tbuckley/cabot-search huggingface dataset:
Novel prime-boost combinations of PSMA-based vaccines for prostate cancer
Authors: J. P. Gardner, R. J. Durso, S. Jacques, R. Arrigale, M. Maughan, G. P. Donovan, N. Schülke, R. J. Israel, W. C. Olson
Journal: Journal of Clinical Oncology (2005)

2572 Background and Methods The development of vaccination strategies targeted to tumor antigens holds great promise for cancer therapy. Prostate-specific membrane antigen (PSMA) is an attractive candidate self-antigen for vaccination based on its expression signature. PSMA is abundantly expressed on the surface of prostate cancer cells and on the neovasculature of a wide array of other tumors, but PSMA has limited expression in normal extraprostatic tissues. In prostate cancer, PSMA expression increases with disease progression, becoming highest in high-grade, metastatic, hormone-refractory disease. Our main goals are to overcome tolerance to PSMA by active immunization and to induce recognition and rejection of tumor cells expressing PSMA. We are investigating non-replicating vaccine replicon particles (VRP) based on the alphavirus, Venezuelan equine encephalitis virus. VRP have demonstrated potency in animal models, and infect cells in the lymph nodes where the replicon drives production of large quantities of the heterologous antigen. Robust immune responses can be further amplified by VRP-induced cell apoptosis leading to cross-priming. We are also evaluating a complementary purified protein vaccine based on a novel recombinant soluble PSMA (rsPMSA) immunogen both alone and with VRP in prime-boost regimens. Results When used as single immunogens, VRP encoding full-length human PSMA elicited vigorous, durable Th1-biased cellular and humoral responses in normal BALB/c mice, whereas rsPSMA vaccines induced high levels of Th2-biased antibodies. We have now extended this analysis to human HLA-A2 transgenic mice, a more pertinent model for quantification of human Class I-restricted cellular responses, and to prime-boost regimens. Mice were immunized with VRP alone or in combination with rsPSMA boosts. PSMA-specific immune responses were measured with a panel of cellular and humoral immunoassays, including ELISPOT and intracellular cytokine staining for IFN-γ and IL-4 in T cell subsets. Conclusions Based on these translational findings, the rsPSMA protein vaccine has been advanced into a dose-escalating Phase I clinical trial in advanced prostate cancer, while the VRP-PSMA vaccine is in late-stage preclinical testing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AlphaVax, PSMA Development Company, LLC
Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer.
Authors: J Baselga, D Tripathy, J Mendelsohn, S Baughman, C C Benz, L Dantis, N T Sklarin, A D Seidman, C A Hudis, J Moore, P P Rosen, T Twaddell, I C Henderson, L Norton
Journal: Journal of Clinical Oncology (1996)

PURPOSE Breast cancer frequently overexpresses the product of the HER2 proto-oncogene, a 185-kd growth factor receptor (p185HER2). The recombinant humanized monoclonal antibody (rhuMAb) HER2 has high affinity for p185HER2 and inhibits the growth of breast cancer cells that overexpress HER2. We evaluated the efficacy and toxicity of weekly intravenous administration of rhuMAb HER2 in patients with HER2-overexpressing metastatic breast cancer. PATIENTS AND METHODS We treated 46 patients with metastatic breast carcinomas that overexpressed HER2. Patients received a loading dose of 250 mg of intravenous rhuMAb HER2, then 10 weekly doses of 100 mg each. Patients with no disease progression at the completion of this treatment period were offered a maintenance phase of 100 mg/wk. RESULTS Study patients had extensive metastatic disease, and most had received extensive prior anticancer therapy. Adequate pharmacokinetic levels of rhuMAb HER2 were obtained in 90% of the patients. Toxicity was minimal and no antibodies against rhuMAb HER2 were detected in any patients. Objective responses were seen in five of 43 assessable patients, and included one complete remission and four partial remissions (overall response rate, 11.6%; 95% confidence interval, 4.36 to 25.9). Responses were observed in liver, mediastinum, lymph nodes, and chest wall lesions. Minor responses, seen in two patients, and stable disease, which occurred in 14 patients, lasted for a median of 5.1 months. CONCLUSION rhuMAb HER2 is well tolerated and clinically active in patients with HER2-overexpressing metastatic breast cancers that had received extensive prior therapy. This is evidence that targeting growth factor receptors can cause regression of human cancer and justifies further evaluation of this agent.
HIV-specific CD8+ T cells and HIV eradication
Authors: R. Brad Jones, Bruce D. Walker
Journal: Journal of Clinical Investigation (2016)

After the success of combination antiretroviral therapy (cART) to treat HIV infection, the next great frontier is to cure infected persons, a formidable challenge. HIV persists in a quiescent state in resting CD4+ T cells, where the replicative enzymes targeted by cART are not active. Although low levels of HIV transcripts are detectable in these resting cells, little to no viral protein is produced, rendering this reservoir difficult to detect by the host CD8+ T cell response. However, recent advances suggest that this state of latency might be pharmacologically reversed, resulting in viral protein expression without the adverse effects of massive cellular activation. Emerging data suggest that with this approach, infected cells will not die of viral cytopathic effects, but might be eliminated if HIV-specific CD8+ T cells can be effectively harnessed. Here, we address the antiviral properties of HIV-specific CD8+ T cells and how these cells might be harnessed to greater effect toward achieving viral eradication or a functional cure.
Incidence of cancer in patients with chronic heart failure: a long-term follow-up study
Authors: Ann Banke, Morten Schou, Lars Videbæk, Jacob E. Møller, Christian Torp‐Pedersen, Finn Gustafsson, Jordi S. Dahl, Lars Køber, Per R. Hildebrandt, Gunnar H. Gislason
Journal: European Journal of Heart Failure (2016)
Abstract 10637: Effects of Pedicle Omentum Flap Combined With Cell Sheet Implantation on Vessel Stability, Myocardial Perfusion, and Left Ventricular Reverse Remodeling in Rat Myocardial Infarction Model
Authors: Satoshi Kainuma, Shigeru Miyagawa, Satsuki Fukushima, Atsuhiro Saito, Yasuhiro Shudo, Akima Harada, Tsuyoshi Ishikawa, Tadashi Watabe, Hiroshi Watabe, Jun Hatazawa, Takashi Sonobe, Hirotsugu Tsuchimochi, Mikiyasu Shirai, Tatsuya Shimizu, Teruo Okano, Koichi Toda, Yoshiki Sawa
Journal: Circulation (2012)

Objective: Cell sheet implantation has been shown to induce therapeutic angiogenesis in damaged myocardium, though instability of newly formed vessels may limit the effects. Accelerating maturation...
Somatic mutation in the EGFR gene in ovarian carcinoma detected by SSCP and direct sequencing
Authors: Y. Terai, M. Sugita, M. Ueda, M. Ueki, L. Bemis, J. Haney, W. A. Franklin
Journal: Journal of Clinical Oncology (2006)

5063 Background: Recently, mutations of the EGFR kinase domain have been described in adenocarcinoma of lung and are particularly common in non-smoking females of Japan. These tumors are more responsive to blockade of the EGFR TK domain than non-mutant tumors. Ovarian tumors are known to express EGFR but the frequency of EGFR mutation at this site has not been explored. Methods: We have searched for mutations in the EGFR gene in ovarian carcinoma in two ways, first by single stranded conformation polymorphism (SSCP) analysis of appropriately amplified DNA from microdissected paraffin sections and then by direct forward and reverse sequencing of the DNA for mutations in exons 18, 19 and 21. Results: There was poor correlation between the two methods. By direct sequencing and evaluation of sequence chromatograms by Mutation Surveyor, mutations were detected in 8 of 79 patients (10.1%). Three of the mutations have been previously described in NSCLC including two in-frame deletions in exon 19 (codons 746–750) and one point mutation in exon 21 (L858R). Previously undescribed point mutations resulting in amino substitutions were found in an additional 5 patients including two patients with multiple mutations. These point mutations included 3 in exon 18 (Q701R, L704S and T725A) and 5 in exon 21 (N830G, R832C, T852M, I853V and Q868D). Deletions were detected by SSCP but point mutations were not detected. Conclusions: We conclude that a low but definite frequency of mutation in the EGFR tyrosine kinase domain occurs in ovarian carcinoma in the Japanese population and that these tumors may be targeted by EGFR blockers. SSCP can detect multibase deletions but is an unreliable method for detection of point mutations. No significant financial relationships to disclose.
Abstract 17029: Periaortic Adipose Tissue-Specific Activation of Renin Angiotensin System Along with the Adipocytes Differentiation Contributes to Atherosclerosis in Apoe-/- Mice
Authors: Daisuke Irie, Hiroyuki Yamada, Taku Kato, Hiroyuki Kawahito, Sou Kishida, Noriyuki Wakana, Kensuke Fukui, Kouji Ikeda, Mitsuhiko Okigaki, Hiroaki Matsubara
Journal: Circulation (2012)

[BACKGROUND] Renin angiotensin system (RAS) in visceral white adipose tissue (WAT) plays a crucial role in lipid metabolism and energy homeostasis; however, the role of perivascular adipose tissue ...
Loss of activity of Erwinia asparaginase on repeat applications.
Authors: J Boos, U Nowak-Göttl, H Jürgens, G Fleischhack, U Bode
Journal: Journal of Clinical Oncology (1995)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1995.13.9.2474 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7666111 Loss of activity of Erwinia asparaginase on repeat applications. J BoosxJ BoosSearch for articles by this author , U Nowak-GöttlxU Nowak-GöttlSearch for articles by this author , H JürgensxH JürgensSearch for articles by this author , G FleischhackxG FleischhackSearch for articles by this author , U BodexU BodeSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.9.2474 PDF "Loss of activity of Erwinia asparaginase on repeat applications.." Journal of Clinical Oncology, 13(9), pp. 2474–2475© 1995 by American Society of Clinical Oncology
Letting Parents Say “No:” A Small Price to Pay for State-Mandated Critical Congenital Heart Disease (CCHD) Screening
Authors: Dalia M. Feltman
Journal: The American Journal of Bioethics (2016)

Why must critical congenital heart disease (CCHD) screening be legislated? This was my first reaction to Hom and colleagues' (2016) analysis. As the authors explain, pulse oximetry is painless and ...
Pharmacodynamic analysis of an agonistic antibody to the costimulatory receptor GITR
Authors: Gordon Moody, Jodi Moriguchi, Ji-Rong Sun, Patricia McElroy, Hong Tan, Yannick Bulliard, Beltran Pedro
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts GITR/TNFRSF18 is a member of the TNF-receptor superfamily preferentially expressed on regulatory T cells (Tregs) and activated T effector cells. Antibody agonists to GITR claim two distinct mechanisms to overcome the repressive tumor microenvironment and drive anti-tumor efficacy
Regular use of a verbal pain scale improves the understanding of oncology inpatient pain intensity.
Authors: E Au, C L Loprinzi, M Dhodapkar, T Nelson, P Novotny, J Hammack, J O'Fallon
Journal: Journal of Clinical Oncology (1994)

PURPOSE This study was undertaken to determine if the daily use of a verbal pain scale could improve the correlation of pain perception between hospitalized oncology patients and their caregivers. PATIENTS AND METHODS Hospitalized oncology patients were asked to rate verbally their average pain over the past 24 hours on a scale ranging from 0 to 10. The patients' primary-care physicians and nurses were asked the same question on the same morning after they had evaluated their patients. RESULTS During a baseline study, only 64% of caregivers' pain scores were within two points of the respective patient's score. Caregivers tended to underestimate patients' pain scores. Caregivers were alerted to these poor results and then requested to ask each patient daily for the average pain score and record this score on the patient's medical record. Nonetheless, correlation between patients' and caregivers' pain scores remained poor (68% within two points of each other) during a second study. The major reason for the poor results appeared to be because caregivers did not routinely ask patients for pain scores. Subsequently, a renewed, more intensive educational effort was undertaken and a third study was conducted. During the third study, 85% of caregivers' and patients' pain scores were within two points of each other (P = .001 when compared with baseline). CONCLUSION The enforced use of a simple verbal pain assessment tool appears to improve caregiver's understanding of the pain status of hospitalized oncology patients.
Comparison of infrared sentinel breastscan (SBS) and bilateral MRI for detection of occult breast cancer: Can this modality assist in surgical planning?
Authors: A. t. Brown, L. C. Thanasoulis, T. G. Frazier
Journal: Journal of Clinical Oncology (2008)

11553 Background: Sentinel BreastScan (Sentinel BreastScan, Infrared Sciences Corp. 2006) is a screening modality that uses digital infrared imaging (DII) and artificial intelligence to identify physiological signs associated with a developing or existing breast abnormality. Usually these signs appear in areas of high metabolic activity, excess blood perfusion and/or angiogenesis, i.e. changes in breast vascularity. Sentinel BreastScan was compared to conventional bilateral breast magnetic resonance imaging (MRI) to evaluate the ability of this technology to detect multifocal or contralateral breast disease. Methods: 24 consecutive patients were evaluated using Sentinel BreastScan (SBS) and bilateral breast MRI modalities; 10 were pre-biopsy and 14 were post- biopsy. All patients’ studies were performed to evaluate SBS detected lesions by MRI, SBS lesions not seen on MRI, and whether or not lymphovascular invasion (LVI) in lesions were seen on final pathology. Results: 24 patients’ lesions were reviewed; exact correlation between MRI and SBS occurred in 9/24 patients (37.5%). Lesions seen bilaterally on MRI but not seen on SBS occurred in 5/24 patients (20.8%). 8/24 patients (33.3%) had additional findings on the opposite side not seen on MRI. These patients continue to be followed closely with mammograms and MRI. Lymphovascular invasion (LVI) occurred in 4/24 patients on final pathology (16.6%). Conclusions: SBS is an inexpensive, non-invasive imaging modality that correlates with MRI findings in at least 50% of patients. It may also detect physiologic changes in the opposite breast that cannot yet be seen on MRI. Because these findings do not seem to correlate with lymphovascular invasion, an additional mechanism may be at play, such as neoangiogenesis. Further studies and follow-up will be necessary to determine the value of this modality in predicting breast risk and surgical treatment planning. No significant financial relationships to disclose.
From C-Reactive Protein to Interleukin-6 to Interleukin-1
Authors: Paul M Ridker
Journal: Circulation Research (2016)

Plasma levels of the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) predict vascular risk with an effect estimate as large as that of total or high-density lipoprotein cholesterol. Further, randomized trial data addressing hsCRP have been central to understanding the anti-inflammatory effects of statin therapy and have consistently demonstrated on-treatment hsCRP levels to be as powerful a predictor of residual cardiovascular risk as on-treatment levels of low-density lipoprotein cholesterol. Yet, although hsCRP is clinically useful as a biomarker for risk prediction, most mechanistic studies suggest that CRP itself is unlikely to be a target for intervention. Moving upstream in the inflammatory cascade from CRP to interleukin (IL)-6 to IL-1 provides novel therapeutic opportunities for atheroprotection that focus on the central IL-6 signaling system and ultimately on inhibition of the IL-1β-producing NOD-like receptor family pyrin domain containing 3 inflammasome. Cholesterol crystals, neutrophil extracellular traps, atheroprone flow, and local tissue hypoxia activate the NOD-like receptor family pyrin domain containing 3 inflammasome. As such, a unifying concept of hsCRP as a downstream surrogate biomarker for upstream IL-1β activity has emerged. From a therapeutic perspective, small ischemia studies show reductions in acute-phase hsCRP production with the IL-1 receptor antagonist anakinra and the IL-6 receptor blocker tocilizumab. A phase IIb study conducted among diabetic patients at high vascular risk indicates that canakinumab, a human monoclonal antibody that targets IL-1β, markedly reduces plasma levels of IL-6, hsCRP, and fibrinogen with little change in atherogenic lipids. Canakinumab in now being tested as a method to prevent recurrent cardiovascular events in a randomized trial of 10 065 post-myocardial infarction patients with elevated hsCRP that is fully enrolled and due to complete in 2017. Clinical trials using alternative anti-inflammatory agents active against the CRP/IL-6/IL-1 axis, including low-dose methotrexate and colchicine, are being explored. If successful, these trials will close the loop on the inflammatory hypothesis of atherosclerosis and serve as examples of how fundamental biologic principles can be translated into personalized medical practice.
28 EFFECT OF HEPATITIS C COINFECTION ON CAUSE-SPECIFIC MORTALITY FOLLOWING HIV SEROCONVERSION IN THE PRE-CART AND CART ERAS
Authors: J. van der Helm, R. Geskus, C. Sabin, L. Meyer, J. del Amo, G. Chène, M. Dorrucci, R. Muga, K. Porter, M. Prins
Journal: Journal of Hepatology (2012)
5-FU/leucovorin (5FU/LV) combined with irinotecan (CPT-11) and oxaliplatin (FOLFIRINOX) as second-line chemotherapy in patients with metastatic pancreatic adenocarcinoma.
Authors: E. Assaf, M. Verlinde-Carvalho, C. Delbaldo, J. Grenier, Z. Sellam, D. Pouessel, I. Sobhani, C. Tayar, P. Piedbois, S. Culine
Journal: Journal of Clinical Oncology (2010)

e14584 Background: The safety profile and efficacy of the Folfirinox regimen as first-line chemotherapy in metastatic pancreatic cancer (MPC) was previously reported in a phase II study (Conroy, J Clin Oncol, 2005:1228). We retrospectively studied the feasability and the efficacy of this regimen as second-line therapy in our institution. Methods: Twenty-seven patients (pts) with MPC were treated by Folfirinox between January 2003 and November 2009. The recommended schedule was oxaliplatin 85 mg/m2 d1 + irinotecan 180 mg/m2 d1 + LV 400 mg/m2 d1 followed by 5-FU 400 mg/m2 bolus d1 and 2,400 mg/m2 46h continuous infusion biweekly. Results: Pts characteristics: M/F = 13/14; median age = 63 years (45-83). Ten had a complete resection of primary tumor, 6 had a adjuvant chemotherpy by gemcitibine, and 4 had an adjuvant radiotherapy concomittant with capecitabine. All patients had a progressive disease after first-line chemotherapy by gemcitabine. Safety: A total of 167 cycles were delivered, with a median number of 6 cycles (1-29) per patient. One toxic death occurred (sepsis). Tolerance was excellent with a good respect of the dose density (Ox: 92.8%, Ir: 89.1%, 5-FU: 96.4%). Grade (G) 3-4 neutropenia occurred in 55.6% of pts, including 1 febrile neutropenia. 44.5% of patients received G-CSF. Other relevant toxicities were: G3-4 thrombopenia (14.8%), G3-4 fatigue (29.6%), G3-4 nausea- vomiting (18.5% pts), G3-4 diarrhea (11% pts) and G3 neuropathy (3.7% pts). Efficacy: 17 of 22 pts were evaluable (WHO and RECIST criterias). 5 PR and 12 SD were observed. Median PFS was 5.4 months. (0.7- 25.48) and median EFS was 3 months (0.5-24.9). Median overall survival was 8.5 months (0-26). Conclusions: These results confirmed the good safety profile and the efficacy of Folfirinox regimen in the treatement of MPC, which merits to be assessed in a phase III trial. No significant financial relationships to disclose.
Changes in specialty's name reflect greater involvement in preoperative and postoperative care
Authors: N. Ellison
Journal: BMJ (1996)

maintenance organisations and capitation are here to stay, and large drops in clinical earnings are predicted.Partners earning high salaries are reducing their holidays and supervising more certified nurse anaesthetists rather than employing another partner and reducing income.It is rumoured that deans of medical schools are dissuading medical students from entering training in anaesthesia.The staffing crisis in teaching hospitals is only just starting and has yet to be resolved.Academic anaesthesiologists, who are accustomed to
N1,N12-Diacetylspermine as a tumor marker for non-small cell lung cancers (NSCLC)
Authors: K. Sakaguchi, K. Hiramatsu, H. Horio, M. Yamamoto, K. Takahashi, M. Kawakita
Journal: Journal of Clinical Oncology (2008)

11089 Background: N1,N12-diacetylspermine (DiAcSpm) is excreted in the urine of healthy persons, with small individual variations in the amount. Previous studies revealed that excretion of DiAcSpm was frequently and markedly elevated in patients with various cancers, but Non-small Cell Lung Cancer (NSCLC) patients have not been examined so far. Methods: Urine samples were collected from 231 patients treated for NSCLC (mean age; 66.9±9.6 year-old, Range;41–87, male;136 female;95) and 64 patients treated for benign thoracic diseases during the period from December 2003 to April 2007 as well as 52 healthy volunteers. DiAcSpm level was analyzed by colloidal gold aggergation method. Results: Patients with NSCLC (n=231) had higher urinary DiAcSpm (0.36±0.57μmol/g creatinine, vs 0.15±0.05,p<0.01) levels than healthy volunteers. The mean urinary DiAcSpm level among NSCLC patients at various pathological stages(stage IIIB and stage IV were included with clinical stages) was 0.24±0.15 in IA (n=104), 0.27±0.17 in IB (n=38), 0.27±0.17 in IIA (n=6), 0.34±0.25 in IIB (n=16), 0.63±1.34 in IIIA (n=26), 0.46±0.48 in IIIB (n=27) and 0.65±0.48 in IV (n=14), respectively. The urinary DiAcSpm level of Stage I NSCLC patients (IA and IB, n=142, 0.33±0.28, p<0.01) was higher than healthy volunteers. The mean level for 164 patients with adenocarcinoma and 54 patients with squamous cell carcinoma was 0.28±0.25 (p<0.01), and 0.55±0.97 (p<0.01), respectively. Urinary DiAcSpm levels were low in non- inflammatory thoracic diseases (0.16±0.04), but high in patients with interstitial pneumonias (n=17, 0.33±0.27) and pleuritis (n=9, 0.34±0.30). We traced the Receiver Operating Characteristic (ROC) curve to assess the values of urinary DiAcSpm, and the area under the ROC curve was 0.74 in NSCLC and 0.88 in squamous cell carcinoma. Conclusions: Urinary DiAcSpm level of NSCLC patients is higher than healthy volunteers and non-inflammatory thoracic diseases. Urine may be readily collected non-invasively, and measurement of urinary DiAcSpm levels is rapid and inexpensive. Urinary DiAcSpm is useful as a tumor marker for detecting early stages of NSCLC, especially squamous cell carcinoma. No significant financial relationships to disclose.