tbuckley/cabot-search huggingface dataset:
Phase I/II study of 72-hour infusional paclitaxel and doxorubicin with granulocyte colony-stimulating factor in patients with metastatic breast cancer.
Authors: J S Fisherman, K H Cowan, M Noone, A Denicoff, S Berg, D Poplack, F Balis, D Venzon, M McCabe, B Goldspiel, C Chow, F P Ognibene, J O'Shaughnessy
Journal: Journal of Clinical Oncology (1996)

PURPOSE We conducted a phase I/II trial of concurrently administered 72-hour infusional paclitaxel and doxorubicin in combination with granulocyte colony-stimulating factor (G-CSF) in patients with previously untreated metastatic breast cancer and bidimensionally measurable disease. PATIENTS AND METHODS We defined the maximum-tolerated dose (MTD) of concurrent paclitaxel and doxorubicin administration and then studied potential pharmacokinetic interactions between the two drugs. Forty-two patients who had not received prior chemotherapy for metastatic breast cancer received 296 total cycles of paclitaxel and doxorubicin with G-CSF. RESULTS The MTD was determined to be paclitaxel 180 mg/m2 and doxorubicin 60 mg/m2 each by 72-hour infusion with G-CSF. Diarrhea was the dose-limiting toxicity (DLT) of this combination, with three of three patients developing abdominal computed tomographic (CT) scan evidence of typhlitis (cecal thickening) at the dose level above the MTD. All patients developed grade 4 neutropenia (absolute neutrophil count [ANC] &lt; 500 microL), generally less than 5 days in duration. This combination was generally safely administered at dose levels at or below the MTD. The overall response rate was 72% (28 of 39 patients; 95% confidence interval [CI], 55% to 85%), with 8% complete responses (CRs) (three of 39; 95% CI, 2% to 21%) and a median response duration of 9 months. The median overall survival time for all patients is 23 months, with a median follow-up duration of 28 months. Pharmacokinetic studies showed that administration of paclitaxel and doxorubicin together by 72-hour infusion did not affect the steady-state concentrations of either drug. CONCLUSION Concurrent 72-hour infusional paclitaxel and doxorubicin can be administered safely, but is associated with significant toxicity. The overall response rate of this combination in untreated metastatic breast cancer patients is similar to that achieved with other doxorubicin-based combination regimens. The modest complete response rate achieved suggests that this schedule of paclitaxel and doxorubicin administration does not produce significant additive or synergistic cytotoxicity against breast cancer.
Diverse functions of defensins and other antimicrobial peptides in periodontal tissues
Authors: Henrik Dommisch, Søren Jepsen
Journal: Periodontology 2000 (2015)

Abstract Defensins are antimicrobial peptides that exhibit direct microbicidal activity as well as mediator‐like functions by, for example, activating immature dendritic cells. This review focuses on defensins and other antimicrobial peptides that are present in periodontal tissues. Their antimicrobial capacity against periodontal microorganisms, their regulation and their expression profiles during periodontal diseases is discussed. As antimicrobial peptides may possess great potential for new diagnostic, preventive and therapeutic strategies, a better understanding of how antimicrobial peptides are regulated as part of the innate host immune response is crucial.
Amplification in human breast cancer of a gene encoding a c-myc mRNA-binding protein.
Authors: Glenn A. Doyle, Jeanne M. Bourdeau-Heller, Stephanie Coulthard, Lorraine F. Meisner, Jeffrey Ross
Journal: Cancer Research (2000)

The coding region determinant-binding protein (CRD-BP) binds in vitro to c-myc mRNA and is thought to stabilize the mRNA and increase c-Myc protein abundance. The CRD-BP gene has 15 exons and 14 introns, is single-copy, and is located on chromosome 11 in mice and 17 in humans, close to HER-2/neu. The CRD-BP gene is moderately amplified in 12 of 40 human breast cancers; it is highly amplified in 2 others (14.4 and 20 copies). Despite their proximity, CRD-BP and HER-2/neu genes can be amplified independently. Amplification of a gene that might up-regulate c-Myc abundance could accelerate breast cancer.
The dynamic change of inflammatory cytokines treated by specific immunity and the analysis of the dynamic change of house dust mites' components-IgE and IgG4
Authors: Peiyan Zheng, Bao Sun, Nili Wei, Wenting Luo, Huimin Huang
Journal: European Respiratory Journal (2014)

Objectives:   This project aimed to Study the correlation between inflammatory cytokines and the dynamic change of sIgE and sIgG4 of Der p, Der p1 and Der p2(3 allergens)during Specific immunotherapy (SIT).   Methods:   Serum inflammatory cytokines and 3 allergens were analyzed from 55 patients with asthma and/or rhinitis SIT.the level of eight kinds of inflammatory cytokines 8 were detected, therefore, the dynamic change & correlation of house dust mites and its components-sIgE and sIgG4 of Der p1 and Der p2 were analyzed.   Results:   There was no significant difference in eight kinds of inflammatory cytokines before and after SIT.Before treatment,there was a correlation in level of IL-5 secreted by Th2 ,level of Der p-IgE,Der p-IgG4 and level of Der p2-IgG4.After17W, there were correlations in IL-5 & Der p2-IgE and three kinds of allergenslevel of IgG4,IL-17 and IgG4 of three kinds of allergens,level of Der p2-IgE and IFN-γ secreted by Th1.After57W,there were correlations in IL-5 and Der p-IgE,Der p1-IgE and Der p1-IgG4,level of IL-8 and level of IgG4.From 0-17 W,there was positive correlation in the increasing range of house dust mites9components- sIgG4 of Der p1&Der p2 and the D-value of IL-5&IL-17 before and after treatment.Moreover,from 17 to 57 weeks,there was negative correlation in the increasing range of sIgG4 of Der p & Der p2 and the D-value of TNF-α before and after treatment.   Conclusions:   SIT was a dynamic immune process and with the process of SIT,immune status of SIT was reflected by house dust mites and its main components-IgE&IgG4of Der p1&Der p2 in clinic detection.
Mucosal human papillomavirus types in squamous cell carcinomas of the uterine cervix and subsequently on fingers
Authors: O. Forslund, P. Nordin, B.G. Hansson
Journal: British Journal of Dermatology (2000)

Human papillomavirus (HPV), especially type 16, is causally involved in the pathogenesis of anogenital cancer. There is an increasing number of reports of HPV infections in squamous cell carcinoma (SCC) of the fingers. A search of the Swedish cancer register covering the period 1958-94 inclusive for women with a history of genital and upper extremity SCC revealed 63 cases. Archival material from both cervical and cutaneous lesions was traced and analysed for the presence of HPV DNA in 32 of these patients. A newly developed 'neighbour primer' polymerase chain reaction (PCR) for HPV 16 DNA, aimed at overcoming the obstacle of cross-linked target DNA, was shown to be superior to conventional general and type-specific HPV PCR tests. HPV DNA was significantly more frequently found in digital tumours than in tumours at other cutaneous sites of the upper extremities [67% (10 of 15) vs. 7% (three of 43); P < 0.001]. Among 13 patients with a history of both cervical and finger SCC, HPV 16 was found in cervical samples from seven patients. From five of these seven patients, HPV 16 was also present in the corresponding finger lesions. The results support the hypothesis of a possible transmission of patients' genital HPV infections to fingers.
Treatment results of CHOP-21, CHOEP-21, MACOP-B and PMitCEBO with and without rituximab in young good-prognosis patients with aggressive lymphomas: Rituximab as an “equalizer” in the MInT (MABTHERA International Trial Group) study
Authors: M. G. Pfreundschuh, A. Ho, M. Wolf, E. Cavallin-Stahl, R. Pettengell, I. Vasova, A. Belch, J. Walewski, P.-L. Zinzani, W. Mingrone, M. Loeffler
Journal: Journal of Clinical Oncology (2005)

6529 Background: The addition of rituximab (R) to 6 cycles of CHOP-like regimens in the MInT trial significantly improved overall results and set a new standard in young good-prognosis patients with DLBCL (Blood 2004,104:48a). As CHOEP-21 had been shown to be superior to CHOP-21 without R (NHL-B1 trial; Blood 2004, 104:626), we investigated whether these differences could be confirmed in the MInT trial where participating countries selected 1 of 4 CHOP-like regimens. Methods: Intent-to-treat-analysis of the primary endpoint time-to-treatment-failure (TTF) and the secondary endpoints complete remission (CR) rate and overall survival (OS) of different regimens with or without rituximab. Results: Of 823 evaluable patients, 48% (197/199) were randomized to CHOP-21±R, 44% (180/181) to CHOEP±R, 4% (17/17) to MACOP-B±R and 4% to (16/16) PMitCEBO. All regimens were well balanced for prognostic factors, except for MACOP-B±R with more favorable patients. Numbers for MACOP-B and PMitCEBO are too small for meaningful comparisons. CHOEP-21 was better than CHOP-21 with respect to CR rates (75% vs. 62%, p=0.02) and 2-year TTF (65% vs. 55%; p=0.04), but not overall survival (86% vs. 83%; p=0.67), confirming the results of the NHL-B1 trial. Rituximab significantly increased efficacy of CHOP-21 (2-year TTF 55% vs. 83%) and CHOEP-21 (65% vs. 80%), and there were no more differences between R-CHOEP and R-CHOP (CR: 87 vs. 87%; 2y-TTF: 80 vs. 83%; OS: 93 vs. 97%). Multivariate Cox-modeling adjusting for prognostic factors confirmed these results (disappearance of difference between CHOP and CHOEP efficacy after R). Conclusions: Differences between different CHOP-like regimens disappear when these regimens are combined with rituximab. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche
Role of CT and PET Imaging in Predicting Tumor Recurrence and Survival in Patients with Lung Adenocarcinoma
Authors: Ho Yun Lee, So Won Lee, Kyung Soo Lee, Ji Yun Jeong, Joon Young Choi, O. Jung Kwon, So Hee Song, Eun Young Kim, Jhingook Kim, Young Mog Shim
Journal: Journal of Thoracic Oncology (2015)
Elevated Tryptase concentration In bronchoalveolar lavage fluid from patients with chronic eosinophilic pneumonia
Authors: Mitsuko Kondo, Etsuko Tagaya, Jun Tamaoki
Journal: European Respiratory Journal (2014)

Background; Chronic eosinophilic pneumonia (CEP) generally responds to steroid therapy. However, relapse frequently occurs and prolonged steroid therapy is needed. Tryptase released from activated mast cells is associated with intractable pathogenesis. Little is known of the clinical significance on measurement of tryptase in bronchoalveolar lavage fluid (BALF) from patients with eosinophilic pneumonia. Methods; The BALF from 20 patients with eosinophilic pneumonia [CEP 11 patients, Acute eosinophilic pneumonia (AEP) 4 patients, Drug-induced eosiophilic pneumonia (Drug) 5 patients] was analyzed by B12 a monoclonal antibody-based tryptase immunofluoroassay. The relationship between clinical characteristics and tryptase in BALF was analyzed retrospectively. Results; Tryptase in BALF could be detected in 9 patients (CEP 8, AEP 1; the tryptase-positive group), but not in 11 patients (CEP 3, AEP 3, Drug 5). The concentrations of tryptase in the tryptase-positive group were 2.23 ± 0.20 ng/ml in CEP (n=9, Mean±SE) and 1.0 ng/ml in AEP (n=1). The tryptase concentration was significantly higher in CEP than in AEP and Drug (p < 0.05). The frequency of recurrence was higher in tryptase-positive group. Ten patients with CEP had asthma history. Of them, one patient had allergic bronchopulmonary aspergillosis and two had chronic eosinophilic sinusitis. The weak correlation between tryptase level and serum IgE in CEP was observed. Conclusion ; Tryptase in BALF can be detected in patients with CEP. The tryptase-positive patients with CEP tended to relapse and have complication of asthma. Mast cell tryptase may be associated with intractable pathogenesis in CEP.
Treatment outcome according to tumor ERCC1 expression status in OPUS study patients with metastatic colorectal cancer (mCRC) randomized to FOLFOX4 with/without cetuximab.
Authors: Carsten Bokemeyer, Claus-Henning Köhne, Igor Bondarenko, Anja von Heydebreck, Hans Juergen Grote, Christopher Stroh, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2013)

3537 Background: The OPUS study showed that the addition of cetuximab to infusional 5-fluorouracil/folinic acid + oxaliplatin (FOLFOX4) significantly improved progression-free survival (PFS) and response in the first-line treatment of patients (pts) with KRAS wild-type (wt) mCRC. High level expression in tumors of ERCC1, a protein involved in nucleotide excision repair, has been associated with resistance to platinum-based chemotherapy in a range of tumor types. This analysis assessed outcome according to ERCC1 expression level and treatment group in OPUS study pts. Methods: ERCC1 expression level was assessed by immunohistochemistry (IHC) in all available formalin-fixed paraffin-embedded tumor samples from OPUS study pts. An ERCC1 IHC score on a continuous scale of 0–300 was calculated for each tumor, based on the intensity of nuclear staining and proportion of positive cells. The median IHC score was used to define low (&lt;median) and high (≥median) ERCC1 expression levels and outcome was assessed in low vs high expression groups in both treatment arms. Results: Of 337 OPUS study intention to treat pts, 97 (29%) were evaluable for ERCC1 expression. Pts in the FOLFOX4 arm in the high ERCC1 expression group (n=27) had shorter PFS (median 5.8 vs 9.2 months; hazard ratio, HR 1.63, 95% CI 0.80–3.34) and overall survival (median 11.5 vs 18.5 months; HR 1.75, 95% CI 0.90–3.40) and a lower response rate (33.3% vs 39.1%) compared with those in the low ERCC1 expression group (n=23). To assess the effect of adding cetuximab to FOLFOX4 according to ERCC1 expression level, outcome was assessed in the KRAS wt subgroup of pts. Although low pt numbers precluded the drawing of definitive conclusions, PFS in the high ERCC1 expression group was longer in the FOLFOX4 + cetuximab arm (n=14) compared with the FOLFOX4 arm (n=13; median 7.7 vs 5.8 months), survival was longer (median 19.7 vs 12.0 months) and the response rate was higher (71.4% vs 30.8%). Conclusions: High tumor ERCC1 expression was associated with poor outcome in pts with mCRC receiving first-line platinum-based chemotherapy. The addition of cetuximab to FOLFOX4 may mitigate this effect in those with KRAS wt tumors. Clinical trial information: NCT00125034.
Experts call for tobacco industry to pay for smoking cessation work
Authors: A. O'Dowd
Journal: BMJ (2015)

The tobacco industry should be forced to pay towards smoking cessation efforts in England as part of a new national tobacco control strategy, a multi-agency report has claimed.

Experts have called for a national annual levy on tobacco companies, fresh targets such as a drop in smoking rates to 5% by 2035, a new five year government tobacco strategy for England, and an increase to the tax escalator on tobacco products to 5% above the level of inflation.

The report, Smoking Still Kills ,1 was published on 10 June by the public health charity Action on Smoking and Health (ASH) and was jointly funded by ASH, Cancer Research UK, and the British Heart Foundation. …
Abstract 15280: Differential Release Mechanisms of Muscle-Enriched miRNAs Upon Ischemic Myocardial Injury: Insights from Transcoronary Gradient Measurements
Authors: David M Leistner, Tino Roexe, Stephan Fichtlscherer, Nils Boeckel, Salvatore De Rosa, Marga Muller-Ardogan, Stefanie Dimmeler, Andreas M Zeiher
Journal: Circulation (2012)

Introduction: Micro-RNAs (miRs) act as intracellular mediators in a variety of pathophysiological processes. Recent studies demonstrated that circulating miRs may serve as blood-based biomarkers for cardiac injury. Since the stability of miRs in blood depends on their packaging into microvesicales or their incorporation into protein-complexes, we measured the release of microvesicale-associated or protein-complex-associated miRs into the coronary circulation in patients with CAD with or without myocardial injury. Methods/Results: Blood was simultaneously obtained from the aorta and the coronary sinus during cardiac catheterization in a total of 102 patients (pts) and circulating miRs were measured by PCR in either total EDTA-plasma or in the microvesicle fraction. High-sensitive troponin T (hsTrop) measured in the coronary sinus blood was used to quantificate myocardial injury. In the coronary sinus, the muscle-enriched miRs, miR-499 and miR-133a, were significantly (p<0.001) increased in pts. with elevat...
Global Mapping of the Inc-Human Interactome Reveals that Retromer Restricts Chlamydia Infection
Authors: Kathleen M. Mirrashidi, Cherilyn A. Elwell, Erik Verschueren, Jeffrey R. Johnson, Andrew Frando, John Von Dollen, Oren Rosenberg, Natali Gulbahce, Gwendolyn Jang, Tasha Johnson, Stefanie Jäger, Anusha M. Gopalakrishnan, Jessica Sherry, Joe Dan Dunn, Andrew Olive, Bennett Penn, Michael Shales, Jeffery S. Cox, Michael N. Starnbach, Isabelle Derre, Raphael Valdivia, Nevan J. Krogan, Joanne Engel
Journal: Cell Host & Microbe (2015)
Are the flow independent NO parameters flow dependent
Authors: Marieann Högman, Pekka Meriläinen
Journal: European Respiratory Journal (2011)

Background:  The interest in alveolar NO, one of the flow independent parameters, is increasing since it is elevated in severe and nocturnal asthma and in COPD. The nonlinear approach (Hogman-Merilainen Algorithm) with low, medium and high flow rates has been used to calculate C A NO, D aw NO and C aw NO. The aim was to set how low and how high these flow rates should be.   Methods:  Subjects (n=32), without classifications of disease, volunteered to exhale with eight flow rates between 10 and 350 mL/s. NO was measured by CLD 88sp NO analyzer (ECO Medics AG, Switzerland). The subjects were grouped according to low, normal and high F E NO 0.05 . The correction for axial diffusion was applied (Condorelli  et al.  2004).   Results:  There was a significant difference (p=0.001) in C aw NO and D aw NO (p=0.001) with the use of 30 instead of 10 mL/s. The C A NO values were significantly different with the use of 250 instead of 350 mL/s (p=0.001). The three groups had C A NO of 0.9±0.2, 0.9±0.1 and 0.9±0.3 ppb respectively. With correction of axial diffusion the C A NO became 0.3±0.2, -0.5±0.2 and -2.7±0.6 ppb with majority of values being negative.   Conclusion:  The flow independent NO parameters are flow dependent. With the use of the nonlinear model with the HMA approach to calculate C A NO, D aw NO and C aw NO the flow rates to be used use are 10, 100 and 350 for adults. Further studies have to be done in children that cannot perform these low and high flow rates. Most importantly, the axial diffusion correction is of limited value with the HMA method.  Abbreviation: HMA=Hogman-Merilainen algorithm, C A NO= alveolar NO, C aw NO=airway wall NO, D aw NO=airway transfer factor of NO
A combination phase I study of weekly paclitaxel and 5'-DFUR in patients with unresectable or recurrent gastric cancer in an outpatient setting
Authors: S. Yoshino, M. Oka, S. Hazama, K. Hamano, H. Hayashi, H. Hasegawa, T. Yamamoto, T. Katoh
Journal: Journal of Clinical Oncology (2004)

4228 Background: Paclitaxel (PTX) and 5'-DFUR have single-agent activity in gastric cancer and have distinct mechanisms of action and no overlap of key toxicities. Synergistic interaction between PTX and 5'-DFUR is mediated by taxane-induced up-regulation of thymidine phosphorylase. Objectives: To determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT) and the recommended dose (RD). The DLT was set in low grade to treat the patients in the outpatient clinic. Patients and methods: Eligibility criteria included patients with histologically proven unresectable or recurrent gastric cancer, no requirement of prior chemotherapy, a performance status of 0–2, adequate organ function and written informed consent. PTX was administered by 1-hour intravenous infusion (level 1, 2, 3, 4: 50, 60, 70, 80 mg/m2) weekly for 3 consecutive weeks every 4 weeks. 5'-DFUR was administered orally at a fixed dose of 600mg/body everyday. Toxicity and efficacy were evaluated during the 2 cycles for 8 weeks. Three or 6 patients were enrolled at each dose level. DLT was defined as grade 3 hematologic toxicity, grade 2 non-hematologic toxicity and treatment delay because of grade 2 hematologic toxicity for more than 8 days of the schedule. The MTD was defined as the dose level at which at least two of three patients or three of six patients presented with DLT. Results: Twenty-one patients with a median age of 66 years (range, 39 to 74) were enrolled in this study. Nine patients have received prior chemotherapy. Seven patients were unresectable and 14 had recurrent tumors. At level 1(n=3), no patients developed DLT. One, 2 and 3 patients developed DLT at level 2(n=6), 3(n=6) and 4(n=6), respectively. All DLT was neutropenia. Only 1 developed grade 4 neutropenia at level 4. Non-hematological toxicity was uncommon. Level 4 was determined as the MTD. Of 16 evaluable patients, responses included 1 CR, 7 PR, 6 SD and 2 PD for an overall response rate of 50%. Conclusion: The MTD of PTX in this combination is 80 mg/m2 and the RD is 70 mg/m2. This regimen is well-tolerated with high response rate in outpatient setting. A phase II study is conducted. No significant financial relationships to disclose.
Lymphatic vessel development: fluid flow and valve-forming cells
Authors: Tsutomu Kume
Journal: Journal of Clinical Investigation (2015)

Hemodynamic forces regulate many aspects of blood vessel disease and development, including susceptibility to atherosclerosis and remodeling of primary blood vessels into a mature vascular network. Vessels of the lymphatic circulatory system are also subjected to fluid flow–associated forces, but the molecular and cellular mechanisms by which these forces regulate the formation and maintenance of lymphatic vessels remain largely uncharacterized. This issue of the JCI includes two articles that begin to address how fluid flow influences lymphatic vessel development and function. Sweet et al. demonstrate that lymph flow is essential for the remodeling of primary lymphatic vessels, for ensuring the proper distribution of smooth muscle cells (SMCs), and for the development and maturation of lymphatic valves. Kazenwadel et al. show that flow-induced lymphatic valve development is initiated by the upregulation of GATA2, which has been linked to lymphedema in patients with Emberger syndrome. Together, these observations and future studies inspired by these results have potential to lead to the development of strategies for the treatment of lymphatic disorders.