tbuckley/cabot-search huggingface dataset:
Bevacizumab-Induced Transient Remodeling of the Vasculature in Neuroblastoma Xenografts Results in Improved Delivery and Efficacy of Systemically Administered Chemotherapy
Authors: Paxton V. Dickson, John B. Hamner, Thomas L. Sims, Charles H. Fraga, Catherine Y.C. Ng, Surender Rajasekeran, Nikolaus L. Hagedorn, M. Beth McCarville, Clinton F. Stewart, Andrew M. Davidoff
Journal: Clinical Cancer Research (2007)

Dysfunctional tumor vessels can be a significant barrier to effective cancer therapy. However, increasing evidence suggests that vascular endothelial growth factor (VEGF) inhibition can effect transient "normalization" of the tumor vasculature, thereby improving tumor perfusion and, consequently, delivery of systemic chemotherapy. We sought to examine temporal changes in tumor vascular function in response to the anti-VEGF antibody, bevacizumab.Established orthotopic neuroblastoma xenografts treated with bevacizumab were evaluated at serial time points for treatment-associated changes in intratumoral vascular physiology, penetration of systemically administered chemotherapy, and efficacy of combination therapy.After a single bevacizumab dose, a progressive decrease in tumor microvessel density to <30% of control was observed within 7 days. Assessment of the tumor microenvironment revealed a rapid, sustained decrease in both tumor vessel permeability and tumor interstitial fluid pressure, whereas intratumoral perfusion, as assessed by contrast-enhanced ultrasonography, was improved, although this latter change abated by 1 week. Intratumoral drug delivery mirrored these changes; penetration of chemotherapy was improved by as much as 81% when given 1 to 3 days after bevacizumab, compared with when both drugs were given concomitantly, or 7 days apart. Finally, administering topotecan to tumor-bearing mice 3 days after bevacizumab resulted in greater tumor growth inhibition (36% of control size) than with monotherapy (88% bevacizumab, 54% topotecan) or concomitant administration of the two drugs (44%).Bevacizumab-mediated VEGF blockade effects alterations in tumor vessel physiology that allow improved delivery and efficacy of chemotherapy, although careful consideration of drug scheduling is required to optimize antitumor activity.
Microvascular Loops and Networks as Prognostic Indicators in Choroidal and Ciliary Body Melanomas
Authors: T. Makitie, P. Summanen, A. Tarkkanen, T. Kivela
Journal: JNCI Journal of the National Cancer Institute (1999)

Malignant melanoma of the ciliary body and choroid of the eye is a tumor that disseminates frequently, and 50% of the diagnosed patients die within 10 years. We investigated the hypothesis that, by histopathologic analysis of the arrangement of microvessels (i.e., small blood vessels) in loops and networks, we might be able to differentiate better those patients with a favorable prognosis from those with a poor prognosis.We conducted a population-based, retrospective cohort study of melanoma-specific and all-cause mortality for 167 consecutive patients who had an eye surgically removed because of malignant choroidal or ciliary body melanoma during the period from 1972 through 1981. Microvascular loops and networks were evaluated independently by two pathologists who were unaware of patient outcome.Microvascular patterns could be assessed in 134 (80%) of 167 melanoma specimens. The 10-year probability of melanoma-specific survival was worse if microvascular loops (0.45 versus 0.83; two-sided P<.0001) and networks (0.41 versus 0.72, two-sided P<.0001) were present. In multivariate Cox regression analysis of melanoma-specific survival, the hazard ratios were 1.66 (95% confidence interval [CI] = 1.19-2.30) for the presence of loops and networks as a combined three-category variable, 2.36 (95% CI = 1.37-4.05) for the presence of epithelioid cells, 1.11 (95% CI = 1.03-1.19) for the largest basal tumor diameter (evaluated as a continuous variable), and 2.14 (95% CI = 1.25-3.67) for ciliary body involvement.Patients with malignant uveal melanoma who have a favorable prognosis can be distinguished from those with a poor prognosis by histopathologic analysis of microvascular patterns in uveal melanoma tumor specimens.
HIV-associated nephropathy
Authors: A Laradi, A Mallet, H Beaufils, M Allouache, F Martinez
Journal: Journal of the American Society of Nephrology (1998)

Records of 102 patients with biopsy-proven HIV-associated nephropathy (HIVAN) admitted to 18 hospitals in the Paris area from 1984 through 1996 were retrospectively reviewed. Demographics and clinical and laboratory features of the cohort were determined, and prognostic factors of renal and patient survival were analyzed. Renal and patient survival curves were estimated with the actuarial method. Prognostic factors were assessed by uni- and multidimensional analyses based on Cox regression models. Values were expressed as median with interquartile. The total population (median age 34) included 97% blacks and 71.5% males. Median patient follow-up was 165 d (range, 43 to 493). At the time of renal biopsy, median values of serum creatinine, proteinuria, and CD4+ cell count were 496 micromol/L, 6.5 g/24 h, and 48.5 cells/mm3, respectively. Fifteen patients were given steroids after the onset of HIVAN. Overall patient survival at 0.5, 1, and 3 yr was 73 +/- 5, 55 +/- 6, and 38 +/- 7%, respectively. The proportion of patients free of dialysis at 0.5, 1, and 3 yr was 73 +/- 5, 60 +/- 7, and 18 +/- 10%, respectively. Predictors of poor patient prognosis were a low CD4+ cell count (relative risk [RR; per 50 cells/mm3 decrease] 1.35; confidence interval [CI], 1.13 to 1.6) and antiretroviral therapy before the onset of HIVAN (RR 1.9; CI, 1.05 to 3.6). Main independent factors associated with better renal outcome were: steroid therapy (RR 0.29; CI, 0.1 to 0.9); low proteinuria level (RR [per 50% decrease] 0.7; CI, 0.5 to 0.98); low serum creatinine (RR [per 1.1 mg/dl decrease] 0.78; CI, 0.7 to 0.87); and hemoglobin level (RR [per g/dl increase] 0.76; CI, 0.58 to 1.00). HIVAN is not a rare nephropathy in Paris and its suburbs. Renal prognosis and patient survival are better than what was reported previously. Steroids may delay the downward course of HIVAN. It is not certain that in the new era of HIV therapy, the possible renal benefits of corticosteroids outweigh their potential risks. The only reliable predictor of patient survival is the intensity of immunodeficiency.
MicroRNAs play a role in spontaneous recovery from acute liver failure
Authors: Katharina John, Johannes Hadem, Till Krech, Kristin Wahl, Michael P. Manns, Steven Dooley, Sandor Batkai, Thomas Thum, Klaus Schulze-Osthoff, Heike Bantel
Journal: Hepatology (2014)

Acute liver failure (ALF) represents a life-threatening situation characterized by sudden and massive liver cell death in the absence of preexisting liver disease. Although most patients require liver transplantation to prevent mortality, some recover spontaneously and show complete liver regeneration. Because of the rarity of this disease, the molecular mechanisms regulating liver regeneration in ALF patients remain largely unknown. In this study, we investigated the role of microRNAs (miRs) that have been implicated in liver injury and regeneration in sera from ALF patients (n = 63). Patients with spontaneous recovery from ALF showed significantly higher serum levels of miR-122, miR-21, and miR-221, compared to nonrecovered patients. In liver biopsies, miR-21 and miR-221 displayed a reciprocal expression pattern and were found at lower levels in the spontaneous survivors, whereas miR-122 was elevated in both serum and liver tissue of those patients. As compared to nonrecovered patients, liver tissue of spontaneous survivors revealed not only increased hepatocyte proliferation, but also a strong down-regulation of miRNA target genes that impair liver regeneration, including heme oxygenase-1, programmed cell death 4, and the cyclin-dependent kinase inhibitors p21, p27, and p57. Our data suggest that miR-122, miR-21, and miR-221 are involved in liver regeneration and might contribute to spontaneous recovery from ALF. Prospective studies will show whether serological detection of those miRNAs might be of prognostic value to predict ALF outcome.
Regulation of p53 Expression in Response to 5-Fluorouracil in Human Cancer RKO Cells
Authors: Jingfang Ju, John C. Schmitz, Bo Song, Kenji Kudo, Edward Chu
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The purpose of the study is to investigate the regulation of p53 expression in response to 5-fluorouracil (5-FU) in human colon cancer cells. Experimental Design: Human colon cancer RKO cells were used as our model system. The levels of p53 expression and p53 protein stability in response to 5-FU and doxorubicin were investigated. In addition, the acetylation and phosphorylation status of p53 after 5-FU and doxorubicin treatment was analyzed by Western immunoblot analysis. Results: Treatment of human colon cancer RKO cells with 10 μmol/L 5-FU resulted in significantly increased levels of p53 protein with maximal induction observed at 24 h. The level of acetylated p53 after 5-FU exposure remained unchanged, whereas the phosphorylated form of p53 was expressed only after 24 h drug treatment. Northern blot analysis revealed no change in p53 mRNA levels after 5-FU treatment. No differences were observed in the half-life of p53 protein in control and 5-FU–treated cells, suggesting that the increase in p53 was the direct result of newly synthesized protein. In contrast, the maximal induction of p53, in response to doxorubicin, occurred at an earlier time point (4 h) when compared with cells treated with 5-FU (24 h). No corresponding change in p53 mRNA was observed. Levels of both the acetylated and phosphorylated forms of p53 were markedly increased upon doxorubicin exposure when compared with treatment with 5-FU, resulting in a significantly prolonged half-life of p53 (120 versus 20 min). Conclusion: These results, taken together, suggest that the regulatory mechanisms controlling p53 expression, in response to a cellular stress, are complex and are dependent upon the specific genotoxic agent. With regard to 5-FU, we show that translational regulation is an important process for controlling p53 expression. Studies are under way to define the specific mechanism(s) that control 5-FU–mediated translational regulation of p53.
Inhibition of MHC class II-restricted T cell response by Lyt-2 alloantigen.
Authors: O Kanagawa, R Maki
Journal: The Journal of Experimental Medicine (1989)

T cell hybridomas were established by fusing a CD8+ V beta 8.1+ CTL clone and a CD4+ V beta 8.1+ helper T lymphocyte (HTL) clone to the thymoma cell line BW5147. In contrast to the HTL x BW hybridomas, which retain the same antigen specificity as the original T cell clone, the CTL x BW hybridomas lost the class I MHC-restricted antigen response but acquired a new specificity to Mlsa antigen. Mlsa reactivity of CTL x BW hybridomas was shown to be mediated by the CTL TCR as assayed by inhibition using an anticlonotypic antibody to the CTL clone. Since hybridomas established with BW5147 lose CD8 expression, we have introduced the CD8 molecule into CTL x BW5147 hybridomas by gene transfection. The CD8+ V beta 8.1+ hybridoma was no longer capable of reacting to Mlsa antigen but exhibited the same antigen specificity as the parental CTL clone. Furthermore, the presence of the transfected CD8 molecule in the HTL x BW hybridomas was found to be inhibitory to class II MHC-restricted antigen reactivity. These results demonstrate that, besides its role in increasing the overall avidity of T cell-class I MHC/antigen interaction, the CD8 molecule inhibits T cell-class II MHC gene product/antigen interaction. This negative effect of the CD8 molecule on a class II MHC-restricted response may account for the failure of CD8+ T cells using either V beta 8.1 or V beta 6, which impart reactivity to the Mlsa antigen on CD4+ T cells, to respond to the Mlsa antigen.
Validation of basophil histamine release against the autologous serum skin test and outcome of serum‐induced basophil histamine release studies in a large population of chronic urticaria patients
Authors: M. H. Platzer, C. E. H. Grattan, L. K. Poulsen, P. S. Skov
Journal: Allergy (2005)

Background: Endogenous histamine‐releasing factors (HRFs) are involved in 30–60% of patients with chronic urticaria (CU). Evidence for their existence comes from in vivo studies of autoreactivity with the autologous serum skin test (ASST), in vitro immunoassays demonstrating autoantibodies against the immunoglobulin E (IgE) or the high affinity IgE receptor (Fc ɛ RI) and serum‐induced histamine release (HR) from basophils and mast cells. We have examined the correlation between the ASST and a new basophil histamine‐releasing assay (the HR‐Urtikaria test) in a group of well‐characterized CU patients and subsequently determined the frequency of HR‐Urticaria‐positive sera from a larger population of CU patients. Subjects: Group 1 consisted of 28 patients with CU (16 were ASST‐positive) 20 patients with atopic dermatitis, 24 patients with allergy to birch and nine healthy controls. Group 2 consisted of 873 unselected CU patients. Methods: White blood cells containing 1–2% basophils from a healthy nonatopic donor were incubated with patients sera in the presence of interleukin (IL)‐3. Histamine was measured by the glass fibre method. Results: Using the ASST as the true outcome, the HR‐Urticaria test showed a sensitivity and specificity of 75% in group 1 using a cut‐off value for HR of &gt;16.5%. None of the controls was positive in the HR‐Urticaria test. In group 2, we found no difference in the frequency of positives between male (34.6%, n = 254) and female adults (35.1%, n = 576) but twice as many females as males were tested. Conclusions: Our studies have shown that the HR‐Urticaria test has a good sensitivity and specificity for endogenous HRFs demonstrated by the ASST in patients with CU and that about one‐third of unselected patients with CU have a positive result.
Fatty Acid Composition of the Subcutaneous Adipose Tissue and Risk of Proliferative Benign Breast Disease and Breast Cancer
Authors: S. J. London, F. M. Sacks, M. J. Stampfer, I. C. Henderson, M. Maclure, A. Tomita, W. C. Wood, S. Remine, N. J. Robert, J. R. Dmochowski, W. C. Willett
Journal: JNCI Journal of the National Cancer Institute (1993)

Background : Studies in animals and geographic correlations across populations suggest that fatty acid intake may have a positive relationship with breast cancer risk, but analytic epidemiologic studies of fat intake have been less supportive. Adipose tissue analysis provides a more objective assessment of intakes of fatty acids that are not endogenously synthesized than do the questionnaire survey methods used in many epidemiologic studies. Purpose : This case-control study of postmenopausal women was designed to examine the relationship between fatty acid composition of subcutaneous adipose tissue and risk of breast cancer and proliferative benign breast disease. In addition, we examined specific hypotheses that breast cancer risk is negatively associated with long-chain N-3 fatty acid intake, positively associated with trans fatty acid intake, and positively associated with increased intake of polyunsaturated fat together with low intake of antioxidants. Methods : Aspirates of subcutaneous fat from the buttocks were obtained from 380 women with newly diagnosed stage I or II breast cancer and 176 with proliferative benign breast disease. A total of 397 women who were evaluated for breast abnormalities at the same institutions but did not require breast biopsy or whose biopsy revealed nonproliferative benign breast disease served as the control group. We examined associations between saturated, monounsaturated, polyunsaturated, trans , or long-chain N-3 fatty acids and breast cancer, atypical hyperplasia, or proliferative benign breast disease without atypia. Results : We observed no consistent patterns of association between breast cancer risk and any of the categories of fatty acids or the individual constituent fatty acids in the adipose tissue. Saturated fatty acids were inversely associated with risk of proliferative benign breast disease without atypia but not with atypical hyperplasia or breast cancer. This association was not observed, however, when total fat intake was taken into account. Women with high levels of polyunsaturated fatty acids in adipose tissue and low serum or dietary levels of antioxidants were not observed to be at higher risk of breast cancer. Conclusions : Using an objective measure of intake, we observed no major associations between polyunsaturated fatty acids, including long-chain N-3 fatty acids and trans fatty acids, and risk of breast cancer or proliferative benign breast disease. Implications: These data do not support the hypothesis that intake of specific fatty acids, particularly polyunsaturated and trans fatty acids, is an important risk factor for malignant or benign breast disease. [J Natl Cancer Inst 85: 785–793, 1993]
Contribution of Fluid Shear Response in Leukocytes to Hemodynamic Resistance in the Spontaneously Hypertensive Rat
Authors: Shunichi Fukuda, Takanori Yasu, Nobuhiko Kobayashi, Nahoko Ikeda, Geert W. Schmid-Schönbein
Journal: Circulation Research (2004)

The mechanisms for elevation of peripheral vascular resistance in spontaneously hypertensive rats (SHR), a glucocorticoid-dependent form of hypertension, are unresolved. An increase in hemodynamic resistance caused by circulating blood may be a factor. Physiological fluid shear stress induces a variety of responses in circulating leukocytes, including pseudopod retraction. Due to high rigidity, leukocytes with pseudopods have greater difficulty to pass through capillaries. Because SHR have more circulating leukocytes with pseudopods, we hypothesize that inhibition of the leukocyte shear response by glucocorticoids in SHR impairs normal leukocyte passage through capillaries and causes enhanced resistance in capillary channels. Fluid shear leads to retraction of pseudopods in normal leukocytes, whereas shear induces pseudopod projection in SHR and dexamethasone-treated Wistar rats. The high incidence of circulating leukocytes with pseudopods results in slower cell passage through capillaries under normal blood flow and during reduced flow enhanced capillary plugging both in vivo and in vitro. SHR blood requires higher pressure (90.0+/-8.2 mm Hg) than Wistar Kyoto rat (WKY, 69.6+/-6.5 mm Hg; P<0.0001) or adrenalectomized SHR (73.5+/-2.1 mm Hg; P=0.0009) at the same flow rate in the resting hemodynamically isolated skeletal muscle microcirculation. Intravenous injection of blood from SHR, but not WKY, causes blood pressure increase in normal rats, which depends on pseudopod formation. We conclude that in addition to enhanced vascular tone, pseudopod formation with lack of normal fluid shear response may serve as mechanisms for an elevated hemodynamic resistance in SHR.
First presentation of a case of pulmonary alveolar microlithiasis with spontaneous pneumothorax
Authors: Naseh Sigari, Shilan Mohammadi
Journal: European Respiratory Journal (2012)

Pulmonary Alveolar Microlithiasis (PAM) is a rare disease of unknown origin. It is characterized by the presence of small calculi within the alveolar spaces, and has various clinical manifestations. Some patients may be asymptomatic for a long period of time with subsequent occurrence of dyspnea, dry cough, chest pain, and eventually, respiratory failure. Recurrent spontaneous pneumothorax episodes are a late complication of the disease. We report the case of an alveolar microlithiasis episode in a 42-year-old male, admitted to Tohid Hospital, Iran, whose first clinical presentation was symptoms of pneumothorax. He was admitted with sudden onset dyspnea and right-sided pleuretic chest pain. Following treatment of pneumothorax after chest tube placement, the pulmonary function revealed normal indices, and chest radiograph demonstrated diffuse confluence of dense micronodular infiltrate. High-resolution computerized tomography scan showed diffuse ground glass attenuation and calcifications along the interlobular septa and subpleural regions. Transbronchial lung biopsy confirmed the diagnosis of PAM.
Quantitative analysis of effect of neodymium-YAG laser on transplanted mouse carcinomas.
Authors: W N Gardner, P Hugh-Jones, M A Carroll, E R Hewitt, H B Hewitt, W Whimster
Journal: Thorax (1982)

Intradermally transplanted non-immunogenic murine carcinomas measuring 3-6 mm in diameter were exposed to a neodymium-YAG laser beam (1060 nm) over a range of exposure times (0.5-6 seconds) and energy densities (expressed as watts/mm2 exposure field). Subsequent growth of the irradiated tumours was compared with that of untreated tumours. A clear dose-response relationship dependent only on power delivered per unit area was found. Below a given dose threshold (about 2 joules/mm2) the tumours continued to grow at the same rate as the control tumours although an effect of irradiation could be seen histologically. Above this threshold the tumours completely disappeared but by 10-14 days started to regrow at a rate slightly greater than in the control mice; the reason for this increased rate remains to be determined. At the highest doses (above about 5.5 joules/mm2) there was complete regression and skin healing, with no evidence of local recurrence in seven animals and with no evidence of distant metastases in six out of seven up to 12 months later, a result not previously achieved by surgical excision. The laser provides a controlled and simply applied method of tumour eradication. This animal model gives a quantitative basis for further studies of the effects of laser irradiation on tumour growth.
Refinement and reduction of the Impact of Psoriasis Questionnaire: Classical Test Theory vs. Rasch analysis
Authors: T. Nijsten, J. Unaeze, R.S. Stern
Journal: British Journal of Dermatology (2006)

Journal Article Refinement and reduction of the Impact of Psoriasis Questionnaire: Classical Test Theory vs. Rasch analysis Get access T. Nijsten, T. Nijsten Department of Dermatology, University Hospital Antwerp, Edegem, BelgiumDepartment of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, U.S.A Search for other works by this author on: Oxford Academic Google Scholar J. Unaeze, J. Unaeze Harvard Medical School, Boston, MA, U.S.A Search for other works by this author on: Oxford Academic Google Scholar R.S. Stern R.S. Stern Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, U.S.A Robert S. Stern. E‐mail: rstern@bidmc.harvard.edu Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 154, Issue 4, 1 April 2006, Pages 692–700, https://doi.org/10.1111/j.1365-2133.2005.07066.x Published: 01 April 2006 Article history Accepted: 09 June 2005 Published: 01 April 2006
Pilot trial of sunitinib therapy in patients with von Hippel–Lindau disease
Authors: E. Jonasch, I.E. McCutcheon, S.G. Waguespack, S. Wen, D.W. Davis, L.A. Smith, N.M. Tannir, D.S. Gombos, G.N. Fuller, S.F. Matin
Journal: Annals of Oncology (2011)