tbuckley/cabot-search huggingface dataset:
Species differences in the metabolism and disposition of inhaled 1,3-butadiene and isoprene.
Authors: A R Dahl, W E Bechtold, J A Bond, R F Henderson, J L Mauderly, B A Muggenburg, J D Sun, L S Birnbaum
Journal: Environmental Health Perspectives (1990)

Species differences in sensitivity to carcinogenic effects from inhaled 1,3-butadiene might stem, at least in part, from differences in uptake, metabolism, and distribution of 1,3-butadiene. To examine this possibility, rats, mice, and monkeys were exposed to stepped concentrations of 14C-labeled 1,3-butadiene and the chemically related compound, isoprene. Respiratory data were collected during exposure and were used to determine fractional uptake. Rates and routes of excretion of retained radioactivity were also determined and blood levels of potentially toxic metabolites were measured. In some cases, the concentrations of hemoglobin adducts were determined. For rodents, the tissue distribution of metabolites was examined. Some results from these continuing studies to date are: a) mice achieve higher blood concentrations of reactive metabolites than do rats; b) blood levels of toxic metabolites are lower in monkeys than in rodents; c) uptake and retention of 1,3-butadiene is nonlinear in the range where long-term toxicity studies have been conducted; d) the efficiency of production of reactive metabolites decreases with increased inhaled concentrations of 1,3-butadiene; e) repeated exposure to 1,3-butadiene does not induce the metabolism of 1,3-butadiene in rodents; f) hemoglobin adducts of 1,3-butadiene are potential dosimeters of exposure; and g) rats inhaling isoprene produce reactive metabolites analogous to those produced during inhalation of 1,3-butadiene. The available data indicate that major differences in the biological fate of inhaled 1,3-butadiene occur among species, and these differences, at least in part, account for those in species sensitivity to the toxicity of inhaled 1,3-butadiene.
Contact dermatitis of the hands: Cross-sectional analyses of North American Contact Dermatitis Group Data, 1994-2004
Authors: Erin M. Warshaw, Rehana L. Ahmed, Donald V. Belsito, Vincent A. DeLeo, Joseph F. Fowler, Howard I. Maibach, James G. Marks, C.G. Toby Mathias, Melanie D. Pratt, Robert L. Rietschel, Denis Sasseville, Frances J. Storrs, James S. Taylor, Kathryn A. Zug
Journal: Journal of the American Academy of Dermatology (2007)
Significance and Mechanism of Lymph Node Metastasis in Cancer Progression
Authors: Kenji Kawada, Makoto M. Taketo
Journal: Cancer Research (2011)

The effect of local therapy, such as surgical lymph node (LN) dissection and radiotherapy, on the survival of cancer patients has been debated for decades. Several lines of recent clinical evidence support that LN metastasis plays significant roles in systemic dissemination of cancer cells, although the effects of surgical LN dissection on survival was downplayed historically because of controversial data. Molecular studies of LN metastasis suggest that the microenvironment within LNs, including chemokines and lymphangiogenesis, can mediate the metastatic spread to the sentinel LNs, and beyond. It has been shown that chemokine receptor CXCR3 is involved in LN metastasis, and its inhibition may improve patient prognosis. Although it remains to be determined whether local therapy is best pursued through LN dissection or through a combination of resection with radiation, prevention of regional metastases is an important goal in the treatment of cancer patients to achieve a better survival.
Multi-Kinase Inhibitor E7080 Suppresses Lymph Node and Lung Metastases of Human Mammary Breast Tumor MDA-MB-231 via Inhibition of Vascular Endothelial Growth Factor-Receptor (VEGF-R) 2 and VEGF-R3 Kinase
Authors: Junji Matsui, Yasuhiro Funahashi, Toshimitsu Uenaka, Tatsuo Watanabe, Akihiko Tsuruoka, Makoto Asada
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Vascular endothelial growth factor (VEGF)-C/VEGF-receptor 3 (VEGF-R3) signal plays a significant role in lymphangiogenesis and tumor metastasis based on its effects on lymphatic vessels. However, little is known about the effect of inhibiting VEGF-R3 on lymphangiogenesis and lymph node metastases using a small-molecule kinase inhibitor. Experimental Design: We evaluated the effect of E7080, a potent inhibitor of both VEGF-R2 and VEGF-R3 kinase, and bevacizumab on lymphangiogenesis and angiogenesis in a mammary fat pad xenograft model of human breast cancer using MDA-MB-231 cells that express excessive amounts of VEGF-C. Lymphangiogenesis was determined by lymphatic vessel density (LVD) and angiogenesis by microvessel density (MVD). Results: In contrast to MDA-MB-435 cells, which expressed a similar amount of VEGF to MDA-MB-231 cells with an undetectable amount of VEGF-C, only MDA-MB-231 exhibited lymphangiogenesis in the primary tumor. E7080 but not bevacizumab significantly decreased LVD within the MDA-MB-231 tumor. E7080 and bevacizumab decreased MVD in both the MDA-MB-231 and MDA-MB-435 models. E7080 significantly suppressed regional lymph nodes and distant lung metastases of MDA-MB-231, whereas bevacizumab significantly inhibited only lung metastases. E7080 also decreased both MVD and LVD within the metastatic nodules at lymph nodes after resection of the primary tumor. Conclusions: Inhibition of VEGF-R3 kinase with E7080 effectively decreased LVD within MDA-MB-231 tumors, which express VEGF-C. Simultaneous inhibition of both VEGF-R2 and VEGF-R3 kinases by E7080 may be a promising new strategy to control regional lymph node and distant lung metastases.
Trisomy of the Long Arm of Chromosome #1 in Human Leukemia
Authors: Mitsuo Oshimura, Shin-ichi Sonta, Avery A. Sandberg
Journal: JNCI Journal of the National Cancer Institute (1976)

We encountered a karyotypic abnormality, i.e., a trisomy of part of or the whole long arm of chromosome #1, in 4 patients with leukemia: 3 with acute myeloblastic leukemia (AML) and 1 with chronic myelocytic leukemia (CML) in the blastic phase. Q- and G-banding techniques revealed that in two patients with AML and in the one with CML, this karyotypic abnormality was not an initial one and was apparently associated with clinical progression of the disease. This chromosome change is a common karyotypic abnormality in blood disorders, especially in AML, and possibly bears a relationship to selective growth advantages of the leukemia cells.
Effect of age on the development of cardiac hypertrophy produced by aortic constriction in the rat.
Authors: S Isoyama, J Y Wei, S Izumo, P Fort, F J Schoen, W Grossman
Journal: Circulation Research (1987)

To test the hypothesis that the capacity to develop left ventricular (LV) hypertrophy might diminish with advancing age, we examined the hypertrophic response to ascending aortic constriction in 3 groups of adult Fischer 344 rats (9 months, 18 months, and 22 months of age). Aortic constriction was created so that aortic cross-sectional areas would be the same for the 3 groups of rats. Four weeks after imposition of aortic constriction, there was no significant difference in peak LV pressure, peak-to-peak and mean systolic pressure gradients between left ventricle and aorta, cardiac output, LV minute work, or cross-sectional area of the aortic constrictions in the 3 groups. In 9-month-old aortic-constricted rats, LV dry wt (LVDW)/body wt, LVDW/tibial length, and myocyte width increased by 23% (p less than 0.01), 14% (p less than 0.01), and 27% (p less than 0.01), respectively, compared with sham-operated rats. In contrast, in 18-month-old and 22-month-old aortic-constricted rats, LVDW/body wt and LVDW/tibial length were unchanged compared with sham-operated controls, and increases in myocyte width were only modest 4 weeks following constriction. RNA concentration in the myocardium 5 days after constriction increased by 21% (p less than 0.001) in 9-month-old rats but showed no significant rise in 18-month-old rats. These results suggest that advancing age is associated with a diminished capacity to develop myocardial hypertrophy in response to acute pressure overload and that a reduced ability to synthesize protein may be one of the major contributing factors to a diminished capacity for hypertrophy in advanced age.
Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update
Authors: Thomas J. Smith, Kari Bohlke, Gary H. Lyman, Kenneth R. Carson, Jeffrey Crawford, Scott J. Cross, John M. Goldberg, James L. Khatcheressian, Natasha B. Leighl, Cheryl L. Perkins, George Somlo, James L. Wade, Antoinette J. Wozniak, James O. Armitage
Journal: Journal of Clinical Oncology (2015)

To update the 2006 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSFs).The American Society of Clinical Oncology convened an Update Committee and conducted a systematic review of randomized clinical trials, meta-analyses, and systematic reviews from October 2005 through September 2014. Guideline recommendations were based on the review of the evidence by the Update Committee.Changes to previous recommendations include the addition of tbo-filgrastim and filgrastim-sndz, moderation of the recommendation regarding routine use of CSFs in older patients with diffuse aggressive lymphoma, and addition of recommendations against routine dose-dense chemotherapy in lymphoma and in favor of high-dose-intensity chemotherapy in urothelial cancer. The Update Committee did not address recommendations regarding use of CSFs in acute myeloid leukemia or myelodysplastic syndromes in adults.Prophylactic use of CSFs to reduce the risk of febrile neutropenia is warranted when the risk of febrile neutropenia is approximately 20% or higher and no other equally effective and safe regimen that does not require CSFs is available. Primary prophylaxis is recommended for the prevention of febrile neutropenia in patients who are at high risk on the basis of age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. Dose-dense regimens that require CSFs should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Current recommendations for the management of patients exposed to lethal doses of total-body radiotherapy, but not doses high enough to lead to certain death as a result of injury to other organs, include the prompt administration of CSFs.
Randomized Controlled Trial of Yttrium-90–Labeled Ibritumomab Tiuxetan Radioimmunotherapy Versus Rituximab Immunotherapy for Patients With Relapsed or Refractory Low-Grade, Follicular, or Transformed B-Cell Non-Hodgkin’s Lymphoma
Authors: Thomas E. Witzig, Leo I. Gordon, Fernando Cabanillas, Myron S. Czuczman, Christos Emmanouilides, Robin Joyce, Brad L. Pohlman, Nancy L. Bartlett, Gregory A. Wiseman, Norman Padre, Antonio J. Grillo-López, Pratik Multani, Christine A. White
Journal: Journal of Clinical Oncology (2002)

Radioimmunotherapy combines biologic and radiolytic mechanisms to target and destroy tumor cells, thus offering a needed therapeutic alternative for refractory non-Hodgkin's lymphoma (NHL) patients. This phase III randomized study compares the novel radioimmunotherapy yttrium-90 ((90)Y) ibritumomab tiuxetan with a control immunotherapy, rituximab, in 143 patients with relapsed or refractory low-grade, follicular, or transformed CD20(+) transformed NHL.Patients received either a single intravenous (IV) dose of (90)Y ibritumomab tiuxetan 0.4 mCi/kg (n = 73) or rituximab 375 mg/m(2) IV weekly for four doses (n = 70). The radioimmunotherapy group was pretreated with two rituximab doses (250 mg/m(2)) to improve biodistribution and one dose of indium-111 ibritumomab tiuxetan for imaging and dosimetry. The primary end point, overall response rate (ORR), was assessed by an independent, blinded, lymphoma expert panel.ORR was 80% for the (90)Y ibritumomab tiuxetan group versus 56% for the rituximab group (P =.002). Complete response (CR) rates were 30% and 16% in the (90)Y ibritumomab tiuxetan and rituximab groups, respectively (P =.04). An additional 4% achieved an unconfirmed CR in each group. Kaplan-Meier estimated median duration of response was 14.2 months in the (90)Y ibritumomab tiuxetan group versus 12.1 months in the control group (P =.6), and time to progression was 11.2 versus 10.1 months (P =.173) in all patients. Durable responses of > or = 6 months were 64% versus 47% (P =.030). Reversible myelosuppression was the primary toxicity noted with (90)Y ibritumomab tiuxetan.Radioimmunotherapy with (90)Y ibritumomab tiuxetan is well tolerated and produces statistically and clinically significant higher ORR and CR compared with rituximab alone.
A Qualitative Analysis of How Physicians with Expertise in Domestic Violence Approach the Identification of Victims
Authors: Barbara Gerbert, Nona Caspers, Amy Bronstone, James Moe, Priscilla Abercrombie
Journal: Annals of Internal Medicine (1999)

Background: Physicians have been called upon to identify victims of domestic violence, but few studies provide insight into how physicians can navigate around the barriers to identification. Objective: To describe how physicians who are committed to helping battered patients identify victims of domestic violence in health care encounters. Design: Six focus groups were conducted. Setting: Focus group research facilities. Participants: 45 emergency department, obstetrician/gynecologist, and primary care physicians in the San Francisco Bay Area who identify and intervene with victims of domestic violence. Measurements: Through constant comparison, a template of open codes was constructed to identify themes that emerged from the data. Data were analyzed according to the conventions of qualitative research. Results: The data revealed five major themes: 1) how physicians framed screening questions to reduce patient discomfort; 2) patient signs that “switched on a light bulb” for physicians to suspect abuse; 3) direct and indirect approaches to identification, with an emphasis on facilitating patient trust and disclosure over time; 4) the rarity of direct patient disclosure; and 5) how physicians redefined successful outcomes of universal screening. Physicians also described two new barriers to screening: mandatory reporting and “burnout” due to lack of direct disclosure. Conclusions: Identifying domestic abuse is difficult even for physicians committed to helping victims. Physician reports illustrate the need to frame questions and develop indirect approaches that foster patient trust. Given the many barriers to screening and the rarity of direct patient disclosure, it may be more productive to redefine the goals of universal screening so that compassionate asking in and of itself constitutes the first step in helping battered patients.
Vitamin B<sub>12</sub> Deficiency and Depression in Physically Disabled Older Women: Epidemiologic Evidence From the Women’s Health and Aging Study
Authors: Brenda W.J.H. Penninx, Jack M. Guralnik, Luigi Ferrucci, Linda P. Fried, Robert H. Allen, Sally P. Stabler
Journal: American Journal of Psychiatry (2000)

It has been hypothesized that adequate concentrations of vitamin B(12) and folate are essential to maintain the integrity of the neurological systems involved in mood regulation, but epidemiologic evidence for such a link in the general population is unavailable. This study examined whether community-dwelling older women with metabolically significant vitamin B(12) or folate deficiency are particularly prone to depression.Serum levels of vitamin B(12), folate, methylmalonic acid, and total homocysteine were assayed in 700 disabled, nondemented women aged 65 years and over living in the community. Depressive symptoms were measured by means of the Geriatric Depression Scale and categorized as no depression, mild depression, and severe depression.Serum homocysteine levels, serum folate levels, and the prevalences of folate deficiency and anemia were not associated with depression status. The depressed subjects, especially those with severe depression, had a significantly higher serum methylmalonic acid level and a nonsignificantly lower serum vitamin B(12) level than the nondepressed subjects. Metabolically significant vitamin B(12) deficiency was present in 14.9% of the 478 nondepressed subjects, 17. 0% of the 100 mildly depressed subjects, and 27.0% of the 122 severely depressed women. After adjustment for sociodemographic characteristics and health status, the subjects with vitamin B(12) deficiency were 2.05 times as likely to be severely depressed as were nondeficient subjects.In community-dwelling older women, metabolically significant vitamin B(12)deficiency is associated with a twofold risk of severe depression.
When Progressive Disease Does Not Mean Treatment Failure: Reconsidering the Criteria for Progression
Authors: G. R. Oxnard, M. J. Morris, F. S. Hodi, L. H. Baker, M. G. Kris, A. P. Venook, L. H. Schwartz
Journal: JNCI Journal of the National Cancer Institute (2012)

Although progression-based endpoints, such as progression-free survival, are often key clinical trial endpoints for anticancer agents, the clinical meaning of “objective progression” is much less certain. As scrutiny of progression-based endpoints in clinical trials increases, it should be remembered that the Response Evaluation Criteria In Solid Tumors (RECIST) progression criteria were not developed as a surrogate for survival. Now that progression-free survival has come to be an increasingly important trial endpoint, the criteria that define progression deserve critical evaluation to determine whether alternate definitions of progression might facilitate the development of stronger surrogate endpoints and more meaningful trial results. In this commentary, we review the genesis of the criteria for progression, highlight recent data that question their value as a marker of treatment failure, and advocate for several research strategies that could lay the groundwork for a clinically validated definition of disease progression in solid tumor oncology.
AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance
Authors: Thomas O'Hare, William C. Shakespeare, Xiaotian Zhu, Christopher A. Eide, Victor M. Rivera, Frank Wang, Lauren T. Adrian, Tianjun Zhou, Wei-Sheng Huang, Qihong Xu, Chester A. Metcalf, Jeffrey W. Tyner, Marc M. Loriaux, Amie S. Corbin, Scott Wardwell, Yaoyu Ning, Jeffrey A. Keats, Yihan Wang, Raji Sundaramoorthi, Mathew Thomas, Dong Zhou, Joseph Snodgrass, Lois Commodore, Tomi K. Sawyer, David C. Dalgarno, Michael W.N. Deininger, Brian J. Druker, Tim Clackson
Journal: Cancer Cell (2009)
Corticosteroids in IgA Nephropathy
Authors: Vladimir Tesar, Stéphan Troyanov, Shubha Bellur, Jacobien C. Verhave, H. Terence Cook, John Feehally, Ian S.D. Roberts, Daniel Cattran, Rosanna Coppo
Journal: Journal of the American Society of Nephrology (2015)

Current guidelines suggest treatment with corticosteroids (CS) in IgA nephropathy (IgAN) when proteinuria is persistently ≥1 g/d despite 3–6 months of supportive care and when eGFR is >50 ml/min per 1.73 m2. Whether the benefits of this treatment extend to patients with an eGFR≤50 ml/min per 1.73 m2, other levels of proteinuria, or different renal pathologic lesions remains unknown. We retrospectively studied 1147 patients with IgAN from the European Validation Study of the Oxford Classification of IgAN (VALIGA) cohort classified according to the Oxford-MEST classification and medication used, with details of duration but not dosing. Overall, 46% of patients received immunosuppression, of which 98% received CS. Treated individuals presented with greater clinical and pathologic risk factors of progression. They also received more antihypertensive medication, and a greater proportion received renin angiotensin system blockade (RASB) compared with individuals without immunosuppressive therapy. Immunosuppression was associated with a significant reduction in proteinuria, a slower rate of renal function decline, and greater renal survival. Using a propensity score, we matched 184 subjects who received CS and RASB to 184 patients with a similar risk profile of progression who received only RASB. Within this group, CS reduced proteinuria and the rate of renal function decline and increased renal survival. These benefits extended to those with an eGFR≤50 ml/min per 1.73 m2, and the benefits increased proportionally with the level of proteinuria. Thus, CS reduced the risk of progression regardless of initial eGFR and in direct proportion to the extent of proteinuria in this cohort.
Mitochondrial Genomes of Clymenella torquata (Maldanidae) and Riftia pachyptila (Siboglinidae): Evidence for Conserved Gene Order in Annelida
Authors: Robert M. Jennings, Kenneth M. Halanych
Journal: Molecular Biology and Evolution (2004)

Mitochondrial genomes are useful tools for inferring evolutionary history. However, many taxa are poorly represented by available data. Thus, to further understand the phylogenetic potential of complete mitochondrial genome sequence data in Annelida (segmented worms), we examined the complete mitochondrial sequence for Clymenella torquata (Maldanidae) and an estimated 80% of the sequence of Riftia pachyptila (Siboglinidae). These genomes have remarkably similar gene orders to previously published annelid genomes, suggesting that gene order is conserved across annelids. This result is interesting, given the high variation seen in the closely related Mollusca and Brachiopoda. Phylogenetic analyses of DNA sequence, amino acid sequence, and gene order all support the recent hypothesis that Sipuncula and Annelida are closely related. Our findings suggest that gene order data is of limited utility in annelids but that sequence data holds promise. Additionally, these genomes show AT bias (approximately 66%) and codon usage biases but have a typical gene complement for bilaterian mitochondrial genomes.