tbuckley/cabot-search huggingface dataset:
One week on/one week off regimen of temozolomide for recurrent glioblastoma: A phase II study
Authors: W. Wick, J. P. Steinbach, J. Schuth, J. Dichgans, M. Bamberg, M. Weller
Journal: Journal of Clinical Oncology (2004)

1536 Background:Median survival for patients with glioblastoma is 12 months. Patients progressing after cytoreductive surgery, radiotherapy and nitrosourea-based adjuvant chemotherapy experience a median survival of 4–6 months. There is no standard treatment for recurrent malignant glioma. Temozolomide has shown activity in phase II studies of malignant gliomas and a phase III study of metastatic malignant melanoma. It is generally administered orally at 200 mg/m2 body surface area in a five-day every 28 days schedule. Methods:Twentyone patients with recurrent or progressive glioblastoma were enrolled in a prospective, unicenter trial to determine whether a one week on/one week off regimen of temozolomide is feasible and effective as a salvage therapy. Chemotherapy consisted of temozolomide at 150 mg/m2 on days 1 to 7 and days 15 to 21 of 28 days treatment cycles. Results:There was no specific treatment-related neurotoxicity, but 3 of 21 patients (14%) had to discontinue chemotherapy because of WHO IV hematological toxicity. There were two partial responses (10%), 17 patients (81%) had stable disease according to MacDonald criteria. The median progression-free survival is 5 months, and the progression-free survival rate at 6 months is 43%. The median overall survival from diagnosis has not yet been reached, but will be more than 16 months. Conclusions:The schedule used in the present study is a feasible and effective treatment of recurrent glioblastoma. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ESSEX Pharma; Thomas-Dehler-St ESSEX Pharma; Thomas-Dehler-St
Validation and application of Vierordt's spectrophotometric method for simultaneous estimation of tamoxifen/coenzyme Q10 in their binary mixture and pharmaceutical dosage forms
Authors: Eman S. El-Leithy, Rania S. Abdel-Rashid
Journal: Asian Journal of Pharmaceutical Sciences (2016)

For the sake of improving patient compliance and sustainability of chemotherapy healthcare system, both TC and CoQ10 were formulated as solid lipid nanoparticles (SLNs). The study was focused on establishing and validating a simple and reproducible spectrophotometric method for simultaneous determination of TC and CoQ10 in their binary mixture or pharmaceutical dosage forms. A new method based on simultaneous estimation of drug mixture without prior separation was developed. Validation parameters were checked with International Conference on Harmonization (ICH) guidelines. The accuracy and reproducibility of proposed method was statistically compared to HPLC. The TC and CoQ10 were quantified at absorptivity wavelengths of 236 nm and 275 nm, respectively. Calibration curves obeyed Beer's law in range of 2–14 µg/ml with a correlation coefficient (R2) of 0.999 in both methanol and simplified simulated intestinal fluid (SSIF). The %means recovery of TC and CoQ10 in pure state or binary mixture at various concentration levels were all around 100%. The low values of SD and %RSD (<2%) confirm high precision and accuracy of the proposed method. Formulated SLNs showed different %means recovery in range 81–92% for TC and 32–59% for CoQ10. The data obtained by applying simultaneous Vierordt's equations showed no statistical significance in comparison to HPLC. Vierordt's method was successfully applied as a simple, accurate, precise, and economical analysis method for estimating TC and CoQ10 concentrations in pure state, binary mixture and pharmaceutical dosage forms.
Naturally Occurring Human Antibody to Neuraminidase-Treated Human Lymphocytes. Antibody Levels in Normal Subjects, Cancer Patients, and Subjects With Immunodeficiency
Authors: G. Nicholas Rogentine
Journal: JNCI Journal of the National Cancer Institute (1975)

Antineuraminidase-treated lymphocyte antibody levels in normal individuals were compared to levels in patients with newly diagnosed malignancies, patients with immunodeficiency syndromes (some of whom subsequently developed cancer), and normal and affected members of multiple malignancy families. No correlation between antibody level and the presence of malignancy was found. In normal individuals, antibody levels were high in childhood and declined with advancing age in accord with behavior of other natural antibodies.
Abstract 328: ES1 Is A Novel Mitochondrial Protein Protecting The Heart Via Direct Regulation Of Mitochondrial Energy Metabolism
Authors: Qinqiang Long, Huan Yang, Yiqun Zhou, Aibing Wang, Lan He, Yuquan Li, Teayoun Kim, Yishu Ding, Olga Zhelyabovska, Qinglin Yang
Journal: Circulation Research (2014)

Defects in the myocardial energy metabolism have been linked to pathological cardiac hypertrophy and congestive heart failure. However, the regulation of myocardial energy metabolism remains obscure. ATP synthase is an enzyme complex in the mitochondria and plays a central role in energy metabolism. In this study, we identified ES1, a mitochondrial protein with unknown function, as a key determinant of myocardial energy metabolism via controlling ATP synthase activities. We uncovered that ES1 interacts with both α and β subunit of ATP synthase, and its expression levels in H9C2 cardiomyocytes were directly correlated to ATP synthesis and inversely to ATP hydrolysis. Cellular energetic analysis revealed that ES1 levels in H9C2 cardiomyocytes were directly correlated with mitochondrial oxidative metabolism. ATP synthase activity assays revealed increased synthesis activities and decreased hydrolysis activities on cardiac mitochondria from a mouse line with Cre-LoxP mediated, tamoxifen inducible, cardiomyocyte-restricted ES1 overexpression (TM-ES1oe) compared with mice of tamoxifen-inducible Mer-Cre-Mer (TMCM). We induced ES1 overexpression in TM-ES1oe mice (3-month-old) 7 days after transverse aortic constriction(TAC) and compared with TMCM mice with identical treatment. Echocardiography assessment revealed a substantially improved Ejection fraction (EF%) and Fractional shortening (FS%) and diminished left ventricular hypertrophy in TM-ES1oe mice compared with TMCM mice. Sections of TM-ES1oe hearts stained with Masson’s Trichrome blue showed markedly decreased interstitial fibrosis compared with TMCM control. We have also generated an ES1 knockout line. ES1 knockout mice(3-month-old)showed cardiac dysfunction with decreased EF% and FS% under a basal condition. Transmission electron microscope examination revealed substantial loss of mitochondrial cristae structure on ES1 knockout hearts. These results indicate that ES1 protecting the heart by direct regulation of mitochondrial energy metabolism. ES1 may be directly involved in pathological development of cardiac hypertrophy and heart failure. We suggest that ES1 is a potential therapeutic target in treating cardiomyopathy and other heart diseases.
A phase II study of combination chemotherapy with gemcitabine, 5-fluorouracil, and cisplatin (GFP) for advanced pancreatic cancer
Authors: S. R. Kim, S. B. Choi, Y. J. Yuh
Journal: Journal of Clinical Oncology (2006)

14066 Background: Gemcitabine has been the standard regimen for advanced pancreatic cancer, but the effect on the response rate and survival is still disappointing. 5-fluorouracil(5-FU) and cisplatin are synergistic with gemcitabine as well as with each other. This study is aimed to determine the efficacy and safety of combination chemotherapy with gemcitabine, 5-FU and cisplatin for advanced pancreatic cancer. Methods: Patients(pt) with recurred or advanced pancreatic cancer were entered into this study, who had histologically proven adenocarcinoma, no prior radiotherapy, measurable lesion (≥2cm), ECOG performance scale (PS) 0–2, age 18–70, adequate bone marrow, cardiac and renal function, ALT ≤ 3× normal, and total bilirubin ≤ 2mg/dL.The pt were treated every 3weeks with gemcitabine 800 mg/m 2 , at 10mg/m 2 /min on days 1 and 8, 5-FU 1g/m 2 /24 hour continuous infusion from day 1 through 3 for 72 hours (extended to 4 days later in 12 pt due to lack of toxicity), and cisplatin 60 mg/m 2 on day 2, 24 hours after the start of gemcitabine. Concurrent chemo-radiotherapy with gemcitabine 250 mg/m 2 /week was given to the pt with response of stable disease or better after 4 cycles of chemotherapy, if PS ≤1 and age ≤ 65. Results: Characteristics of 25 eligible pt; 17 male/ 8 female, PS 0,1 in 20 pt, 2 in 4 pt, Stage III in 3 pt, IV in 22, age 40–69 (median 62). Five pt had prior 5-FU-based chemotherapy. A total of 109 cycles were given (median 4; 1–10 cycles/person). Response by WHO criteria: 3 PR (14.3%; 95% confidence interval: 0 - 29.6%), 11 SD (52.4%) and 7 PD in 21 assessable pt. The median time to progression was 230 days (48 + -478 + ) and median survival was 322 days (70 + -757 + ). WHO grade ≥3 toxicity: neutropenia 19.3% (/cycle), thrombocytopenia 28.4%, mucositis 1.8%, and nausea and vomiting 5.6%. The clinical benefit response and correlation of tumor response with CA-19–9 level will be detailed on presentation. Conclusions: The chemotherapy with gemcitabine, 5-FU and cisplatin for advanced pancreatic cancer is safe, active and may have better survival benefit than gemcitabine alone. Based on these results, a nationwide phase III trial comparing with gemcitabine alone has been started. No significant financial relationships to disclose.
Breast self examination
Authors: R. J Epstein
Journal: BMJ (2003)

Editor—Given what is now known about the long subclinical growth phase of human breast cancers, the finding of a recent study from Shanghai, that teaching breast self examination did not detectably improve survival, is not surprising.1 None the less, Austoker's related editorial, proclaiming the death of breast self examination, should not go unchallenged.2

Many studies have reported a reduction in primary tumour size dependent on breast self examination, which may in turn enable more conservative surgery.3 The editorial's implication that all such end points are rendered illusory by the Shanghai study is overstated; as if to acknowledge this, Austoker concedes that prompt symptomatic presentation (“breast awareness”) remains important. But is the timely presentation of breast symptoms—of which palpation of a lump is the commonest—so different from what most people understand by breast self examination?

False positive and false negative “costs” are attached to breast self examination and to any preventive diagnostic interventions. However, an individual who is informed of both the negative randomised data and of the inverse association of tumour stage with survival might still reasonably opt for the potential costs of a biopsy dependent on breast self examination, rather than for the implied comfort of ignorance or uncertainty.

In Asia, where high rates of late presentation persist owing to cultural and economic factors,4 there seems little reason to be cheered by the debunking of breast self examination. As one facet of an expanding spectrum of patient empowering initiatives, breast self examination at least provides an entry strategy towards the gradual improvement of cancer awareness and outcomes.

Kline has proposed that the rhetoric of breast self examination should be modified so that healthcare consumers are accurately informed and thus empowered, rather than misled or inadvertently coerced.5 Surely this is the insight that public health in the 21st century should be striving to attain.
Prognostic relationship of SATB1 gene expression and estrogen receptor status in breast cancer cells.
Authors: L. Mavrova, T. Karn, L. Hanker, E. Ruckhäberle, V. Mueller, U. Holtrich, M. Kaufmann, A. Rody
Journal: Journal of Clinical Oncology (2010)

661 Background: Several recent reports have linked the expression of SATB1, a genome organizer recruiting chromatin remodeling/modifying enzymes and transcription factors, to the potential for metastasis of breast cancer cells and therefore its negative prognosis on survival. Still uncertain remains the relation of estrogen receptor (ER) status of the cancer cells to the prognostic value of the higher expression of the SATB1 in primary breast cancer cells. Methods: A database of 1910 Affymetrix microarrays and clinical characteristics from primary breast cancer patients was established. Log-transformed values were median centered over arrays and gene normalization was done separately in each dataset. To allow comparison of SATB1 expression between different datasets we used a quartile split of each dataset. Chi-square test was used to test for associations between SATB1 expression of tumors and categorical parameters. Kaplan-Meier curves were constructed and the log-rank test used to determine the univariate significance of the variables. Results: Univariate analysis revealed no significant difference of SATB1 expression according to lymph node status, tumor size, histological subtype, pathohistological grading, Ki67 expression and erbB2-status. However, a strong correlation was found for patients' age (p < 0.001) and the ER status of the tumor with higher SATB1 expression among ER-negative samples (p < 0.001). The survival analysis of our cohort revealed that while there was no significant difference among ER-negative cancers there was instead a benefit for high SATB1 expression among ER-positive tumors. Conclusions: The prognostic impact of SATB1 expression is mainly confined to ER-positive breast cancers, suggesting that SATB1 is an estrogen dependent marker when analyzing gene expression data. No significant financial relationships to disclose.
<scp>S</scp>tatin use is safe and does not impact prognosis in patient with de novo follicular lymphoma treated with immunochemotherapy: <scp>A</scp>n exploratory analysis of the PRIMA cohort study
Authors: Emmanuel Bachy, Jane A. Estell, Eric Van de Neste, Réda Bouabdallah, Joan Bargay, Alain Delmer, Bénédicte Gelas‐Dore, Maria Gomes da Silva, Olivier Fitoussi, David Belada, Hervé Maisonneuve, Tanin Intragumtornchai, Thierry Lamy, Peggy Dartigues, John Francis Seymour, Gilles Salles
Journal: American Journal of Hematology (2016)

An adverse prognostic impact of statin use in lymphoma was first suspected from in vitro data showing an impairment of anti-CD20 antibody binding. However, further clinical studies suggested an improved outcome associated with their use in hematological malignancies. In particular, a survival benefit was reported for patients with follicular lymphoma on statins. Our objective was to assess the outcome of follicular lymphoma patients treated in the PRIMA study with immunochemotherapy according to the use of statins. Among the 1,217 patients enrolled in the PRIMA study, 1,135 were included in the present study. Concomitant treatments at registration were available for all patients. Among those 1,135 patients, 119 were on statins (10.5%) at diagnosis. Adverse events frequencies, event-free survival (EFS), time to next lymphoma treatment (TTNLT), time to next chemotherapy (TTNCT), and overall survival (OS) were evaluated according to the use of statins. The rates of overall and specific cardiovascular adverse events between the two groups of patients were comparable both during induction and maintenance. Outcome in terms of response rates or EFS, TTNLT, TTNCT, and OS were similar regardless of the use of statins (P = 0.57, P = 0.85, P = 0.30, and P = 0.43, respectively) in univariate analysis and after further adjustments for potential confounding factors in multivariate analysis. In conclusion, statin use does not impact the prognosis of patients with follicular lymphoma treated with immunochemotherapy.
Genetic variant<i>PLCE1</i>rs2274223 and gastric cancer: more to be explored?
Authors: Yazhou He, Chengdi Wang, Ziqiang Wang, Zongguang Zhou
Journal: Gut (2015)

We read with great interest the comprehensive study by Mocellin and colleagues1 who developed a quantitative summary of candidate genetic variants for gastric cancer susceptibility. Based on different tumour sites, the authors conducted a subgroup analysis for cardia cancer (CC) and non-cardia cancer (NCC). It is well established that CC has distinctive characteristics compared with NCC, but shares some common risk factors and pathogenesis with oesophageal cancer (OSC). In addition, there are some different genetic factors such as genetic variants between patients with CC and NCC. There is an argument that CC, located at oesophago-gastric junction, belongs to oesophageal more than gastric cancer.

According to the results of subgroup analysis, Mocellin and colleagues1 found several variants showing different results with CC and NCC risk. However, only PLCE1 rs2274223 was reported to be significantly associated with CC but not NCC risk with high credibility …
Abstract 15196: Diastolic Dysfunction by Tissue Doppler Imaging Predicts All-Cause Mortality in Patients with Cerebral Infarction
Authors: Flemming J Olsen, Peter G Jørgensen, Rasmus Møgelvang, Jan S Jensen, Thomas Fritz-Hansen, Jan Bech, Jacob C Sivertsen, Tor Biering-Sørensen
Journal: Circulation (2014)

Introduction: Several clinical prediction score models have been investigated for predicting mortality in patients with cerebral infarction. However none of these include echocardiographic measures...
Cohort KBP-2000-CPHG: Evaluation of prognosis factors for survival in primary bronchial cancer (PBC)
Authors: F. Blanchon, M. Grivaux, M. Zureik, B. Asselain, J. Breton, B. Duvert, A. Legroumellec, M. Level, G. Berthiot, M. Carlier
Journal: Journal of Clinical Oncology (2006)

7204 Background: PBC has a guarded prognosis despite advances in treatment. The main epidemiologic changes observed during the last fifteen years are the strong progression in its incidence in women and the increase in adenocarcinomas. A prospective study of overall survival and survival according to sex and prognosis factors was set up from the cohort of study KBP-2000-CPHG. Methods: KBP-2000-CPHG is a prospective epidemiological study conducted throughout the year 2000 on histologically confirmed PBC patients treated in general hospitals. 5,667 patients were included. A survival study based on patient outcomes was launched between September 2004 and March 2005 in 137 centres. Each centre had to provide information on the vital status of its patients with, in the event of death, the date and cause. In the absence of vital status data, a graduated tracing strategy was set up including the interrogation of various files: city hall of the place of birth,etc. Results: 135 investigator centres out of the 137 initial centres took part. The 2 non-participating centres represented 56 patients. The vital status could be defined for 5441 of the other 5611 patients (97.0%). 88.4% of these patients had died (average time between inclusion and death: 10.5–10.7 months). In univariate study, survival status is linked with age (p &lt; 0.0001), tobacco consumption (p &lt; 0.0001), performance status (p &lt; 0.0001), cancer type (small versus non small cell lung cancer-NSCLC: p &lt; 0.0001) and for the NSCLC, with histological type (p &lt; 0.0001) and TNM stage (p &lt; 0.0001). According to multivariate analysis, survival status is related to age, performance status, cancer type and among the NSCLC, to age, sex, performance status, histological type and TNM stage. Conclusions: The survival study on PBC is the first one in France, including more than 5,400 patients. The first results show the prognosis role of age, sex, histological type, performance status and TNM stage. No significant financial relationships to disclose.
Low dose spiral computed tomography for early diagnosis of lung cancer. Results of baseline screening in 5,000 high-risk volunteers
Authors: G. Veronesi, M. Bellomi, L. Spaggiari, G. Pelosi, P. Maisonneuve, G. Paganelli, E. De Fiori, F. Leo, N. Rotmensz, U. Veronesi
Journal: Journal of Clinical Oncology (2006)

7029 Background: The high lethality of lung cancer is related to the advanced stage at diagnosis. Early studies have demonstrated that screening with CT is effective to diagnose lung cancer at earlier stage but the optimal clinical approach for the management of patients identified with nodules during screening has yet to be defined. We report the first-year results of our CT screening trial. Method: Between October 2004 and October 2005, 5,189 asymptomatic current or former smokers of more than 20 packs/year, older than 50 years, were enrolled in a single-institution screening trial using annual low-dose multidetector CT for 5 years. A protocol for the diagnostic work-up of nodules identified by CT was LD-CT at 1 year for nodules with maximum diameter less than 5 mm, LD-CT at 3 months for lesions between 5.1 and 8 mm and FDG-PET for lesions larger than 8.1 mm. Trans cutaneous biopsy was not routine part of this protocol. End-points were: prevalence and incidence rates of lung cancer, stage distribution, resectability, recall rate and invasive procedure for benign disease. Results: Median age of volunteers was 57 years, 66% were males and 80% current smokers. The prevalence of lung cancer diagnosed at first CT was 1.0% (54 cases; 65% stage I; 9% stage II; 22% stage III and 4% Stage IV). Forty-seven tumors (87%) were radically resected (45 lobectomies, 1 pneumonectomy, 1 atypical segmentectomy). Major surgical morbidity and mortality were 4% and 2% respectively. Recall rate was 10%. Seven patients (1.3% of all recalled subjects) underwent surgical diagnostic procedures for non-malignant disease representing 12% of all screening surgical procedures versus 16% in a non-screening control group treated in the same unit and period. Conclusions: Our results confirmed that screening with low-dose CT allows the detection of early stage lung cancer in a high proportion of cases increasing the probability of cure. Although follow-up is necessary to confirm the efficacy of the proposed work-up protocol, the initial results are promising, with a very low number of invasive procedures performed for benign lesions. No significant financial relationships to disclose.
Abstract 16597: FDG-PET-CT Measurement of Arterial Inflammation Provides Insight into Both Risk for and Timing of Future Cardiovascular Events
Authors: Amparo L Figueroa, Amr Abdelbaky, Megan H MacNabb, Zachary R Lavender, Meredith A Lawler, Shanmugam Uthamalingam, Quynh A Truong, Thomas J Brady, Udo Hoffmann, Ahmed Tawakol
Journal: Circulation (2012)

Background: It has previously been demonstrated that arterial FDG Uptake is associated with cardiovascular events. Here, we test the hypothesis that baseline arterial inflammation is higher in indi...
Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo
Authors: Thomas Luke, Hua Wu, Jincun Zhao, Rudragouda Channappanavar, Christopher M. Coleman, Jin-An Jiao, Hiroaki Matsushita, Ye Liu, Elena N. Postnikova, Britini L. Ork, Gregory Glenn, David Flyer, Gabriel Defang, Kanakatte Raviprakash, Tadeusz Kochel, Jonathan Wang, Wensheng Nie, Gale Smith, Lisa E. Hensley, Gene G. Olinger, Jens H. Kuhn, Michael R. Holbrook, Reed F. Johnson, Stanley Perlman, Eddie Sullivan, Matthew B. Frieman
Journal: Science Translational Medicine (2016)

Anti–MERS-CoV human IgG produced from transchromosomic bovines neutralizes MERS-CoV in vitro and in vivo.