tbuckley/cabot-search huggingface dataset:
GR 38032F (GR-C507/75): a novel compound effective in the prevention of acute cisplatin-induced emesis.
Authors: P J Hesketh, W K Murphy, E P Lester, D R Gandara, A Khojasteh, E Tapazoglou, G P Sartiano, D R White, K Werner, J M Chubb
Journal: Journal of Clinical Oncology (1989)

We evaluated, in a multi-center trial, the safety and efficacy of GR 38032F (GR-C507/75), a novel and selective serotonin antagonist, in preventing acute emesis in chemotherapy-naive patients receiving treatment with regimens containing high-dose cisplatin (greater than or equal to 100 mg/m2). Eighty-five patients were randomized to receive GR 38032F, 0.18 mg/kg, either every six or every eight hours for three doses, beginning 30 minutes before cisplatin. Patients were evaluated for emetic episodes (vomiting or retching) over a 24-hour period following cisplatin. All patients were evaluable for toxicity and 83 were evaluable for efficacy. The overall antiemetic response rate was 75% (55% complete response [CR], 20% major response). No difference in antiemetic control between the two administration schedules was noted. Patients with histories of heavy ethanol use had significantly better antiemetic control (74% CR) than modest or non-drinkers (33% CR). Toxicity of GR 38032F was modest and independent of administration schedule. The most common adverse events included mild hepatic transaminase elevations, self-limited diarrhea, dry mouth, headache, and mild sedation. Our data indicate that GR 38032F is a safe and effective agent in the control of acute cisplatin-induced nausea and vomiting. Additional trials exploring dosing, schedule, and comparison to standard antiemetic agents are indicated.
Dose Escalation Phase 2 Trial Of Carfilzomib Combined With Thalidomide and Low-Dose Dexamethason In Newly Diagnosed, Transplant Eligible Patients With Multiple Myeloma. A Trial Of The European Myeloma Network
Authors: Pieter Sonneveld, Emilie Asselberg-Hacker, Sonja Zweegman, Bronno van der Holt, Marie Jose Kersten, Edo Vellenga, Marinus van Marwijk Kooy, Okke de Weerdt, Sarah Lonergan, Antonio Palumbo, Henk Lokhorst
Journal: Blood (2013)
Molecular analysis of the responder satellite DNA in Drosophila melanogaster: DNA bending, nucleosome structure, and Rsp-binding proteins.
Authors: P Doshi, S Kaushal, C Benyajati, C I Wu
Journal: Molecular Biology and Evolution (1991)

The Responder (Rsp) locus of Drosophila melanogaster, the target locus of segregation distortion, is a satellite DNA array. This repeat array imparts some fitness advantage to the chromosomes bearing it. In this paper, we report the following three related molecular properties of this satellite repeat: (1) Sequence-directed curvature--On a polyacrylamide gel, Rsp-containing fragments migrate slower than would be predicted on the basis of their physical sizes. The extent of migration retardation correlates with the size and position of the Rsp sequence in a DNA fragment, suggesting that Rsp DNA is bent. The bending is shown to be affected by a DNA-binding drug (Hoechst 33258). (2) Nucleosome structure--Nucleosomes associated with Rsp repeats have an unusual spacing pattern. Instead of being spaced at approximately 190-bp intervals as is the bulk chromatin, they are separated at approximately 240-bp intervals, roughly the size of a dimeric Rsp repeat. The nucleosomal structure in the Rsp region is preferentially disrupted by Hoechst 33258, whereas the bulk chromatin appears to be insensitive to the drug. (3) Rsp-DNA binding proteins--Gel mobility-shift assays using nuclear extracts from pupae and end-labeled Rsp repeat demonstrate the presence of three distinct DNA-protein complexes. Competition assays suggest that these complexes are specific to the Rsp sequence, and two of these nucleoprotein complexes seem to be influenced by the presence of Hoechst 33258. The observed complexes are formed by nonhistone proteins of somatic origin and may be related to the normal functions of Rsp, rather than to the germ-line segregation distortion activities.
The use of cannabinoids (CBs) for the treatment of chemotherapy-induced peripheral neuropathy (CIPN): A retrospective review
Authors: J. Gingerich, D. Wadhwa, L. Lemanski, M. Krahn, P. J. Daeninck
Journal: Journal of Clinical Oncology (2009)

e20743 Background: CIPN is a common toxicity associated with the use of chemotherapy (CT) agents such as platinums, taxanes and vinca alkaloids. Patients (pts) may suffer from pain that adversely affects their quality of life, regardless of their disease trajectory. Preclinical research has shown CBs to be effective in preventing CIPN. CBs can be beneficial for cancer pain, although their specific benefit in pts with CIPN remains unknown. Methods: A retrospective chart review was conducted to identify all pts with CIPN treated with CBs at our institution between 7/07–10/08. Results: Eight pts were identified; 6 were male. Six pts had received platinum-based CT. Four had colon cancer. Four pts had metastatic disease. The median time to CIPN treatment (post-chemotherapy) was 4 months (0–84 months). All pts had 2+ neuropathy based on the NCI-CTC for Adverse Events. Pain improved in 7/8 pts with CB treatment. In those who responded, the improvement was as much as 7 points on an 11 point VAS. Two pts who transiently stopped treatment noted increased CIPN symptoms. Three pts eventually stopped treatment (1 due to side effects). Conclusions: Treatment with CBs appears to benefit some pts with CIPN. Further research is needed to explore the optimal use of CBs in pts with CIPN. No significant financial relationships to disclose.
European IPF Patient Charter: unmet needs and a call to action for healthcare policymakers
Authors: Francesco Bonella, Marlies Wijsenbeek, Maria Molina-Molina, Annette Duck, Rosalba Mele, Klaus Geissler, Wim Wuyts
Journal: European Respiratory Journal (2015)

Patient advocacy groups play an important role in supporting patients with chronic diseases and promoting better care. The aim of this patient–physician initiative was to gather perceptions from European idiopathic pulmonary fibrosis (IPF) patient advocacy groups regarding inequalities and unmet needs in IPF care, in order to develop a Patient Charter to advocate for better care. In total, 11 European patient advocacy groups were interviewed regarding the care of patients with IPF in their countries. Interview feedback was presented to a Working Group including patient advocacy group representatives and IPF specialists; key areas of agreement were developed into the European IPF Patient Charter. The interviews identified five key themes that fed into the final Charter: the need for improved diagnosis, treatment access, holistic care, disease awareness and palliative care. The final Charter was endorsed by patient advocacy groups and presented to 26 Members of the European Parliament in September 2014. It has received &gt;8900 signatures to date. This patient–physician initiative highlights the inequalities and unmet needs in IPF care across Europe, and demonstrates how this insight can inform the development of a Patient Charter, designed as a call to action for healthcare policymakers to drive improvement in European IPF care.
Serum albumin in patients on continuous ambulatory peritoneal dialysis--predictors and correlations with outcomes.
Authors: P G Blake, G Flowerdew, R M Blake, D G Oreopoulos
Journal: Journal of the American Society of Nephrology (1993)

Serum albumin (SA) is a powerful predictor of patient morbidity and mortality in hemodialysis, but data are limited for continuous ambulatory peritoneal dialysis (CAPD). SA was monitored in 76 new CAPD patients over 222 6-month periods and mean SA was correlated with morbidity and mortality during those periods. The influence of initial SA on duration of technique survival was also investigated. To determine which factors best predict SA, correlations with patient demographics and with 6-month measurements of dialytic dose, protein intake, and peritoneal transport were sought. Mean SA overall was 34.1 +/- 3.3 g/L, and mean initial SA was 33.4 +/- 3.1 g/L. Mean SA was lower in diabetics and in those aged 65 or over. Mean SA tended to increase during the first year on CAPD, and this increase was maintained, except in patients aged 65 or over, where it tended to revert to initial values. SA correlated with hospital days (r = -0.20; P < 0.005), fatigue index (r = -0.20; P < 0.005), nerve conduction (P < 0.001), and a variety of laboratory values, and lower SA was associated with technique failure (P < 0.03) and death (P < 0.07). Initial, as well as ongoing, SA was predictive of technique failure (P < 0.05) and Cox proportional hazards regression showed that this predictive power was independent of age, sex, diabetes, and other factors (P = 0.05). The strongest predictors of low SA by stepwise multiple regression were diabetes, a higher dialysate-to-plasma creatinine equilibration ratio, older age, lower body weight, and shorter time on CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)
Tumorigenicity of Simian Papovavirus SV40 and of Virus-Transformed Cells&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Asaria Ashkenazi, Joseph L. Melnick
Journal: JNCI Journal of the National Cancer Institute (1963)

The tumorigenicity of the simian papovavirus SV40 and of virus-transformed cells was investigated in hamsters. A genetically purified stock of the virus readily produced tumors in newborn hamsters, and the virus could be recovered from most tumors. About half the animals developed antibodies against the virus; those failing to make antibodies did not become tolerant to a later challenge of the virus. Virus-free tumors were transplanted serially in hamsters, but no virus could be recovered from the transplanted tumors. The recipient animals did not produce SV40 antibody when tested 2 to 3 months after the tumors appeared. SV40 virus transformed human fibroblast cultures derived from embryonic lung. Cells changed from fibroblastic to epithelioid. SV40 was produced by the infected lung fibroblasts, but the virus yield declined when the cells became epithelioid. The transformed cells failed to produce tumors when inoculated in the hamster cheek pouch. Transformation in vitro of hamster embryo cells was produced by SV40. The transformed cells produced tumors when inoculated in hamsters by various routes. No virus was recovered from these cells or from the tumors produced by them. The transformed cells produced soft, highly cellular, rapidly growing tumors. Metastases were found in tumor-bearing animals. The primary hamster tumors produced by inoculation of SV40 in newborn hamsters were hard, less cellular, and slow growing; no metastases were observed. The cells from the two types of tumors were similar, appearing as a pleomorphic undifferentiated sarcoma. The chief difference was in the cellularity of the tumors, the virus-induced primary neoplasm being less cellular than the one produced by the hamster embryo cells transformed in vitro. The cells from these tumors when grown in tissue culture and the transformed cells maintained for long periods in culture had the same appearance.
Improving cancer care by linking community cancer center physicians to breast cancer disease site-specific experts.
Authors: Patricia H. Hardenbergh
Journal: Journal of Clinical Oncology (2012)

70 Background: The goal of this project is to improve the quality of cancer care across the U.S. by connecting community cancer center radiation oncologists with highly specialized, disease site-specific radiation oncologists. Methods: We have developed a website named chartrounds.com that allows community radiation oncologist members to interact online in a peer review forum with disease site-specific specialists on a scheduled basis. At the conclusion of each session, participants are asked to complete a questionnaire which requests feedback on the quality and relevance of the session and the manner in which it might result in changes to their practice. Results: To date, 575 community radiation oncology physician members from 50 states have enrolled online. In the initial 18-month period, nine disease site-specific specialists have led 81 breast-specific chart rounds sessions with an average attendance ratio, during the past six months, of eight community physician members to one breast cancer disease site-specific specialist. From 309 initial responses, on a five-point Likert scale with five representing the greatest impact possible, the mean response to feedback questions is as follows: session quality; 4.7, time used effectively; 4.6, discussions relevant to daily practice; 4.7, session is likely to result in a change in practice; 4.0. More specifically, 139 members reported that they would make the following changes in their practice: change in clinical management of the radiation patient: 37%, change in the selection of patients for radiation: 22%, change in the technical delivery of radiation including target, field and dose adjustments: 20%. Conclusions: The chartrounds.com website appears to be making an impact on individual radiation oncology practices resulting in changes in management and the delivery of treatment to patients in community cancer centers. Future directions of this project are aimed at demonstrating how these changes may result in significant improvements in survival of breast cancer patients across the U.S. This work is funded by the Improving Cancer Care Grant of the ASCO Conquer Cancer Foundation supported by Susan G. Komen for the Cure.
Subcutaneous granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndrome: toxicity, pharmacokinetics, and hematological effects.
Authors: J A Thompson, D J Lee, P Kidd, E Rubin, J Kaufmann, E M Bonnem, A Fefer
Journal: Journal of Clinical Oncology (1989)

The toxicity, pharmacokinetics, and hematologic effects of granulocyte-macrophage colony-stimulating (GM-CSF) were studied in a phase I/II trial of 16 patients with myelodysplastic syndrome (MDS). The GM-CSF was administered subcutaneously (SC) daily so as to achieve prolonged blood levels and to establish an outpatient treatment regimen. Four dose levels were administered for ten days: 0.3 microgram/kg/d (three patients), 1.0 microgram/kg/d (three), 3.0 micrograms/kg/d (four), and 10.0 micrograms/kg/d (six). The most common toxicities were fever and a flu-like syndrome, which were dose-dependent. The maximum-tolerated dose was 10.0 micrograms/kg/d, which induced severe rigors (two patients), fever greater than 40 degrees C (one), severe bronchospasm (one), and WBC 60,000 (one). In one patient, refractory anemia with excess blasts in transformation (RAEB-T) progressed to acute nonlymphocytic leukemia after two doses of GM-CSF, and the patient died of leukemia that did not respond to chemotherapy. After doses of 3.0 and 10.0 micrograms/kg, serum GM-CSF levels peaked at 3.8 to 6.3 hours, and persisted for 14 and 24 hours, respectively. Circulating granulocytes (neutrophils and bands) increased in a dose-dependent manner, as 11 of 13 patients who received greater than or equal to 1.0 microgram/kg/d responded with a two- to 194-fold increase. Although the neutrophils usually returned to pretreatment levels shortly after stopping GM-CSF, two patients continue to exhibit an elevation of neutrophils for 6 months. Dose-related increases in circulating monocytes and eosinophils were also noted. Transient increases in platelet and reticulocyte counts were observed in two and three patients, respectively. Five of the 16 patients later received maintenance GM-CSF at 3 micrograms/kg/d for 2 to 9 weeks. All showed a dramatic increase in neutrophils after 2 weeks. Thereafter, despite continued therapy, the neutrophil count in four patients declined markedly. In conclusion, GM-CSF is well tolerated by the SC route and induces striking, but usually temporary, improvement in the neutropenia of MDS. Larger prospective phase III trials will determine the duration of hematologic responses and the impact on infection, morbidity, and mortality.
&lt;TITLE&gt;Pedestrian Safety&lt;/TITLE&gt;
Authors: Janet M Torpy, Cassio Lynm, Richard M Glass
Journal: JAMA (2002)

Pedestrian SafetyW ith so many vehicles on the road, pedestrians need to be aware of their surroundings and the "rules of the road" to avoid being hit by a car or other motor vehicle.In 2000, over 4700 US pedestrians were killed and 78 000 injured when struck by a motor vehicle.Older pedestrians are at especially high risk.Nighttime is a particularly dangerous time because visibility is reduced, and both pedestrians and drivers may be more likely to have been drinking alcohol.The November 6, 2002, issue of JAMA includes a study reporting that the risk of older pedestrians being struck by a car or truck was particularly high at marked crosswalks with no traffic signal or stop sign.This might occur because marked crosswalks may give older pedestrians a false sense of security.
Role of time to progression as a surrogate marker for overall survival in patients with advanced non-small-cell lung cancer (NSCLC)
Authors: K. Hotta, K. Kiura, Y. Fujiwara, N. Takigawa, M. Tabata, H. Ueoka, M. Tanimoto
Journal: Journal of Clinical Oncology (2008)

8022 Background: With the increasing number of active compounds available both in the first- and second-line settings for advanced NSCLC, it is useful to evaluate whether surrogate endpoints can replace overall survival as the primary end point in randomized trials for rapid and efficient assessment of their efficacy. Here, we examined the association between the difference in median survival time (MST) and that in time to progression (TTP) through a literature survey. Methods: We identified median TTP (MTTP) and MST from each phase III trial of first-line treatment in advanced NSCLC and analyzed them for a linear regression analysis. The MST ratio in each trial was defined as the ratio of the MST in the investigational arm to that in the reference arm. The MTTP ratio in each trial was defined similarly. Results: A total of 79 trials involving 31,965 advanced NSCLC patients were identified to have data regarding MST and MTTP. There was a moderate correlation between the difference in MST and that in MTTP among the trials (p<0.001; R2=0.400). The multiple stepwise regression analysis revealed the MTTP ratio was a sole independent predictive factor for the MST ratio (regression coefficient=0.330, p<0.001). When trials were limited to those with larger sample sizes (a total of 32 trials with 500 or more randomized patients), a strong association was observed (p<0.001; R2=0.718). In the validation model, the actual MST ratios fell within the 95% prediction intervals among 26 (81.3%) of the 32 trials with larger sample sizes. Conclusions: There was only a modest correlation between the MST and MTTP ratios in phase III trials of first-line chemotherapy for advanced NSCLC, while there was a stronger association among trials with larger sample sizes, indicating that TTP may be a useful surrogate marker in such situations. Our findings raise important issues that should be further addressed in future studies. No significant financial relationships to disclose.
Patient-specific vaccines derived from proliferating autologous tumor cell lines and dendritic cells: Results of a phase II trial in metastatic melanoma
Authors: R. O. Dillman, S. R. Selvan, P. M. Schiltz, C. DePriest, C. Peterson, C. DeLeon, E. F. McClay, N. M. Barth, P. F. Sheehy, K. Allen
Journal: Journal of Clinical Oncology (2007)

8555 Background: Patient-specific vaccines utilizing proliferating tumor cells, or tumor stem cells, may be the ideal products for active specific immunotherapy. Methods: Eligible patients had recurrent or metastatic melanoma from which a cell line was established, expanded to 200 million cells, incubated with interferon-gamma, irradiated and cryopreserved. Autologous dendritic cells (DC) were derived from peripheral blood mononuclear cells cultured in IL-4 and GM-CSF. DC were incubated with the irradiated tumor cells, then cryopreserved in 20- million-cell aliquots, which were thawed, washed and suspended in 500 micrograms of GM-CSF for injection. Treatment consisted of s.c. injections weekly × 3, then monthly × 5 in a 2-stage phase II trial with two stratifications. Patients were characterized as having objectively measurable disease (OMD) or non-measurable disease (NMD). Plans were to enroll 30 to 80 patients: 15 to 40 with OMD, 15 to 40 with MD. Objectives were to determine safety, frequency of conversion of delayed type hypersensitivity (DTH) reactions to irradiated autologous tumor cells, objective response rate (ORR) using RECIST criteria, progression-free survival (PFS), overall survival (OS), and comparison to a historical control group. Results: Between January 2001 and April 2006, 55 patients were enrolled; 53 were eligible and evaluable. The 30 men and 23 women had a median age of 50 years; 15 had OMD and 38 NMD. Patients received an average of 7.4 vaccinations out of a possible 8. Treatment was well- tolerated. 25% had a positive tumor DTH test: 1 at baseline, 7 after 3 injections, 5 after 8 injections. ORR was 0/15. Follow up for the 39 surviving patients ranges from 7 to 67 months with a median of 30 months. Median PFS is 7.1 months with 24 patients remaining progression-free. Only 14 patients have died; median OS has not been reached. 5-year projected survival is 70%; 20 patients are alive 2.5 to 5.5 years from start of vaccine. OS is better than observed for 48 comparable patients that we treated previously in a trial with irradiated tumor cells without DC (p=0.016). Conclusion: This patient-specific vaccine approach is feasible, safe, associated with encouraging survival, and warrants further investigation. No significant financial relationships to disclose.
Vocal Fold Tissue Regeneration: Investigation of the Viability, Adhesion, and Migration of Human Fibroblasts in a Hyaluronic Acid/Gelatin Microgel‐Reinforced Composite Hydrogel for Vocal Fold Tissue Regeneration (Adv. Healthcare Mater. 2/2016)
Authors: Hossein K. Heris, Jamal Daoud, Sara Sheibani, Hojatollah Vali, Maryam Tabrizian, Luc Mongeau
Journal: Advanced Healthcare Materials (2016)

On page 255, M. Tabrizian, L. Mongeau, and co-workers show how human fibroblast cells establish effective adhesion to a scaffold biomaterial consisting of crosslinked hyaluronic acid–gelatin composite microgels. The higher magnification image shows the connection of β1 integrin with the cells' actin filaments and with the microgels' gelatin molecules. Integrins used in the cover art were made from modifications to 2VDO and 3FCS structures from protein data bank.
Modular Assembly Approach to Engineer Geometrically Precise Cardiovascular Tissue
Authors: Benjamin W. Lee, Bohao Liu, Adam Pluchinsky, Nathan Kim, George Eng, Gordana Vunjak‐Novakovic
Journal: Advanced Healthcare Materials (2016)

This modular assembly approach to microfabricate functional cardiovascular tissue composites enables quantitative assessment of the effects of microarchitecture on cellular function. Cardiac and endothelial modules are micromolded separately, designed to direct cardiomyocyte alignment and anisotropic contraction or vascular network formation. Assembled cardiovascular tissue composites contract synchronously, facilitating the use of this tissue-engineering platform to study structure–function relationships in the heart. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.