mostly benign (WHO grade 1) and comprise either peripheral nerve sheath tumors (neurofibromas and schwannomas) or meningiomas. Complete resection can be performed on both lesions and is often curative. Radiotherapy is indicated for primary malignant tumors (WHO grade 3 and higher) and for patients in whom surgery is contraindicated. For grade 1 and 2 tumors, the role of radiotherapy is controversial. Chemotherapy is reserved for recurrent primary spinal cord tumors with no other options. However, the lack of clinical trials for these tumors is problematic. Consequently, treatment is similar to that for intracranial histologies. Early recognition of the signs and symptoms of primary spinal cord tumors facilitates early treatment, potentially minimizes neurologic morbidity, and improves outcome. Primary treatment for almost all spinal cord tumors is surgery, with predictors of outcome being preoperative functional status, grade of tumor, and extent of resection.
Correlation Between the Sensitivity of Polyoma-Induced Mouse Tumors to Polyoma and Vaccinia Virus &lt;italic&gt;In Vitro&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: I. Hellström, K. E. Hellström
Journal: JNCI Journal of the National Cancer Institute (1963)

Explants of 15 polyoma-induced mouse tumor lines of known degree of sensitivity to polyoma challenge were infected with vaccinia virus, and the appearance of cytopathic changes and hemadsorption by the infected cells was scored. A correlation was found between the degree of polyoma and vaccinia sensitivity of the different lines. The findings are interpreted as probably reflecting differences in interferon production or virus adsorption between the tumor lines studied, which will be further investigated.
Murine Colon Adenocarcinomas: Methods for Selective Culture In Vitro 2
Authors: M. H. Tan, E. D. Holyoke, M. H. Goldrosen
Journal: JNCI Journal of the National Cancer Institute (1976)

Two murine colon adenocarcinoma cell lines were established from primary cultures. The MCA-38 cell line was begun by treatment of the primary culture with trypsin to remove the fibroblastoid elements. The MCA-36 epithelial cells were sensitive to trypsin; therefore, the growth medium of MCA-36 primary cultures was augmented with collagenase to release the tumor-cell elements from the fibroblast network. These tumor elements were dissociated with trypsin and placed in tissue culture. Each cell line was cultured for at least 10 passages in vitro and gave rise to tumors when reimplanted in vivo.
Sleep position trainer vs. tennis ball technique in positional OSA
Authors: Michiel Eijsvogel, Frans de Jongh, Marjolein Brusse-Keizer
Journal: European Respiratory Journal (2013)

Introduction: standard tennis ball techniques like the positional band (PB) can be as effective as CPAP in positional OSA (POSA) but compliance is low.  Objectives: can compliance of positional therapy in POSA be improved with a new device, the sleep position trainer (SPT)  Therapies: The SPT is a small in supine position vibrating device with position sensors placed on the ventral thorax. The PB is a belt with three inflatable airbags worn on the back preventing supine position.  Methods: 55 new patients with POSA were randomized to SPT (29) or PB (26). Standard home-PSG was done at baseline and after 1-month therapy. Quebec Sleep Questionnaire (QSQ), ESS and VAS scores were taken. The SPT device was, in a non-vibrating mode, also build in the PB for measuring daily compliance  Results: comparing PSG: AHItot, AHIsup, %supTST was respectively 11.4, 30.7, 27.9% for SPT and 13.2, 37.3, 31.1% for PB. After 1 month the same parameters were respectively reduced to 3.9, 0.0, 0.0 for SPT and 5.8, 0.0, 0.0 for PB. After 1 month therapy no differences in QSQ, ESS, PSG sleep parameters were observed, however perceived therapeutic effectiveness by means of VAS was 74,5 for SPT and 55,2 for PB (P 0.02). Compliance decreased with time. At 1 month SPT and PB was used respectively in 70% and 42%. Compliance expressed as use >4 hours/night for > 5 days/week was 76% for SPT, 42% for PB (P 0.01). Dropouts were 7% in SPT, 28% in PB.  Conclusions: SPT and PB effectively treat POSA when used. Only the SPT does have an acceptable compliance after 1 month.
Dose-response relationship of epirubicin in the treatment of postmenopausal patients with metastatic breast cancer: a randomized study of epirubicin at four different dose levels performed by the Danish Breast Cancer Cooperative Group.
Authors: L Bastholt, M Dalmark, S B Gjedde, P Pfeiffer, D Pedersen, E Sandberg, M Kjaer, H T Mouridsen, C Rose, O S Nielsen, P Jakobsen, S M Bentzen
Journal: Journal of Clinical Oncology (1996)

PURPOSE To test for possible correlations between dose of single-drug epirubicin and efficacy/toxicity in postmenopausal women with metastatic breast cancer. The study also included analysis of a correlation between pharmacokinetic and pharmacodynamic parameters. PATIENTS AND METHODS Two hundred eighty-seven women were randomized to receive either 40, 60, 90, or 135 mg/m2 of epirubicin intravenously (IV) every 3 weeks. Treatment consisted of first-line cytotoxic therapy for metastatic disease. In patients with early progressive disease after either 40 or 60 mg/m2, dose escalation to 135 mg/m2 was performed. A full pharmacokinetic analysis was performed in 78 patients. RESULTS Among 263 eligible patients, an increase in response rate and time to progression was found with an increase in dose from 40 to 90 mg/m2, while no increase in efficacy was found from 90 to 135 mg/m2. Multivariate analysis, using the Cox proportional hazards model with time to progression as the end point, confirmed that epirubicin dose more than 60 mg/m2 was an independent prognostic covariate. Furthermore, a significant association was established between randomized dose and both hematologic and nonhematologic toxicity. No association between pharmacokinetic parameters and efficacy parameters was demonstrated. On the other hand, a significant correlation between pharmacokinetic parameters and both hematologic and nonhematologic toxicity was found. CONCLUSION An increase in dose of epirubicin from 40 to 90 mg/m2 is accompanied by increased efficacy. Further increases in dose do not yield increased efficacy. A positive correlation between epirubicin dose and toxicity, as well as a correlation between pharmacokinetic parameters and toxicity, was also established.
Brain-Type Natriuretic Peptide Levels in the Prediction of Adverse Outcome in Patients with Pulmonary Embolism
Authors: Frederikus A. Klok, Inge C. M. Mos, Menno V. Huisman
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

The potential role of elevated brain-type natriuretic peptides (BNP) in the differentiation of patients suffering from acute pulmonary embolism at risk for adverse clinical outcome has not been fully established.We evaluated the relation between elevated BNP or N-terminal-pro-BNP (NT-pro-BNP) levels and clinical outcome in patients with pulmonary embolism.Articles reporting on studies that evaluated the risk of adverse outcome in patients with pulmonary embolism and elevated BNP or NT-pro-BNP levels were abstracted from Medline and EMBASE. Information on study design, patient and assay characteristics, and clinical outcome was extracted. Primary endpoints were overall mortality and predefined composite outcome of adverse clinical events.Data from 13 studies were included. In 51% (576/1,132) of the patients, BNP or NT-pro-BNP levels were increased. The different analyses were performed in subpopulations. Elevated levels of BNP or NT-pro-BNP were significantly associated with right ventricular dysfunction (P < 0.001). Patients with high BNP or NT-pro-BNP concentration were at higher risk of complicated in-hospital course (odds ratio [OR], 6.8; 95% confidence interval [CI], 4.4-10) and 30-day mortality (OR, 7.6; 95% CI, 3.4-17). Patients with a high NT-pro-BNP had a 10% risk of dying (68/671; 95% CI, 8.0-13%), whereas 23% (209/909; 95% CI, 20-26%) had an adverse clinical outcome.High concentrations of BNP distinguish patients with pulmonary embolism at higher risk of complicated in-hospital course and death from those with low BNP levels. Increased BNP or NT-pro-BNP concentrations alone, however, do not justify more invasive treatment regimens.
Randomized clinical trial comparing mitoxantrone with doxorubicin in previously treated patients with metastatic breast cancer.
Authors: I C Henderson, J C Allegra, T Woodcock, S Wolff, S Bryan, K Cartwright, G Dukart, D Henry
Journal: Journal of Clinical Oncology (1989)

Three hundred twenty-five women with metastatic adenocarcinoma of the breast who had failed one prior chemotherapeutic regimen for advanced disease were randomized to receive 14 mg/m2 of mitoxantrone or 75 mg/m2 of doxorubicin intravenously (IV) every 3 weeks. Enrollment was closed on October 31, 1984, after 165 patients were randomized to mitoxantrone and 160 patients to doxorubicin. Patients randomized to the two treatment groups were compared for response rate, duration of response, time to progression or death, time to treatment failure (TTF), and survival. The response rate to mitoxantrone was 20.6%, to doxorubicin 29.3% (P = .07). The median response duration was 151 days for the mitoxantrone group and 126 days for the doxorubicin group (P = .16). The median TTF was 70 days in the mitoxantrone group and 104 days in the doxorubicin group (P = .36). The median survival of patients initially randomized to receive mitoxantrone was 273 days; for doxorubicin 268 days (P = .40). There were three responses among 77 patients crossed over to mitoxantrone after initial treatment with doxorubicin. The major dose-limiting toxicity for both drugs was leukopenia. There was significantly less severe and less frequent toxicity with mitoxantrone administration. Severe nausea and vomiting occurred in 9.5% of mitoxantrone patients and 25.3% of doxorubicin patients (P less than .001). The incidence of severe stomatitis and mucositis was 0.6% in the mitoxantrone group and 8.4% in the doxorubicin group (P = .001). Severe alopecia occurred in 5.1% of mitoxantrone patients and 61.0% of doxorubicin patients (P less than .001). A life-table comparison of the cumulative dose to the development of a cardiac event showed that mitoxantrone had significantly less cardiotoxicity than doxorubicin (P = .0005). This study demonstrates that mitoxantrone is active as a single agent in the treatment of metastatic breast cancer. Compared with doxorubicin it appears to be marginally less active and significantly less toxic. We conclude that mitoxantrone can be used alone or with other standard drugs to palliate the symptoms of metastatic breast cancer, especially in settings where drug toxicity is an important consideration.
Preclinical evaluation of a novel and orally active proteasome inhibitor as a therapy in relapsed/refractory multiple myeloma
Authors: D. Chauhan, L. Catley, G. Li, T. Hideshima, P. Richardson, M. Palladino, K. C. Anderson
Journal: Journal of Clinical Oncology (2005)

3122 Multiple Myeloma (MM) remains fatal despite all available therapies, and novel approaches which target mechanisms regulating MM cell growth, survival, and apoptosis are urgently needed. Proteasome is a promising target in the treatment of MM. The proteasome inhibitor Bortezomib/PS-341/Velcade has shown potent preclinical activity in vitro as well as therapeutic activity in MM and is the first treatment in more than a decade to be FDA approved for patients with MM. However, prolonged exposure is associated with attendant toxicity and development of bortezomib-resistance. Here we demonstrate that novel proteasome inhibitor NPI-0052, distinct in its chemical structure from bortezomib, induces apoptosis even in MM cells resistant to bortezomib, dexamethasone (Dex), melphalan and thalidomide without significantly affecting the viability of normal cells. NPI-0052 overcomes growth/survival and drug-resistance in MM cells conferred by bone marrow (BM) microenvironment, and/or altered expression of anti-apoptotic proteins Bcl2, Hsp27, and IAPs. Mechanistic studies demonstrate that NPI-0052-triggered MM apoptosis is associated with loss of mitochondrial membrane potential; Superoxide generation; release of mitochondrial proteins cytochrome-c/Smac; and activation of caspase-8/9/3. Alternatively, pretreatment of MM cells with the pan-caspase inhibitor Z-VAD-fmk blocks NPI-0052-induced cell death. In vivo studies in animal models show that oral administration of NPI-0052 decreased proteasome activity in packed whole blood lysates in a dose dependent fashion. Moreover, studies using a human plasmacytoma xenograft mouse model show that NPI-0052 is orally active and has significant anti-MM activity at doses that are not only well tolerated, but also inhibit MM cell growth and prolong survival. Collectively, these data provide the framework for clinical evaluation of NPI-0052 to trigger apoptosis in MM cells, reduce bortezomib-associated toxicity, overcome bortezomib-resistance, and improve patient outcome in MM. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Nereus Nereus Nereus Nereus
Pharmacotherapy for Status Epilepticus
Authors: Eugen Trinka, Julia Höfler, Markus Leitinger, Francesco Brigo
Journal: Drugs (2015)

Status epilepticus (SE) represents the most severe form of epilepsy. It is one of the most common neurologic emergencies, with an incidence of up to 61 per 100,000 per year and an estimated mortality of 20 %. Clinically, tonic-clonic convulsive SE is divided into four subsequent stages: early, established, refractory, and super-refractory. Pharmacotherapy of status epilepticus, especially of its later stages, represents an "evidence-free zone," due to a lack of high-quality, controlled trials to inform clinical decisions. This comprehensive narrative review focuses on the pharmacotherapy of SE, presented according to the four-staged approach outlined above, and providing pharmacological properties and efficacy/safety data for each antiepileptic drug according to the strength of scientific evidence from the available literature. Data sources included MEDLINE and back-tracking of references in pertinent studies. Intravenous lorazepam or intramuscular midazolam effectively control early SE in approximately 63-73 % of patients. Despite a suboptimal safety profile, intravenous phenytoin or phenobarbital are widely used treatments for established SE; alternatives include valproate, levetiracetam, and lacosamide. Anesthetics are widely used in refractory and super-refractory SE, despite the current lack of trials in this field. Data on alternative treatments in the later stages are limited. Valproate and levetiracetam represent safe and effective alternatives to phenobarbital and phenytoin for treatment of established SE persisting despite first-line treatment with benzodiazepines. To date there are no class I data to support recommendations for most antiepileptic drugs for established, refractory, and super-refractory SE. Limiting the methodologic heterogeneity across studies is required and high-class randomized, controlled trials to inform clinicians about the best treatment in established and refractory status are needed.
Cutaneous Malignant Melanoma and Indicators of Total Accumulated Exposure to the Sun: An Analysis Separating Histogenetic Types&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C. D'Arcy J. Holman, Bruce K. Armstrong
Journal: JNCI Journal of the National Cancer Institute (1984)

Evidence associating malignant melanoma with semiquantitative and questionnaire indicators of past sunlight exposure is presented from a case-control study of 511 patients and 511 matched control subjects in Western Australia. That melanoma is related to sun exposure was supported by associations with actinic skin damage graded by cutaneous microtopography, history of nonmelanotic skin cancer, duration of residence of migrants to Australia, and mean annual hours of bright sunshine received at locations where the subjects had resided. Separate analyses of histogenetic subtypes revealed that Hutchinson's melanotic freckle melanoma had the strongest associations with indicators of sunlight exposure. For superficial spreading melanoma, a specific relationship was observed with age at arrival as against duration of residence in Australia. Migrants arriving before age 10 years appeared to have a risk similar to that of native-born Australians, whereas the estimated incidence in those arriving after age 15 years was around one-quarter of the native-born rate, with arrival at later ages giving no additional advantage. Control subjects arriving in Australia before age 10 years had an increased number of nevi on their arms, suggesting that sun exposure in early life may be a factor in nevus production and, therefore, a determinant of later potential to develop superficial spreading melanoma.