tbuckley/cabot-search huggingface dataset:
Docetaxel: Standard Recommended Dose of 100 mg/m<sup>2</sup> Is Effective But Not Feasible for Some Metastatic Breast Cancer Patients Heavily Pretreated With Chemotherapy—A Phase II Single-Center Study
Authors: E. Salminen, M. Bergman, S. Huhtala, E. Ekholm
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Patients with metastatic breast cancer, especially those with progression after several prior chemotherapy treatments, need efficient chemotherapy. This study investigates the efficacy and toxicity of docetaxel in metastatic breast cancer patients with previous chemotherapy for metastatic disease. PATIENTS AND METHODS: Thirty-one women (median age, 52 years; range, 40 to 65 years) treated for metastatic breast cancer with docetaxel were included. Eleven patients had one metastatic site, 10 patients had two, and 10 patients had three or more. The planned dose of docetaxel per course was the standard treatment of 100 mg/m 2 (or 75 mg/m 2 if liver enzyme levels were abnormal) every 3 weeks, given for six or eight cycles. RESULTS: The overall response rate was 48% (three complete responses [CR] and 11 partial responses [PR] ), and the median duration of response was 7 months (range, 2 to 16 months). Twenty patients (65%) experienced fatigue, and 27 patients (87%) had alopecia. Fifteen cases (48%) of grade 4 leukopenia were observed. Edema with a weight gain of 2 to 15 kg was seen in 12 patients (39%), and mucositis occurred in 20 patients (65%). Twenty-three patients (74%) interrupted treatment before reaching the planned number of courses, nine patients owing to progression of cancer and 14 owing to toxicity. Dose reduction was required in 18 (61%) of the patients. Only two patients were able to receive the planned eight courses without dose reduction. CONCLUSION: Docetaxel is highly active in metastatic breast cancer, even as a third-line treatment, and can be considered as an efficient standard option in second-line treatment. The standard recommended dose level of 100 mg/m 2 is not feasible in heavily pretreated patients; therefore, for such patients, an initial dose level not exceeding 75 mg/m 2 is recommended.
The correlation of new GOLD classification (2011 version) with exercise capacity and mortality
Authors: Po-An Chou, Shih-Feng Liu, Chin-Chou Wang, Chien-Hung Chin, Meng-Chih Lin
Journal: European Respiratory Journal (2013)

Background:  New GOLD guideline recommends assessing the severity of COPD by combination of FEV1, symptom scoring, and exacerbation frequency. However, whether the new GOLD classification is more closely associated with exercise capacity and mortality remains unclear.   Method:  The correlation of 6MWD (6-minute walking distance) and mortality rate with COPD staging in a cohort of 114 clinically stable COPD patients was compared by using old (2007) and new (2011) GOLD classifications.   Results:  In the new classification set, patients were divided into group A (29 patients, 25.4%), B (21 patients, 18.4%), C (14 patients, 12.3%), and D (50 patients, 43.9%). Those patients were re-divided in the old GOLD classification group into stage I (17 patients, 14.9%), stage II (36 patients, 31.6%), stage III (50 patients, 43.9%), and stage IV (11 patients, 9.6%). FEV1 and mMRC score showed a significant correlation (P   Conclusions:  New GOLD classification is a better applicable tool in assessment of exercise capacity and mortality in COPD patients than old GOLD classification.
Comparison of PCR and culture based detection of pathogens in bronchoalveolar fluid in neutropenic children
Authors: Florian Stehling, Joerg Steinmann, Peter Micheal Rath, Uwe Mellies
Journal: European Respiratory Journal (2013)

Problem:  Respiratory tract infections are a frequent complication in neutropenic children and treated with broad spectrum antibiotic therapy. If the clinical situation worsens, we perform a chest CT-scan and bronchoalveolar lavage (BAL) before antifungal treatment is started. The aim of this study was to investigate the impact of a polymerase chain reaction (PCR) assay for the detection of pathogens in BAL fluid compared to standard culture methods in neutropenic children receiving broad spectrum antibiotics.   Methods:  BAL fluids from nine neutropenic children (10,2 ± 5,9 years) under broad-spectrum antibiotics were investigated by a multiplex PCR system for DNA detection (LightCycler SeptiFast, Roche, Mannheim, Germany) and by conventional culture on solid media.   Results:  SeptiFast detected more pathogens than conventional culture (7 vs. 1). In two patients clinical significant  Aspergillus fumigatus  was identified by SeptiFast, but not conventional culture.   Conclusion:  Multiplex PCR for DNA detection can improve the detection of causative pathogens - including  Aspergillus fumigatus  - in neutropenic children under broad spectrum antibiotics.
Synergy between high-dose cytarabine and asparaginase in the treatment of adults with refractory and relapsed acute myelogenous leukemia--a Cancer and Leukemia Group B Study.
Authors: R L Capizzi, R Davis, B Powell, J Cuttner, R R Ellison, M R Cooper, R Dillman, W B Major, E Dupre, O R McIntyre
Journal: Journal of Clinical Oncology (1988)

One hundred ninety-five adult patients with refractory or first relapse acute myelogenous leukemia (AML) were randomly assigned to receive high-dose cytarabine (HiDAC), 3 g/m2 as a three-hour intravenous (IV) infusion every 12 hours for four doses, followed by 6,000 IU/m2 asparaginase (ASNase) administered at hour 42, or HiDAC without ASNase. Treatment was repeated on day 8. The median patient age was 52 years. There was an overall superior complete remission (CR) rate for HiDAC/ASNase (40%) v HiDAC (24%), P = .02. Subset analysis according to prior response and age showed the following CR rates: 54% from HiDAC/ASNase treatment of refractory AML in patients less than 60 years, and 31% in patients greater than 60 years; CR from HiDAC in the same refractory groups were 18% (less than 60) and 0% (greater than 60); 37% from HiDAC/ASNase treatment of relapsed AML in patients less than 60 years, and 43% in patients greater than 60 years; CRs from HiDAC in the same relapsed groups were 33% (less than 60) and 21% (greater than 60). Toxicity in the two treatment arms was comparable and consisted primarily of leukopenia, thrombocytopenia, mild hepatic dysfunction, diarrhea, conjunctivitis and serositis, and hyperglycemia. There was only one case of transient cerebellar toxicity and no cutaneous toxicity. Median time to full hematologic recovery was 5 weeks. There was an overall survival benefit for patients treated with HiDAC/ASNase (19.6 weeks) compared with HiDAC (15.9 weeks), P = .046, primarily attributable to effects in refractory patients. Median time to failure for refractory patients who achieved CR was 38.5 weeks with HiDAC/ASNase, and 13.3 weeks for those treated with HiDAC. For relapsed patients in CR from HiDAC/ASNase the median time to failure was 17.7 weeks and 18.3 weeks for HiDAC. The overall 42% CR rate from HiDAC/ASNase v 12% from HiDAC in patients with refractory AML indicates that HiDAC/ASNase is not cross-resistant with standard-dose cytarabine (SDAC) and anthracyclines. We conclude that HiDAC/ASNase has substantial activity in poor-prognosis AML and that this combination warrants further trials in earlier stage disease.
Butyrate inhibits pro-proliferative miR-92a by diminishing c-Myc-induced miR-17-92a cluster transcription in human colon cancer cells
Authors: Shien Hu, Lan Liu, Eugene B. Chang, Jian-Ying Wang, Jean-Pierre Raufman
Journal: Molecular Cancer (2015)

Compromised colonic butyrate production resulting from low dietary fiber or altered gut microbiota may promote colon neoplasia. Previous reports indicate these actions are mediated in part by altered levels of miRNAs, including suppressed expression of the oncogenic miR-17-92a cluster. Here, we sought to identify the mechanisms underlying these effects of butyrate in colon cancer. miR-92a levels were measured in archived human colon cancer and adjacent normal colon specimens by microarray and quantitative RT-PCR (qPCR). The effects of butyrate and other histone deacetylase inhibitors (suberoylanilide hydroxamic acid (SAHA) and valproic acid) on primary (pri-miR17-92a), precursor and mature miR-92a were analyzed in HCT-116 and HT-29 human colon cancer cells using qPCR. The effects of butyrate, SAHA and valproic acid on protein levels of c-Myc, Drosha and p57 were measured in HCT-116 cells using immunoblotting. Regulation of C13orf25 promoter activity by butyrate was analyzed by luciferase reporter assay using modified pGL3 constructs containing a wild-type or mutated c-Myc binding site. Expression of c-Myc was modulated using siRNA or adenovirus vectors. p57 mRNA and protein were measured before and after transfection with miR-92a-mimic molecules. Following butyrate treatment and miR-92a-mimic transfection, apoptosis was analyzed by TUNEL staining and caspase-3 immunoblotting. Microarray, confirmed by qPCR, revealed a seven-fold increase in miR-92a levels in sporadic human colon cancer tissue compared to adjacent normal colon. Treating human colon cancer cells with butyrate reduced the levels of pri-miR17-92a, precursor and mature miR-92a, as well as c-Myc. SAHA and valproic acid had similar effects. Mutation of the c-Myc binding site diminished butyrate's inhibitory effects on C13orf25 promoter activity. Silencing c-Myc expression reduced miR-92a levels. c-Myc over-expression neutralized butyrate-induced attenuation of pri-miR17-92a. Exogenous miR-92a inhibited butyrate-induced p57 expression and reversed the beneficial actions of butyrate on colon cancer cell proliferation and apoptosis. Our findings identify a novel cellular mechanism whereby butyrate inhibits miR-92a transcription by reducing c-Myc, thus augmenting p57 levels. These actions diminish colon cancer cell proliferation and stimulate apoptosis. This newly described regulation of oncogenic miRNA biogenesis expands our understanding of colon cancer cell biology and identifies novel therapeutic targets.
Defects in DNA Repair Genes Predict Response to Neoadjuvant Cisplatin-based Chemotherapy in Muscle-invasive Bladder Cancer
Authors: Elizabeth R. Plimack, Roland L. Dunbrack, Timothy A. Brennan, Mark D. Andrake, Yan Zhou, Ilya G. Serebriiskii, Michael Slifker, Katherine Alpaugh, Essel Dulaimi, Norma Palma, Jean Hoffman-Censits, Marijo Bilusic, Yu-Ning Wong, Alexander Kutikov, Rosalia Viterbo, Richard E. Greenberg, David Y.T. Chen, Costas D. Lallas, Edouard J. Trabulsi, Roman Yelensky, David J. McConkey, Vincent A. Miller, Erica A. Golemis, Eric A. Ross
Journal: European Urology (2015)
Food allergy in children: threshold distribution curves for 6 major food allergens
Authors: W.M. Blom, B.J. Vlieg-Boerstra, M.I.Q. Spanjersberg, A.G. Kruizinga, Heide, S., van der, A.E.J. Dubois, G.F. Houben
Journal: Allergy (2010)

Background

The subtropical Bahia grass
(Paspalum notatum) is an important source
of pollen allergens with an extended season
of pollination and wide distribution in warmer
climates. The immunological relationship
between pollen allergens of Bahia
grass and temperate grasses is unresolved.

Methods

Serum IgE reactivity of grass
pollen-allergic patients with Bahia, Ryegrass
and Bermuda grass pollen extracts
and their purified group 1 allergens, Pas n
1, Lol p 1 and Cyn d 1, were compared by
immunoblotting, ELISA, inhibition
ELISA, basophil activation by flow cytometry
and molecular modeling.

Results

Differences in antibody recognition
of allergenic components between Bahia
grass and Ryegrass pollen were
observed by immunoblotting. Eight grass
pollen-allergic patients from a temperate
region showed greater serum IgE reactivity
with Ryegrass pollen than Bahia grass by
ELISA. For seven of these sera, Ryegrass
pollen inhibited IgE reactivity with Bahia
grass pollen but not the converse. For 51
sera from grass pollen-allergic patients in
this temperate region, IgE reactivity with
Lol p 1 was greater than Pas n 1 or Cyn d
1. IgE reactivity with Lol p 1 was not
inhibited by Pas n 1 or Cyn d 1, but Pas n
1 IgE reactivity was inhibited by Lol p 1.
Two group 1 grass pollen allergen-specific
mAb distinguished between temperate and
subtropical grass pollens. Basophil activation
for three patients tested was greater by Ryegrass pollen than Bahia or Bermuda
grass, and by Lol p 1 than Pas n 1 or Cyn
d 1. In contrast, two patients from a subtropical
region had higher serum IgE reactivity
with Bahia grass pollen than
Ryegrass and Bahia grass pollen inhibited
IgE reactivity with Ryegrass. A structural
model of Pas n 1 showed amino acids
implicated in IgE epitopes of other group 1
allergens were juxtaposed on the surface.

Conclusion

Allergens from subtropical Bahia
grass pollen, including Pas n 1, share
antigenic determinants with temperate
grass pollen allergens, but patients exhibit
higher serum IgE reactivity to their locally
predominant grass pollen. Basophil activation
by Bahia grass pollen and Pas n 1 in
patients from a temperate climate indicates
clinically relevant cross-sensitization
between temperate and subtropical grass
pollens.
Bile acids and nonalcoholic fatty liver disease: An intriguing relationship
Authors: Lucia Carulli, Chiara Gabbi, Marco Bertolotti
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. To the Editor: Nonalcoholic fatty liver disease stands nowadays as a leading cause of progressive impairment of liver function. We read with great interest the paper by Nagahashi et al.1 recently published in Hepatology which highlights the role of conjugated bile acids, sphingosine‐1 phosphate receptor 2, and sphingosine kinase 2 in regulating hepatic lipid metabolism and liver lipid content. Such results are exciting and stimulating. The role of bile acids in the modulation of hepatic lipid metabolism is interesting and controversial; previous evidence by Watanabe et al.2 showed an inhibitory effect of bile acids on lipogenesis, which was attributed to activation of the farnesoid X receptor (FXR)–small heterodimer partner (SHP) axis and consequent depression of the liver X receptor (LXR)‐α–sterol regulatory element binding protein (SREBP) 1c lipogenic pathway. Evidence from our research group has shown that both exogenous administration of bile acids and endogenous exposure to bile acid overload (as in cholestasis) may reduce hepatic fat accumulation in rat models, although by different mechanisms3: (1) by activating of the FXR‐SHP axis and (2) by inducing cytochrome P450 7A1, which leads to reduced oxysterol hepatic bioavailability and in turn down‐regulation of the LXR‐α–controlled lipogenic pathway. The findings in the paper by Nagahashi et al.1 are quite surprising, showing the development of fatty liver disease in SphK2–/– mice in association with decreased expression of SREBP 1c and lipogenic enzymes like FAS. As the authors comment, hepatic fat accumulation might be induced by mechanisms different from increased lipogenesis, such as the reduction of lipid and lipoprotein output from the liver, according to previous evidence in humans.4 Data from our group are consistent with this hypothesis. Indeed, we detected a beneficial effect of cholic acid feeding in the choline‐deficient dietary model (in which hepatic lipid export is reduced) but not in the high‐fat model.2 In other words, the metabolic effects of bile acids on hepatic lipid metabolism seem to be strictly dependent on the experimental model utilized to induce fat liver accumulation as well as on the modality of bile acid exposure (exogenous versus endogenous) and the relative activation of the LXR and FXR pathways. Experimental evidence like that brought by Nagahashi et al.1 may bring an enormous contribution to this field, in the perspective of novel pharmacological targets for the treatment of nonalcoholic fatty liver disease.
Effects of inhaled salmeterol/fluticasone on lung function in patients with bronchiectasis
Authors: Panhatai Thongmak, Nitra Piyavisetpat, Somkiat Wongtim, Kamon Kawkitinarong
Journal: European Respiratory Journal (2014)

Background: Bronchiectasis is a chronic irreversible airway disease. Patients usually suffer from breathlessness, productive cough and poor quality of life. The efficacy of combination LABA/ICS in bronchiectasis is lack of evidence.

Objective: To evaluate the effect of inhaled salmeterol/fluticasone (S/F) on lung function, health-related quality of life, and exercise capacity in bronchiectasis patients.

Method: Thirty-two symptomatic bronchiectasis patients diagnosed by high-resolution CT scan of the thorax were enrolled into the study. Patients who smoked more than 10 pack-years or have bronchodilator response were excluded. Patients were randomized to receive inhaled S/F 50/250 mcg twice daily via spacer or placebo. Demographic data, spirometry results, Saint George respiratory questionnaire (SGRQ) score and six-minute walk distance (6MWD) were collected at baseline and at 12 week.

Results: At 12 week, treatment with S/F improved pre-bronchodilator FEV1 0.164 L (p = 0.010), pre-bronchodilator FVC 0.201 L (p = 0.016) and post-bronchodilator FVC 0.128 L (p = 0.040) compared with placebo. In S/F group, an improvement in total SGRQ from baseline was observed while no statistical improvement in total SGRQ score in placebo group (mean change of total SGRQ score -11.64 (p < 0.001), 4.91 (p = 0.236), respectively. There are no differences in 6MWD from baseline in both groups (mean change of S/F and placebo group = 18.0, -5.6 m: p = 0.178). Mild exacerbation was observed in 3 and 1 case of S/F and placebo group, respectively.

Conclusion: Salmeterol/fluticasone treatment improves pulmonary function and overall quality of life in bronchiectasis patients.
Increased arterial stiffness in patients with psoriasis is associated with active systemic inflammation
Authors: K-H. Yiu, C-K. Yeung, H-T. Chan, R.M.Y. Wong, S. Tam, K-F. Lam, G.H. Yan, W.S. Yue, H.H. Chan, H-F. Tse
Journal: British Journal of Dermatology (2010)

Journal Article Increased arterial stiffness in patients with psoriasis is associated with active systemic inflammation Get access K‐H. Yiu, K‐H. Yiu Division of Cardiology Search for other works by this author on: Oxford Academic Google Scholar C‐K. Yeung, C‐K. Yeung Division of Dermatology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China Search for other works by this author on: Oxford Academic Google Scholar H‐T. Chan, H‐T. Chan Division of Cardiology Search for other works by this author on: Oxford Academic Google Scholar R.M.Y. Wong, R.M.Y. Wong Division of Cardiology Search for other works by this author on: Oxford Academic Google Scholar S. Tam, S. Tam Department of Clinical Biochemistry Unit, Queen Mary Hospital, Hong Kong, China Search for other works by this author on: Oxford Academic Google Scholar K‐F. Lam, K‐F. Lam Statistics and Actuarial Science, The University of Hong Kong, Hong Kong, China Search for other works by this author on: Oxford Academic Google Scholar G.H. Yan, G.H. Yan Division of Cardiology Search for other works by this author on: Oxford Academic Google Scholar W.S. Yue, W.S. Yue Division of Cardiology Search for other works by this author on: Oxford Academic Google Scholar H.H. Chan, H.H. Chan Division of Dermatology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China Search for other works by this author on: Oxford Academic Google Scholar H‐F. Tse H‐F. Tse Division of CardiologyResearch Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China Hung‐Fat Tse. E‐mail: hftse@hkucc.hku.hk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 3, 1 March 2011, Pages 514–520, https://doi.org/10.1111/j.1365-2133.2010.10107.x Published: 01 March 2011
Immunolocalization of the secretory isoform of Na-K-Cl cotransporter in rat renal intercalated cells.
Authors: S M Ginns, M A Knepper, C A Ecelbarger, J Terris, X He, R A Coleman, J B Wade
Journal: Journal of the American Society of Nephrology (1996)

Two bumetanide-sensitive ion cotransporters that carry Na+, K+, and Cl- in a coupled fashion have been identified. One type, the "absorptive" isoform, carries these ions across the apical plasma membrane of the thick ascending limb of Henle's loop. Another isoform, the "secretory" cotransporter, has been identified in a number of epithelial tissues by physiological means, but its sites of expression in the kidney have not been fully characterized. Complementary DNA believed to code for the secretory isoform (called "BSC2" or "NKCC1") have recently been cloned. This study used a specific affinity-purified antipeptide antibody to this protein for immunolocalization in the rat kidney. Immunoblot studies using this antibody show abundant immunoreactivity against bands of 140-190 and 120 kd in the parotid gland, colon, and stomach, sites where the secretory form of the cotransporter has been identified by physiological techniques. This distribution supports the hypothesis that this isoform represents the secretory form of the cotransporter. Studies in the kidney revealed that the same bands are associated with membrane fractions chiefly in the outer medulla. Immunolocalizations show that immunoreactivity is selectively and intensely localized to the basolateral plasma membrane of a subfraction of outer medullary collecting duct cells. An independently produced monoclonal antibody (T4) specific for Na-K-Cl cotransporter displays the same localization. Dual localizations of cotransporter antibody with respect to antibody specific for principal cells (aquaporin-2) and intercalated cells (band 3 and H(+)-ATPase) show that cotransporter immunoreactivity is localized to alpha-intercalated cells of the outer medullary collecting duct in the rat. This distinctive localization suggests that the secretory form of the cotransporter may play a role in renal NH4+ and/or acid secretion by this cell type.
Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Efficacy Results From a Randomized, Double-Blind, Placebo-Controlled Study
Authors: George I. Papakostas, Maurizio Fava, Lee Baer, Michaela B. Swee, Adrienne Jaeger, William V. Bobo, Richard C. Shelton
Journal: American Journal of Psychiatry (2015)

Objective: The authors sought to test the efficacy of adjunctive ziprasidone in adults with nonpsychotic unipolar major depression experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram. Method: This was an 8-week, randomized, double-blind, parallel-group, placebo-controlled trial conducted at three academic medical centers. Participants were 139 outpatients with persistent symptoms of major depression after an 8-week open-label trial of escitalopram (phase 1), randomly assigned in a 1:1 ratio to receive adjunctive ziprasidone (escitalopram plus ziprasidone, N=71) or adjunctive placebo (escitalopram plus placebo, N=68), with 8 weekly follow-up assessments. The primary outcome measure was clinical response, defined as a reduction of at least 50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D). The Hamilton Anxiety Rating scale (HAM-A) and Visual Analog Scale for Pain were defined a priori as key secondary outcome measures. Results: Rates of clinical response (35.2% compared with 20.5%) and mean improvement in HAM-D total scores (–6.4 [SD=6.4] compared with –3.3 [SD=6.2]) were significantly greater for the escitalopram plus ziprasidone group. Several secondary measures of antidepressant efficacy also favored adjunctive ziprasidone. The escitalopram plus ziprasidone group also showed significantly greater improvement on HAM-A score but not on Visual Analog Scale for Pain score. Ten (14%) patients in the escitalopram plus ziprasidone group discontinued treatment because of intolerance, compared with none in the escitalopram plus placebo group. Conclusions: Ziprasidone as an adjunct to escitalopram demonstrated antidepressant efficacy in adult patients with major depressive disorder experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram.