tbuckley/cabot-search huggingface dataset:
Randomized, surgical adjuvant clinical trial of recombinant interferon alfa-2a in selected patients with malignant melanoma.
Authors: E T Creagan, R J Dalton, D L Ahmann, S H Jung, R F Morton, R M Langdon, J Kugler, L J Rodrigue
Journal: Journal of Clinical Oncology (1995)

PURPOSE We conducted a randomized prospective trial in selected patients with fully resected high-risk stage I and II malignant melanoma. PATIENTS AND METHODS Interferon alfa-2a (IFN-alpha 2a) 20 x 10(6) U/m2 was administered three times each week for 12 weeks by the intramuscular route. Both the treatment group (n = 131) and the control group (n = 131) were evenly balanced with regard to relevant prognostic discriminants. RESULTS The median disease-free survival (DFS) time was 2.4 years for the IFN-alpha 2a group and 2.0 years for the observation group (log-rank P = 0.19). The median survival times were 6.6 years for IFN-alpha 2a and 5.0 years for observation (log-rank P = .40). For stage I patients (n = 102), there was no apparent therapeutic advantage from IFN-alpha 2a therapy. The DFS for stage II patients was a median of 10.8 months in the control group versus 17 months in the treatment group. The overall survival time was 4.1 years for the treatment group versus 2.7 years for the control group. The differences in DFS for stage II patient were significant in a Cox model. These results must be interpreted cautiously because of subset analysis. A severe flu-like toxicity occurred in 44% of patients, 13% lost at least 10% of their baseline weight, and 45% experienced a worsening of Eastern Cooperative Oncology Group (ECOG) performance score. CONCLUSION Our findings indicate trends that suggest a possible benefit for selected patients with high-risk malignant melanoma. The results will require further study in a larger patient population for confirmation.
Preliminary results from a phase II study of infusional 5-FU, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for metastatic colorectal cancer (mCRC)
Authors: S. Kopetz, J. L. Abbruzzese, C. Eng, R. B. Adinin, J. Morris, R. A. Wolff, E. Lin, D. Z. Chang, P. Hoff, K. Bogaard
Journal: Journal of Clinical Oncology (2006)

3579 Background: Irinotecan (I) plus bolus 5-FU (F) and leucovorin (L) comprise the IFL regimen, a very active treatment in mCRC when combined with bevacizumab (B). The response rate (RR) for IFL-B given as first-line treatment is 45%, with a median progression-free survival (PFS) of 10.6 months and a median survival of 20.3 months. The IFL regimen is now considered inferior to infusional 5-FU regimens, such as FOLFIRI, which have less toxicity and improved efficacy. Methods: We designed a 43 patient (pt), single-arm phase II trial of FOLFIRI-B with B (5mg/kg), I (180mg/m 2 ), bolus of F (400mg/m 2 ) and L (400mg/m 2 ) followed by a 46-hour infusion of F (2400mg/m 2 ), with a primary endpoint of progression-free survival (PFS). Chemotherapy naïve mCRC patients (pts) with adequate organ function and performance status 0–2 received B alone on Day minus 14, starting FOLFIRI + B on Day 1. DCE-MRI and laboratory correlates were completed before and after B alone and cycle 1. Once cycle is equivalent to two weeks. Results: 21 pts, median age 59 y/o (range 26–75), M:F = 15:6, 4 with prior F in adjuvant setting, have been enrolled to date. 20 pts are evaluable for response. One pt is too early. A total of 215 cycles have been administered (median 11). Median PFS has not been reached after a median follow-up of 8 months. By intent-to-treat analysis, there were 14 PRs (70%), and 5 (25%) pts with stable disease observed (including 1 unconfirmed PR). PRs were observed from 9 to 35 weeks after the first cycle (median: 18 weeks). 9 pts remain on treatment (1–12 months); 12 pts are off study (3 for progressive disease, 1 withdrew, 4 sent for curative surgery, 2 for toxicity, 2 sent for surgery unrelated to cancer). Toxicity included 10 cases of grade 3 neutropenia, including 1 febrile neutropenia, 4 venous thrombi, and 6 cases of hypertension requiring medication change. One pt included in the analysis developed peritonitis, considered a possible microperforation, after B alone and never received FOLFIRI. No ≥ grade 3 diarrhea was observed. Analysis of correlative studies will be presented at a later date. Conclusion: Our preliminary results indicate that FOLFIRI-B is well tolerated and an excellent choice as a first-line treatment for mCRC. [Table: see text]
Role of common cytokine receptor γ chain (γc)– and Jak3-dependent signaling in the proliferation and survival of murine mast cells
Authors: Kotaro Suzuki, Hiroshi Nakajima, Norihiko Watanabe, Shin-ichiro Kagami, Akira Suto, Yasushi Saito, Takashi Saito, Itsuo Iwamoto
Journal: Blood (2000)
Euarchontan Opsin Variation Brings New Focus to Primate Origins
Authors: Amanda D. Melin, Konstans Wells, Gillian L. Moritz, Logan Kistler, Joseph D. Orkin, Robert M. Timm, Henry Bernard, Maklarin B. Lakim, George H. Perry, Shoji Kawamura, Nathaniel J. Dominy
Journal: Molecular Biology and Evolution (2016)

Debate on the adaptive origins of primates has long focused on the functional ecology of the primate visual system. For example, it is hypothesized that variable expression of short- (SWS1) and middle-to-long-wavelength sensitive (M/LWS) opsins, which confer color vision, can be used to infer ancestral activity patterns and therefore selective ecological pressures. A problem with this approach is that opsin gene variation is incompletely known in the grandorder Euarchonta, that is, the orders Scandentia (treeshrews), Dermoptera (colugos), and Primates. The ancestral state of primate color vision is therefore uncertain. Here, we report on the genes (OPN1SW and OPN1LW) that encode SWS1 and M/LWS opsins in seven species of treeshrew, including the sole nocturnal scandentian Ptilocercus lowii. In addition, we examined the opsin genes of the Central American woolly opossum (Caluromys derbianus), an enduring ecological analogue in the debate on primate origins. Our results indicate: 1) retention of ultraviolet (UV) visual sensitivity in C. derbianus and a shift from UV to blue spectral sensitivities at the base of Euarchonta; 2) ancient pseudogenization of OPN1SW in the ancestors of P. lowii, but a signature of purifying selection in those of C. derbianus; and, 3) the absence of OPN1LW polymorphism among diurnal treeshrews. These findings suggest functional variation in the color vision of nocturnal mammals and a distinctive visual ecology of early primates, perhaps one that demanded greater spatial resolution under light levels that could support cone-mediated color discrimination.
Hepatic resection of initially unresectable liver metastases from colorectal cancer after hepatic arterial infusion of oxaliplatin and systemic 5-fluorouracil and leucovorin
Authors: D. Goere, I. Dsehais, T. de Baere, V. Boige, D. Malka, S. Bonnet, C. Dromain, D. Elias, M. Ducreux
Journal: Journal of Clinical Oncology (2009)

e15015 Background: About 80% of patients (pts) presenting colorectal liver metastases (CRLM) are initially unresectable. A subgroup will become eligible for surgery after chemotherapy administration. Efficacy of hepatic arterial infusion (HAI) of oxaliplatin with systemic 5-Fluorouracil and leucovorin (LV5FU2) in with unresectable CRLM was previously demonstrated. This study was performed to evaluate the resection rate of pts with initially unresectable CRLM after oxaliplatin HAI and systemic LV5FU2. Methods: Patients treated in our hospital with oxaliplatin HAI and systemic LV5FU2 for unresectable CRLM from May 1999 to May 2007 were analyzed. Inclusion criteria were : unresectable CRLM, no extensive extrahepatic disease, HAI performed in our hospital, minimal follow up of 24 months. Eighty-seven pts were selected from a prospective database Results: Hepatic arterial infusion was delivered after previous systemic chemotherapy failure in 69 pts (80%). Main criterion for unresectability was massive liver involvement (80%). CRLM were synchronous and bilateral in respectively 85% and 90% of pts. The median number of oxaliplatin HAI cycles was 8 (0- 25). Thirty-one pts experienced technical problems with the arterial catheter, which was responsible for HAI withdrawal in seven. A total of 23 pts (26.4%) were operated, leading to resection and/or radiofrequency ablation of CRLM in 21 pts. No post-operative mortality was observed and the morbidity rate was 30%. The 3-year overall survival for patients operated was 72.5% versus 12% for non operated pts (p&lt;0.0001). After a median follow-up of 75 months [24–118], intra-hepatic recurrence occurred in 10 pts. Conclusions: Hepatic artery infusion of oxaliplatin and systemic LV5FU2 increase the resectability rate in pts with advance CRLM even after previous systemic chemotherapy failure. Future studies combining oxaliplatin HAI and recent IV chemotherapy are needing to achieve an increase disease-free survival. No significant financial relationships to disclose.
Jun N-terminal Kinase: a potential target for the treatment of head and neck squamous cell carcinoma (HNSCC)
Authors: Neil D. Gross, Jay O. Boyle, Baoheng Du, Agnieszka Lantowski, Valerie Yaremenko, Babette B. Weksler, Kotha Subbaramaiah, Andrew J. Dannenberg
Journal: Cancer Research (2005)

2564   Jun N-terminal Kinase (JNK) is a stress-activated protein kinase responsible for the phosphorylation of c-Jun, a component of the activator protein-1 (AP-1) transcription factor complex. Changes in JNK or AP-1 activity can potentially affect a range of processes that are important for tumor growth including cell proliferation and angiogenesis. This preclinical study was carried out to investigate whether JNK is a potential target for treating HNSCC. Initially, JNK activity was evaluated in twenty paired samples (tumor vs. adjacent normal) of human HNSCC. Increased JNK activity was observed in >90% of the tumor samples. Subsequently, a HNSCC (1483 cell line) xenograft model was used to evaluate the anti-tumor activity of SP600125, a selective inhibitor of JNK. Treatment of mice bearing HNSCC xenografts with SP600125 (50 mg/kg/day) resulted in >60% inhibition of tumor growth relative to vehicle-treated animals [p in vitro  studies to characterize the growth inhibitory and anti-angiogenic effects of SP600125. Treatment with SP600125 led to both dose- and time-dependent growth inhibition of 1483 cells. Growth inhibition was a consequence of reduced DNA synthesis and slowing of cell cycle progression through the S and G2 phases. To define the anti-angiogenic effects of SP600125, both 1483 tumor cells and human endothelial cells were employed. Treatment of 1483 cells with SP600125 caused a dose-dependent reduction in the production of VEGF. Inhibition of JNK activity also inhibited human microvascular endothelial cell proliferation and impaired endothelial cell capillary tube formation. Thus, SP600125-mediated inhibition of JNK activity appears to suppress angiogenesis via effects on both tumor cells and endothelial cells. Taken together, the results of this study provide a strong rationale for evaluating whether selective inhibitors of JNK activity will have a role in the treatment of HNSCC.
The diagnostic dartboard: is the bullseye a correct pathoanatomical diagnosis or to guide treatment?
Authors: S I Docking, J Cook, E Rio
Journal: British Journal of Sports Medicine (2016)

It is a very human trait to try and rationalise our complicated world by placing things into distinct groups. There are countless examples where this is the case; good and evil, believers and non-believers, the politically left and right. While it aids our decision-making process, there are some negatives in classifying the world in this way, especially in sports medicine.

Diagnosis of conditions/diseases in patients is the cornerstone of clinical sports medicine. Every clinician aims to take an extensive history and perform clinical tests to accurately diagnose the condition, and then to prescribe the most appropriate intervention. A number of publications have quantified the accuracy (number of correct diagnoses, both negative and positive for the condition, divided by the total number of participants), sensitivity (number of positive diagnoses correctly identified divided by the total number of positive participants) and specificity (number of negative diagnoses correctly identified divided by the total number of negative participants) of various clinical tests in a multitude of conditions. However, the majority of these studies need to be viewed with caution due to a number of methodological issues.

To …
Sustained viral load and ALT reduction following 48 weeks of entecavir treatment in subjects with chronic hepatitis B who have failed lamivudine.
Authors: Ting-Tsung Chang, S Hadziyannis, J Cianciara, M Rizzeto, E Schiff, G Pastore, K Klesczewski, G Denisky, D DeHertogh, R Hindes
Journal: Hepatology (2002)
Abstract P079: Disparities in Heart Failure in Older Age: Do Individual or Neighbourhood Measures of Deprivation Affect Incidence Over a 10-Year Follow-up?
Authors: Sheena Ramsay, P H Whincup, R W Morris, A.O. Papacosta, L T Lennon, S G Wannamethee
Journal: Circulation (2015)

Background: Few studies have examined the prospective associations between socioeconomic measures and incident heart failure, and in particular effects of neighbourhood deprivation. The aim of this study was to investigate the association of socioeconomic measures (individual and neighbourhood-level) with incident heart failure in older adults and to examine possible underlying pathways. Methods: A socially and geographically representative cohort of men aged 60-79 years in 1998-2000 from 24 British towns was followed for 10 years for incident heart failure (fatal and non-fatal based on death certificates and doctor-diagnosis). Individual-level socioeconomic measures included longest-held occupational social class, education, pension (state only or state with private), and amenities (car and house ownership, access to central heating) - a cumulative score of adverse socioeconomic measures from 0 to ≥4 was used. Index of multiple deprivation (IMD) was the small area-level socioeconomic measure (based on income, employment, health, housing, education, access to services and crime) grouped into quintiles of increasing deprivation. Prevalent myocardial infarctions and heart failures were excluded.Results: Among 3839 men, 232 incident cases of heart failure occurred over 10 years. Heart failure risk increased with increasing cumulative score of adverse (individual-level) socioeconomic measures (p for trend=0.0006). Compared to men with a score of 0, the hazard ratio for men with a score of ≥4 was 2.19 (95%CI 1.34-3.55) which weakened to 1.99 (95%CI 1.16-3.45), but remained significant after adjusting for neighbourhood deprivation (IMD), systolic blood pressure, body mass index, smoking, HDL-cholesterol, diabetes and lung function. Adjustment for left ventricular hypertrophy, atrial fibrillation, heart rate and renal function made little difference. Further adjustment for C-reactive protein, von Willebrand Factor and plasma vitamin C slightly weakened the hazard ratio to 1.78 (95%CI 1.01-3.13). Hazard ratio per IMD quintile (neighbourhood deprivation) was 1.04 (95%CI 0.95-1.14). Conclusions: Disparities in heart failure in older populations need to be addressed - the risk of heart failure in older age was greater in the lowest socioeconomic groups, which was only partly explained by established and novel risk factors for heart failure. This increased risk of heart failure according to individual-level socioeconomic measures was independent of neighbourhood-level deprivation. Neighbourhood level deprivation does not in itself appear to influence risk of heart failure.
Reply
Authors: Eloisa Arbustini, Navneet Narula, G. William Dec, K. Srinath Reddy, Barry Greenberg, Sudhir Kushwaha, Thomas Marwick, Sean Pinney, Riccardo Bellazzi, Valentina Favalli, Christopher Kramer, Robert Roberts, William A. Zoghbi, Robert Bonow, Luigi Tavazzi, Valentin Fuster, Jagat Narula
Journal: Journal of the American College of Cardiology (2014)
Abstract 13691: Right Ventricular Remodeling Post MitraClip Insertion for Severe Mitral Regurgitation - Single Centre Echocardiographic Study
Authors: Kalilur Anvardeen, Eric Yamen, Jurgen Passage, Chris Finn, Brendan McQuillan
Journal: Circulation (2014)

Introduction: Percutaneous mitral valve repair (Mitraclip) has expanded treatment options for high risk surgical patients with severe mitral regurgitation (MR). Hypothesis: The impact of amelioration of MR by Mitraclip on right ventricular (RV) remodeling and the pulmonary vasculature has received limited investigation. Methods: We undertook a prospective evaluation of consecutive patients who underwent Mitraclip insertion at our centre. Transthoracic echocardiograms were performed pre Mitraclip, 1 day, 1 month, 6 months and 12 months post Mitraclip procedure. We assessed right ventricular (RV) size, fractional area change (FAC), Myocardial performance index (MPI), right atrial (RA) area, left ventricular ejection fraction (LVEF), and estimated pulmonary artery systolic pressure (PASP) from the tricuspid regurgitant spectral Doppler signal according to published ASE guidelines. Results: Twenty-nine patients underwent Mitraclip procedure from March 2011 to June 2013. Six patients were excluded from 12 month analysis because of incomplete data (2 patients), insertion of a LV assist device (1), and mortality (3), Among the 23 study patients, mean age was 73 y (range 52 to 85). The following table shows the mean values and standard errors with significant differences indicated in * (p&lt;0.05), ** (p&lt;0.01) Linear mixed effects models were used to compare pre treatment measurements with post treatment measurements. Conclusion: Right ventricular function by FAC and MPI improved post Mitraclip. Pulmonary artery pressures also improved although the benefit appeared limited to 6 months post procedure. We observed no clear change in other parameters of right heart function or chamber size. Larger long term studies are required to evaluate these results.
Usefulness of the On-Line Data Base CANCERLIT: An Evaluation Study Based on Consecutive Searches in CANCERLIT and MEDLINE for Oncologists
Authors: E Kjellander, P O Olsson, E Zajicek
Journal: JNCI Journal of the National Cancer Institute (1985)

Two on-line data bases of the National Library of Medicine, CANCERLIT and MEDLINE, were evaluated in a user-oriented study for their usefulness for oncologists in cancer research and in clinical practice. The CANCERLIT data base was preferred for 12 of 16 literature searches requested by oncologists, and in 4 instances no preference was indicated. The implications of the study are discussed with regard to data base content and user preferences.
3-D non-coplanar conformal radiotherapy compared to traditional beam arrangements for the adjuvant treatment of gastric cancer
Authors: V. Soyfer, B. Corn, A. Melamud, S. Alani, H. Tempelhof, R. Agai, A. Shmueli, A. Figer, F. Kovner
Journal: Journal of Clinical Oncology (2007)

15145 Background: The Current standard of adjuvant treatment for gastric cancer following curative resection is concurrent administration of radiation and 5FU-based chemotherapy (INT0116). Radiation fields are often arranged as AP-PA opposed parallel fields with general recommendations for sparing at least two thirds of one kidney. In the current trial we investigated whether a better radiation distribution is achievable with 3-D conformal approaches as opposed to classical AP-PA fields. Methods: Nineteen patients with adenocarcinoma of stomach were treated by adjuvant chemoradiotherapy using a non-coplanar four field arrangement. In each case parallel planning by AP-PA arrangement and four fields “box was carried out and the generated plans were subsequently compared with dose volume histograms (DVH). Adequate coverage of the CTV was the basis for a comparison between other planning parameters. Separate analysis was performed not for right and left kidney but rather for kidneys exposed to higher and lower doses in each patient (since kidney dose is mostly a function of tumor location inside the stomach and respective nodal drainage). Mean dose of irradiation (MD) and percentage of kidney volume receiving radiation over 20 Gy (V20) were registered. Statistical analysis was performed by 2-tailed T-test. Results: The clinical target volume was adequately covered in all three plannings. In the “higher dose” kidneys group all the differences were statistically significant with the benefit of 3-D plan. In the “lower dose” kidneys group MD differences didn’t reach the level of statistical significance, while V20 data showed statistically significant benefit for 3-D plan. These data indicate that even when the mean doses of radiation are similar, 3-D planning can result in better distribution within the organ - thereby reducing the percentage of organ receiving dose above 20 Gy. DVH of spine was significantly better in 3-D planning. The exposure of liver was minimal in AP-PA technique. Conclusion: Noncoplanar 3-D based conformal planning for postoperative radiation therapy of gastric cancer provides the best results regarding kidney and spinal cord exposure with adequate CTV coverage. No significant financial relationships to disclose.
Predictive value of serum MALDI-TOF proteomic profiling from patients treated with erlotinib and bevacizumab for survival in patients with non-small cell lung cancer (NSCLC) treated with erlotinib alone
Authors: T. P. Dang, J. S. Salmon, H. Chen, S. Chen, J. W. Lee, A. B. Sandler, R. S. Herbst, J. Brahmer, D. P. Carbone, Y. Shyr
Journal: Journal of Clinical Oncology (2008)

11014 Background: A multicenter phase I/II study found that inhibition of VEGF and EGFR with the combination of bevacizumab and erlotinib had significant antitumor efficacy in NSCLC (Herbst, et al JCO 2005). We undertook a pilot project to determine if Matrix-Assisted Laser Desorption/Ionization- Time of Flight Mass Spectrometry (MALDI-TOF MS) proteomic analysis of pretreatment patient serum could be used to develop a profile predictive of improved time to progression and overall survival after treatment with the erlotinib and bevacizumab. Methods: Pretreatment serum was available for 35 of 40 patients with advanced NSCLC treated with bevacizumab and erlotinib. MALDI-TOF mass spectra were obtained with a Voyager-DE STR instrument (PerSeptive Biosystems) and the raw spectra were calibrated, baseline-corrected, and normalized prior to analysis. A Compound Covariate based Cox PH model (Tukey, CCT 1993) was fit to the normalized intensities at each m/z value to evaluate correlation with OS and PFS while accounting for replicate sample variability. Results: The reproducibility and variability were tested in total of 276 spectra from 35 samples. Eleven peaks, or distinct m/z regions, were considered to be predictive of outcome using Cox proportional hazard model (training data: p =0.0006 for OS; p=0.004 for PFS ). The proteomic signature obtained was able to predict OS and PFS outcome when applied to samples from a blinded test set of patients treated with erlotinib alone on ECOG 3503 using Cox PH model (n = 82, p < 0.0001 and p=0.0018 respectively) but not from the Vanderbilt cohort that was treated with chemotherapy alone (n=61, p=0.128). Conclusions: MALDI-TOF MS proteomic analysis of pretreatment serum was able to identify protein/peptide expression patterns that predicted survival in patients treated with erlotinib and bevacizumab and independently predicted survival in patients treated with erlotinib, but not those treated with chemotherapy alone. To further confirm these results, we will test this model using the recently completed randomized phase II trial comparing chemotherapy with/without bevacizumab and erlotinib plus bevacizumab (Herbst, et al JCO 2007). No significant financial relationships to disclose.