tbuckley/cabot-search huggingface dataset:
Phase I study of a fully human monoclonal antibody to the tumor necrosis factor-related apoptosis-inducing ligand death receptor 4 (TRAIL-R1) in subjects with advanced solid malignancies or non-Hodgkin's lymphoma (NHL)
Authors: L. H. Le, H. W. Hirte, S. J. Hotte, M. Maclean, A. Iacobucci, A. Corey, N. L. Fox, A. M. Oza
Journal: Journal of Clinical Oncology (2004)

2533 Background: TRAIL is a member of the TNF ligand superfamily. There is strong evidence for its ability to induce apoptosis in cancer cell lines. TRAIL causes apoptosis via 2 death receptors [DR4 (TRAIL-R1) & DR5 (TRAIL-R2)] which are upregulated in different cancer cell types. TRM-1 (HGS-ETR1) is a fully human monoclonal antibody agonistic to TRAIL-R1 with preclinical evidence of anti-tumor activity. Methods: Primary objective of this open-label, dose-escalation Phase I study is to evaluate the safety and tolerability of ≥2 doses of TRM-1 in patients (pts) with advanced solid tumors or NHL. Secondary objectives are to evaluate the immunogenicity and pharmacokinetics (PK) of repeated TRM-1 and to assess tumor response. In addition to standard Phase I eligibility criteria, pts who have had previous hematopoietic stem cell transplant or other potentially immunosuppressive therapy are ineligible. Pts are given TRM-1 IV once every 28 days until progression or unacceptable toxicity. Tumor measurements are done every second cycle. Blood samples are collected for PK and immunogenicity analysis. Results: To date, 15 pts have been enrolled into 3 cohorts: 0.01 (7 pts), 0.03 (4 pts), and 0.3 mg/kg (4 pts), with planned escalation to 1, 3, 10, and 20 mg/kg. Mean number of cycles delivered: 2.27 (range 1–5). Tumor types include: colorectal (5), ovary (5), cervix (2), breast (1), prostate (1) and salivary gland (1). TRM-1 has been well tolerated with no clearly attributable toxicities other than 1 case of grade 3 thrombocytopenia thought possibly related. Eight subjects were removed from the trial for progressive disease, 1 died of progressive disease during follow-up, 1 died suddenly during follow-up, and 1 died of progressive disease while on study and was replaced. This pt was in the 1st cohort which was expanded. Preliminary PK results are linear across a 30-fold dose range with CL=3.3 mL/kg/day, V1=35 mL/kg, Vss=62 mL/kg, t1/2β=16days. Conclusions: TRM-1 is well tolerated and the maximum tolerated dose has not been reached. Accrual to this study continues. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Human Genome Sciences, Inc. Human Genome Sciences, Inc. Human Genome Sciences, Inc. Human Genome Sciences, Inc.
Direct in vivo evaluation of tumor VEGFR in response to treatment with pazopanib: A novel molecular imaging study.
Authors: S. K. Sarkar, Z. Levashova, J. Pizzonia, M. V. Backer, J. M. Backer, F. G. Blankenberg
Journal: Journal of Clinical Oncology (2010)

3049 Background: Several small molecule tyrosine kinase inhibitors (TKI) targeting VEGFR are already approved for use in anti- angiogenic therapy either alone or in combination with chemotherapeutics. Unfortunately, the clinical response to such therapy varies markedly among individuals. We hypothesize that noninvasive assessment of changes in VEGFR prevalence in response to TKI treatment would identify responsive patients. We report here that SPECT(single photon emission computed tomography) imaging of VEGFR-2 in HT29 tumor xenografts allows for detailed assessment of its prevalence in the course of treatment with pazopanib, a TKI targeting VEGFR, PDGFR and c-Kit, recently approved for the treatment of advanced renal carcinoma. Methods: VEGFR-2 SPECT imaging was done using scVEGF/Tc, an engineered single chain (sc) form of VEGF radiolabeled with 99mTc. This tracer binds to and is internalized by VEGFR-2 in tumor vasculature, allowing for selective accumulation of 99mTc in tumor endothelial cells. All SPECT imaging experiments were carried out on HT29 tumor xenografts on Swiss nude mice. A dose of 2-4 mCi of [99mTc]scVEGF was injected into the retro-orbital venous sinus in a volume of 100 to 220 μ L followed by imaging two hours later. Quantitative histogram analysis of the SPECT images was performed. At the end of imaging experiments the mice were sacrificed and the tumors were harvested for immunohistochemical analysis (IHC) of VEGFR-2 and VEGFR-1, as well as panendothelial marker CD31. Results: The imaging results, which are consistent with IHC analysis, show that VEGFR-2 levels in tumors were significantly reduced upon treatment with pazopanib as early as day 5 after the initiation of therapy, when morphological changes were barely detectable. A detailed kinetic study to understand the dose dependence of the effects of pazopanib on tumor VEGFR is in progress and those results will also be presented. Conclusions: This is the first direct evaluation of tumor VEGFR in response to a VEGFR targeted therapy. In principle, this technology can be extended to human use providing for new opportunities in treatment management of VEGFR-targeted therapies including patient selection, dose, and optimal drug regimen. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline, Sib Tech Inc GlaxoSmithKline, Sib Tech Inc GlaxoSmithKline
Impact Of Route Of Bortezomib (B) Administration On Dose Intensity and Time To Dose Reduction In Previously Untreated Patients (Pts) With Multiple Myeloma (MM)
Authors: Robert M Rifkin, Clara Chen, Rahul Dhanda, Debra Rembert, Abbie Ba-Mancini, Esprit Ma, Yanyan Zhu, Edward Dow, Liviu Niculescu
Journal: Blood (2013)
Chemotherapy of Chemically-induced Colorectal Tumours
Authors: J M Gilbert, G Slavin, E M Thompson, A E Kark
Journal: Journal of the Royal Society of Medicine (1983)

Benign and malignant tumours were induced in the large bowel of rats by the carcinogen 1,2-dimethylhydrazine (DMH). Benign tumours appeared from week 20 onwards and malignant tumours from week 30. 5-Fluorouracil was administered intraperitoneally in maximally tolerated doses from week 26 onwards and failed to influence significantly the development of either benign or malignant tumours. Tumours induced by DMH are a close model of human colorectal cancer and suitable for testing anticancer drugs. Agents with greater activity against colorectal cancer are required.
Abstract 10341: Contrast-Enhanced Ultrasound Overlay Imaging of Carotid Plaque Neovascularization is Useful for Identifying Risk for Acute Coronary Syndrome
Authors: Juntaro Deyama, Takamitsu Nakamura, Jun Nakamura, Isao Takishima, Mika Futamata, Tetsuji Mochida, Manabu Uematsu, Wataru Sugamata, Daisuke Fujioka, Yukio Saito, Kazuto Nakamura, Yoshinobu Kitta, Ken–ichi Kawabata, Jun–ei Obata, Kiyotaka Kugiyama
Journal: Circulation (2013)

Backgrounds: Contrast-enhanced ultrasound (CEUS) in the carotid arteries using microbubbles has been shown to be a potential technique for detecting the plaque neovascularization, a feature of unst...
Social theory and the cognitive-emotional brain
Authors: Marco Verweij, Timothy J. Senior
Journal: Behavioral and Brain Sciences (2015)

Abstract Pessoa's (2013) arguments imply that various leading approaches in the social sciences have not adequately conceptualized how emotion and cognition influence human decision making and social behavior. This is particularly unfortunate, as these approaches have been central to the efforts to build bridges between neuroscience and the social sciences. We argue that it would be better to base these efforts on other social theories that appear more compatible with Pessoa's analysis of the brain.
Modulation of ion channel activity: a key function of the protein kinase C enzyme family.
Authors: M S Shearman, K Sekiguchi, Y Nishizuka
Journal: Pharmacological Reviews (1989)

The considerable volume of data now available strongly implicates the modulation of ion channel activity as a key function of the PKC enzyme family. In some systems, such as the PC 12, RINm5F, and NG108-15 clonal cell lines, the action of the enzyme is becoming clear, whereas in others, such as cardiac and smooth muscle cells, contradictory evidence exists, and clarification of the role of PKC in these tissues must await further analysis. Few general statements can be made concerning the regulation of ion conductance through the various classes of channel, or through one particular species of channel that is expressed in and subject to regulation in different cell types. Rather, it seems that many different patterns of modulation can occur in different cells, and so, elucidation of the molecular mechanisms that determine these diverse patterns represents a major challenge. To summarize, we will focus on three aspects of the modulatory action of PKC.
The clinical significance of a PSA nadir &gt; 0.2 to patients with a rising post-operative or post-radiation PSA treated with androgen deprivation
Authors: A. J. Stewart, H. Scher, M.-H. Chen, D. McLeod, P. Carroll, J. Moul, A. D’Amico
Journal: Journal of Clinical Oncology (2005)

4547 Purpose: For men receiving androgen deprivation therapy (ADT) for a rising post-operative or post-radiation prostate-specific antigen (PSA) state, we evaluated whether a PSA nadir level of > 0.2 ng/ml as compared to 0.2 ng/ml or less was significantly associated with prostate cancer-specific mortality (PCSM). Patients and Methods: The study cohort comprised 747 men with a rising PSA and negative bone scan following surgery (N = 486) or radiation therapy (N = 261) that were treated with ADT and followed for a median of 2.2 (0.8 - 9.5) years following PSA nadir. Cox regression was used to evaluate whether a significant association existed between the PSA nadir level and the time to PCSM following PSA nadir controlling for treatment and known prognostic factors. Results: The post-ADT PSA nadir (pCox < 0.0001), the pre-ADT PSA DT (pCox = 0.002), and Gleason 8 to 10 cancers (pCox = 0.01) were significantly associated with time to PCSM; whereas initial local therapy (pCox = 0.19), interval to PSA failure (pCox = 0.20), Gleason score 7 cancer (pCox = 0.17) were not. The adjusted hazard ratio for PCSM was 20 [95% Confidence Interval (CI): 7, 61; pCox < 0.0001] for men with a PSA nadir of > 0.2 ng/ml as compared to all others. A PSA DT < 3 months was observed in 30% (224/747) of the study cohort. Of the 28 observed prostate cancer deaths, 21 (75%) and 3 (11%) occurred in men whose PSA nadir was > 0.2 ng/ml and who had a PSA DT < 3 months or between 3 and 8.99 months respectively as shown in the Table. Conclusion: A PSA nadir > 0.2 ng/ml following ADT given for a post-operative or post-radiation PSA DT < 3 months is closely associated with PCSM and clinically significant because it accounted for nearly all of the cancer death observed in this study. No significant financial relationships to disclose.
포스터 전시 : Epstein-Barr virus 감염에 의한 급성 담즙정체성 간염과 이후 속발한 자가면역성 간염 1예
Authors: 김종표, 손주현, 이항락, 김진배, 한동수, 함준수, 이동후, 기춘석, 장세진
Journal: Clinical and Molecular Hepatology (2003)

배경/목적: Epstein-Barr virus(EBV)는 herpes DNA 바이러스로서 전염성 단핵구증이라는 특징적인 임상 증후군을 유발한다. EBV 감염으로 인한 간 손상은 대개 aminotransferase와 alkaline phosphatase의 경미한 상승을 보이며 심한 황달은 매우 드문 것으로 보고되고 있다. 또한 거의 대부분에서 특별한 치료 없이 자연 호전된다. 자가면역성 간염의 원인은 밝혀져 있지 않으나, 아주 드물게 급성 바이러스성 간염 이후에 속발한 경우가 보고된 바있다. 저자들은 EBV에 의한 심한 황달을 동반한 급성 간염으로 치료받았던 환자에서 속발된 자가면역성 간염 양상의 만성간염의 1 예를 경험하였기에 보고하는 바이다. 증례: 64세 남자가 내원 10일전 갑자기 발생한 고열, 황달과 가려움증을 주소로 내원하였다. 환자는 30년전 원인 모르는 간염의 과거력이 있었으며 이후 특별한 문제없이 지내왔다. 평소 약간의 음주(하루 10g이하)를 하였고, 수혈, 문신, 약물복용 등은 부정하였다. 내원시 체온은 39.4?였다. 신체 검사에서 인후부의 염증 소견은 관찰되지 않았고 경부 임파절은 촉지되지 않았다. 내원시 일반화학검사에서 총빌리루빈 22.7 mg/dl, ALT/AST 980/814 IU/L, ALP/GGT 1202/1652 IU/L로 측정되었고 복부초음파 검사에서 담도계의 확장소견은 관찰할 수 없었다. IgM anti-HAV, HBsAg, IgM anti-HBc, anti-HCV, HCV RNA PCR은 음성이었고, HBsAb와 IgG antiHBc 양성이었다. EBV IgM과 heterophil antibody는 양성이었고, IgM anti-CMV는 음성이었다. Anti-nuclear antibody (ANA)는 speckled level 1, cytoplasmic level 2로 양성, anti-mitochondrial antibody (AMA)는 양성이었으나 anti-smooth muscle antibody는 음성이었다. 내원 6일째 시행한 경피적 간조직 검사에서 문맥주위 염증과 섬유화는 관찰되지 않았으며 주로 간소엽내의 염증과 담즙정체를 보이는 급성간염의 조직학적 소견을 보였다. 환자는 EBV에 의한 급성 담즙정체성 간염으로 진단되었고 이후 환자는 특별한 치료없이 호전양상을 보여 외래 추적관찰 하였다. 추적관찰에서 ALT/AST는 간헐적으로 경미한 상승이 있었으나 ALP/GGT는 지속적으로 상승을 보였고 총빌리루빈은 정상이었다. 또한 지속적으로 ANA (1:2560이상)와 AMA 양성으로 측정되었고, 2년 후 시행한 간조직 검사에서 주로 임파구와 형질세포의 침윤에 의한 중등도의 문맥주위 염증과 섬유화를 보이는 자가면역성 간염에 합당한 소견을 보였다. 스테로이드 투여 후 상승되어 있던 GGT와 ALP이 호전되었으며 ANA titer가 1:80으로 감소되었다.
Radioactive Isotopes in Clinical Medicine
Authors: Solomon Silver
Journal: New England Journal of Medicine (1965)

Body Water and ElectrolytesTotal Body WaterTotal body water141 ranges from 75 to 61 per cent in the first ten years of life. In the adult the values are 51.5 per cent in males and 45.5 per cent in females although values as high as 60 and 50 per cent respectively have been reported. Either stable H2 2O or radioactive H2 3O may be used. Equilibration142 is complete in a few hours after an intravenous dose, and a sample of urine or plasma at that time is representative of the general body concentration of the labeled water. . . .
Long term results for cladribine induction and interferon maintenance treatment in previous untreated follicular lymphoma
Authors: M. A. Fridrik
Journal: Journal of Clinical Oncology (2005)

6680 Background: Follicular lymphoma in advanced stage is an incurable disease. The main treatment goal is palliation with low treatment related toxicity. Methods: Eligible were previously untreated patients with histological confirmed follicular lymphoma stage 3 or 4 and symptomatic disease. In a multicenter setting we prospectively treated 52 patients with intravenous cladribine 0.12 mg/kg body weight for 4 or 5 consecutive days every 4 weeks for 4 cycles. Following the cladribine induction treatment an interferon-2c maintenance therapy was started until progression. Primary endpoint was remission rate. Secondary endpoints were survival, time to treatment failure (TTF), and toxicity. Results: Remission rate was 88.5% with 32.7% complete remissions. Only 7.7% of patients progressed during cladribine treatment. After a median follow up of 7 years overall survival was 60% and TTF 53%. Four lymphomas transformed to a high-grade histology. Two patients acquired a secondary malignancy. Conclusions: With a short therapy of 4 months durable remissions can be achieved with cladribine treatment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Janssen-Cilag Pharma GMBH, Wien Janssen-Cilag Pharma GMBH, Wien
Abstract P075: Influence of Systemic Interleukin-6 on the Inverse Association between Your-Choice American Heart Diet and a 41-Year Mortality Risk from Coronary Heart Disease among Men
Authors: Jun Dai, Anthony J Acton, Robert V Considine, Ruth E Krasnow, Terry Reed
Journal: Circulation (2014)

Introduction: Whole diet evaluated using dietary pattern is associated with systemic inflammation and coronary heart disease (CHD). Systemic inflammation also contributes to CHD risk. Genetic factors explain variations in whole diet, systemic inflammation, and CHD. However, it is unknown whether systemic inflammation is a mechanism linking whole diet to the long-term mortality risk from coronary heart disease independent of genes. Hypothesis: Systemic inflammation measured as plasma interleukin-6 levels medicates the association between whole diet and long-term mortality risk from coronary heart disease independent of genes. Methods: From the National Heart, Lung, and Blood Institute Twin Study, we included 554 white, middle-aged, veteran male twins (105 monozygotic and 109 dizygotic twin pairs; 65 monozygotic and 61 dizygotic unpaired twins). The twins were not on antihypertensive medication and had diastolic blood pressure below 105 mmHg at baseline (1969-1973) and did not have suspected acute inflammation [plasma levels of interleukin-6 (IL-6) above 10 pg/mL or C-reactive protein above 30 mg/L)]. Usual dietary data at baseline were collected through nutritionist-administered dietary history interview. Your-Choice American Heart Diet (YCARD) score was devised to quantitatively evaluate whole diet. Plasma interleukin-6 and C-reactive protein levels were measured with ELISA. Data on vital status and death causes were collected through death certificates until Dec 31, 2010. A frailty survival model was used to estimate various associations: overall (equivalent to the association in the general population), within-pair (independent of genes and environment common to co-twins), and between-pair (indicating influence of the common factors). We controlled for total caloric intake and known CHD risk factors including body mass index and modified Framingham Risk Score. Results: There were 75 CHD deaths during a 41-year follow-up (median follow-up of 34 years). The adjusted overall association between YCARD score and the CHD mortality risk was negative [partial coefficient for a 10-unit increment in the YCARD score: βo (95% confidence interval (CI)): -0.13 (-0.24, -0.02); hazard ratio (95% CI): 0.88 (0.78, 0.98)]. The partial regression coefficient was -0.02 [95% CI (-0.23, 0.19)] for the within-pair effect of YCARD (βw) and -0.12 [95% CI (-0.26, 0)] for the between-pair effect of YCARD (βb) in relation to CHD mortality risk. Additional adjustment for IL-6 led to a 15.4% reduction in the βo, a 100% increment in the βw, and a 16.7% reduction in the βb. Conclusions: Systemic inflammation measured as interleukin-6 mediates the association between whole diet and long-term coronary heart mortality risk, which is largely through genetic and environmental factors shared between co-twins.
Cancer Trends in a Population at Risk of Acquired Immunodeficiency Syndrome
Authors: R J Biggar, J Horm, J H Lubin, J J Goedert, M H Greene, J F Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1985)

Journal Article Cancer Trends in a Population at Risk of Acquired Immunodeficiency Syndrome Get access Robert J. Biggar, M.D., Robert J. Biggar, M.D. 3 3Address reprint requests to Dr. Biggar, Landow Building, Room 3C19, National Institutes of Health, Bethesda, MD 20205. Search for other works by this author on: Oxford Academic PubMed Google Scholar John Horm, M.S., John Horm, M.S. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jay H. Lubin, Ph.D., Jay H. Lubin, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar James J. Goedert, M.D., James J. Goedert, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Mark H. Greene, M.D., Mark H. Greene, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph F. Fraumeni, Jr., M.D. Joseph F. Fraumeni, Jr., M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 74, Issue 4, April 1985, Pages 793–797, https://doi.org/10.1093/jnci/74.4.793 Published: 01 April 1985 Article history Received: 17 August 1984 Accepted: 07 December 1984 Published: 01 April 1985
A New Era of Innovation for CAR T-cell Therapy
Authors: Robert M Frederickson
Journal: Molecular Therapy (2015)

The field of chimeric antigen receptor (CAR) T-cell therapies has entered a new stage of development, and the tremendous promise of this new cancer treatment was evident at the recent CAR-T Summit held in Boston 12–13 November 2015. The meeting was organized by Hanson-Wade, a commercial enterprise specializing in business conferences, including some within the biotechnology and life-sciences sectors. The aim of the conference was to bring together diverse stakeholders to discuss how to facilitate the commercial development of this rapidly evolving field.
Perceptions of clinical trial participation between community practitioners and older cancer patients
Authors: J. T. Tam, J. Payne, B. Teplitzky, W. Ershler, L. Balducci
Journal: Journal of Clinical Oncology (2004)

8260 Background: Older cancer patients are underrepresented in clinical trials. As the number of older cancer patients treated in community practices increases, understanding the interaction of community practitioners and patients' perception of barriers to participate in clinical trials may help increase patient participation. Methods: Community practitioners and elderly patients (age 70 and older) were surveyed on their perception of clinical trial participation. Phase I asked practitioners to rate the degree various factors impact their decision to consider a patient for clinical trials participation. Phase II involved surveying elderly patients to rate the degree these similar factors impact their willingness to consider clinical trials participation. Results: Preliminary data identified several factors impacting practitioners' decision to consider an older patient for clinical trial participation. The factors include: patient's existing co-morbid conditions, high toxicity potential to treatment with older patients; patients not having adequate home assistance; study designs not specific to elderly patients; compensation for trial conduct not correspond to amount of work required to enroll elderly patients. Practitioners surveyed stated that elderly cancer patients are routinely offered clinical trials; this was not reflective of recent data which showed that patients age 70 and older comprise only 20% of clinical trials participants (Talarico et al, 2003). Conclusions: The lack of data involving elderly participation in clinical trials data suggests that researchers and clinicians need to work together to build a consensus on how to operationalize clinical trials in the elderly population. The patient survey phase is ongoing with the aim to provide complementary data to help better understand and address clinical trials participation issues from both practitioner and patient perspectives. Information on potential similarities and differences with these groups can help influence the design of future clinical trials involving elderly patients with cancer. No significant financial relationships to disclose.
Implications of Lymphatic Transport to Lymph Nodes in Immunity and Immunotherapy
Authors: Susan N. Thomas, Nathan A. Rohner, Erin E. Edwards
Journal: Annual Review of Biomedical Engineering (2016)

Adaptive immune response consists of many highly regulated, multistep cascades that protect against infection while preserving the health of autologous tissue. The proper initiation, maintenance, and resolution of such responses require the precise coordination of molecular and cellular signaling over multiple time and length scales orchestrated by lymphatic transport. In order to investigate these functions and manipulate them for therapy, a comprehensive understanding of how lymphatics influence immune physiology is needed. This review presents the current mechanistic understanding of the role of the lymphatic vasculature in regulating biomolecule and cellular transport from the interstitium, peripheral tissue immune surveillance, the lymph node stroma and microvasculature, and circulating lymphocyte homing to lymph nodes. This review also discusses the ramifications of lymphatic transport in immunity as well as tolerance and concludes with examples of how lymphatic-mediated targeting of lymph nodes has been exploited for immunotherapy applications.
Maximal Androgen Depletion with Abiraterone Acetate (Aa) Followed By Randomization of Maximal Androgen Ablation with Molecular Targeted Therapies Dasatinib or Sunitinib Malate in Metastatic Castrate Resistant Prostate Cancer (Mcrpc). Report on Candidate Predictive Androgen Signaling Signature
Authors: E. Efstathiou, E. Li Ning Tapia, A. Aparicio, S.M. Tu, S. Wen, A. Hoang, L. Pagliaro, C. Harmon, P. Troncoso, J.C. Araujo, C. Logothetis
Journal: Annals of Oncology (2014)