tbuckley/cabot-search huggingface dataset:
Abstract 5026: Tumor associated targeting with Manocept: HIV associated Kaposi's sarcoma as a model system
Authors: Rongzhen Zhang, Frederick O. Cope, Paige M. Bracci, Michael S. McGrath
Journal: Cancer Research (2015)

Abstract Introduction Inflammation appears to play a critical role in tumor development of HIV-associated Kaposi's sarcoma (KS). Specifically, emerging data show that KS tumor cells that co-express various macrophage (MO) antigens become resistant to current anti-viral therapies used to treat KS and AIDS. MOs also are a known source of KS tumor cell growth factors and substantial evidence suggests that tumor associated macrophages (TAMs) may represent a reservoir for HIV and its evolved retroviral variants. The MO pool driving these two pathological pathways share a common element rooted in the MOs, the CD206 human macrophage mannose receptor. Manocept, a molecular targeting agent, binds and enters MOs via pinocytosis of holo-CD206, providing a cell portal for the evaluation of Manocept as a MO and KS targeting agent. Methods Manocept was prepared as a synthetic molecule with a dextran backbone, and 12-20 mannose moieties. The reporter molecule (Cy3) was included as a fluorescent tracer for locating Manocept on and in MOs and KS tumor cells. Binding and localization Cy3-Manocept was assessed through intracellular visualization and flow cytometric quantitation of Cy3-Manocept binding and uptake using in vitro generation of monocyte-derived CD206+ MOs. The fresh HIV+ KS tumor tissue culture followed by immunofluorescence staining and confocal imaging was performed to confirm Cy3-Manocept uptake in KS tumor cells and TAMs. Results In vitro culture showed that Cy3-Manocept binds avidly to CD206 expressing MOs. Time course studies of increasing Cy3-Manocept concentrations confirmed continuous and ongoing uptake of Manocept into CD206+ MOs at 37°C. Fresh HIV+ KS tissue culture studies showed both Manocept uptake and CD206 staining of TAMs as well as KS tumor spindle cells (HHV8+ cells). Cy3-Manocept co-localized with CD206 in nearly all KS-associated cells expressing HHV8 and/or CD68 (Tissue MO marker), confirming that CD206 acts both as a target and Manocept concentrating receptor for TAMs and KS tumor cells. Conclusions Our results support the potential use of CD206 macrophage mannose receptor-targeted Manocept for imaging KS tumor cells, TAMs, and more importantly, for delivery of therapeutic/diagnostic agents capable of targeting all KS-associated cells including a potential MO reservoir for HIV. Citation Format: Rongzhen Zhang, Frederick O. Cope, Paige M. Bracci, Michael S. McGrath. Tumor associated targeting with Manocept: HIV associated Kaposi's sarcoma as a model system. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5026. doi:10.1158/1538-7445.AM2015-5026
Surgical treatment plus low-dose weekly CPT-11 therapy have prognostic significance in stage IV colorectal cancer
Authors: K. Sasaki, H. Takasaka, E. Ezoe, K. Okuya, T. Furuhata, F. Hata, T. Katsuramaki, K. Hirata, Y. Takada
Journal: Journal of Clinical Oncology (2005)

3741
Phase II study of preirradiation chemotherapy for CNS germ cell malignancies: Long-term complications.
Authors: S. I. Robinson, J. C. Buckner, C. Raffel, J. E. Hammack, B. W. Scheithauer, W. Wu, E. G. Shaw
Journal: Journal of Clinical Oncology (2010)

2005 Background: This prospective multicenter phase II study was designed to assess the response rate and survival of patients with CNS germ cell malignancies treated with etoposide and cisplatin chemotherapy followed by limited dose and field radiation, as well as to document the long term complications including endocrine and cognitive complications associated with this approach to treatment. Methods: Thirty-four patients aged 6 to 24 who met eligibility criteria including histologically confirmed CNS germ cell tumors were enrolled and received four cycles at three- weekly intervals of cisplatin 20 mg/m2/day followed by etoposide 100 mg/m2/day over days 1-5 followed by radiation therapy. 59% (or 20/34) were germinomas. 5 of 20 patients with germinomas had disseminated disease, and all the non-germinomas were localized. Results: 20 of 20 patients (100%) with germinomas achieved complete response vs. 12 of 14 (86%) with nongerminomas. After median follow up time of 10.2 years, 19 of 20 (95%) and 12 of 14 (86%) of patients with germinomas and nongerminomas are alive, respectively. Interestingly all the patients who required hormone replacement at the time of last follow-up had evidence of one or more deficiencies at initial enrollment. Of these deficiencies, hypothyroidism and diabetes insipidus were the most common, 17/20 and 18/20 respectively. Similarly the majority of patients who presented with extra- ocular muscle impairment continued to have evidence of dysfunction at long term follow-up 12/15. Neurovascular complications were seen in 3/34 (8%), one with transient ischemic attacks secondary to radiation induced vasculitis, one with massive stroke and one with incidentally discovered intracranial aneurysm. Neurocognitive effects were minimal with 2/34 (5%) having documented cognitive difficulties and residing in a nursing home, and 5/34 (15%) patients noted to have memory issues, of which one had normalization at the time of last follow-up. Conclusions: Chemotherapy followed by radiation is highly effective with low incidence of neurovascular and subjective neurocognitive complications in patients with CNS germ cell malignancies. No significant financial relationships to disclose.
Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial
Authors: Michael Manns, Didier Samuel, Edward J Gane, David Mutimer, Geoff McCaughan, Maria Buti, Martín Prieto, José Luis Calleja, Markus Peck-Radosavljevic, Beat Müllhaupt, Kosh Agarwal, Peter Angus, Eric M Yoshida, Massimo Colombo, Mario Rizzetto, Hadas Dvory-Sobol, Jill Denning, Sarah Arterburn, Phillip S Pang, Diana Brainard, John G McHutchison, Jean-François Dufour, Hans Van Vlierberghe, Bart van Hoek, Xavier Forns
Journal: The Lancet Infectious Diseases (2016)
Canine Lymphoma: Relative Risk in the Boxer Breed
Authors: William A. Priester
Journal: JNCI Journal of the National Cancer Institute (1967)

Two hundred forty cases of canine lymphoma, from three regions, Midwest, South, end West Coast, and appropriate dog licensure control populations were analyzed, with relative risk techniques, to test the hypothesis that the boxer breed is at excess risk of developing canine lymphoma. Relative riskwas, in every instance, significantly higher (P<O.0005) for boxers than for other purebreds combined. No other single common breed demonstrated a similar pattern of increased risk. The summary relative risk of boxers for canine lymphoma, compared to all other purebreds, was approximately 6. There was no significant difference in sex distribution of dogs with lymphoma and controls. The question is raised as to whether the excess risk of boxers for canine lymphoma reflects an excess risk of boxers for all cancer. Possible implications to cancer research of this excess boxer risk are also discussed.
First-line therapy for advanced pancreatic cancer with gemcitabine and docetaxel versus gemcitabine and erlotinib: A multivariate matched pair analysis.
Authors: P. Stuebs, P. Habermann, K. Zierau, K. Schuette, J. Fahlke, K. Ridwelski, E. Kettner, H. Lippert
Journal: Journal of Clinical Oncology (2010)

e14572 Background: Comparison of first-line-treatment based on gemcitabine of inoperable and/or metastasized pancreatic cancer regarding effectiveness and feasibility. Methods: A total of 69 patients were included in the analysis. The gemcitabine/docetaxel regiment was evaluated within a phase II study administering 1,000mg/m2 gemcitabine and 35 mg/m2 docetaxel (G/Do) to 40 patients. In accordance with specified study criteria 1,000 mg/m2 gemcitabine and 100 mg/die erlotinib (G/E) were administered to 29 patients, which were reviewed in a matched pair analysis. Results: Comparison was made in reference to response and survival rates as well as the toxicity profile. 1 CR in G/Do (2.6%), 5 PR (12.8%) G/Do versus 3 (11.5%) G/E, 19 SD (48.7%) G/Do versus 6 (23.1%) G/E, 14 PD (35.9%) G/Do versus 17 (65.4%) G/E. The difference in response rates were not significant (p = 0.14). TTP was 4.85 months in the G/Do group and 5.94 months in the G/E group. OS was 8.59 months in G/Do and 8.36 months in G/E. NCI-CTC grade 3-4 toxicity was observed in 24 patients (60%) receiving G/Do and in 19 patients (66%) receiving G/E. The most relevant hematologic events per patient were leukopenia and neutropenia (32% G/Do, 31% G/E). Major grade 3-4 nonhematologic toxicities were nausea (15% G/Do, 8% G/E), diarrhea (20% G/Do, 10% G/E) and acne (14% G/E). In regard to survival rate and toxicity profile no significant differences were observed. Conclusions: In advanced pancreatic carcinoma both treatment options can be applied safely and effectively with a moderate toxicity profile as first-line treatment. There were no advantages observed for one treatment over the other. No significant financial relationships to disclose.
Phase I/II study of bexarotene in combination with weekly paclitaxel and monthly carboplatin for the treatment of patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: V. Beggs, W. M. Disalvo, K. Dragnev, J. Rigas
Journal: Journal of Clinical Oncology (2004)

7356 Background: This trial was based on a multicenter randomized phase II trial in advanced NSCLC where weekly paclitaxel and monthly carboplatin demonstrated favorable results. This trial was designed to combine this chemotherapy regimen with bexarotene, a retinoid that binds selectively to the nuclear receptor RXR now in phase III development. Methods: Pt eligibility: pathologic stage: IIIB/IV or recurrent metastatic disease, adequate hematological, hepatic, thyroid, lipid and renal function. Prior chemotherapy was allowed. Bexarotene oral capsules are administered daily starting on initial day of chemotherapy. Two dose levels of bexarotene were evaluated (300 mg/m2/day and 400 mg/m2/day). All patients were scheduled to receive paclitaxel 100 mg/m2 weekly for 3 doses every 4 weeks and carboplatin AUC = 6 monthly. Results: As of December 2003, 21 pts were enrolled, 8 receiving 300mg/m2/day and 13 at 400 mg/m2/day of bexarotene. Pt characteristics include: age (median 58), gender (female 43%), stage (86% stage IV), 24% Karnofsky performance status 60–70%, 29% prior chemotherapy, 33% prior radiation, 48% prior surgery. At the 300 mg/m2/day bexarotene dose level, 52% of the pts required a dose reduction in paclitaxel . At the 400 mg/m2/day dose level of bexarotene, 34% of the pts acquired a dose reduction in paclitaxel. Dose modification rates were higher in our study (52%/34%) than in the prior randomized study without bexarotene (14%). The primary serious adverse events (grade 3 or 4) were neutropenia (19%), hypertriglyceridemia (14%) and anemia (10%). Conclusions: Daily administration of bexarotene at 400 mg/m2/day in combination with weekly paclitaxel and monthly carboplatin is safe and feasible. Enrollment of chemotherapy naïve pts into the phase II portion of this trial continues. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ligand Ligand Ligand; Genentech; Abbott; Amgen; Aventis; Bristol-Myers Squibb; GlaxoSmithKline; Ortho Biotech; Merck; Pfizer; OSI; Roche
Ethics Consultation Quality Assessment Tool: A Novel Method for Assessing the Quality of Ethics Case Consultations Based on Written Records
Authors: Robert A. Pearlman, Mary Beth Foglia, Ellen Fox, Jennifer H. Cohen, Barbara L. Chanko, Kenneth A. Berkowitz
Journal: The American Journal of Bioethics (2016)

Although ethics consultation is offered as a clinical service in most hospitals in the United States, few valid and practical tools are available to evaluate, ensure, and improve ethics consultation quality. The quality of ethics consultation is important because poor quality ethics consultation can result in ethically inappropriate outcomes for patients, other stakeholders, or the health care system. To promote accountability for the quality of ethics consultation, we developed the Ethics Consultation Quality Assessment Tool (ECQAT). ECQAT enables raters to assess the quality of ethics consultations based on the written record. Through rigorous development and preliminary testing, we identified key elements of a quality ethics consultation (ethics question, consultation-specific information, ethical analysis, and conclusions and/or recommendations), established scoring criteria, developed training guidelines, and designed a holistic assessment process. This article describes the development of the ECQAT, the resulting product, and recommended future testing and potential uses for the tool.
Phase II trial of sequential temozolomide (TMZ) and high-dose bolus (HDB) IL-2 in patients with metastatic melanoma
Authors: S. S. Agarwala, A. A. Tarhini, J. M. Kirkwood, C. Cai, L. Stover, S. Moschos, W. Gooding
Journal: Journal of Clinical Oncology (2006)

8037 Background: Previous biochemotherapy (BCT) regimens for metastatic melanoma have utilized lower doses of IL-2 and multiple chemotherapeutic agents, adding to toxicity, but not to efficacy. Methods: We designed a 2-stage Simon phase II study testing a unique BCT approach of single agent chemotherapy with TMZ given in an extended schedule (75 mg/m² per day for 3 weeks PO) followed by HDB IL-2 (600,000 U/Kg/dose, maximum 14 doses administered over 5 days). Cycles were repeated every 28 days with a two-week interval between alternate cycles. The first stage accrued 20 patients with promising activity and safety permitting enrollment of additional patients. Results: Thirty-one patients (20 male, 11 female), age 27–74 (median 47) have been enrolled to date. All had AJCC stage IV melanoma (7 M1a, 5 M1b, 19 M1c) and had not previously received therapy for metastatic disease. Twelve had received prior adjuvant interferon. A total of 88 cycles of therapy have been administered (median of 2 cycles per patient; 5 patients continue on therapy). The median number of doses was 9 (range 7–12) during cycle 1, and 6 (range 4–11) during cycle 2. Three patients did not receive any IL-2 due to disease progression, and 6 patients received only one cycle of IL-2. Twenty two patients who received at least 2 cycles are evaluable for response. All 31 patients are evaluable for toxicity. Grade 3 toxicities included hepatic (8), hematologic (4 leukopenia, 2 thrombocytopenia), diarrhea (1). No grade 3–4 cardiovascular or renal toxicities were noted. Overall response rate is 22.7% (2 complete lasting 10.8 and 17+ months, 3 partial lasting 3.7 and 16+ months, 1+ month). Responses were seen in both M1a and M1c disease. Fourteen patients had stable disease after 2 cycles and 10 of these have progressed. As of 12/31/2005, the 4 month PFS rate is 74% [40%, 88%], median TTP is 24 weeks [11, 32] and median OS is 71 weeks (31.4, inf). Conclusions: HDB IL-2 can be safely administered in combination with single agent temozolomide in an extended schedule and appears to have promising efficacy and lower toxicity than previously used BCT regimens. Further follow-up will determine if durability of response exceeds that of single agent HDB IL-2. [Table: see text]
A phase II trial of gemcitabine, docetaxel, and bevacizumab (GDB) in metastatic pancreas cancer
Authors: V. J. Picozzi, L. A. Canlas, P. L. Sicuro, T. W. Malpass
Journal: Journal of Clinical Oncology (2009)

4606 Background: Metastatic pancreas cancer (MPC) remains identified with poor outcome. Benchmark response statistics in MPC include response rate (RR) 20–30%, time to disease progression (TTP) 3.5–5.5 mo, median overall survival (OS) 6–9 mo and 1- year (yr) OS 20–30%. At our center, adding docetaxel (D) to G in MPC produced 6.0 mo TTP and 10.5 mo OS (Jacobs et.al. Canc Invest 2004). As bevacizumab (B) added to combination chemotherapy has produced major improvement in OS for other cancers (e.g. colon cancer), we chose to study the GDB regimen in MPC. Methods: Our study was phase II, single-phase. Eligiblity criteria included 1) diagnosis of MPC, 2) chemotherapy naivity, 3) ECOG performance status 0 /1, 4) organ function adequate for therapy. Therapy included G 1000 mg/m 2 IV bolus, D 40 mg/m 2 IV and B 10 mg/kg IV every 2 weeks (wks) for 1 yr unless disease progression or prohibitive treatment toxicity occurred. Patients were radiographically restaged every 8 wks. Primary endpoint was TTP. Secondary endpoints included therapy toxicity, radiographic RR (RECIST criteria), tumor marker RR (CA 19.9) and OS. Results: Of 27 enrolled patients (pts), 25 pts are currently evaluable for response, 24 pts for TTP. Median age is 58 yrs. Primary metastatic disease sites were liver (n=18), peritoneum ( n=6), lymph node ( n=2) and lung (n=1). 7/27 pts (26%) experienced grade 3 or higher treatment-related toxicity, including pulmonary (n=3), neutropenia (n=3), bleeding events (n=3), VTE (n=2), hypertension (n=1), hypokalemia (n=1) and skin rash (n=1). 1 pt died from respiratory failure, possibly therapy-related. To date, disease control at 8 wks is 100% (24/24 pts) radiographic RR is 48% (12/25 pts) and tumor marker RR is 95% (18/19 evaluable pts expressed CA19.9, median decline 80%, 5 pts normalized) . Of 24 pts evaluable for TTP, 9/18 (50%) initial pts achieved &gt; 9 mo TTP (range 9.2–18.5 mo); the remaining 6 pts continue progression-free on therapy (range 2+-7+ mo). Median OS has not been reached and will be &gt; 8.3 mo. Response data will be updated at the meeting. Conclusions: 1) The GDB regimen is overall well-tolerated; pulmonary toxicity was the major therapy-related toxicity concern. 2) GDB is significantly active in MPC as witnessed by response rates achieved. 3) Further study of the GDB regimen in MPC is warranted. [Table: see text]
Clinical and immunological analysis of melanoma patients receiving immunization using particle-mediated gene transfer of genes for gp100 and GM-CSF into uninvolved skin
Authors: R. Cassaday, P. Sondel, D. King, T. Warner, A. Bridges, J. Gan, H. Schalch, J. Hank, D. Mahvi, M. Albertini
Journal: Journal of Clinical Oncology (2006)

13033 Background: To investigate a new method of activating melanoma-specific immune responses, we examined in vivo particle-mediated gene transfer (PMGT) of cDNAs for gp100 and GM-CSF into uninvolved skin of melanoma patients (pts). We now report the analysis of a completed Phase I clinical study. Methods: Two treatment groups of 6 pts each were evaluated. Group I received PMGT with cDNA for gp100 during each 3 week cycle; Group II received PMGT with cDNA for GM-CSF followed 3 days later by PMGT for gp100 at the same site. PMGT used 0.25 ug DNA and 250 ug gold/treatment. Endpoints included vaccine toxicity, transgene expression, immunological activation, and antitumor effects. Results: No systemic toxicity could be attributed to the vaccines, while local toxicity in both groups included mild erythema and induration which resolved within 2 weeks. Monitoring for autoimmunity showed no induction of pathologic autoantibodies. Biopsies of vaccine sites obtained 2 days after the gp100 PMGT showed 16% of gold beads to be in the dermis in Group I vs 3% in Group II, suggesting the prior GM-CSF PMGT inhibited bead penetration (p &lt; 0.001 by chi-square; each bead penetration was analyzed as an independent event). Biopsies in Group I obtained 2 days after vaccination showed 16% of beads in the dermis vs 22% after 4 days (p &lt; 0.001 by chi-square; each bead penetration was analyzed as an independent event). Transgene expression in vaccinated skin sites was detected by ELISA (GM-CSF) and IHC (gp100). One of 4 HLA-A2+ subjects showed a 5 × 5-mm DTH response to gp100 peptide 210M after Cycle 1. Preliminary in vitro studies suggest minimal immunological activation. Of 4 pts who enrolled with no evidence of disease, 2 remain disease-free after 61–73 months of follow-up. Conclusions: PMGT with cDNA for gp100 and GM-CSF yields transgene expression in normal human skin with minimal local or systemic toxicity. Pathologic autoimmunity was not demonstrated. Bead concentration in the dermis increases over time, suggesting persistence of beads in this skin level. Conclusions related to melanoma-specific immune induction await T-cell and antibody studies. Supported in part by the UW General Clinical Research Center (M01 RR03186). No significant financial relationships to disclose.
Development of integrated high-resolution three-dimensional MRI and computational modelling techniques to identify novel genetic and anthropometric determinants of cardiac form and function
Authors: Antonio de Marvao, Hannah Meyer, Timothy Dawes, Catherine Francis, Wenzhe Shi, Wenjia Bai, Daniel Rueckert, Ewan Birney, Declan P O'Regan, Stuart Cook
Journal: The Lancet (2016)
TLR3 LIGAND POLY I:C AMELIORATES ALCOHOLIC STEATOHEPATITIS OF MICE VIA IL-10 MEDIATED SUPPRESSION OF KUPFFER CELLS AND HEPATIC STELLATE CELLS
Authors: Jin-Seok Byun, Yang-Gun Suh, Hyon-Seung Yi, Young-Sun Lee, Heui-La Kim, Won-il Jeong
Journal: Hepatology (2011)
A ban on smoking in psychiatric hospitals would reduce self burn injuries
Authors: Natasha L Wielogorska, Victoria Harries, Daniel Gearon, Baljit Dheansa
Journal: BMJ (2016)

The head to head debate on whether psychiatric hospitals should completely ban smoking provided a balanced summary of the social, ethical, and risk related issues surrounding the debate,1 but another important concern warrants discussion.

The role of smoking related paraphernalia in deliberate self burn injury is well documented. Common mechanisms of self burn injury include the use of cigarettes, lighters, aerosols, and …
Sputum mast cell subtypes relate to eosinophilia and corticosteroid response in asthma
Authors: Gang Wang, Katherine J. Baines, Juan Juan Fu, Lisa G. Wood, Jodie L. Simpson, Vanessa M. McDonald, Douglas C. Cowan, D. Robin Taylor, Jan O. Cowan, Peter G. Gibson
Journal: European Respiratory Journal (2015)

Mast cells are a resident inflammatory cell of the airways, involved in both the innate and adaptive immune response. The relationship between mast cells and inflammatory phenotypes and treatment response of asthma is not clear. Clinical characteristics of subjects with stable asthma (n=55), inflammatory cell counts and gene expression microarrays in induced sputum were analysed. Sputum mast cell subtypes were determined by molecular phenotyping based on expression of mast cell biomarkers (tryptase ( TPSAB1 ), chymase ( CMA1 ) and carboxypeptidase A3 ( CPA3 )). Effects of mast cell subtypes on steroid response were observed in a prospective cohort study (n=50). MC T (n=18) and MC T/CPA3 (mRNA expression of TPSAB1 and CPA3 ; n=29) subtypes were identified, as well as a group without mast cell gene expression (n=8). The MC T/CPA3 subtype had elevated exhaled nitric oxide fraction, sputum eosinophils, bronchial sensitivity and reactivity, and poorer asthma control. This was accompanied by upregulation of 13 genes. Multivariable logistic regression identified CPA3 (OR 1.21, p=0.004) rather than TPSAB1 (OR 0.92, p=0.502) as a determinant of eosinophilic asthma. The MC T/CPA3 subtype had a better clinical response and reduced signature gene expression with corticosteroid treatment. Sputum mast cell subtypes of asthma can be defined by a molecular phenotyping approach. The MC T/CPA3 subtype demonstrated increased bronchial sensitivity and reactivity, and signature gene expression, which was associated with airway eosinophilia and greater corticosteroid responsiveness.