tbuckley/cabot-search huggingface dataset:
Colon Cancer Cell–Derived Tumor Necrosis Factor-α Mediates the Tumor Growth–Promoting Response in Macrophages by Up-regulating the Colony-Stimulating Factor-1 Pathway
Authors: Karin Zins, Dietmar Abraham, Mouldy Sioud, Seyedhossein Aharinejad
Journal: Cancer Research (2007)

Abstract The interplay between malignant and stromal cells is essential in tumorigenesis. We have previously shown that colony-stimulating factor (CSF)-1, matrix metalloprotease (MMP)-2, and vascular endothelial growth factor (VEGF)-A production by stromal cells is enhanced by CSF-1–negative SW620 colon cancer cells. In the present study, the mechanisms by which colon cancer cells up-regulate host factors to promote tumorigenesis were investigated. Profiling of tumor cell cytokine expression in SW620 tumor xenografts in nude mice showed increased human tumor necrosis factor (TNF)-α mRNA expression with tumor growth. Incubation of macrophages with small interfering (si) RNAs directed against TNF-α or TNF-α–depleted SW620 cell conditioned medium versus SW620 cell conditioned medium failed to support mouse macrophage proliferation, migration, and expression of CSF-1, VEGF-A, and MMP-2 mRNAs. Consistent with these results, human TNF-α gene silencing decreased mouse macrophage TNF-α, CSF-1, MMP-2, and VEGF-A mRNA expression in macrophages cocultured with human cancer cells. In addition, inhibition of human TNF-α or mouse CSF-1 expression by siRNA reduced tumor growth in SW620 tumor xenografts in mice. These results suggest that colon cancer cell–derived TNF-α stimulates TNF-α and CSF-1 production by macrophages, and that CSF-1, in turn, induces macrophage VEGF-A and MMP-2 in an autocrine manner. Thus, interrupting tumor cell–macrophage communication by targeting TNF-α may provide an alternative therapeutic approach for the treatment of colon cancer. [Cancer Res 2007;67(3):1038–45]
Adenovirus-Mediated Heme Oxygenase-1 Gene Transfer Inhibits the Development of Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Shu-Hui Juan, Tzong-Shyuan Lee, Kuang-Wen Tseng, Jun-Yang Liou, Song-Kun Shyue, Kenneth K. Wu, Lee-Young Chau
Journal: Circulation (2001)

Background Increasing evidence supports the role of heme oxygenase-1 (HO-1) in cytoprotective response and iron homeostasis. The object of this study was to investigate whether adenovirus-mediated gene transfer of HO-1 in arteries reduces iron overload and inhibits lesion formation in apolipoprotein E (apoE)–deficient mice. Methods and Results Infection of rat aortic smooth muscle cells with adenovirus carrying the human HO-1 gene (Adv-HO-1) resulted in a high-level expression of HO-1 protein, which effectively reduced the hemin-induced iron overload in these cells. Adenovirus-mediated gene transfer in arteries in vivo was achieved by direct injection of Adv-HO-1 into the left ventricles of anesthetized animals. Transgene was expressed in the endothelium and aortic lesion of apoE-deficient mice after they had received recombinant adenovirus for 1 week and gradually decayed during the next 5 weeks. When young apoE-deficient mice (14 weeks old) received Adv-HO-1 (2.5×10 9 pfu) for 6 weeks, lesions that developed in the aortic root or aortic arch were significantly smaller than those in control littermates receiving empty viral vector. Furthermore, the iron deposition as well as tissue iron content was much less in aortic tissue of Adv-HO-1–treated mice. The inhibitory effect of HO-1 gene transfer on the progression of advanced lesions was also observed in older apoE-deficient mice (20 weeks old) receiving Adv-HO-1 intraventricularly. Conclusions Overexpression of HO-1 in vascular cells facilitates iron metabolism and attenuates development of atherosclerosis in apoE-deficient mice.
Chemical extraction technique for tattoo removal
Authors: W. Cheng
Journal: British Journal of Dermatology (2004)

Journal Article Chemical extraction technique for tattoo removal Get access W. Cheng W. Cheng Rejuvi Laboratory, Inc., South San Francisco, CA 94080, U.S.A. E‐mail: rejuvi@mindspring.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 151, Issue 6, 1 December 2004, Pages 1282–1283, https://doi.org/10.1111/j.1365-2133.2004.06287.x Published: 01 December 2004
Tuberculosis prevalence in China, 1990–2010; a longitudinal analysis of national survey data
Authors: Lixia Wang, Hui Zhang, Yunzhou Ruan, Daniel P Chin, Yinyin Xia, Shiming Cheng, Mingting Chen, Yanlin Zhao, Shiwen Jiang, Xin Du, Guangxue He, Jun Li, Shengfen Wang, Wei Chen, Caihong Xu, Fei Huang, Xiaoqiu Liu, Yu Wang
Journal: The Lancet (2014)
Bortezomib Mediates Antiangiogenesis in Multiple Myeloma via Direct and Indirect Effects on Endothelial Cells
Authors: Aldo Maria Roccaro, Teru Hideshima, Noopur Raje, Shaji Kumar, Kenji Ishitsuka, Hiroshi Yasui, Norihiko Shiraishi, Domenico Ribatti, Beatrice Nico, Angelo Vacca, Franco Dammacco, Paul Gerard Richardson, Kenneth Carl Anderson
Journal: Cancer Research (2006)

Abstract Bone marrow angiogenesis plays an important role in the pathogenesis and progression in multiple myeloma. Recent studies have shown that proteasome inhibitor bortezomib (Velcade, formerly PS-341) can overcome conventional drug resistance in vitro and in vivo; however, its antiangiogenic activity in the bone marrow milieu has not yet been defined. In the present study, we examined the effects of bortezomib on the angiogenic phenotype of multiple myeloma patient–derived endothelial cells (MMEC). At clinically achievable concentrations, bortezomib inhibited the proliferation of MMECs and human umbilical vein endothelial cells in a dose-dependent and time-dependent manner. In functional assays of angiogenesis, including chemotaxis, adhesion to fibronectin, capillary formation on Matrigel, and chick embryo chorioallantoic membrane assay, bortezomib induced a dose-dependent inhibition of angiogenesis. Importantly, binding of MM.1S cells to MMECs triggered multiple myeloma cell proliferation, which was also abrogated by bortezomib in a dose-dependent fashion. Bortezomib triggered a dose-dependent inhibition of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) secretion by the MMECs, and reverse transcriptase-PCR confirmed drug-related down-regulation of VEGF, IL-6, insulin-like growth factor-I, Angiopoietin 1 (Ang1), and Ang2 transcription. These data, therefore, delineate the mechanisms of the antiangiogenic effects of bortezomib on multiple myeloma cells in the bone marrow milieu. (Cancer Res 2006; 66(1): 184-91)
Limited Tissue Penetration of Taxanes: A Mechanism for Resistance in Solid Tumors
Authors: Alastair H. Kyle, Lynsey A. Huxham, Devon M. Yeoman, Andrew I. Minchinton
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Limited drug penetration in solid tumors is a potential mechanism of resistance for many anticancer drugs. Taxanes represent a class of drugs that are currently undergoing a new round of development, but with little known of their ability to penetrate and distribute relative to blood vessels within solid tumors. Experimental Design: We assessed the tissue penetration of paclitaxel and docetaxel in HCT-116 tumor xenografts and in multilayered cell culture (MCC), a three-dimensional cell culture model of the tumor extravascular compartment. In xenografts, taxanes were mapped relative to blood vessels to obtain drug profiles as a function of distance from vasculature. For MCC, cultures were exposed to stirred drug reservoirs and taxanes measured as a function of depth into tissue. Results: Both taxanes exhibited limited penetration, with little drug reaching further than 100 μm into the tissue. Of the two, paclitaxel exhibited up to 2-fold greater penetration than docetaxel. Mapping tumor cell proliferation following treatment allowed the consequences of limited drug penetration to be assessed. In tumor xenografts where reduced drug exposure to cells far from vasculature is one of several factors influencing response to treatment, up to a 75% reduction in S-phase cells was achieved in cells nearest the vessels, but only 50% reduction was observed in the tissue 150 μm away. In MCC-based data, where the influence of reduced cell proliferation with depth into tissue was circumvented, a 5-fold (paclitaxel) and 10-fold (docetaxel) increase in reservoir drug concentration was required to produce a response in cells 150 μm into the tissue equivalent to that seen in cells directly exposed to the drug. Conclusion: These results indicate that limited distribution is an important mechanism of tumor resistance to taxanes.
Use of continuous positive airway pressure reduces airway reactivity in adults with asthma
Authors: Michael Busk, Nancy Busk, Paula Puntenney, Janet Hutchins, Zhangsheng Yu, Susan J. Gunst, Robert S. Tepper
Journal: European Respiratory Journal (2012)

Asthma is characterised by airway hyperreactivity, which is primarily treated with β-adrenergic bronchodilators and anti-inflammatory agents. However, mechanical strain during breathing is an important modulator of airway responsiveness and we have previously demonstrated in animal models that continuous positive airway pressure (CPAP) resulted in lower in vivo airway reactivity. We now evaluated whether using nocturnal CPAP decreased airway reactivity in clinically-stable adults with asthma. Adults with stable asthma and normal spirometry used nocturnal CPAP (8–10 cmH 2 O) or sham treatment (0–2 cmH 2 O) for 7 days. Spirometry and bronchial challenges were obtained before and after treatment. The primary outcome was the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC 20 ). The CPAP group (n=16) had a significant decrease in airway reactivity (change in (Δ)logPC 20 0.406, p&lt;0.0017) while the sham group (n=9) had no significant change in airway reactivity (ΔlogPC 20 0.003, p=0.9850). There was a significant difference in the change in airway reactivity for the CPAP versus the sham group (ΔlogPC 20 0.41, p&lt;0.043). Our findings indicate that chronic mechanical strain of the lungs produced using nocturnal CPAP for 7 days reduced airway reactivity in clinically stable asthmatics. Future studies of longer duration are required to determine whether CPAP can also decrease asthma symptoms and/or medication usage.
Comparison of tiotropium once daily, formoterol twice daily and both combined once daily in patients with COPD
Authors: J. A. van Noord, J-L. Aumann, E. Janssens, J. J. Smeets, J. Verhaert, B. Disse, A. Mueller, P. J. G. Cornelissen
Journal: European Respiratory Journal (2005)

This study compared the bronchodilator effects of tiotropium, formoterol and both combined in chronic obstructive pulmonary disease (COPD). A total of 71 COPD patients (mean forced expiratory volume in one second (FEV 1 ) 37% predicted) participated in a randomised, double-blind, three-way, crossover study and received tiotropium 18 μg q.d. , formoterol 12 μg b.i.d. or both combined q.d. for three 6-week periods. The end-points were 24-h spirometry (FEV 1 , forced vital capacity (FVC)) at the end of each treatment, rescue salbutamol and safety. Compared with baseline (FEV 1 prior to the first dose in the first period), tiotropium produced a significantly greater improvement in average daytime FEV 1 (0–12 h) than formoterol (127 versus 86 mL), while average night-time FEV 1 (12–24 h) was not different (tiotropium 43 mL, formoterol 38 mL). The most pronounced effects were provided by combination therapy (daytime 234 mL, night-time 86 mL); both differed significantly from single-agent therapies. Changes in FVC mirrored the FEV 1 results. Compared with both single agents, daytime salbutamol use was significantly lower during combination therapy (tiotropium plus formoterol 1.81 puffs·day −1 , tiotropium 2.41 puffs·day −1 , formoterol 2.37 puffs·day −1 ). All treatments were well tolerated. In conclusion, in chronic obstructive pulmonary disease patients, tiotropium q.d. achieved a greater improvement in daytime and comparable improvement in night-time lung function compared with formoterol b.i.d. A combination of both drugs q.d. was most effective and provided an additive effect throughout the 24-h dosing interval.
Characteristics of Lung Cancers Harboring <i>NRAS</i> Mutations
Authors: Kadoaki Ohashi, Lecia V. Sequist, Maria E. Arcila, Christine M. Lovly, Xi Chen, Charles M. Rudin, Teresa Moran, David Ross Camidge, Cindy L. Vnencak-Jones, Lynne Berry, Yumei Pan, Hidefumi Sasaki, Jeffrey A. Engelman, Edward B. Garon, Steven M. Dubinett, Wilbur A. Franklin, Gregory J. Riely, Martin L. Sos, Mark G. Kris, Dora Dias-Santagata, Marc Ladanyi, Paul A. Bunn, William Pao
Journal: Clinical Cancer Research (2013)

We sought to determine the frequency and clinical characteristics of patients with lung cancer harboring NRAS mutations. We used preclinical models to identify targeted therapies likely to be of benefit against NRAS-mutant lung cancer cells.We reviewed clinical data from patients whose lung cancers were identified at six institutions or reported in the Catalogue of Somatic Mutations in Cancer (COSMIC) to harbor NRAS mutations. Six NRAS-mutant cell lines were screened for sensitivity against inhibitors of multiple kinases (i.e., EGFR, ALK, MET, IGF-1R, BRAF, PI3K, and MEK).Among 4,562 patients with lung cancers tested, NRAS mutations were present in 30 (0.7%; 95% confidence interval, 0.45%-0.94%); 28 of these had no other driver mutations. 83% had adenocarcinoma histology with no significant differences in gender. While 95% of patients were former or current smokers, smoking-related G:C>T:A transversions were significantly less frequent in NRAS-mutated lung tumors than KRAS-mutant non-small cell lung cancer [NSCLC; NRAS: 13% (4/30), KRAS: 66% (1772/2733), P < 0.00000001]. Five of 6 NRAS-mutant cell lines were sensitive to the MEK inhibitors, selumetinib and trametinib, but not to other inhibitors tested.NRAS mutations define a distinct subset of lung cancers (∼1%) with potential sensitivity to MEK inhibitors. Although NRAS mutations are more common in current/former smokers, the types of mutations are not those classically associated with smoking.
Neurophysiological Study of Peripheral Neuropathy after High-Dose Paclitaxel
Authors: Harry Openshaw, Karen Beamon, Timothy W. Synold, Jeff Longmate, Neal E. Slatkin, James H. Doroshow, Stephen Forman, Kim Margolin, Robert Morgan, Stephen Shibata, George Somlo
Journal: Clinical Cancer Research (2004)

To determine if there is a beneficial effect of amifostine in preventing or reducing the neuropathy induced by high-dose paclitaxel.Breast cancer patients receiving high-dose infusional paclitaxel (725 mg/m(2)/24 h) in combination with doxorubicin (165 mg/m(2)/96 h) and cyclophosphamide (100 mg/kg/2 h; ACT) were studied on two autologous peripheral blood stem cell transplant protocols, one with and one without amifostine (740 mg/m(2) administered over 10 min before and 12 h after initiation of the paclitaxel infusion). Patients were evaluated before ACT and 20-40 days later with neurological examination, a composite peripheral neuropathy score, peroneal and sural nerve conduction studies, and quantitative sensory testing.There was no significant difference in paclitaxel maximum concentration, systemic clearance, or area under the curve determinations. Narcotic requirement as well as recovery of hematopoietic counts were also similar in subjects with or without amifostine. After ACT was administered, there was a decrease in peroneal nerve compound muscle action potential amplitude and sural nerve sensory action potential amplitude, as well as an increase in vibratory and cold detection thresholds. Clinical composite peripheral neuropathy scores were similar despite amifostine treatment; and logarithm to the base 2 ratios post/pre ACT showed no significant effect of amifostine on peroneal nerve compound muscle action potential, sural nerve sensory action potential, vibratory detection thresholds, or cold detection thresholds. All subjects had acroparesthesias and lost their ankle deep-tendon reflexes after administration of ACT.Single high-dose paclitaxel produces predictable clinical and neurophysiological changes so that patients receiving high-dose therapy are ideal subjects to test the effectiveness of neuroprotective agents. Amifostine was ineffective in preventing or reducing the neurotoxicity of high-dose paclitaxel.
Creativity, psychosis, autism, and the social brain
Authors: Michael Fitzgerald, Ziarih Hawi
Journal: Behavioral and Brain Sciences (2008)

Abstract In the target article, Crespi &amp; Badcock (C&amp;B) propose a novel hypothesis based on observations that a large set of phenotypic traits exhibit diametrically opposite phenotypes in autism-spectrum versus psychotic-spectrum conditions. They propose that development of these conditions is mediated in part by alterations in “genomic imprinting.” This hypothesis is based on the model of the Prader-Willi and Angelman syndromes. The authors have produced a masterful discussion of the differences between psychosis and autism. Of course, another article could be written on the similarities.
Second-Line Oxaliplatin, Folinic Acid, and Fluorouracil Versus Folinic Acid and Fluorouracil Alone for Gemcitabine-Refractory Pancreatic Cancer: Outcomes From the CONKO-003 Trial
Authors: Helmut Oettle, Hanno Riess, Jens M. Stieler, Gerhard Heil, Ingo Schwaner, Jörg Seraphin, Martin Görner, Matthias Mölle, Tim F. Greten, Volker Lakner, Sven Bischoff, Marianne Sinn, Bernd Dörken, Uwe Pelzer
Journal: Journal of Clinical Oncology (2014)

To assess the efficacy of a second-line regimen of oxaliplatin and folinic acid-modulated fluorouracil in patients with advanced pancreatic cancer who have experienced progression while receiving gemcitabine monotherapy.A randomized, open-label, phase III study was conducted in 16 institutions throughout Germany. Recruitment ran from January 2004 until May 2007, and the last follow-up concluded in December 2012. Overall, 168 patients age 18 years or older who experienced disease progression during first-line gemcitabine therapy were randomly assigned to folinic acid and fluorouracil (FF) or oxaliplatin and FF (OFF). Patients were stratified according to the presence of metastases, duration of first-line therapy, and Karnofsky performance status.Median follow-up was 54.1 months, and 160 patients were eligible for the primary analysis. The median overall survival in the OFF group (5.9 months; 95% CI, 4.1 to 7.4) versus the FF group (3.3 months; 95% CI, 2.7 to 4.0) was significantly improved (hazard ratio [HR], 0.66; 95% CI, 0.48 to 0.91; log-rank P = .010). Time to progression with OFF (2.9 months; 95% CI, 2.4 to 3.2) versus FF (2.0 months; 95% CI, 1.6 to 2.3) was significantly extended also (HR, 0.68; 95% CI, 0.50 to 0.94; log-rank P = .019). Rates of adverse events were similar between treatment arms, with the exception of grades 1 to 2 neurotoxicity, which were reported in 29 patients (38.2%) and six patients (7.1%) in the OFF and FF groups, respectively (P < .001).Second-line OFF significantly extended the duration of overall survival when compared with FF alone in patients with advanced gemcitabine-refractory pancreatic cancer.
Combined Blockade of Src Kinase and Epidermal Growth Factor Receptor with Gemcitabine Overcomes STAT3-Mediated Resistance of Inhibition of Pancreatic Tumor Growth
Authors: Nagathihalli S. Nagaraj, M. Kay Washington, Nipun B. Merchant
Journal: Clinical Cancer Research (2011)

Abstract Purpose: We previously established a mechanistic rationale for Src inhibition as a novel therapeutic target in pancreatic cancer and have identified activated STAT3 as a potential biomarker of resistance to Src inhibition. The purpose of this study was to translate the current understanding of complementary activated tyrosine kinase signaling pathways by targeting Src kinase and epidermal growth factor receptor (EGFR). Experimental Design: IC50 values for dasatinib, a Src kinase inhibitor, erlotinib, an EGFR tyrosine kinase inhibitor and gemcitabine were determined and sensitive and resistant pancreatic cancer cell lines were identified. The in vitro and in vivo effects of these agents on multiple signaling pathways and tumorigenicity in pancreatic cancer were investigated. Results: The combination of dasatinib, erlotinib, and gemcitabine resulted in cooperative inhibition of cell migration and invasion of both sensitive and resistant pancreatic cancer cells as well as cooperative inhibition of multiple signaling pathways including FAK, AKT, ERK, JNK, MAPK, and STAT3 at concentrations that were ineffective as individual agents or as double combinations of agents. The triple combination of agents was also most effective at inhibiting the growth of xenografts of both sensitive and resistant pancreatic cancer cells in vivo without increasing toxicity. Furthermore, combined inhibition of Src and EGFR with gemcitabine inhibited constitutively activated STAT3 in vitro and in vivo. Conclusions: These results provide evidence that combined targeted biological therapy in addition to cytotoxic chemotherapy can overcome treatment resistance. Such treatment strategies may be used to tailor therapy based on identified biomarkers of resistance to targeted monotherapy. Clin Cancer Res; 17(3); 483–93. ©2011 AACR.
Quality of COPD diagnosis in Ukraine: A phone survey
Authors: Ivan Vyshnyvetskyy, Olga Khitrenko, Tetiana Kugler
Journal: European Respiratory Journal (2012)

Background. Quality of COPD diagnosis remains poor in post-Soviet countries. There is limited information about beliefs and patterns of care of COPD in Ukrainian general practitioners (GP).

Aim. To explore the knowledge, beliefs and working stereotypes about diagnosis of COPD in Ukrainian GPs.

Methods. We performed a telephone survey of 85 GPs in Donetsk region, Ukraine. As indicators of quality of COPD diagnosis we used answers on these questions: 1) “How many of COPD patients in your practice are both > 40 years old and smokers > 10 pack-years?” (correct was considered 80% and more); 2) “How many of COPD patients in your practice needed spirometry (SM) to confirm the diagnosis?” (correct was considered 100%); 3) “And how many of them actually had SM performed?”

Results. Just 43 of 85 (50,6%) GPs demonstrated reliable knowledge of dominant COPD risk factors (age and smoking history). Two GPs could not answer the first question. Seventy two of 85 (71,8%) GPs considered SM essential to confirm diagnosis of COPD. Fourteen of 85 (16,4%) GPs deem that just less than half of COPD patients need SM to be performed. One physician (1,2%) did not know what SM is, and one considered it was suitable just in persons less than 60 years old. In real life setting confirmation by SM of COPD diagnosis in all patients perform 37.6% (32 of 85) GPs. Almost half of doctors (44,7%) really perform SM less than in 50% COPD patients. All indicators of sufficient quality of COPD diagnosis (knowledge of risk factors, knowledge of importance of SM and real use of SM) were present just in 20% (17 of 85) GPs.

Conclusions. Quality of COPD diagnosis in is very poor. Just 20% of GPs demonstrate adequate knowledge and practice in correct COPD diagnosis.