tbuckley/cabot-search huggingface dataset:
The trifunctional antibody catumaxomab (anti-EpCAM × anti-CD3) in patients with malignant ascites: Immunomonitoring results of a pivotal phase II/III study (pooled population).
Authors: M. Jäger, A. Schoberth, M. Hennig, A. Burges, M. Heiss, P. Wimberger, B. Schmalfeldt, H. Lindhofer
Journal: Journal of Clinical Oncology (2010)

2521 Background: Malignant ascites (MA) is a symptom of late-stage tumor disease and associated with a poor prognosis. The trifunctional antibody catumaxomab is approved for treatment of MA. Methods: 258 EpCAM-positive ovarian (n=129) and nonovarian cancer (n=129) patients with MA were compared in an open-label, multicenter, randomized study for efficacy and tolerability of intraperitoneally administered catumaxomab. Various immunological and pharmacodynamical parameters were measured from ascites cell preparations. Results: In 170 patients randomized to catumaxomabtumor cells strongly decreased from a median of 6510 to 0 (after the last infusion). The in vivo target/effector ratio (EpCAM+/CD45+) showed a pronounced decrease from a baseline of 0.4404 at screening to 0.000 after the last infusion (all median). Leukocyte expansion was accompanied by in vivo upregulation of T-cell activation marker CD69 on CD4+ and CD8+ T cells in the MA samples. Concentration of the vascular endothelial growth factor (VEGF) was significantly decreased from screening (147 × 10-9) to after therapy (55 × 10-9) in MA samples (median; VEGF compared to total protein). Interestingly, at re-puncture visit catumaxomab patients (re- puncture at day 77, median) had a 9-fold lower and statistically significant (p=0.0012) tumor cell load compared to control patients (re-puncture at day 13, median). In vitro studies were carried out with screening samples to further validate the in vivo results. Similarly, the in vitro experiments showed EpCAM+ tumor cell elimination, leukocyte expansion, and activation of T cells. A strong upregulation of activating cytokines IL2, IL6, TNFα, and IFNγ (TH1 cytokine profile) was observed compared to control samples without catumaxomab. Conclusions: Intraperitoneal catumaxomab treatment triggers activation and proliferation of different types of immune cells and leads to long-lasting elimination of EpCAM+ tumor cells within malignant ascites. These data confirm the postulated trifunctional mode of action of catumaxomab in vivo and are in line with clinical efficacy in patients with MA. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Fresenius Biotech, TRION Research, TRION Pharma TRION Pharma TRION Pharma, TRION Research
Octreotide acetate (LAR) dose effect on plasma octreotide levels: Impact on neuroendocrine tumor management
Authors: E. Woltering, P. M. Mamikunian, S. Zeitz, S. R. Krutzik, V. L. W. Go, A. I. Vinik, E. Vinik, T. O’Dorisio, G. Mamikunian
Journal: Journal of Clinical Oncology (2005)

3177 Background: Octreotide acetate (LAR) is commonly used for symptom control in carcinoid tumors. At doses of 20 or 30 mg, up to 40% of carcinoid patients require additional aqueous octreotide several times a week for symptom control. 20–40% of patients receiving LAR are given monthly doses higher than the current maximum recommended 30 mg dose. This implies that patients may need higher octreotide blood levels than 20 or 30mg LAR doses can provide. In vitro, octreotide acetate binds to the sst 2 receptor with an affinity (Kd, 50% receptor saturation) of 1x10-9 M (≈1,000 pg /ml) but higher (≈10,000 pg/ml) concentrations of octreotide are required for saturation. Aim: The current study determined the plasma octreotide levels in patients receiving 20, 30 or 60 mg/month of LAR and calculated the effect of weight BSA and BMI on drug levels. Methods: Thirty- seven patients from the www.Yahoo.com carcinoid group sent height and weight information and sent plasma and serum samples for octreotide levels, determined by specific and sensitive RIA. Samples were drawn immediately before the patient’s next dose of LAR. Patients were on 20mg (n=8), 30mg (n=19) or 60 mg/month (n=10) of LAR. Results: Serum and plasma octreotide levels in individuals were essentially identical (p= ns, ANOVA). Mean ± SD plasma octreotide levels for patients receiving 20, 30 or 60 mg/month LAR doses were 2,518 ±1,020, 5,241± 3,004 and 10,926 ± 5,530 pg/ml respectively. No adverse events were reported with patients receiving 60 mg/month LAR dose. Weight, BSA and BMI were inversely related to plasma octreotide levels. Conclusions: The clinical availability of a plasma octreotide assay may be useful to guide octreotide therapy in patients with poorly controlled symptoms or those with progressive tumor growth. Circulating octreotide levels in patients receiving 20 or 30 mg/month LAR doses are often inadequate to saturate sst 2. These individuals may require LAR doses of 60 mg/month to completely saturate sst 2 and optimize symptom or tumor control. The decision to increase LAR doses should be made with the help of plasma octreotide level measurements. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Final analysis: A randomized, blinded, placebo (P)-controlled phase III study of adjuvant postoperative lapatinib (L) with concurrent chemotherapy and radiation therapy (CH-RT) in high-risk patients with squamous cell carcinoma of the head and neck (SCCHN).
Authors: Kevin J. Harrington, Stéphane Temam, Anil D'Cruz, Minish Mahendra Jain, Ida D'Onofrio, Georgy M. Manikhas, Geza Horvai, Yan Sun, Stefan Dietzsch, Pavol Dubinsky, Petra Holeckova, Hisham Mehanna, Iman El-Hariry, Natalie Franklin, Nigel Biswas-Baldwin, Philippe Legenne, Paul Stephen Wissel, Thelma Netherway, Sergio Santillana, Jean Bourhis
Journal: Journal of Clinical Oncology (2014)

6005 Background: Epidermal growth factor receptor (EGFR) and ErbB2 are overexpressed in up to 90% and 40% of SCCHN, respectively. L, a tyrosine kinase inhibitor (TKI) of both EGFR and ErbB2, demonstrates tumor responses in SCCHN. Methods: Patients with resected stage II-IVA SCCHN, with a surgical margin ≤5mm and/or extracapsular extension were randomized to CT-RT with either P or L. RT was 66Gy (2Gy per day, 5 days per week).100 mg/m2of cisplatin was administered on days 1, 22 and 43 of RT. P or L 1500 mg/day was given for up to one week prior to CT-RT, during CT-RT and for up to 12 months as monotherapy maintenance. Patients were stratified by nodal status, primary tumor location, geographical region and ErbB1 expression. The study had 80% power to detect a 10% absolute difference in disease free survival (DFS) rate (55% to 65%). Results: 688 patients were in the ITT population, 346 L and 342 P. Treatment arms were well balanced for prognostic factors. Median total doses of cisplatin (266.5 and 280 mg/m2, L and P respectively) and median doses and duration of RT were similar in both arms. At the time of unblinding, recurrence/death from any cause was seen in 35% in L and 32% in P by independent review committee (IRC): Median DFS (95% CI) L: 53.6 mo (45.8, Not Reached [NR]); P: NR (54.6, NR), HR (95% CI) = 1.10 (0.85, 1.43) 2-sided p value = 0.45. Investigator results confirmed the IRC assessment: HR 1.03 (0.81, 1.30), p=0.82. No significant differences were observed in DFS for any of the pre-specified subgroups, including HPV. Death occurred in 30% L and 32% P; HR (95% CI) = 0.96 (0.73, 1.25). At least one adverse event was seen in 99% L and 98% P (SAEs 48% L/40% P, fatal AEs 7% L/5% P). AEs seen more in L were those expected with a TKI: diarrhea 42% vs 12%, rash 49% vs 30%, vomiting 46% vs 35%. Decrease in left ventricular ejection fraction SAEs were noted in 10 (3%) subjects L vs 3 (<1%) P. Conclusions: In patients with resected SCCHN at high risk for recurrence, L, when added to standard therapy RT/CDDP, does not extend DFS. DFS in both treatment arms exceeded adjuvant CT-RT compared with historical randomized data. Clinical trial information: NCT00424255.
Providing welfare advice in GP surgeries can benefit patients, says report
Authors: J. Wise
Journal: BMJ (2015)

Welfare advice provided within healthcare settings results in better health and wellbeing among patients and can reduce demand on the NHS, a new report concludes.1 It says that advice on social welfare can deliver a range of health related benefits such as lower anxiety, better general health, and more stable relationships and housing situations.

The report by the Low Commission, an independent body on …
Abstract 125: Genetic Deletion Of Telomerase Promotes Premature Cardiac Aging
Authors: Junghyun Kim, Fumihiro Sanada, Maria Cimini, Polina Goihberg, Toru Hosoda, Marcello Rota, Jan Kajstura, Piero Anversa, Annarosa Leri
Journal: Circulation Research (2013)

Telomeropathies are a group of human diseases characterized by mutations in the telomerase gene, accelerated telomere attrition, and premature organ aging. Manifestations of telomere disease include bone marrow failure, liver cirrhosis, and lung fibrosis. It remains, however, to be documented whether loss of telomerase activity is coupled with alterations in cardiac structure and function. To address this issue, the heart of mice carrying a deletion of the RNA component of telomerase (Terc -/- mice) was studied at 3-13 months of age. This allowed us to define whether defects in telomerase function in cardiac stem cells (CSCs) and their progeny promote ventricular dysfunction independently from chronological age, which is typically associated with significant telomere erosion. For this purpose, the characteristics of the aging cardiomyopathy were defined first in 30-month-old wild-type mice (WT). Deteriorations in systolic and diastolic indices of myocardial contractility were detected in senescent mice by echo-Doppler, MRI, and invasive hemodynamics. Importantly, 6-month-old Terc -/- mice showed severe ventricular dysfunction comparable to that seen in 30 month-old WT. Telomere length in Terc -/- mouse CSCs was ~50% shorter than in age-matched WT cells but was comparable to that found in 30 month-old WT cells. The number of CSCs was 60% lower in Terc -/- than age-matched WT mice, and the fraction of BrdU-positive CSCs decreased 1.4-fold, from 25% to 14%. The absence of Terc led to a 50% reduction in myocyte turnover, which was coupled with myocyte hypertrophy and myocyte loss. BrdU labeling was reduced 60% in Terc -/- myocytes. Old CSCs formed a senescent progeny composed of cardiomyocytes, which carried markedly shortened telomeres and showed a severe depression in cell shortening and re-lengthening. Moreover, the renewal of endothelial cells was 75% lower in Terc -/- mice mimicking the rarefaction in capillary typically seen in the old myocardium. Our findings document that loss of telomerase activity is a critical determinant of cardiac aging with reduced cardiomyogenesis and vasculogenesis. These maladaptive responses may be operative in patients carrying mutations of telomerase.
Prevalence of specific suicidal behaviors in a high school sample
Authors: J M Harkavy Friedman, G M Asnis, M Boeck, J DiFiore
Journal: American Journal of Psychiatry (1987)

Of 380 high school students who completed an anonymous survey concerned with their experience with suicidal behavior, 60% reported that they had thought about killing themselves. These thoughts varied with respect to persistence and planfulness. Almost 9% reported that they had actually made at least one attempt to kill themselves and over half of the suicide attempters reported at least two attempts. Fewer than half of the attempters reached the attention of mental health professionals. The data on family history of suicidal behavior suggest that the suicidal ideators and the suicide attempters represent overlapping groups.
Observations on the Growth Phases of Human Amnion Cell Cultures&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R. Shihman Chang
Journal: JNCI Journal of the National Cancer Institute (1968)

Human amnion cells in their first and second subculture underwent 3 phases: 1) a limited initial proliferative, 2) a prolonged stationary and degenerative, and 3) a slow recovery phase. The initial proliferative phase lasted about 6–10 weeks; in most cultures, the stationary and degenerative phase about 20–42 weeks. In the initial phase, cell number increased threefold to tenfold. In the stationary and degenerative phase there was a slow decrease in cell number, and the mitotic activity was extremely low or nondetectable by the methods employed. In the recovery phase, foci of proliferating cells appeared and enlarged slowly but persistently for several months. In 7 experiments, 29 of 32 hydrocortisone-treated cultures showed evidence of recovery between the 22d and 52d week. Addition of hydrocortisone to nutrient medium appeared crucial in bringing the amnion culture into the recovery phase regularly.
Improved Method to Stratify Elderly Patients With Cancer at Risk for Competing Events
Authors: Ruben Carmona, Kaveh Zakeri, Garrett Green, Lindsay Hwang, Sachin Gulaya, Beibei Xu, Rohan Verma, Casey W. Williamson, Daniel P. Triplett, Brent S. Rose, Hanjie Shen, Florin Vaida, James D. Murphy, Loren K. Mell
Journal: Journal of Clinical Oncology (2016)

To compare a novel generalized competing event (GCE) model versus the standard Cox proportional hazards regression model for stratifying elderly patients with cancer who are at risk for competing events.We identified 84,319 patients with nonmetastatic prostate, head and neck, and breast cancers from the SEER-Medicare database. Using demographic, tumor, and clinical characteristics, we trained risk scores on the basis of GCE versus Cox models for cancer-specific mortality and all-cause mortality. In test sets, we examined the predictive ability of the risk scores on the different causes of death, including second cancer mortality, noncancer mortality, and cause-specific mortality, using Fine-Gray regression and area under the curve. We compared how well models stratified subpopulations according to the ratio of the cumulative cause-specific hazard for cancer mortality to the cumulative hazard for overall mortality (ω) using the Akaike Information Criterion.In each sample, increasing GCE risk scores were associated with increased cancer-specific mortality and decreased competing mortality, whereas risk scores from Cox models were associated with both increased cancer-specific mortality and competing mortality. GCE models created greater separation in the area under the curve for cancer-specific mortality versus noncancer mortality (P < .001), indicating better discriminatory ability between these events. Comparing the GCE model to Cox models of cause-specific mortality or all-cause mortality, the respective Akaike Information Criterion scores were superior (lower) in each sample: prostate cancer, 28.6 versus 35.5 versus 39.4; head and neck cancer, 21.1 versus 29.4 versus 40.2; and breast cancer, 24.6 versus 32.3 versus 50.8.Compared with standard modeling approaches, GCE models improve stratification of elderly patients with cancer according to their risk of dying from cancer relative to overall mortality.
Strategies to improve minority patient accrual to cancer clinical trials
Authors: D. M. Wujcik, C. Ikpeazu, W. Chinratanalab, S. N. Wolff, C. Kinnard, N. McCullough, H. R. C. Mason, S. Stain
Journal: Journal of Clinical Oncology (2004)

6017 Background: Clinical trials (CT) provide the basis for standards of care. However, the rate of accrual to adult cancer CT is 3% and even lower for minorities. The lack of minority patients on CT results in difficulty ascribing standards to these groups. Proposed obstacles for inadequate accrual for ethnic minority participation are speculated to be socio-economic such as an unwillingness to participate in research and a fear of experimentation. We hypothesized that obstacles to accrual on CT for minority populations are predominantly disease-related and not socio-economic. Methods: An NCI funded CT shared resource was established between a comprehensive cancer center and a public hospital serving ethnic minority and economically disadvantaged patients. Over a 3-year period, all patients were screened to determine eligibility for a cooperative or institutional CT. A dedicated team, including nurses experienced in CT, undertook extensive interaction with all patients to facilitate accrual. Results: 462 patients were screened with 134 (29%) having an identified study available. Screened patients included 238 (56%) African Americans (AA), 165 (39%) Caucasians (C), and 20 (5%) Hispanics (H). 73 subjects, 54% of eligible and 16% of all patients, were accrued to a CT. Ethnicity on CT was: AA = 61%, C = 37%, and H = 2%. These accrual rates far exceed the national norm. Reasons eligible patients did not enter a CT were: medical co-morbidities (25%), not meeting eligibility criteria (21%) and inadequate performance status (10%). Only three patients (5%) indicated they did not wish to participate in research. Conclusion: This experience documents how a dedicated research team can enter ethnic minority and low-income patients onto CT. The largest group of patients not entered was due to a study not being available. All ethnic groups were proportionately accrued to CT. Strategies to improve applicability of CT may require design of studies for patients with co-morbidities or advanced disease. No significant financial relationships to disclose.
Abstract 12827: Prior Coronary Artery Bypass Grafting Diminishes the Initial Success Rate of Percutaneous Coronary Intervention in Chronic Total Occlusion of a Native Coronary Artery
Authors: Tomohiko Teramoto, Etsuo Tsuchikane, Tatsuya Ito, Hitoshi Matsuo, Yoriyasu Suzuki, Tsuyoshi Ito, Kenya Nasu, Masashi Kimura, Yoshihisa Kinoshita, Mitsuyasu Terashima, Yasushi Asakura, Takahiko Suzuki
Journal: Circulation (2012)

Background: Landmark techniques for percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) have contributed to the improvement of initial success of PCI of CTO lesions. However,...
Synthesis and Half-Life of a Serum Factor in Normal and Tumor-Bearing Animals 2
Authors: Mary L. Dolan, Byron Sudbury, Peter Ove
Journal: JNCI Journal of the National Cancer Institute (1976)

The synthesis and disappearance of a serum factor from the circulating blood of rats bearing Morris hepatomas 7777 or 7800 were described. We provided evidence that the factor was synthesized by the livers of normal rats and continued to be synthesized in tumor-bearing animals. Despite very low levels in the sera of tumor-bearing animals, the factor was synthesized at twice the rate in these animals compared to that in normal rats. The half-life of the serum protein factor in the circulating blood of normal and hepatoma-bearing animals was also compared. The half-life of the total serum protein was 2 days in normal rats and 2.9 days in hepatoma 7777-bearing animals. The half-life of the serum factor, on the other hand, was 23 hours in normal rats but only 9 hours in hepatoma-bearing rats. This rapid disappearance of the factor from the circulating blood, despite an increased synthesis, accounts for the complete absence of the factor in the sera of hepatoma-bearing animals with tumor weights larger than the liver weights.
Abstract 213: Physiogenomic Response to Prolonged Cardiac Arrest and Resuscitation: Hyporesponders Fail to Upregulate Certain Genes
Authors: James J Menegazzi, David D Salcido, Greggory J Housler, Deborah J Hollingshead, Haiwen Shi, James Lyons-Weiler
Journal: Circulation (2012)

Background: In our porcine laboratory studies of prolonged cardiac arrest and resuscitation we have observed that approximately one out of every four animals appears to be hyporesponsive to vasopressor drug therapy during CPR. These hyporesponsive animals fail to generate an increase in coronary perfusion pressure (CPP) sufficient to attain a return of spontaneous circulation (ROSC) and cannot be resuscitated. Some humans unexplainably fail resuscitation despite promising conditions (age, witnessed arrest, bystander CPR, rapid EMS response). We conducted this natural experiment in order to compare the physiogenomic responses of animals that were hyporesponsive, to those that responded as expected to vasopressor therapy. Hypothesis: We hypothesized that we would identify genes that were differentially expressed between the two groups (hyporesponders and normal responders). Methods: We sedated, anesthetized, and instrumented 14 female swine (mean mass 28.6 kgs). Micro-manometer tipped catheters were placed to measure CPP for determination of response status. Ventricular fibrillation (VF) was induced and untreated for 10 minutes, then CPR was begun. Two minutes later pressors were given (epinephrine 0.1 mg/kg and vasopressin 0.6 U/kg). At minute 15 the first rescue shock was delivered. Twenty-eight minutes after the induction of VF, femoral artery samples were harvested and snap-frozen. Gene expression was assessed on the Affymetrix Porcine Genome Array, and affected pathways were ordered with Pathway Express (with Impact Analysis of p&lt;0.05 considered significant). Results: We compared 4 hyporesponsive pigs to a sample of 5 normal responders. There were 213 differentially expressed genes affecting 10 pathways shown in the Table (with the apoptosis pathway at p=0.056). Conclusion: Hyporesponders differentially express genes that affect vasoregulation, myocardial contractility, calcium regulation and 7 other pathways.
Abstract 15182: Calibration and Feedback of Speckle Strain Measurement Improves Segmental Strain Concordance
Authors: Tomoko Negishi, Kazuaki Negishi, Krassimira Hristova, Koji Kurosawa, Satoshi Yuda, Bogdan A Popescu, Dragos Vinereanu, Paaladinesh Thavendiranathan, Martin Penicka, Manish Bansal, Nobuaki Fukuda, Goo-Yeong Cho, Stéphanie Seldrum, Thomas H Marwick
Journal: Circulation (2014)

Purpose: Inter-institutional agreement of imaging measurements is important in shared clinical management and in trials. 2D strain is sensitive to changes in LV function, automated and may be less variable than ejection fraction (EF), which is used widely but has inherent variability. We sought whether strain would have better concordance between different centers and that feedback from a calibration exercise would reduce the variability among institutions. Methods: 108 global longitudinal strain (GLS) measurements, calculated from 1944 segmental strains, were performed blindly by 21 experienced readers from 12 different institutes (5 Europe, 5 Asia, 1 North America and 1 Australia) in 6 cases. Intraclass correlation coefficients (ICCs) were used to determine concordance. All individual measurements were reviewed and some key points were identified to optimize strain measurement. After feedback, strain was remeasured and improvement of agreement sought using coefficient variance (CV) and mean difference (MD) from the reference standard. Results: GLS was -17.9±3.3%, while EF was 60±7%. The ICC in GLS (0.994 [95%CI 0.983, 0.999]) was better than that of 2DEF (0.928 [0.809, 0.988], p&lt;0.001) at baseline. Two main sources of discordance in GLS measurements were the width and location of regions of interest, especially at mitral annulus and apex. After feedback, re-measurement showed the CV (p=0.02) and MD (p=0.03) of segmental strain improved, but comparison of 2nd vs 1st GLS showed no changes of ICC (p=0.85), CV (p=0.80) or MD (p=0.92). Conclusions: Feedback significantly decreased segmental strain variability, but did not improve the concordance in GLS, which had better precision than EF at baseline.