tbuckley/cabot-search huggingface dataset:
Human recombinant erythropoietic agents (rHuEPO) do not induce changes in circulating levels of endoglin and vascular endothelial growth factor (VEGF) in anaemic cancer patients
Authors: A. Ocana, A. Rodríguez-Barbero, M. Pericacho, L. Bellido, E. Fonseca, C. Delgado, D. Soto de Prado, J. J. Cruz- Hernández, J. M. López-Novoa
Journal: Journal of Clinical Oncology (2007)

19569 Background: The expression of Erythropoietin (EPO) receptors on cancer cells and the correlation of EPO receptor levels with angiogenesis and progression in some cancers have suggested that EPO could acts directly as an angiogenic factor. The purpose of this study was to assess the effect of treatment with human recombinant erythropoietic agents (rHuEPO) in cancer patients with chemotherapy-induced anaemia on Endoglin and Vascular Endothelial Growth Factor (VEGF) circulating levels as a possible marker of angiogenesis. Methods: Endoglin and VEGF were measured in serum samples from 25 cancer patients with chemotherapy-induced anaemia before and after 3 to 4 weeks of treatment with rHuEPO (Epoetin alfa 150 UI/Kg three times per week; darbepoetin alfa 150 mcg/weekly). A group of 28 healthy voluntaries were used as control. Endoglin and VEGF were analyzed using an ELISA commercial Kit (R&amp;D Systems; Ciudad-Pais). T- student test was used to study the association between variables. Paired comparisons before and after treatment were performed using the Wilcoxon rank-sum test. Results: VEGF serum levels were significantly higher in cancer patients than in controls (476,66±72,56 pg/ml versus 227,34±24,58 pg/ml, p&lt;0.001, respectively). Endoglin levels were significantly higher in patients than controls, although this difference did not reach statistical significance (4.75±0.30ng/ml versus 4.18±0.12 ng/ml, p=0.075). Similar results were found in the different subgroups of patients (Breast cancer, endoglin p=0.019; VEGF p=0.009; Colon cancer, endoglin p=0.084; VEGF p&lt;0.001). Using the Wilcoxon rank-sum test no statistically significant differences in endoglin (p=0.510) and VEGF (p=0.313) serum levels were found between samples obtained before and after treatment with rHuEPO agents. When considering the type of rHuEPO, no differences were observed. In a similar manner, no difference was observed depending on chemotherapy regimen or cancer type. Conclusions: Although the follow up is short and the number of patients is small, our exploratory results do not support that rHuEpo treatment in anaemic cancer patients induce angiogenic serum markers. No significant financial relationships to disclose.
Anal sphincter disruption from a snowboarding injury
Authors: A Huang, C Kellett, G A D Mcpherson
Journal: Journal of the Royal Society of Medicine (1998)

As snowboarding becomes increasingly popular, the number of accidents increasesl. The pattern of injuries is different from that in downhill skiers, upper limb injuries being more likely in snowboarders (especially beginners), knee and thumb injuries in skiers2. Over two-thirds of snowboarding accidents occur on icy or hard courses3. Non-orthopaedic lesions in snowboarders have included splenic as well as chest, head and spinal injuries4'5. Anal sphincteric disruption has not been reported.
Abstract 335: Murine Model of Chronic Right Ventricular Diastolic Heart Failure Is Associated with Energetic Alterations and Extracellular Matrix Remodeling
Authors: Sushma Reddy, Mingming Zhao, Dong-Qing Hu, Giovanni Fajardo, Ethan Katznelson, Joshua Spin, Frandics P Chan, Daniel Bernstein
Journal: Circulation Research (2012)

Introduction: Pulmonary insufficiency (PI) is a common long-term complication after repair of congenital heart diseases such as tetralogy of Fallot, causing progressive right ventricular (RV) dilation and eventual RV failure. We characterize the physiologic and molecular characteristics of the first murine model of RV volume overload Methods: PI was created by entrapping the pulmonary valve leaflets with 2 sutures. Echo, MRI, catheterization and exercise testing were compared to sham controls at 1, 3 and 6 mos. RNA from RV free wall was hybridized to Agilent whole-genome microarrays. Results: Data is presented as sham vs. PI at 1, 3 and 6 mos (*p&lt;0.05). PI resulted in increased RV end-diastolic volume (5.6±1.4 vs. 8.7±2.5, 9.8±1.3, 10.5±1.1μ l*) and diastolic heart failure: early reversal of E/A ratio followed by pseudonormalization (1.04±0.07 vs. 0.87±0.15, 0.82±0.17 and 0.96±0.16*), elevated RV end-diastolic pressure (2.7±0.5 vs. 7.6±1.3, 6.9±1.6 and 7±1mmHg*) and decreased exercise capacity (30±2.3 vs. 26±0.8, 26±2 and 22±2.6min*). Systolic function (RV outflow tract shortening) was relatively preserved (49±6 vs. 39±4, 44±3 and 41±3%, p=NS). At 1 mo, 372 genes were downregulated, with metabolic pathways, including Complex I, III and V, and G protein-coupled receptor signaling being the most enriched. At 3 mos, 434 genes were upregulated featuring numerous collagen genes, while 307 were downregulated, including fatty acid transport and Ca2+ signaling. During this time course, pathways involving TGFβ signaling, extracellular matrix and p53 signaling transitioned from down- to up-regulated. Key hubs in upregulated gene networks were TGFβ1, thrombospondin1, VEGFa, TNFα and GSK3β while NFκB1 was a downregulated hub. RV Fibrosis increased over time (0 vs. 0.6±0.5, 5.9±2.9, 3.92±0.2%*). Conclusion: We describe a novel murine model of chronic RV volume overload which recapitulates many aspects of clinical disease including RV dilation, impaired relaxation and decreased exercise capacity but preserved RV systolic function. Gene expression changes suggest mitochondrial bioenergetic dysfunction, ECM remodeling, enhanced TGF-β signaling and apoptosis. Many of these processes of RV diastolic heart failure are also known mechanisms of LV failure.
Late-breaking abstract: Airway remodelling induced by ADAM33 is reversible
Authors: Elizabeth R Davies, Liqian Zhang, Stephen T Holgate, Donna E Davies, Jeffrey A. Whitsett, Hans Michael Haitchi
Journal: European Respiratory Journal (2014)

Background   ADAM33, an asthma susceptibility gene associated with BHR, is a membrane-anchored protein with metalloprotease (MP) activity that can be released in a soluble form. Soluble (s)ADAM33-MP is increased in asthmatic airways and inversely correlated with FEV1.   Aims   We now investigate if human(h) sADAM33-MP causes asthma-like airway remodelling in mouse lungs and if this is reversible when ADAM33 expression is ablated.   Methods   A Doxycycline (Dox) inducible transgenic mouse expressing hsADAM33-MP in the airways was generated. Dox was administered to double- and single-transgenic control mice to induce hsADAM33 expression until 1 and 2 months post partum and lungs were harvested for mRNA, protein and immunohistochemical analyses.   Results   Induction of hsADAM33-MP for 1 and 2 months resulted in significantly increased airway  α-smooth muscle actin (α-Sma), fibronectin, collagens I, III, IV, and Pecam-1  mRNAs, suggesting regulation of pulmonary myogenesis, fibrogenesis, and angiogenesis. There was no evidence for airway inflammation. In the group where Dox was stopped at 1 month and analysed at 2 months, these markers were reversed to baseline. Consistent with this, immunohistochemistry indicated reversibility of airway remodelling as a decrease in smooth muscle, collagen and vessel formation in lung sections from hsADAM33 expressing mice.   Conclusions   For the first time, this study demonstrates that expression of hsADAM33-MP in mouse airways induces airway remodelling that is both independent of inflammation and reversible when induction of hsADAM33 is arrested. These findings support the hypothesis that inhibition of hsADAM33-MP is a therapeutic target for treatment or prevention of airway remodelling in asthma.
구연 : 블루벨 ; 한국의 간세포암 환자 중 치료적 종괴제거술(경피적에탄올주입술, 고주파절제술 또는 수술적 절제술)을 받은 환자에서 (주)이노셀 이뮨셀-엘씨(R) 처치군과 무처치군의 유효성 및 안전성 평가를 위한 무작위배정, 공개, 다기관 제 3상 임상시험: 중간분석결과 (초)
Authors: 이준혁, 임영석, 송태진, 연종은, 윤정환
Journal: Clinical and Molecular Hepatology (2010)
Genetic Associations of Primary Angle-Closure Disease
Authors: Shi Song Rong, Fang Yao Tang, Wai Kit Chu, Li Ma, Jason C.S. Yam, Shu Min Tang, Jian Li, Hong Gu, Alvin L. Young, Clement C. Tham, Chi Pui Pang, Li Jia Chen
Journal: Ophthalmology (2016)
Phase I study of CPT-11 and etoposide in patients with refractory solid tumors.
Authors: A Karato, Y Sasaki, T Shinkai, K Eguchi, T Tamura, Y Ohe, F Oshita, M Nishio, H Kunikane, H Arioka
Journal: Journal of Clinical Oncology (1993)

PURPOSE To determine the maximum-tolerated dose (MTD) and acceptable dose level of a cytotoxic regimen of CPT-11, a new camptothecin derivative, in combination with etoposide (VP-16) and to describe the principal toxicities associated with it. PATIENTS AND METHODS Patients with refractory solid tumors received VP-16 and CPT-11 daily for 3 consecutive days (days 1 through 3) every 3 or 4 weeks. Groups entered the trial at escalating CPT-11/VP-16 dose levels of 40/60, 60/60, 60/80, and 80/60 mg/m2. Thirty-four patients entered this study, of whom 33 were assessable for toxicity and 22 for therapeutic efficacy. RESULTS Granulocytopenia was so severe that this regimen required supportive therapy with recombinant human granulocyte colony-stimulating factor (G-CSF). The majority of the patients experienced a 5% weight loss and diarrhea was the dose-limiting toxicity. The MTDs were 60/80 and 80/60 mg/m2 administered on days 1 through 3. Five of seven previously untreated patients with non-small-cell lung cancer (NSCLC) achieved partial responses (PRs) to this therapy, as did two with NSCLC who had received prior chemotherapy, two with head and neck cancer, and one with an adenocarcinoma (primary tumor unknown). CONCLUSION The recommended dose of CPT-11/VP-16 for this regimen with G-CSF is 60/60 mg/m2 on days 1 through 3 every 3 to 4 weeks. We suggest that the combination of topoisomerase I and II inhibitors is likely to be an effective treatment strategy. The activity of this regimen against NSCLC is particularly encouraging and should be evaluated in a phase II trial.
The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression
Authors: Tatsuya Atsumi, Kazuhiko Yamamoto, Tsutomu Takeuchi, Hisashi Yamanaka, Naoki Ishiguro, Yoshiya Tanaka, Katsumi Eguchi, Akira Watanabe, Hideki Origasa, Shinsuke Yasuda, Yuji Yamanishi, Yasuhiko Kita, Tsukasa Matsubara, Masahiro Iwamoto, Toshiharu Shoji, Toshiyuki Okada, Désirée van der Heijde, Nobuyuki Miyasaka, Takao Koike
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> To evaluate efficacy and safety of combination therapy using certolizumab pegol (CZP) and methotrexate (MTX) as first-line treatment for MTX-naive, early rheumatoid arthritis (RA) with poor prognostic factors, compared with MTX alone. <h3>Methods</h3> MTX-naive, early RA patients with ≤12 months persistent disease, high anti-cyclic citrullinated peptide, and either rheumatoid factor positive and/or presence of bone erosions were enrolled in this multicentre, double-blind, randomised placebo (PBO)-controlled study. Patients were randomised 1:1 to CZP+MTX or PBO+MTX for 52 weeks. Primary endpoint was inhibition of radiographic progression (change from baseline in modified Total Sharp Score (mTSS CFB)) at week 52. Secondary endpoints were mTSS CFB at week 24, and clinical remission rates at weeks 24 and 52. <h3>Results</h3> 316 patients randomised to CZP+MTX (n=159) or PBO+MTX (n=157) had comparable baseline characteristics reflecting features of early RA (mean disease duration: 4.0 vs 4.3 months; Disease Activity Score 28-joint assessment (DAS28)) (erythrocyte sedimentation rate (ESR)): 5.4 vs 5.5; mTSS: 5.2 vs 6.0). CZP+MTX group showed significantly greater inhibition of radiographic progression relative to PBO+MTX at week 52 (mTSS CFB=0.36 vs 1.58; p&lt;0.001) and week 24 (mTSS CFB=0.26 vs 0.86; p=0.003). Clinical remission rates (Simple Disease Activity Index, Boolean and DAS28 (ESR)) of the CZP+MTX group were significantly higher compared with those of the PBO+MTX group, at weeks 24 and 52. Safety results in both groups were similar, with no new safety signals observed with addition of CZP to MTX. <h3>Conclusions</h3> In MTX-naive early RA patients with poor prognostic factors, CZP+MTX significantly inhibited structural damage and reduced RA signs and symptoms, demonstrating the efficacy of CZP in these patients. <h3>Trial registration number</h3> (NCT01451203).
Circulating tumor cells during and beyond maintenance therapy with SERM or aromatase inhibitors for decision making in long-term survivorship.
Authors: Katharina Pachmann, Carola Rabenstein, Oumar Camara, Matthias Rengsberger, Ingo B. Runnebaum, Ulrich A. Pachmann
Journal: Journal of Clinical Oncology (2014)

119 Background: Although current guidelines still support 5 years of hormone blocking therapy after primary breast cancer due to earlier results showing no benefit of longer treatment, recent data have shown that longer treatment with tamoxifen can better reduce recurrence and death. However, side effects with this therapy can be considerable and compliance declines with time. We, here, report data on monitoring circulating epithelial tumor cells (CETC) beyond maintenance therapy showing that even if maintenance therapy with SERM or aromatase inhibitors had been effective in reducing tumor cells in blood, there can be a reincrease after the end of maintenance therapy and that this is highly correlated with relapse. Methods: 7.5ml of anti-coagulated blood was drawn before the start of chemotherapy, after each cycle and after the end of chemotherapy. Using a nondissipative approach with only red blood cell lysis the white blood cells including the tumor cells were stained with a fluorescent labelled anti-epithelial antibody, positive events counted using an automated image analysis microscope and calculated per volume blood. Results: 96 patients with nonmetastatic breat cancer were observed beyond maintenance treatment with hormone blocking therapy. Results on CETC were evaluable from 35 patients even after completion of therapy. Increasing cell numbers after the end of therapy were able to predict relapsing from long term relapse free survivors (p = 0.0001). Conclusions: In breast cancer, a debate has been reiinitated with respect to the length of maintenane treatment. Even if hormone blocking maintenance treatment is capable of reducing or even eliminating tumor cells circulating in peripheral blood and this is related to improved relapse free survival there may remain tumor cells in the body capable of re-growing and leading to late relapse. Monitoring of CETC in peripheral blood even after completion of maintenance therapy can early predict imminent relapse and help to decide whether to reinitiate hormone blocking therapy.
Susceptibility of Cells Transformed by Polyoma Virus and Simian Virus 40 to the Cytotoxic Effect of the Carcinogenic Hydrocarbon Benzo[&lt;italic&gt;a&lt;/italic&gt;]pyrene
Authors: Huberman, Eliezer, Sachs, Leo
Journal: JNCI Journal of the National Cancer Institute (1968)

Journal Article Susceptibility of Cells Transformed by Polyoma Virus and Simian Virus 40 to the Cytotoxic Effect of the Carcinogenic Hydrocarbon Benzo[a]pyrene Get access Eliezer Huberman, Eliezer Huberman Section of Genetics, Weizmann Institute of Science, Rehovoth, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar Leo Sachs Leo Sachs Section of Genetics, Weizmann Institute of Science, Rehovoth, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 40, Issue 2, February 1968, Pages 329–336, https://doi.org/10.1093/jnci/40.2.329 Published: 01 February 1968 Article history Received: 27 June 1967 Accepted: 23 August 1967 Published: 01 February 1968
춘계학술대회 : 구연 ; C형간염 : 한국인 만성 C형간염환자에서 pegylated-interferon과 ribavirin 병합요법의 재치료 성적
Authors: 강풍, 백승운, 신동현, 길재숙, 송순미, 곽금연, 최문석, 이준혁, 고광철, 유병철
Journal: Clinical and Molecular Hepatology (2007)
Definition and Morphologic Features of Chromosome Pulverization: A Hypothesis to Explain the Phenomenon&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Avery A. Sandberg, Takao Aya, Tatsuro Ikeuchi, Herbert Weinfeld
Journal: JNCI Journal of the National Cancer Institute (1970)

The chromosome pulverization phenomenon and cell fusion were studied in a Chinese hamster cell line, Don, during the initial period of Sendai virus treatment. Pulverized nuclei in the G2 phase or prophase were characterized by variety in morphologic appearance. These phases were recognized by the presence of paired chromatin particles in the pulverized nuclei. Pulverized nuclei in the S phase of the cell cycle had a relatively constant morphologic picture consisting of fine particles or threads. These observations were confirmed by the autoradiographic behavior of the pulverized nuclei. More difficult to define were pulverizations in the G1 phase. It was concluded that the morphology of chromosome pulverization basically depended on the cellular phase at which exposure to the virus and fusion occurred. Metaphase chromosomes are extremely resistant to pulverization, with cells becoming less resistant in the anaphasic, telophasic, and interphasic parts of the cycle in the order cited. The nuclei of interphase cells fused with anaphase or telophase cells undergo pulverization less frequently than when fusion occurs with metaphase cells. The chromosome pulverization phenomenon is defined as a total loss of nuclear architectural integrity in fused, multinucleate cells in which the presence of an intact, mitotic nucleus is a prerequisite for the induction of the phenomenon. A hypothesis is advanced that implicates the system responsible for nuclear membrane lysis in the mitotic cell in the induction of chromosome pulverization. This hypothesis is explained in terms of morphologic features observed in experiments with Sendai-virus-induced cellular fusions containing chromosome pulverizations.
Epidermal Growth Factor Receptor (EGFr) status detection in correlation to objective response on cetuximab-based therapy in patients (pts) with advanced colorectal cancer (ACC)
Authors: A. Gevorgyan, M. Di Bartolomeo, S. Andreola, M. Orsenigo, P. Casieri, S. Signoroni, D. Cortinovis, A. Martinetti, S. Pilotti, E. Bajetta
Journal: Journal of Clinical Oncology (2007)

21070 Background: In current clinical practice Cetuximab represents a standard therapy for Irinotecan resistant pts with ACC, where EGFR-immunohistochemistry (IHC) evaluation is positive. In absence of reliable molecular predictors of the clinical benefit to anti-EGFR therapy, we have studied EGFR protein expression and gene status in order to correlate them to the clinical response. Methods: We investigated 40 primary colorectal carcinoma specimens. EGFR-protein expression was evaluated by Immunohistochemistry (IHC) using PharmDX-Kit DAKO Cytomation. IHC evaluation was performed using combined score based on the sum of percentage of positive cells and the staining of each sample. We identified three EGFR-score categories: 0–2, 3–5, 6–7 corresponding to low, intermediate and high expression respectively. EGFR-genetic status was conducted by Dual-Colour FISH (LSI EGFR-probe Vysis Inc).Gene and chromosome 7 copy numbers were identified by fluorescence in situ hybridization (FISH-LSI EGFR-Dual-colour-probe Vysis-Inc) as follows: tumor samples had a high EGFR-gene copy number if there was high polysomy ( 4-copies 40% of cells) or gene amplification (gene-clusters, gene/chromosome ratio per cell of 2, 15 copies of EGFR/ cell in 10% of cells) . The analysis of clinical data from all patients treated with Cetuximab (400–250mg/m 2 /w) and Irinotecan (300mg/m 2 /d1q21) was then performed. Results: EGFR-(IHC) high score was observed in 7pts from which only 2 had an objective response (OR). Intermediate (13pts) with 3 OR, low (12pts) with 1 OR and negative (8pts) with 2OR. Main FISH patterns were: high polisomy/amplification in 8pts with no response on cetuximab therapy. Low polisomy described in 19pts with 3 cases of disease remission. Disomy in 13pts with 5OR. No relationship was detected between IHC-score evaluation and FISH pattern. The clinical benefit (OR+stable disease =6months) was 65% in score-group 0–2; whereas 46% and 57% in groups 3–5/6–7 respectively, without statistical significance. Conclusion: According to our experience, IHC and FISH are unable to provide adequate selection criteria for the patients with different EGFR-status expression, who can benefit from Cetuximab therapy. No significant financial relationships to disclose.
The paradoxical effect of targeted antivascular agents in the therapy of CNS malignancies
Authors: E. A. Neuwelt, E. Frenkel
Journal: Journal of Clinical Oncology (2009)

2013 Background: The rationale of vascular targeted agents (i.e., inhibitors of vascular endothelial growth factors [VEGF] or endothelial intergrins) in the therapy of central nervous system (CNS) malignancies is based upon the concept that normalization of tumor vasculature, with a decrease in tumor interstitial pressure, will improve access of cytoreductive drugs. However, previous studies in our laboratory have raised the serious concern that these agents rapidly normalize the blood-brain barrier (BBB) and therefore may result in restoration of the low permeability characteristics of the BBB. Methods: To evaluate this, we studied the effects of bevacizumab, an anti-VEGF agent on tumor vasculature by MRI, using gadolinium-enhanced T1 weighted sequences to assess permeability and the blood pool agent ferumoxytol to assess blood volume. Patient imaging studies were done on IRB approved protocols. Results: Utilizing two rat brain tumor models, we documented that bevacizumab rapidly decreases tumor enhancement, a pattern equivalent to administration of high dose steroid therapy. Correlative studies in rats and humans exploiting T2 weighted imaging, demonstrated resolution of tumor enhancement with occasional concomitant increase in tumor volume. In a parallel evaluation, pseudo-progression was seen in 9 of 14 glioblastoma patients treated with combined chemo-radiation. These inflammatory responses to treatment, when examined by dynamic MRI, were associated with a transient increase in tumor permeability and decreased cerebral blood volume. This increase could be blocked or reduced by decreasing vascular permeability with bevacizumab. Conclusions: These animal and human studies provide evidence that anti-vascular agents have a steroid-like effect; and in the CNS, may result in reduced delivery of cytoreductive agents to the tumor, thereby compromising standard chemo-radiotherapy. [Table: see text]