tbuckley/cabot-search huggingface dataset:
The role of bisphosphonates and bone health issues in Japanese Breast Cancer patients: Efficacy of alendronate with aromatase inhibitors
Authors: K. Yamada, N. Kohno, K. Endoh, D. Kimura, F. Ueno, A. Ogata, D. Ohta, H. Kaise, H. Kato
Journal: Journal of Clinical Oncology (2006)

10777 Background: Adjuvant hormonal therapy for postmenopausal breast cancer is now one of the most significant therapies in the world. From the results of the ATAC trial and the ITA trial, standard hormonal therapy for postmenopausal breast cancer has changed from tamoxifen to aromatase inhibitor. However concerning the rate of bone-relating complications including bone fracture, osteoporosis, a decrease in bone mineral density (BMD), aromatase inhibitor is reported higher than tamoxifen. According to the 2003 ASCO guidelines on the role of bisphosphonates in women with breast cancer, most women with newly diagnosed breast cancer are at risk of osteoporosis due to either their age or their breast cancer treatment. The Panel recommended an algorithm for patient management to maintain bone health. The purpose of the study is to investigate the efficacy of bisphosphonate for prevention from osteoporosis by aromatase inhibitor in Japanese women with breast cancer. Methods: From 2002 to 2004, we experienced 92 cases of postmenopausal Japanese women who underwent breast cancer operations and take aromatase inhibitor after operations in Tokyo Medical University hospital. We selected two medicines. One is Anastrozole (Arimidex R ) as an aromatase inhibitor, and the other is Alendronate (Bonalon R ) as a bisphosphonate medicine.We investigated the change of BMD, calcium, bone absorption marker like NTX, I-CTP. Results: The value of NTX which patients take Alendronate with Anastrozole decreased about 40% than which patients take Anastrozole alone. Also the rate of bone-relating complications is lower.The mean value of BMD, % YAM, T-score, Z-score is 0.86, 81.0, −1.52, 1.47, respectively. Conclusions: The results suggest the efficacy of bisphosphonate for prevention from bone-relating complications osteoporosis by aromatase inhibitor in Japanese women with breast cancer. No significant financial relationships to disclose.
Deciphering the Insights of Poly(ADP-Ribosylation) in Tumor Progression
Authors: María Isabel Rodríguez, Jara Majuelos-Melguizo, Juan Manuel Martí Martín-Consuegra, Mariano Ruiz de Almodóvar, Abelardo López-Rivas, Francisco Javier Oliver
Journal: Medicinal Research Reviews (2015)

Poly (ADP-ribose) polymerase (PARP) inhibitors are particularly efficient against tumors with defects in the homologous recombination repair pathway. Nonetheless poly(ADP-ribosylation) (PARylation) modulates prometastasic activities and adaptation of tumor to a hostile microenvironment. Modulation of metastasis-promoting traits is possible through the alteration of key transcription factors involved in the regulation of the hypoxic response, the recruitment of new vessels (or angiogenesis), and the stimulation of epithelial to mesenchymal transition (EMT). In this review, we summarized some of the findings that focalize on PARP-1's action on tumor aggressiveness, suggesting new therapeutic opportunities against an assembly of tumors not necessarily bearing DNA repair defects. Metastasis accounts for the vast majority of mortality derived from solid cancer. PARP-1 is an active player in tumor adaptation to metastasis and PARP inhibitors, recognized as promising therapeutic agents against homologous recombination deficient tumors, has novel properties responsible for the antimetastatic actions in different tumor settings.
Increased alveolar nitric oxide by trumpet model in patients with obstructive sleep apnoea
Authors: Thong Hua-Huy, Thanh-Tam Ly, Sy Duong-Quy, Nhat-Nam Le-Dong, Saïd Rouhani, Anh Tuan Dinh-Xuan
Journal: European Respiratory Journal (2012)

Background  We assessed distal/alveolar inflammation in patients with suggestive symptoms of obstructive sleep apnoea (OSA) and measured exhaled alveolar concentration of nitric oxide (CANO) using 2-compartment model (2-CM) and the trumpet model (with correction for axial NO back-diffusion).  Methods  Ninety five patients suspected for OSA without advanced cardio-respiratory disease underwent pulmonary function test, overnight polysomnography, and exhaled NO measurement using 2-CM model and the trumpet model. Patients with apnoea-hypopnoea index (AHI)  Results  CANO was significantly higher in OSA patients (n=71; 4.07±1.7ppb) as compared with controls (n=24; 2.24±1.06ppb; p 1%) was 0.855 (0.777-0.933) (p  Conclusions  Increased alveolar NO concentration was related to the severity of nocturnal oxygen desaturation in patients with OSA, linking the distal lung inflammation to intermittent hypoxia. CANO could be used to screen for severe OSA in suspected and symptomatic patients.
Extramedullary hematopoiesis is associated with lower cardiac iron loading in chronically transfused thalassemia patients
Authors: Paolo Ricchi, Antonella Meloni, Anna Spasiano, Maria Giovanna Neri, Maria Rita Gamberini, Liana Cuccia, Vincenzo Caruso, Calogera Gerardi, Domenico Giuseppe D'Ascola, Rosamaria Rosso, Saveria Campisi, Michele Rizzo, Fabrizia Terrazzino, Alessandra Briatico Vangosa, Elisabetta Chiodi, Massimiliano Missere, Maurizio Mangione, Vincenzo Positano, Alessia Pepe
Journal: American Journal of Hematology (2015)

The aim of this study was to evaluate, in a large cohort of chronically transfused patients, whether the presence of extramedullary hematopoiesis (EMH) accounts for the typical patterns of cardiac iron distribution and/or cardiac function parameters. We retrospectively selected 1,266 thalassemia major patients who had undergone regular transfusions (611 men and 655 women; mean age: 31.3 ± 8.9 years, range: 4.2-66.6 years) and were consecutively enrolled within the Myocardial Iron Overload in Thalassemia network. The presence of EMH was evaluated based on steady-state free precession sequences; cardiac and liver iron overloads were quantified using a multiecho T2* approach; cardiac function parameters and pulmonary diameter were quantified using the steady-state free precession sequences; and myocardial fibrosis was evaluated using the late gadolinium enhancement technique. EMH was detected in 167 (13.2%) patients. The EMH+ patients had significantly lower cardiac iron overload than that of the EMH- patients (P = 0.003). The patterns of cardiac iron distribution were significantly different in the EMH+ and EMH- patients (P < 0.0001), with a higher prevalence of patients with no myocardial iron overload and heterogeneous myocardial iron overload and no significant global heart iron in the EMH+ group EMH+ patients had a significantly higher left ventricle mass index (P = 0.001) and a significantly higher pulmonary artery diameter (P = 0.002). In conclusion, in regularly transfused thalassemia patients, EMH was common and was associated with a thalassemia intermedia-like pattern of cardiac iron deposition despite regular transfusion therapy.
Prognostic significance of actual dose intensity in diffuse large-cell lymphoma: results of a tree-structured survival analysis.
Authors: L W Kwak, J Halpern, R A Olshen, S J Horning
Journal: Journal of Clinical Oncology (1990)

While diffuse large-cell lymphoma (DLCL) is considered to be highly curable with current therapy, treatment failures are observed even with intensive combination chemotherapy regimens. In order to study the prognostic significance of actual dose intensity of chemotherapy in DLCL, we retrospectively analyzed 115 previously untreated patients treated as Stanford between 1975 and 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP), methotrexate, bleomycin, Adriamycin, cyclophosphamide, vincristine, and dexamethasone ([M]BACOD), or methotrexate, Adriamycin, cyclosphosphamide, vincristine, prednisone, and bleomycin (MACOP-B). The actual relative dose intensity (RDI), the amount of drug actually administered to each patient during the first 12 weeks of therapy, was calculated as standardized to CHOP and analyzed in addition to clinical factors prognostic for survival by univariate analysis. Multivariate recursive partitioning (tree-structured) survival analysis identified the actual RDI of Adriamycin greater than 75% as the single most important predictor of survival. A model incorporating the actual RDI of Adriamycin and performance status, in combination with serum lactate dehydrogenase (LDH) and extranodal disease, defined three overall prognostic groups of patients with respective 3-year survival rates of 89%, 63%, and 18%. The three prognostic groups remained distinct, even when restricted to complete responders. This model was also predictive of survival when dose intensity was analyzed relative to the optimum dose defined for each of the three regimens and when applied to a subgroup of patients aged 50 years or younger. We conclude that actual RDI is an important prognostic factor for survival in DLCL and that analysis of RDI early in the course of treatment may allow modification of the treatment plan.
Immunohistology of Malignant Rabbit Fibroma Virus—a Comparative Study With Rabbit Myxoma Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: D S Strayer, S Sell
Journal: JNCI Journal of the National Cancer Institute (1983)

Malignant rabbit fibroma virus (MV) causes a syndrome that consists of disseminated malignant tumors and immunosuppression complicated by severe Pasteurella multocida infection and death. Tissues from rabbits given MV and rabbit myxoma virus were examined by direct immunofluorescence with the use of antibody against virus antigens. Primary and metastatic tumors caused by MV and rabbit myxoma virus were composed of soft tissue cells containing virus antigens. Skin appendages and epidermis overlying the respective tumors showed scant MV but abundant myxoma virus antigen. Both viruses were present systemically in the reticuloendothelial system. Epithelial cells from the liver, kidney, and lung of myxoma virus-infected rabbits contained virus, whereas in MV tumor-bearing rabbits, these cells were uninvolved. However, nasal mucosal and conjunctival epithelia, the locations of Pasteurella infection, showed squamous metaplasia and contained large amounts of MV and myxoma antigens. By analogy to other respiratory tract pathogens, these epithelial changes were probably etiologically significant for development of pasteurellosis in rabbits bearing virus-induced tumors. Thus by immunopathologic as well as clinical examination, MV produces a syndrome distinct from that seen with rabbit myxoma virus. MV induced severe immunosuppression despite T-lymphocyte hyperplasia in the lymphoid tissues observed. The combination of a systemic virus infection, epithelial alterations that impaired clearance mechanisms, and immunologic dysfunction is likely to contribute to the inability of rabbits given MV to survive their gram-negative infection.
Home environment and asthma, respiratory symptoms, FeNO and tear film break up time (BUT) among junior high school students in Penang, Malaysia
Authors: Dan Norbäck, Jamal Hisham Hashim, Gunilla Wieslander, Zailina Hashim
Journal: European Respiratory Journal (2013)

Background:  We investigated associations between home environment and respiratory symptoms, FeNO (NIOX-MINO) and tear film break up time (BUT) in students in Malaysia.   Methods:  Totally 8 junior high schools were selected in Penang, 4 classes per school, and 20 students per class, 368 (58%) participated. Multiple logistic and linear regression was used, adjusting for gender, race, smoking and atopy.   Results:  Median FeNO was 17ppb (IQR 10-39), and 14% had wheeze, 38% daytime and 11% night time attacks of breathlessness last 12 months, 11% doctors’ diagnosed asthma and 37% any respiratory infection last 3 months. Wheeze was more common in wooden houses (OR 2.4 95% CI 1.2-4.7) and homes with dampness/moulds (OR 2.0 95% CI 1.04-3.9) especially floor dampness (OR 3.6 95% CI 1.2-11.2). Daytime breathlessness was more common if keeping cats (OR 1.8 95% CI 1.02-3.2). Night time breathlessness was more common in wooden houses (OR 2.4; 95% CI 1.1-5.3) and homes with mouldy odour (OR=9.3; 95% CI 1.5-56.6) or other odour (OR 3.6; 1.1-11.6). Respiratory infections were more in homes with ETS (OR 1.5 95% CI 1.0-2.3). BUT was shorter in homes with new floor material (p=0.02) or with pets (p=0.02) especially birds (p=0.01). FeNO was higher in students with eye symptoms (p=0.001) and shorter BUT (p=0.03). FeNO was not associated with any home environment factor.   Conclusion:  Respiratory symptoms were more common if living in a home made of wood, with a cat, ETS; dampness/mould or indoor odour. Pet keeping and emissions from new floor material could impair tear film stability. There results indicate a link between lower airway inflammation and eye irritation.
Aryl hydrocarbon receptor–fibroblast growth factor 21 dissociation of fatty liver from insulin resistance: A timely matter?
Authors: Manlio Vinciguerra, Gianluigi Mazzoccoli
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. To the Editor: We read with great interest the article by Lu et al.1 in which the authors demonstrate, using aryl hydrocarbon receptor (AHR, a xenobiotic receptor that senses exogenous toxicants) liver‐specific and inducible transgenic mice fed an obesogenic diet, that activation of the AHR signaling pathway exacerbates hepatic steatosis with a paradoxical protection from obesity and systemic insulin resistance. Moreover, the authors identify fibroblast growth factor 21 (FGF21) as a direct hepatic target of AHR and as the mediator of the systemic metabolic benefits as well as of the hepatic steatosis observed in AHR transgenic mice.1 Although these findings are very impactful, because they establish a new AHR–FGF21 endocrine pathway integrating chemical and nutrient signaling in the liver, there is an important aspect to be stressed. Liver metabolic pathways are driven by circadian biological clocks, and hepatic health is maintained by proper timing of circadian patterns of metabolic gene expression, with the alternation of anabolic processes corresponding to feeding/activity during wake times and catabolic processes characterizing fasting/resting during sleep.2 An intricate relationship has been shown between the clock gene machinery and the AHR signaling pathway.3 The AHR/ARNT protein and the circadian protein BMAL1/ARNTL share structural similarities, and AHR influences the rhythmicity of biological clocks, also through its interaction with BMAL1, the activity of which is altered in AHR knockout mice.4 The AHR has no effects on the biological clock in the absence of exogenous agonist, whereas AHR activation alters circadian rhythmicity and clock gene expression.3 In turn, liver‐produced FGF21 can regulate metabolism and circadian behavior by acting on the nervous system.5 It is plausible that the authors missed interpreting their intriguing mouse phenotype as due to a disruption of the circadian homeostasis as a result of a continuous, time‐disconnected AHR/FGF21 activation. The elegant doxycycline‐inducible transgenic model of Lu et al. would be useful to exploit for time window–restricted experiments of AHR/FGF21 activation. At the patient level, it would be crucial to connect these molecular studies to lifestyle patterns and eventually to chronotherapy based on nontoxic AHR agonists.
Abstract 54: Genome-Wide Association Analysis of Gene-Sodium Interactions on Blood Pressure Phenotypes: The GenSalt Study
Authors: Changwei Li, Jiang He, James Hixson, Dongfeng Gu, Dabeeru Rao, Lawrence Shimmin, Jianfeng Huang, Charles Gu, Jichun Chen, Jianxin Li, Cashell Jaquish, Tanika N Kelly
Journal: Circulation (2015)

Background: Elevated blood pressure (BP) is a major public health challenge. Although the heritability of BP has been long established, current findings can explain only a small proportion of the BP variability attributed to genetic factors. Recent studies indicate that gene-environmental interactions may help to identify novel BP loci. Hence, the current study aimed to identify genetic variants influencing BP regulation by conducting genome-wide gene-sodium interaction analyses among 1,906 participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Methods: GenSalt recruited 1,906 Chinese participants from 633 families. At baseline, one 24-hour and two 8-hour urine specimens were collected to measure urinary sodium excretion. Nine BP measurements were taken using a random zero sphygmomanometer. A total of 868,158 autosomal single nucleotide polymorphisms (SNPs) were genotyped using Affymetrix Genomewide Human SNP array 6.0 (Affymetrix, Inc, Santa Clara, CA). Mixed effects models were used to test genome-wide SNP-sodium interactions on BP, adjusting for age, gender, and body mass index. Promising findings (interaction term P &lt;1.00х10 -6 ) from GenSalt were further evaluated for replication among Chinese participants of the Multi-Ethnic Study of Atherosclerosis (MESA) with available data from the database of genotypes and phenotypes (dbGaP). SNP effects in GenSalt and MESA were meta-analyzed using inverse-variance weighted fixed effect models. Results: The meta-analyses identified 3 novel loci that significantly interacted with sodium to influence BP phenotypes. SNP-sodium interactions on systolic BP were identified for NEK2 variant rs10494938 at 1q32.3 (GenSalt P =2.19х10 -6 , MESA P =4.35х10 -4 , and Meta-analysis P = 3.93х10 -8 ). In addition, CASP4 variant rs1944900 at 11q22.3 interacted with sodium to influence both systolic BP (GenSalt P =1.24х10 -9 , MESA P =4.22х10 -2 , and Meta-analysis P = 1.14х10 -10 ) and mean arterial pressure (GenSalt P =1.68х10 -9 , MESA P =4.27х10 -2 , and Meta-analysis P = 1.91х10 -10 ). Furthermore, C9orf3 variant rs17679141 at 9q22.32 interacted with sodium to influence diastolic BP (GenSalt P =2.85х10 -8 , MESA P =4.55х10 -2 , and Meta-analysis P =4.61х10 -9 ). The 3 variants all physically mapped to the intronic regions of their corresponding genes. Conclusion: The current study identified 3 novel loci which may interact with dietary sodium intake to influence BP phenotypes.
Sorafenib Action in Hepatitis B Virus X–Activated Oncogenic Androgen Pathway in Liver through SHP-1
Authors: Sheng-Han Wang, Shiou-Hwei Yeh, Chung-Wai Shiau, Kuen-Feng Chen, Wei-Hsiang Lin, Ting-Fen Tsai, Yuan-Chi Teng, Ding-Shinn Chen, Pei-Jer Chen
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) shows a higher incidence in men, mainly because of hepatitis B X (HBx)–mediated enhancement of androgen receptor (AR) activity. We aimed to examine this pathway in hepatocarcinogenesis and to identify drug(s) specifically blocking this carcinogenic event in the liver.
Exacerbations of Bronchitis
Authors: JIE ZHU, YU SHENG QIU, SWATI MAJUMDAR, ELIZABETH GAMBLE, DEAN MATIN, GRAZIELLA TURATO, LEONARDO M. FABBRI, NEIL BARNES, MARINA SAETTA, PETER K. JEFFERY
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Eosinophilia has been reported during exacerbations of bronchitis, but the mechanisms of tissue recruitment of eosinophils are unclear. We quantified eosinophils and the concurrent expression of cytokines and chemokines probably responsible for the tissue eosinophilia in bronchial biopsies obtained from three groups of nonatopic subjects: (1) healthy nonsmokers (n = 7; FEV1 % predicted = 108 ± 4 [mean ± SEM]); (2) nonasthmatic smokers with chronic bronchitis (CB) in a stable phase of their disease (n = 11; FEV1 % predicted: 75 ± 5); and (3) nonasthmatic subjects with CB who sought medical advice for an exacerbation of their condition (n = 9; FEV1 % predicted: 61 ± 8). We applied anti-EG2 antibody and immunostaining to detect and count eosinophils. We performed in situ hybridization to visualize and enumerate cells expressing the genes for interleukin (IL)-4 and IL-5 and the eosinophil chemokines eotaxin, monocyte chemoattractant protein (MCP)-4, or regulated on activation, normal T-cell expressed and secreted (RANTES). We confirmed an increase in EG2-positive eosinophils in patients with CB in exacerbation. We found messenger RNA (mRNA) positivity for IL-4 and IL-5 in CB, but the between-group differences were not statistically significant. However, the numbers of lymphomononuclear cells expressing eotaxin mRNA were significantly greater in the smokers with CB than in the healthy nonsmokers without CB (p < 0.01). Following an exacerbation, RANTES expression was upregulated and this chemokine was strongly expressed in both the surface epithelium and in subepithelial lymphomononuclear cells: only RANTES showed a significant positive correlation with the increasing number of EG2-positive cells (r = 0.51; p < 0.03). In conclusion, an allergic profile of inflammation can also occur in CB: the marked upregulation of RANTES in the epithelium and subepithelium most likely accounts for the increased eosinophilia associated with an exacerbation of bronchitis.
Characteristics of pulmonary MAC disease diagnosed later in follow-up after negative mycobacterial cultures by bronchoscopy
Authors: Kazuya Koyama, Nobuharu Ohshima, Keita Takeda, Takahiro Andoh, Ryota Satoh, Masahiro Kawashima, Hideaki Nagai, Hirotoshi Matsui, Shinobu Akagawa, Akira Hebisawa, Ken Ohta
Journal: European Respiratory Journal (2014)

Background: We occasionally experienced cases suspected of pulmonary Mycobacterium avium complex (MAC) by radiological findings without positive bacterial cultures. In this study, we evaluated features of pulmonary MAC cases diagnosed later in the follow-up after negative close investigation.

Methods: We defined two groups of pulmonary MAC cases; first study negative (FSN) group and first study positive (FSP) group. The FSN group consisted of patients whose first close examinations including bronchial washings revealed negative for MAC isolation, but turned positive later in the follow-up studies. The first examination was performed between 2007 and 2011 in our hospital. On the other hand, the FSP group consisted of patients with positive MAC cultures in the first study between 2007 and 2011.

Results: We recruited 24 patients in the FSN group and 266 patients in the FSP group. Radiological findings were categorized into four entities; isolated mass (n=7 in FSN, n=6 in FSP), nodular/bronchiectasis (NB) (n=17 in FSN, n=245 in FSP), fibrocavitary (FC) type (n=0 in FSN, n=9 in FSP), and others (n=0 in FSN, n=6 in FSP). The FSN group exhibited more “isolated mass” cases (p<0.001) and less NB type (p<0.001). When limited to NB type patients, FSN group showed less cavitations (FSN 6% vs FSP 32%; p=0.04).

Conclusion: Pulmonary MAC patients with an isolated mass were difficult to diagnose by proving mycobacteria with bronchial washings. MAC tended to be isolated in the first study of FC type and NB type especially NB type with cavities.