tbuckley/cabot-search huggingface dataset:
Benzene and the Dose-Related Incidence of Hematologic Neoplasms in China
Authors: R. B. Hayes, M. Dosemeci, S. Wacholder, L. B. Travis, N. Rothman, R. N. Hoover, M. S. Linet, S.-N. Yin, G.-L. Li, C.-Y. Li
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: Benzene is a widely distributed environmental contaminant known to cause leukemia, particularly acute nonlymphocytic leukemia, and perhaps other hematologic neoplasms and disorders. Few epidemiologic studies, however, have been able to address relationships between the extent of benzene exposure and the level of risk. Purpose: A large cohort study was carried out in China to evaluate the risks of developing specific hematologic neoplasms and selected related disorders in relationship to quantitative estimates of occupational benzene exposure. Methods: A cohort of 74 828 benzeneexposed and 35 805 unexposed workers employed from 1972 through 1987 in 12 cities in China was identified and followed to determine the incidence of hematologic neoplasms and related disorders. Estimates of benzene exposure were derived from work histories and available historic benzene measurements. Existing pathologic material and supporting medical records were reviewed to establish diagnoses of disease. Relative risks (RRs) (i.e., ratios of incidence rates for specific hematologic neoplasms and related disorders in the benzene-exposed group to incidence rates in the unexposed group) were determined by use of Poisson regression analysis, with stratification by age and sex. Results: For workers historically exposed to benzene at average levels of less than 10 parts per million (ppm), the RR for all hematologic neoplasms combined was 2.2 (95% confidence interval [CI] = 1.1-4.2), and, for the combination of acute nonlymphocytic leukemia and related myelodysplastic syndromes, the RR was 3.2 (95% CI = 1.0-10.1). For individuals who were occupationally exposed to benzene at constant levels of 25 ppm or more, the RR for the combination of acute nonlymphocytic leukemia and related myelodysplastic syndromes was 7.1 (95% CI = 2.1-23.7). Workers with 10 or more years of benzene exposure had an RR of developing non-Hodgkin's lymphoma of 4.2 (95% CI = 1.1-15.9), and the development of this neoplasm was linked most strongly to exposure that had occurred at least 10 years before diagnosis (i.e., distant exposure) (P for trend = .005, two-sided). In contrast, the risk for the combination of acute nonlymphocytic leukemia and related myelodysplastic syndromes was significantly increased among those with more recent benzene exposure (P for trend = .003, two-sided), but it was not linked to distant exposure (P for trend = .51, two-sided). Conclusions: The results of this study suggest that benzene exposure is associated with a spectrum of hematologic neoplasms and related disorders in humans. Risks for these conditions are elevated at average benzene- exposure levels of less than 10 ppm and show a tendency, although not a strong one, to rise with increasing levels of exposure. The temporal pattern of benzene exposure appears to be important in determining the risk of developing specific diseases.
PARP-1 Inhibits Glycolysis in Ischemic Kidneys
Authors: Kishor Devalaraja-Narashimha, Babu J. Padanilam
Journal: Journal of the American Society of Nephrology (2008)

After ischemic renal injury (IRI), selective damage occurs in the S(3) segments of the proximal tubules as a result of inhibition of glycolysis, but the mechanism of this inhibition is unknown. We previously reported that inhibition of poly(ADP-ribose) polymerase-1 (PARP-1) activity protects against ischemia-induced necrosis in proximal tubules by preserving ATP levels. Here, we tested whether PARP-1 activation in proximal tubules after IRI leads to poly(ADP-ribosyl)ation of the key glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a modification that inhibits its activity. Using in vitro and in vivo models, under hypoxic conditions, we detected poly(ADP-ribosyl)ation and reduced activity of GAPDH; inhibition of PARP-1 activity restored GAPDH activity and ATP levels. Inhibition of GAPDH with iodoacetate exacerbated ATP depletion, cytotoxicity, and necrotic cell death of LLCPK(1) cells subjected to hypoxic conditions, whereas inhibition of PARP-1 activity was cytoprotective. In conclusion, these data indicate that poly(ADP-ribosyl)ation of GAPDH and the subsequent inhibition of anaerobic respiration exacerbate ATP depletion selectively in the proximal tubule after IRI.
Regulatory mechanisms in cell-mediated immune responses. Role of I-J and I-C determinants in the activation of H-2I and H-2K/D alloantigen-specific suppressor T cells.
Authors: S Rich
Journal: The Journal of Experimental Medicine (1983)

The role of individual H-2I subregion determinants in the activation of H-2I alloantigen-primed mixed leukocyte response suppressor T cells (MLR Ts), as well as their possible expression on stimulator cells required to trigger primed H-2K- or D-specific MLR Ts, was addressed in these studies. Both genetic and serologic studies demonstrated that MLR Ts potentially primed to alloantigens encoded by the entire H-2I region were triggered to MLR Ts factor production only by stimulator cells bearing the priming I-J and/or I-C, but not I-A or I-E alloantigens. The relevant I-J and I-C determinants were demonstrated on a single antigen-presenting cell population that is used in common by independent I-J-specific and I-C-specific MLR Ts. Unexpectedly, the stimulator cell population necessary to trigger MLR Ts primed to class I H-2K or D alloantigens expressed not only the priming class I determinant, but in addition, I-C alloantigens syngeneic with the MLR Ts haplotype. Stimulator populations bearing the appropriate H-2K or D alloantigen but serologically depleted of I-C+ cells or genetically constructed to display MLR Ts-disparate I-C determinants were ineffective stimulators of class I antigen-primed MLR Ts. Thus these data suggest that as allogeneic determinants, I-J- and I-C-encoded molecules are together the major triggering elements for MLR Ts primed to disparate H-2I region determinants. In addition, self-I-C molecule recognition appears to constitute an important feature of the triggering, and by implication, priming process of H-2 class I antigen-specific Ts cells.
Cancer Stem Cells: At the Headwaters of Tumor Development
Authors: Ryan J. Ward, Peter B. Dirks
Journal: Annual Review of Pathology Mechanisms of Disease (2006)

According to the cancer stem cell hypothesis, only a subpopulation of cells within a cancer has the capacity to sustain tumor growth. This subpopulation of cells is made up of cancer stem cells, which are defined simply as the population of cells within a tumor that can self-renew, differentiate, and regenerate a phenocopy of the cancer when injected in vivo. Cancer stem cells have now been prospectively isolated from human cancers of the blood, breast, and brain, and putative cancer stem cells have been identified from human skin, bone, and prostate tumors and from multiple established mammalian cancer cell lines. Furthermore, researchers are actively seeking cancer stem cells in every human cancer type. We present the current scientific evidence supporting the cancer stem cell hypothesis and discuss the experimental and therapeutic implications of the discovery of human cancer stem cells.
Hepatic Resection: The Last Surgical Frontier for Colorectal Cancer
Authors: Nicholas J. Petrelli, James Abbruzzese, Paul Mansfield, Bruce Minsky
Journal: Journal of Clinical Oncology (2005)

This issue of the Journal of Clinical Oncology is devoted to gastrointestinal tumors. Pancreatic, gastric, colorectal, esophageal, and biliary tract tumors are discussed. Therapy, diagnostic modalities, and molecular markers are presented by experts in the oncology field. Readers will find the contents informative and, more importantly, very current. The latter was a top priority given to the authors so that the contents of the manuscripts would not be outdated. With regard to gastric cancer, two articles dealing with resectable disease are included. The first, by Soetikno et al, examines the role of endoscopic mucosal resection (EMR) for early disease. Although T1 tumors still comprise a relatively small percentage of the patients with gastric cancers seen in the United States, that percentage appears to be slowly increasing. The techniques of EMR are highly specialized, and few centers in the United States have significant experience with them. Nevertheless, given the excellent prognosis of appropriately selected patients, and the far superior quality of life with an intact stomach, EMR will likely see increasing application. Centers in which large numbers of patients are treated with this approach (primarily in Japan) are expanding the limits of what can be removed safely by this technique. The second article, by Jansen et al, examines more aggressive local therapy for gastric cancer. The role of extended lymphadenectomy in Western patients continues to simmer despite the failure of two prospective randomized trials to show a benefit. While these studies suffered from such high operative mortality from the extended resections that any potential benefit would be obscured, single centers routinely perform extended node dissections with mortality rates dramatically lower than that of the control arm of the randomized trials. A large prospective randomized trial of extended node dissections in Japan has completed accrual with a mortality rate of less than 1%. For some, the question of extended resections remains an issue given the highly positive results of the INT-0116 trial (utilizing chemoradiotherapy), in which many contend that substandard surgery was performed, implying that adjuvant therapy was simply making up for inadequate surgery. Perhaps the most important lesson out of this is that future studies of multimodality therapy for gastric cancer must pay at least as much attention to the surgical procedures performed as to the chemotherapy regimens and radiotherapy portals.
Gene-Transfer Study Approval Awaits More Data
Authors: Charles Marwick
Journal: JAMA (1988)

APPROVAL of the gene-transfer study in cancer patients has been delayed. The proposal was recommended for approval by a National Institutes of Health (NIH) advisory committee, but has been put on hold by James B. Wyngaarden, MD, NIH director, pending submission in writing of further information. Some of this information, now forthcoming, had been withheld because data on preliminary studies had been submitted to peer-reviewed journals. The study involves placing the gene for neomycin-resistance into tumor-infiltrating lymphocytes as a marker. When these cells are injected into the patient, the presence of the marker should enable their fate to be studied over a prolonged period and an improved antitumor regimen could result. The use of tumor-infiltrating lymphocytes as immunotherapy has been studied for two years at the NIH's National Cancer Institute under the overall supervision of Steven A. Rosenberg, MD, chief, Surgery Branch. The patients' tumors are removed and the tumor-infiltrating
Lack of A1 Adenosine Receptors Augments Diabetic Hyperfiltration and Glomerular Injury
Authors: Robert Faulhaber-Walter, Limeng Chen, Mona Oppermann, Soo Mi Kim, Yuning Huang, Noriyuki Hiramatsu, Diane Mizel, Hiroshi Kajiyama, Patricia Zerfas, Josephine P. Briggs, Jeffrey B. Kopp, Jurgen Schnermann
Journal: Journal of the American Society of Nephrology (2008)

Intraglomerular hypertension and glomerular hyperfiltration likely contribute to the pathogenesis of diabetic nephropathy, and tubuloglomerular feedback (TGF) has been suggested to play a role in diabetic hyperfiltration. A1 adenosine receptor (A1AR) null mice lack a TGF response, so this model was used to investigate the contribution of TGF to hyperfiltration in diabetic Ins2<sup>+/−</sup> Akita mice. TGF responses in Ins2<sup>+/−</sup> A1AR<sup>−/−</sup> double mutants were abolished, whereas they were attenuated in Ins2<sup>+/−</sup> mice. GFR, assessed at 14, 24, and 33 wk, was approximately 30% higher in Ins2<sup>+/−</sup> than in wild-type (WT) mice and increased further in Ins2<sup>+/−</sup> A1AR<sup>−/−</sup> mutants (<i>P</i> &lt; 0.01 <i>versus</i> both WT and Ins2<sup>+/−</sup> mice at all ages). Histologic evidence of glomerular injury and urinary albumin excretion were more pronounced in double-mutant than single-mutant or WT mice. In summary, the marked elevation of GFR in diabetic mice that lack a TGF response indicates that TGF is not required to cause hyperfiltration in the Akita model of diabetes. Rather, an A1AR-dependent mechanism, possibly TGF, limits the degree of diabetic hyperfiltration and nephropathy.
Myopia and advanced-stage open-angle glaucoma
Authors: Chihiro Mayama, Yasuyuki Suzuki, Makoto Araie, Kyoko Ishida, Tsuji Akira, Tetsuya Yamamoto, Yoshiaki Kitazawa, Shigeo Funaki, Motohiro Shirakashi, Haruki Abe, Hidetoshi Tsukamoto, Koji Okada, Hiromu K Mishima
Journal: Ophthalmology (2002)
An Organometallic Protein Kinase Inhibitor Pharmacologically Activates p53 and Induces Apoptosis in Human Melanoma Cells
Authors: Keiran S.M. Smalley, Rooha Contractor, Nikolas K. Haass, Angela N. Kulp, G. Ekin Atilla-Gokcumen, Douglas S. Williams, Howard Bregman, Keith T. Flaherty, Maria S. Soengas, Eric Meggers, Meenhard Herlyn
Journal: Cancer Research (2007)

Abstract Unlike other tumors, melanomas harbor wild-type (WT) p53 but exhibit impaired p53-dependent apoptosis. The mechanisms for the impaired p53 activation are poorly understood but may be linked to the high expression of the p53 suppressor Mdm2, which is found in &amp;gt;50% of melanoma lesions. Here, we describe an organometallic glycogen synthase kinase 3β (GSK3β) inhibitor (DW1/2) as a potent activator of p53 and inducer of cell death in otherwise highly chemoresistant melanoma cells. Using RNA interference and pharmacologic approaches, we show that p53 is required for the cytotoxic effects of this organometallic inhibitor. The DW1/2 compound was barely able to induce cell death in melanoma cells with p53 mutations, further confirming the requirement for p53-WT in the cytotoxic effects of the GSK3β inhibition. Mechanistic analysis of the p53-dependent cell death indicated an apoptotic mechanism involving depolarization of mitochondrial membrane potential, caspase cleavage, and elevated NOXA expression. The effect of p53 was not simply due to passive up-regulation of protein expression as adenoviral-mediated overexpression of p53 was not able to induce cell death. Treatment of melanoma cells with DW1/2 was instead found to decrease levels of Mdm2 and Mdm4. The importance of Mdm2 down-regulation in DW1/2-induced apoptosis was confirmed by treating the p53-WT cells with the p53/Mdm2 antagonist Nutlin-3. Taken together, our data provide a new strategy for the pharmacologic activation of p53 in melanoma, which may be a viable approach for overcoming apoptotic resistance in melanoma and offer new hope for rational melanoma therapy. [Cancer Res 2007;67(1):209–17]
Exhaled carbon monoxide levels during treatment of acute asthma
Authors: M. Yamara, K. Sekizawa, S. Ishizuka, M. Monma, H. Sasaki
Journal: European Respiratory Journal (1999)

Carbon monoxide is known to be present in measurable quantities in the exhaled air of normal subjects and at higher concentrations in asthmatic patients not treated with glucocorticoids. To examine whether exhaled CO is useful in monitoring asthma control, time course changes in peak expiratory flow rate (PEFR) and exhaled CO concentration before and after treatment of acute asthma exacerbations were measured in 20 asthmatic patients. Exhaled CO was measured in triplicate by a portable CO analyser. Exhaled CO was reproducible at all time points. Asthma exacerbations caused a fall in PEFR and a rise in exhaled CO (towards an average of 3.3 parts per million (ppm)) in all patients, and treatment with oral glucocorticoids reversed these changes in both parameters. An improvement of PEFR was closely associated with a reduction of exhaled CO (to an average of 1.5 ppm) after treatment. The maximal exhaled CO concentration significantly correlated with recovery time of PEFR after treatment with oral glucocorticoids (p<0.01). The present study suggests that exhaled CO may be a useful noninvasive means of monitoring the control of asthma.
ADVANCES IN RISK ASSESSMENT AND COMMUNICATION
Authors: Bernard D. Goldstein
Journal: Annual Review of Public Health (2004)

Risk analysis continues to evolve. There is increasing depth and breadth to each component of the four-step risk-assessment paradigm of hazard identification, dose-response analysis, exposure assessment, and risk characterization. Basic conceptual approaches to understanding how people perceive risk are being tested against a growing body of empirical observations, many involving stakeholders. Emerging ideas such as the precautionary principle have provided challenges that have led to a rethinking of the role of risk assessment in environmental health. Newer problems, such as intergenerational issues posed by long-lasting radiation pollution, environmental justice, and the assessment and communication of risks related to terrorism, have spurred innovative approaches to risk analysis.
Effect of dietary sodium on the severity of bronchial asthma.
Authors: D Lieberman, D Heimer
Journal: Thorax (1992)

BACKGROUND: A high sodium intake has been found to increase bronchial reactivity in men with asthma. The effects of change in sodium intake on peak flow rate have not been determined. METHODS: The effect of changing dietary salt intake for two weeks on the severity of asthma as measured by peak expiratory flow (PEF) was studied in 17 patients with mild asthma in an open randomised crossover trial. PEF measurements were made by the patients in their own homes. Patients were placed on three levels of dietary sodium intake: normal, low, and high. Sodium intake was assessed by 24 hour urine collection. RESULTS: The mean (SD) urine sodium was 147 (45), 84 (32), and 201 (73) mmol/24 hours in the normal, low, and high sodium intake periods respectively. There were no significant differences in PEF or PEF amplitude (highest--lowest PEF), an index of asthma lability, between the three dietary salt periods. CONCLUSION A low and high dietary salt intake for two weeks has no effect on peak expiratory flow in patients with mild asthma.
FOLFOXIRI/Bevacizumab Versus FOLFIRI/Bevacizumab as First-Line Treatment in Unresectable Metastatic Colorectal Cancer: Results of Phase III Tribe Trial by Gono Group
Authors: Chiara Cremolini, Fotios Loupakis, Gianluca Masi, Sara Lonardi, Vittorina Zagonel, Lisa Salvatore, Patrizia Trenta, Gianluca Tomasello, Monica Ronzoni, Libero Ciuffreda, Alberto Zaniboni, Giuseppe Tonini, Angela Buonadonna, Cecilia Barbara, Francesca V. Negri, Carlo Barone, Stefano Vitello, Nicola Giuntini, Andrea Bonetti, Mauro D'Amico, Luca Boni, Alfredo Falcone
Journal: Annals of Oncology (2013)
Cuba Eliminates Mother-to-Child Transmission of HIV and Syphilis
Authors: M. J. Friedrich
Journal: JAMA (2015)

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Arteriosclerosis Obliterans
Authors: Donald E. Strandness
Journal: JAMA (1966)

The manner and rate of progression of atherosclerosis was evaluated in 60 patients (99 limbs) with occlusive disease and 18 patients (36 limbs) with abdominal aortic aneurysms. The measurement of segmental limb pressure gradients was utilized in evaluating disease progression. Progression of disease during the average three-year follow-up occurred in 34 (43%) of the limbs that had occlusive disease at the outset. When patients rather than limbs are considered, 31 (52%) had progression of disease. Of the 31 patients, 12 were unaware progression had occurred. Of 19 limbs without occlusion at the outset of the study, nine developed a major artery obstruction. Ten of the 12 patients with diabetes mellitus exhibited progression of disease. Four of the 18 patients with abdominal aortic aneurysm had coexisting arterial obstruction with disease progression occurring in six patients.
Dietary Administration of the Proapoptotic Vitamin E Analogue α-Tocopheryloxyacetic Acid Inhibits Metastatic Murine Breast Cancer
Authors: Tobias Hahn, Lajos Szabo, Mikhal Gold, Lalitha Ramanathapuram, Laurence H. Hurley, Emmanuel T. Akporiaye
Journal: Cancer Research (2006)

Abstract The ability of the vitamin E (RRR-α-tocopherol) derivatives α-tocopheryl succinate (α-TOS) and α-tocopheryloxyacetic acid (α-TEA) to suppress tumor growth in preclinical animal models has recently led to increased interest in their potential use for treating human cancer. To make the use of these vitamin E analogues more clinically relevant, we compared the antitumor efficacy of orally and i.p. delivered forms of α-TEA and α-TOS against a murine mammary cancer (4T1) that bears resemblance to human breast cancer because of its poor immunogenicity and high metastatic potential. In cell culture studies, we showed that both compounds inhibited tumor colony formation and induced apoptotic death of tumor cells. To avoid solubility concerns associated with the hydrophobicity of α-TEA and α-TOS, we used the vesiculated forms of α-TEA (Vα-TEA) and α-TOS (Vα-TOS) for the in vivo tumor studies. Both compounds inhibited the growth of preestablished 4T1 tumors when given i.p. However, when given by oral gavage, only the esterase-resistant Vα-TEA was able to suppress primary tumor growth and reduce lung metastasis. To make this approach more translatable to the clinic, α-TEA was incorporated into the diet and fed to tumor-bearing mice. We report here for the first time that dietary α-TEA delivery significantly inhibited primary tumor growth and dramatically reduced spontaneous metastatic spread to the lung in prophylactic and therapeutic settings. This study suggests that dietary α-TEA could prove useful as a relatively easy and effective modality for treating metastatic breast cancer. (Cancer Res 2006; 66(19): 9374-8)