tbuckley/cabot-search huggingface dataset:
Effect of R-verapamil on the pharmacokinetics of paclitaxel in women with breast cancer.
Authors: S L Berg, A Tolcher, J A O'Shaughnessy, A M Denicoff, M Noone, F P Ognibene, K H Cowan, F M Balis
Journal: Journal of Clinical Oncology (1995)

PURPOSE To study the effect of the multidrug-resistance reversal agent R-verapamil on the pharmacokinetic behavior of paclitaxel. METHODS Six women with breast cancer who received paclitaxel as a 3-hour infusion with and without R-verapamil were monitored with frequent plasma sampling up to 24 hours postinfusion. Paclitaxel concentrations were measured using a reverse-phase high-pressure liquid chromatography assay. RESULTS Concomitant administration of R-verapamil resulted in a decrease in mean (+/- SD) paclitaxel clearance from 179 +/- 67 mL/min/m2 to 90 +/- 34 mL/min/m2 (P &lt; .03) and in a twofold increase in paclitaxel exposure (area under the curve [AUC]). The mean end-infusion paclitaxel concentration was also twofold higher: 5.1 +/- 1.8 mumol/L versus 11.3 +/- 4.1 mumol/L (P &lt; .03). CONCLUSION The alteration in paclitaxel pharmacokinetics when paclitaxel and R-verapamil are coadministered complicates the interpretation of response and toxicity data from clinical trials of this drug combination.
LNA aptamer based multi-modal, Fe 3 O 4 -saturated lactoferrin (Fe 3 O 4 -bLf) nanocarriers for triple positive (EpCAM, CD133, CD44) colon tumor targeting and NIR, MRI and CT imaging
Authors: Kislay Roy, Rupinder K Kanwar, Jagat R Kanwar
Journal: Biomaterials (2015)
Dynamics of methicillin-resistant Staphylococcus aureus and methicillin-susceptible Staphylococcus aureus carriage in pig farmers: a prospective cohort study
Authors: B.A.G.L. van Cleef, B.H.B. van Benthem, E.J.M. Verkade, M. van Rijen, M.F.Q. Kluytmans-van den Bergh, L.M. Schouls, B. Duim, J.A. Wagenaar, H. Graveland, M.E.H. Bos, D. Heederik, J.A.J.W. Kluytmans
Journal: Clinical Microbiology and Infection (2014)
The European Organization for Research and Treatment of Cancer breast cancer-specific quality-of-life questionnaire module: first results from a three-country field study.
Authors: M A Sprangers, M Groenvold, J I Arraras, J Franklin, A te Velde, M Muller, L Franzini, A Williams, H C de Haes, P Hopwood, A Cull, N K Aaronson
Journal: Journal of Clinical Oncology (1996)

PURPOSE To construct a breast cancer-specific quality-of-life questionnaire (QLQ) module to be used in conjunction with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and to test its reliability and validity cross-culturally. PATIENTS AND METHODS Module construction took place after the EORTC guidelines for module development. The module--the QLQ-BR23--consists of 23 items covering symptoms and side effects related to different treatment modalities, body image, sexuality, and future perspective. This module was tested in 170 Dutch, 168 Spanish, and 158 American cancer patients at two points in time. The timing for the Dutch and Spanish patients was before and during treatment with radiotherapy or chemotherapy. For the American patients, the questionnaire was administered at admission at the breast clinic and 3 months after the first assessment. RESULTS Multitrait scaling analysis confirmed the hypothesized structure of four of the five scales. Cronbach's alpha coefficients were, in general, lowest in Spain (range; .46 to .94) and highest in the United States (range; .70 to .91). On the basis of known-groups comparisons, selective scales distinguished clearly between patients differing in disease stage, previous surgery, performance status, and treatment modality, according to expectation. Additionally, selective scales detected change over time as a function of changes in performance status and treatment-induced change. CONCLUSION These results lend support to the clinical and cross-cultural validity of the QLQ-BR23 as a supplementary questionnaire for assessing specific quality-of-life issues relevant to patients with breast cancer.
Hepatic stellate cells regulate liver immunity to visceral leishmaniasis through P110δ‐dependent induction and expansion of regulatory T cells in mice
Authors: Forough Khadem, Xiaoling Gao, Zhirong Mou, Ping Jia, Hesamaldin Movassagh, Chukwunonso Onyilagha, Abdelilah S. Gounni, Matthew C. Wright, Jude E. Uzonna
Journal: Hepatology (2015)

Visceral leishmaniasis (VL) is associated with severe immune dysfunction and if untreated leads to death. Because the liver is one of the primary target organs in VL, unraveling the mechanisms governing the local hepatic immune response is important for understanding the immunopathogenesis of VL. We previously reported that mice with inactivating knockin mutation in the p110δ gene (p110δ D910A ) are resistant to VL, due in part to impaired regulatory T‐cell (Treg) expansion. In this study, we investigated the mechanism of this resistance by focusing on hepatic stellate cells (HSCs), which are known to regulate Treg induction and expansion. We show that HSCs are infected with Leishmania donovani in vivo and in vitro and that this infection leads to the production of interleukin‐2, interleukin‐6, and transforming growth factor‐β, cytokines known to induce Tregs. We further demonstrate that L. donovani infection leads to expansion of HSCs in a p110δ‐dependent manner and that this correlated with proliferation of hepatic Tregs in vivo . In vitro studies clearly show that L. donovani –infected HSCs induce CD4 + T cells to become Tregs and expand Tregs in a p110δ‐dependent manner. Targeted depletion of HSCs during infection caused a dramatic reduction in liver Treg numbers and proliferation, which was associated with a decrease in interleukin‐10 production by hepatic T cells and a more efficient parasite control. Conclusion : These results demonstrate the critical role of HSCs in the pathogenesis of VL and suggest that the enhanced resistance of p110δ D910A mice to L. donovani infection is due in part to impaired expansion and inability of their HSCs to induce and expand Tregs in the liver. (H epatology 2016;63:620–632)
ACE and sIL2-R predict lung function improvement in sarcoidosis during methotrexate therapy
Authors: Adriane D.M. Vorselaars, Coline H.M. Van Moorsel, Pieter Zanen, Henk J.T. Ruven, Anke Claessen, Heleen van Velzen-Blad, Jan C. Grutters
Journal: European Respiratory Journal (2013)

Introduction  In sarcoidosis, the search for a disease activity marker that correlates with treatment response is ongoing. The aim of this study was to assess the course of serum angiotensin-converting enzyme (ACE) and soluble IL-2 receptor (sIL-2R) during methotrexate (MTX) therapy, and to determine the predictive value of baseline levels and change in ACE and sIL-2R for lung function improvement in sarcoidosis.  Methods  In this retrospective cohort study we reviewed all sarcoidosis patients who used MTX for six months. Correlation coefficients (R) and Odds ratios (ORs) were calculated to study the correlation and predictive effect of serum ACE and sIL-2R levels.  Results  114 patients were included, 76 of whom had a pulmonary indication for initiating treatment. After six months of MTX treatment, mean ACE decreased with 17.2 U/l (p  Baseline levels of ACE >90 U/l predicted a 10% improvement in overall lung function (OR 3.55; CI 1.34-9.38), with a higher prediction level for 10% improvement in DLCO (OR 4.63; CI 1.23-17.4).  Conclusion  Serum ACE and sIL-2R levels correlate with lung function improvement during treatment with MTX. Serial measurements of these easily available markers could be of important value to physicians when monitoring treatment in sarcoidosis patients.
Cytoskeleton Regulator PAK4 Plays a Role in Growth and Survival of Myeloma with a Potential Therapeutic Intervention Using PAK4 Allosteric Modulators (PAMs)
Authors: Mariateresa Fulciniti, Rajya Lakshmi Bandi, Nicola Amodio, Antonia Cagnetta, William Senapedis, Erkan Baloglu, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2014)
Treatment of primary hepatobiliary cancers with conformal radiation therapy and regional chemotherapy.
Authors: J M Robertson, T S Lawrence, L M Dworzanin, J C Andrews, S Walker, M L Kessler, D J DuRoss, W D Ensminger
Journal: Journal of Clinical Oncology (1993)

PURPOSE To develop more effective regional therapy for patients with unresectable primary hepatobiliary cancer using concurrent conformal radiation therapy and intraarterial hepatic (IAH) fluorodeoxyuridine (FdUrd). PATIENTS AND METHODS Twenty-six patients with unresectable, nonmetastatic primary hepatobiliary cancer were treated with concurrent IAH FdUrd (0.2 mg/kg/d) and conformal hepatic radiation therapy (1.5 to 1.65 Gy per fraction twice per day). The total dose of radiation administered to the tumor depended on the fraction of normal liver excluded from the high-dose volume. All patients were assessed for toxicity, hepatobiliary relapse, and survival; 17 patients were assessable for response (eight had cholangiocarcinoma not assessable by computed tomographic [CT] scan and one progressed distantly during treatment). The median potential follow-up duration was 27 months. RESULTS Whole-liver radiation was administered to six patients with diffuse hepatocellular carcinoma (HCC). Eleven patients with localized HCC and nine with cholangiocarcinoma received focal radiation to a dose of 48 to 72.6 Gy. An objective response for assessable patients was observed in 11 of 11 patients treated with focal radiation, but only one of six patients treated with whole-liver radiation. Whole-liver radiation accounted for five of seven patients with &gt; or = grade 3 toxicity and four of six local treatment failures. Two patients had nonfatal radiation hepatitis. The median survival duration for patients with localized hepatobiliary cancer was 19 months, while patients with diffuse HCC had a median survival duration of 4 months. The rate of actuarial freedom from hepatobiliary progression in patients with localized disease was 72% at 24 months. CONCLUSION These findings suggest that three-dimensional planned focal liver radiation and IAH FdUrd can produce a high, durable response rate and an encouraging median survival duration in patients with nondiffuse, unresectable primary hepatobiliary cancer.
Eradication of B-ALL using chimeric antigen receptor–expressing T cells targeting the TSLPR oncoprotein
Authors: Haiying Qin, Monica Cho, Waleed Haso, Ling Zhang, Sarah K. Tasian, Htoo Zarni Oo, Gian Luca Negri, Yongshun Lin, Jizhong Zou, Barbara S. Mallon, Shannon Maude, David T. Teachey, David M. Barrett, Rimas J. Orentas, Mads Daugaard, Poul H. B. Sorensen, Stephan A. Grupp, Terry J. Fry
Journal: Blood (2015)
Functional improvement precedes structural regression of atherosclerosis.
Authors: K H Benzuly, R C Padgett, S Kaul, D J Piegors, M L Armstrong, D D Heistad
Journal: Circulation (1994)

BACKGROUND Vasoconstrictor responses to serotonin are augmented in monkeys with diet-induced atherosclerosis and improve after 18 months of normal diet. We tested the hypothesis that functional improvement may occur early during regression, before evidence of structural improvement. METHODS AND RESULTS Responses of the iliac artery to serotonin were measured by quantitative angiography and a Doppler flow probe in several groups of monkeys: (1) normal monkeys, (2) monkeys fed an atherogenic diet for 2 years (atherosclerotic), and (3) monkeys fed an atherogenic diet for 2 years (preregression) followed by a normal diet for 4, 8, or 12 months (regression). In normal monkeys, serotonin produced minimal constriction of the iliac artery, and blood flow to the legs increased. In atherosclerotic monkeys, there was pronounced constriction of the iliac artery, and blood flow to the legs decreased markedly. After 4 months of regression diet, four of eight monkeys demonstrated marked reduction in hyperresponsiveness to serotonin angiographically, and by 8 months, six of eight monkeys had significant improvement. After regression, serotonin produced minimal changes in flow. There was no reduction in intimal area (ie, atherosclerotic lesion) in iliac arteries from regression monkeys compared with atherosclerotic monkeys, but there was a marked reduction in cholesteryl ester in arteries from regression monkeys. CONCLUSIONS Abnormal vasoconstrictor responses to serotonin usually return to or toward normal within a few months during regression of atherosclerosis. Functional improvement occurs in conjunction with early resorption of lipid from the arterial wall and occurs before detectable changes in mass of the atherosclerotic lesion.
Cryptosporidiosis and Microsporidiosis.
Authors: R C G Pollok
Journal: Gut (2001)

Cryptosporidiosis and Microsporidiosis . Edited by F Petry (Contributions to Microbiology, vol 6), (Pp 268; illustrated). Switzerland: Karger, 2000. ISBN 3805570503.

There is a great need to raise the profile of parasitic diarrhoeal disease, and this book serves the cause well. World wide the prevalence of Cryptosporidium among individuals with diarrhoea is approximately 5%. The common notion that cryptosporidiosis is purely a disease of the immunocompromised is wrong. Since the well publicised Milwaukee outbreak in the USA, affecting 420 000 individuals, large waterborne outbreaks of cryptosporidiosis repeatedly occur at an alarming rate despite “state of the art” water treatment facilities, illustrated by two examples. In 1998, Sydney water supplies became heavily contaminated with Cryptosporidium leading to a full scale enquiry by the Australian government. A large outbreak occurred in London and Hertfordshire in 1997, affecting a population of half a …
Hypoxia inducible prolyl hydroxylase PHD3 maintains carcinoma cell growth by decreasing the stability of p27
Authors: Heidi Högel, Petra Miikkulainen, Lucia Bino, Panu M. Jaakkola
Journal: Molecular Cancer (2015)

Hypoxia can halt cell cycle progression of several cell types at the G1/S interface. The arrest needs to be overcome by cancer cells. We have previously shown that the hypoxia-inducible cellular oxygen sensor PHD3/EGLN3 enhances hypoxic cell cycle entry at the G1/S boundary.We used PHD3 knockdown by siRNA and shRNA in HeLa and 786-0 renal cancer cells. Flow cytometry with cell synchronization was used to study cell growth at different cell cycle phases. Total and phosphospecific antibodies together with cycloheximide chase were used to study p27/CDKN1B expression and fractionations for subcellular protein localization.Here we show that PHD3 enhances cell cycle by decreasing the expression of the CDK inhibitor p27/CDKN1B. PHD3 reduction led to increased p27 expression under hypoxia or VHL mutation. p27 was both required and sufficient for the PHD3 knockdown induced cell cycle block. PHD3 knockdown did not affect p27 transcription and the effect was HIF-independent. In contrast, PHD3 depletion increased the p27 half-life from G0 to S-phase. PHD3 depletion led to an increase in p27 phosphorylation at serine 10 without affecting threonine phosphorylation. Intact serine 10 was required for normal hypoxic and PHD3-mediated degradation of p27.The data demonstrates that PHD3 can drive cell cycle entry at the G1/S transition through decreasing the half-life of p27 that occurs by attenuating p27S10 phosphorylation.
Patients’ Perceptions of Receiving Bad News About Cancer
Authors: J. T. Ptacek, John J. Ptacek
Journal: Journal of Clinical Oncology (2001)

The purpose of this investigation was to document patients' recollections about what transpired during bad news interactions between physicians and themselves.One hundred twenty cancer patients provided information about the most recent time they received bad cancer-specific news. Using a series of descriptive statements, patients reported on what the physician did while communicating the bad news. Patients also indicated the extent to which they were satisfied with the transaction and whether they believed that the interaction had any long-lasting impact on their adjustment or on their subsequent interactions with the physician who delivered the news.Overall, patients reported having similar experiences, with most physicians behaving in ways that were consistent with advice published in the medical literature. Satisfaction with the bad news transaction was high. Younger patients and women found the transaction to be more stressful, and older patients believed that the transaction was less important for subsequent interactions with the physician. Logistic regression analyses indicated that satisfaction with the transaction was uniquely predicted by factors related to the environment, to what the physician said, and to how the physician said it.Despite high levels of self-reported satisfaction by patients, some factors differentiated the most satisfied patients from patients who were less satisfied. The findings suggest that special attention should be given to making the environment comfortable, taking plenty of time with the patient, and attempting to empathize with the patient's experiences.
Comparative Outcomes of T-Cell–Depleted and Non–T-Cell–Depleted Allogeneic Bone Marrow Transplantation for Chronic Myelogenous Leukemia: Impact of Donor Lymphocyte Infusion
Authors: Laurie H. Sehn, Edwin P. Alyea, Edie Weller, Christine Canning, Stephanie Lee, Jerome Ritz, Joseph H. Antin, Robert J. Soiffer
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Donor lymphocyte infusion (DLI) can restore complete remission in patients with chronic myelogenous leukemia (CML) who have relapsed after T-cell–depleted (TCD) allogeneic bone marrow transplantation (BMT). The existence of salvage treatment for patients with DLI after TCD allogeneic BMT prompted an evaluation of overall outcome after CD6 + -TCD allogeneic BMT for patients treated during the time when DLI has been available. PATIENTS AND METHODS: We performed a retrospective analysis of outcomes of 46 patients who underwent TCD allogeneic BMT for stable-phase CML and compared these outcomes with those of 40 patients who underwent non-TCD allogeneic BMT. All subjects were patients at one of two neighboring institutions during a period when DLI was available. All patients received marrow from HLA-identical sibling donors, underwent similar myeloablative regimens, and had similar pretreatment characteristics. RESULTS: After BMT, the TCD group had a lower incidence of grade 2 to 4 acute (15% v 37%, P = .026) and chronic graft-versus-host disease (GVHD) (18% v 42%, P = .024) than did the non-TCD group. The 1-year treatment-related mortality rates for the TCD group and the non-TCD group were 13% and 29%, respectively (P = .07). The estimated 3-year probability of relapse (cytogenetic or hematologic) was higher for patients in the TCD group than for patients in the non-TCD group (62% v 24%, P = .0003). Twenty-three patients (20 in the TCD group and three in the non-TCD group) received and were assessable for response to DLI. After DLI, 17 of 20 patients in the TCD group and two of three patients in the non-TCD group achieved complete remission. Donor lymphocyte infusion induced GVHD in nine of 23 patients. Thirty (65%) of 46 patients in the TCD group and 27 (69%) of 39 assessable patients in the non-TCD group remained alive without evidence of disease. The estimated 3-year overall survival rates were similar for the TCD group and the non-TCD group (72% v 68%, respectively; P = .38). At last follow-up, there was no difference in the overall prevalence of GVHD or the proportion of patients requiring immunosuppressive agents between groups. CONCLUSION: These results suggest that the combination of T-cell depletion and post-BMT DLI is a viable treatment option for patients undergoing allogeneic BMT for CML and should be prospectively compared with traditional forms of GVHD prophylaxis.
Alveolar accumulation of fibronectin and hyaluronan precedes bleomycin-induced pulmonary fibrosis in the rat
Authors: J Hernnas, O Nettelbladt, L Bjermer, B Sarnstrand, A Malmstrom, R Hallgren
Journal: European Respiratory Journal (1992)

The development of bleomycin-induced pulmonary fibrosis in rats was studied over a period of 30 days after an intratracheal instillation of bleomycin. Fibronectin was visualized in histological sections and quantified in bronchoalveolar lavage fluid (BALF) and related to simultaneous measurements of hyaluronan, collagen and albumin in BALF and/or lung tissue extracts. An increase in BALF fibronectin levels was noted after 3 days and the peak value a sixty fold increase was noted at day 7. Thereafter, the fibronectin levels declined and reached control values on day 21. A pronounced, patchily distributed staining for fibronectin appeared in the injured alveolar tissue parallel to the increased lavage fluid fibronectin levels on days 3-7. A fainter, streakily distributed fibronectin staining remained within the alveolar walls in areas with proliferating fibroblasts on days 14-30. Albumin in BALF increased to a peak level, 20 times control values, after 3 days and then rapidly declined. Thus, the ratio of fibronectin to albumin increased to a peak value of 43 times control values on day 7, indicating that plasma leakage cannot be the only source of the observed increase in lavage fibronectin. Lung tissue hydroxyproline increased between days 7 and 30, whereas extractable hyaluronan in lung tissue and bronchoalveolar lavage fluid peaked on days 3-7 and then gradually declined towards normal values on days 21-30. These data demonstrate that fibronectin accumulates in the alveolar tissue during the early inflammatory phase of the bleomycin-induced lung injury, parallelling hyaluronan accumulation and preceding the development of pulmonary fibrosis.
CD44 and Hyaluronan Promote the Bone Morphogenetic Protein 7 Signaling Response in Murine Chondrocytes
Authors: Na Luo, Warren Knudson, Emily B. Askew, Roberta Veluci, Cheryl B. Knudson
Journal: Arthritis & Rheumatology (2014)

Cell-matrix interactions promote cartilage homeostasis. We previously found that Smad1, the transcriptional modulator of the canonical bone morphogenetic protein 7 (BMP-7) pathway, interacted with the cytoplasmic domain of CD44, the principal hyaluronan receptor on chondrocytes. To elucidate the physiologic function of CD44-Smad1 interactions, as well as the role of hyaluronan, we studied the response of chondrocytes isolated from CD44(-/-) and BALB/c (wild-type [WT]) mice to stimulation with BMP-7.In primary murine chondrocytes, CD44 expression was decreased by small interfering RNA (siRNA) transfection or was enhanced by plasmid transfection. Pericellular hyaluronan was removed by hyaluronidase treatment, or its endogenous synthesis was inhibited. Changes in response to BMP-7 stimulation were evaluated by Western blotting of Smad1 phosphorylation and aggrecan messenger RNA (mRNA) expression.Chondrocytes from CD44(-/-) mice and WT mice transfected with CD44 siRNA were less responsive than untransfected chondrocytes from WT mice to BMP-7. CD44(-/-) mouse chondrocytes transfected with pCD44 showed increased sensitivity to BMP-7. Significant increases in aggrecan mRNA were observed in WT mouse chondrocytes in response to 10 ng/ml of BMP-7, whereas at least 100 ng/ml of BMP-7 was required for CD44(-/-) mouse chondrocytes. However, in chondrocytes from CD44(-/-) and WT mice, hyaluronidase treatment decreased cellular responses to BMP-7. Treatment of both bovine and murine chondrocytes with 4-methylumbelliferone to reduce the synthesis of endogenous hyaluronan confirmed that hyaluronan promoted BMP-7 signaling.Taken together, these investigations into the mechanisms underlying BMP-7 signaling in chondrocytes revealed that while hyaluronan-dependent pericellular matrix is critical for BMP-7 signaling, the expression of CD44 promotes the cellular response to lower concentrations of BMP-7.