tbuckley/cabot-search huggingface dataset:
Glycated Albumin Is a Better Glycemic Indicator than Glycated Hemoglobin Values in Hemodialysis Patients with Diabetes
Authors: Masaaki Inaba, Senji Okuno, Yasuro Kumeda, Shinsuke Yamada, Yasuo Imanishi, Tsutomu Tabata, Mikio Okamura, Shigeki Okada, Tomoyuki Yamakawa, Eiji Ishimura, Yoshiki Nishizawa
Journal: Journal of the American Society of Nephrology (2007)

The significance of glycated albumin (GA), compared with casual plasma glucose (PG) and glycated hemoglobin (HbA(1c)), was evaluated as an indicator of the glycemic control state in hemodialysis (HD) patients with diabetes. The mean PG, GA, and HbA(1c) levels were 164.5 +/- 55.7 mg/dl, 22.5 +/- 7.5%, and 5.85 +/- 1.26%, respectively, in HD patients with diabetes (n = 538), which were increased by 51.5, 31.6, and 17.7%, respectively, compared with HD patients without diabetes (n = 828). HbA(1c) levels were significantly lower than simultaneous PG and GA values in those patients in comparison with the relationship among the three parameters in patients who had diabetes without renal dysfunction (n = 365), as reflected by the significantly more shallow slope of regression line between HbA(1c) and PG or GA. A significant negative correlation was found between GA and serum albumin (r = -0.131, P = 0.002) in HD patients with diabetes, whereas HbA(1c) correlated positively and negatively with hemoglobin (r = 0.090, P = 0.036) and weekly dose of erythropoietin injection (r = -0.159, P < 0.001), respectively. Although PG and GA did not differ significantly between HD patients with diabetes and with and without erythropoietin injection, HbA(1c) levels were significantly higher in patients without erythropoietin. Categorization of glycemic control into arbitrary quartile by HbA(1c) level led to better glycemic control in a significantly higher proportions of HD patients with diabetes than those assessed by GA. Multiple regression analysis demonstrated that the weekly dose of erythropoietin, in addition to PG, emerged as an independent factor associated with HbA(1c) in HD patients with diabetes, although PG but not albumin was an independent factor associated with GA. In summary, it is suggested that GA provides a significantly better measure to estimate glycemic control in HD patients with diabetes and that the assessment of glycemic control by HbA(1c) in these patients might lead to underestimation likely as a result of the increasing proportion of young erythrocyte by the use of erythropoietin.
Prospective Study of Hyperglycemia and Cancer Risk
Authors: Samantha L. Bowker, Jeffrey A. Johnson
Journal: Diabetes Care (2007)

The recent article by Stattin et al. (1) examined whether hyperglycemia was associated with an increased risk of cancer. Using the Vasterbotten Intervention Project of northern Sweden, the authors calculated relative risks of incident cancer for levels of fasting and postload glucose. They observed an association between hyperglycemia and total cancer risk in women and men for several cancer sites, suggesting that their results provide further evidence for an association between …
Effects of Timing of Administration and Dose of Difluoromethylornithine on Rat Colonic Carcinogenesis
Authors: G. D. Luk, S.-Z. Zhang, S. R. Hamilton
Journal: JNCI Journal of the National Cancer Institute (1989)

During azoxymethane (AOM)-induced colonic carcinogenesis in rats, biphasic induction of ornithine decarboxylase (ODC) activity occurs in the colonic mucosa. The relative contributions of these two phases of ODC induction to the carcinogenesis process were examined by studying the effects of the specific ODC inhibitor, difluoromethyl-ornithine (DFMO), administered during either the initial phase of ODC increase or during both phases continuously. The effects of 1% and 0.25% DFMO administered continuously were also compared. Continuous oral administration of DFMO at 1% (≈8 mg/g body wt/wk) and 0.25% (≈2 mg/g body wt/wk) produced 93% inhibition of ODC induction by AOM in the right and left colons throughout the study. Despite suppression of ODC activity to near-normal levels, colon tumor incidence at 26 weeks in the right colon was not affected by either initial-phase or continuous administration of DFMO. In contrast, tumor incidence in the left colon was reduced from 35% to 5% by DFMO given continuously at doses of both 1% and 0.25% over the entire 26 weeks (P <.05). No significant reduction in left colon tumor incidence resulted from the short initial 11-week course of DFMO although the tumor incidence was reduced (15% vs. 35%). Results suggest that the second (“post-initiation”) phase of ODC induction may be of particular importance in carcinogenesis. [J Natl Cancer Inst 81:421–427, 1989]
Antitumor Efficacy of <i>bcl-2</i> and <i>c-myc</i> Antisense Oligonucleotides in Combination with Cisplatin in Human Melanoma Xenografts: Relevance of the Administration Sequence
Authors: Gabriella Zupi, Marco Scarsella, Sean C. Semple, Marcella Mottolese, Pier G. Natali, Carlo Leonetti
Journal: Clinical Cancer Research (2005)

Abstract Purpose: bcl-2 and c-myc oncogenes are frequently overexpressed in different human tumors, including melanoma. Here, we evaluate the combined efficacy of two antisense oligonucleotides targeting bcl-2 mRNA (ODN bcl-2) and c-myc mRNA (ODN c-myc) in combination with cis-diammine dichloroplatinum (cisplatin, DDP) on three human melanoma lines (LM, NG, and M20). Experimental Design: Two different sequences were designed to treat tumor-bearing mice: in the first one, ODN bcl-2 at a dose of 0.2 mg/day ×4, followed by DDP given i.p. at a dose of 3.3 mg/kg/day ×3 and ODN c-myc i.v. at 0.5 mg/day ×7, whereas the other sequence consisted of ODN c-myc given as first agent followed by DDP and ODN bcl-2 at the same doses. Mice received three complete cycles of treatment in 1-week intervals. Results: The treatment sequence with ODN bcl-2/DDP/ODN c-myc combination completely inhibited growth in NG tumor and induced a 35-day delay in LM tumor growth. In contrast, the M20 tumor growth was unaffected by the combination. A discrete amount of c-Myc and bcl-2 protein expression in both LM and NG tumors was detected, whereas no detectable levels of the two proteins were observed in M20 tumors. Compared with the other combination, the sequence (ODN bcl-2/DDP/ODN c-myc) produced the most effective results, producing a significant decrease in bcl-2 and c-Myc protein expression, which in turn significantly increased the survival of NG- and LM-bearing mice, with 4 mice out of 11 and 1 out of 7 mice being cured, respectively. Finally, this combination increased the apoptotic rate and produced an antiangiogenetic effect. Conclusions: These results show that an antisense approach to the treatment of melanoma xenografts overexpressing either bcl-2 or c-myc oncogenes represents a successful strategy to improve the response to chemotherapy in melanoma, with particular attention to the treatment sequence.
Organic Anion Transporters and Their Implications in Pharmacotherapy
Authors: Arian Emami Riedmaier, Anne T. Nies, Elke Schaeffeler, Matthias Schwab
Journal: Pharmacological Reviews (2012)

Organic anion transporters play an essential role in the distribution and excretion of numerous endogenous metabolic products and exogenous organic anions, including a host of widely prescribed drugs. The expression and activity of these transporters is influenced by several conditions, including transcriptional regulation, gender-dependent regulation, and genetic variation. In addition, the interaction of these transporters with several drugs and endogenous substrates has been well documented and may play a significant role in drug disposition and development of various disease states, such as nephrotoxicity and familial idiopathic hypouricemia. Members of this family of transporters have been localized mainly to the renal epithelia of various species. Much of the early research in this field has focused on their role in renal drug transport, yet increasing research on this family of transporters has localized them to various other epithelial tissues, including liver, brain, and placenta. Thus, an understanding of the role of these transporters in drug interaction and disposition in the kidney and other tissues may help in the determination of individual drug response, susceptibility to drug toxicity, and chemical carcinogenesis. This review seeks to summarize current knowledge of the molecular function and substrate profile of cloned organic anion transporters and to discuss recent progress in the understanding of the impact of interindividual variability, transcriptional regulation, and tissue distribution on individual drug response.
Recent developments in the molecular characterization and treatment of oligodendroglial tumors
Authors: Martin van den Bent, Olivier-Louis Chinot, J. Gregory Cairncross
Journal: Neuro-Oncology (2003)

Although many patients with oligodendrogliomas (ODs) and oligoastrocytomas (OAs) benefit from a combination of surgery and adjuvant radiotherapy, most patients eventually experience recurrence of their disease. Recent evidence has shown that ODs are more chemosensitive than other gliomas, including astrocytomas or glioblastoma multiforme. These initial findings have prompted further study of chemotherapy in treating ODs and mixed OAs. Advances in molecular genetic analysis have led to improvements in predicting response to chemotherapy and prognosis for ODs, OAs, and astrocytomas. Pure ODs are more chemosensitive than mixed ODs. This difference is related to different proportions of 1p/19q loss of heterozygosity in these neoplasms. Therefore, genetic analysis is likely to be key in determining appropriate treatment. The most common first-line chemotherapy for patients with OD is a procarbazine, lomustine, and vincristine (PCV) combination regimen. However, this regimen is associated with cumulative myelosuppression, nausea, vomiting, and weight loss. Therefore, other chemotherapy agents and regimens have been investigated. Perhaps the most promising is temozolomide, a novel alkylating agent that freely crosses the blood-brain barrier. Temozolomide is approved in the United States for the treatment of recurrent anaplastic astrocytomas and in Europe for any recurrent high-grade gliomas. Initial reports suggest that temozolomide is effective in treating ODs as first- and second-line chemotherapy. Unlike the PCV regimen, temozolomide is not associated with cumulative myelosuppression and is usually well tolerated. Further studies are needed to confirm the efficacy and safety profile of temozolomide and to determine the optimal dose and schedule for treating ODs.
STUDIES ON FOWL PARALYSIS (NEUROLYMPHOMATOSIS GALLINARUM)
Authors: Alwin M. Pappenheimer, Leslie C. Dunn, S. M. Seidlin
Journal: The Journal of Experimental Medicine (1929)

1. Inoculation of suspensions of brain, cord, ganglia or nerves of chickens with neurolymphomatous lesions, into newly hatched chicks, is followed by the development of typical lesions in approximately 25 per cent of cases. 2. In control chickens kept under laboratory conditions the incidence of the disease is about 7 per cent. 3. The disease does not become manifest until at least 2 months after inoculation; symptoms may not appear until after 4 months. 4. The active agent is not destroyed by 50 per cent glycerol in 9 days at ice box temperature.
Incidence and Management of Restenosis After Treatment of Unprotected Left Main Disease With Drug-Eluting Stents
Authors: Imad Sheiban, Dario Sillano, Giuseppe Biondi-Zoccai, Alaide Chieffo, Antonio Colombo, Sabine Vecchio, Massimo Margheri, Julian P. Gunn, Tushar Raina, Francesco Liistro, Leonardo Bolognese, Michael S. Lee, Jonathan Tobis, Claudio Moretti
Journal: Journal of the American College of Cardiology (2009)
Genomic Profiling of Viable and Proliferative Micrometastatic Cells from Early-Stage Breast Cancer Patients
Authors: Rainer Gangnus, Sabine Langer, Elisabeth Breit, Klaus Pantel, Michael R. Speicher
Journal: Clinical Cancer Research (2004)

Metastases in distant organs are the major cause of death for cancer patients, and bone marrow is a prominent homing organ for early disseminated cancer cells. However, it remains still unclear which of these cells evolve into overt metastases. We therefore established a new approach based on the analysis of viable and proliferating cancer cells by single-cell comparative genomic hybridization.The bone marrow of early-stage breast tumor patients (pN(0)M(0)) was screened for tumor cells by immunostaining. By applying special short-term culturing, we selected for viable and proliferative tumor cells. The short-term culturing allowed us to evaluate the proliferative potential of micrometastatic cells, which we had previously shown to represent an independent prognostic marker. We assessed genomic changes in single disseminated cancer cells by single-cell comparative genomic hybridization.We found that these viable disseminated cancer cells already had a plethora of copy number changes in their genome. All of these cells showed chromosomal copy number changes with a substantial intercellular heterogeneity and differences to the matching primary tumors.The established experimental strategy might pave the way for the identification of metastatic stem cells in cancer patients. Our preliminary results support the new concept that early disseminated cancer cells evolve independently from their primary tumor.
Changing Sensitivity of Neonatal Rats to Tumorigenic Effects of &lt;italic&gt;N&lt;/italic&gt;-Nitroso- &lt;italic&gt;N&lt;/italic&gt;-ethylurea and X-Radiation, Given Singly or Combined&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: J F Knowles
Journal: JNCI Journal of the National Cancer Institute (1985)

After neonatal injection of rats with 10 mg N-nitroso-N-ethylurea [(ENU) CAS: 759-73-9]/kg body weight, whole-body X-irradiation with 1.25 Gy X-radiation caused a reduction in induced neurogenic tumors which was dependent on the interval between the two treatments. The reduction was greatest when radiation was given 1 day after ENU and progressively decreased with irradiation at 5 and 30 days. Changes in radiosensitivity in the neonatal period were also seen for ovarian tumors and squamous cell carcinomas of the mouth. Ovarian tumors were induced by 1.25 Gy X-rays alone, with a higher incidence occurring after irradiation at 5 days than at 30 days of age. Squamous cell carcinomas of the mouth have a high spontaneous incidence in this strain of rat, but 1.25 Gy X-radiation caused a significant reduction which was greater after irradiation at 5 than at 30 days of age. Pituitary tumors occurred in untreated and treated rats with a higher incidence in females. Only in males was there any suggestion of an effect of the various treatments on pituitary tumor incidence.
Ciz1, a Novel DNA-Binding Coactivator of the Estrogen Receptor α, Confers Hypersensitivity to Estrogen Action
Authors: Petra den Hollander, Suresh K. Rayala, Dawn Coverley, Rakesh Kumar
Journal: Cancer Research (2006)

Abstract The transcriptional activity of the estrogen receptor (ER) is affected by regulatory cofactors, including chromatin-remodeling complexes, coactivators, and corepressors. Coregulators are recruited to target gene promoters through protein-protein interactions with ER and function as linker molecules between the DNA, DNA-binding proteins, and DNA-modifying enzymes. We recently showed that Cip-interacting zinc finger protein 1 (Ciz1) participates in the regulation of the cell cycle in estrogen-stimulated breast cancer cells. Despite the emerging significance of Ciz1 in the biology of breast cancer cells, regulation of endogenous Ciz1 in hormone-responsive cancer cells remains unknown. To shed light on the role of Ciz1 in breast tumorigenesis, we defined the regulation of Ciz1 by the ER pathway and found that Ciz1 is an estrogen-responsive gene. We also discovered that Ciz1 protein, a DNA-binding factor, coregulates ER by enhancing ER transactivation activity by promoting the recruitment of the ER complex to the target gene chromatin. In addition, we found that Ciz1 overexpression confers estrogen hypersensitivity to breast cancer cells and promotes the growth rate, anchorage independency, and tumorigenic properties of breast cancer cells. These findings revealed the inherent role of Ciz1, a novel DNA binding and ER coactivator, in amplifying estrogenic responses and promoting breast cancer tumorigenesis. (Cancer Res 2006; 66(22): 11021-9)
The Prognostic Value of Circulating Tumor Cells in Patients with Melanoma: A Systematic Review and Meta-analysis
Authors: Simone Mocellin, Dave Hoon, Alessandro Ambrosi, Donato Nitti, Carlo Riccardo Rossi
Journal: Clinical Cancer Research (2006)

Abstract Background: The detection of circulating tumor cells (CTC) in patients with melanoma represents an appealing prognostic tool, but no consensus exists on this topic. We aimed to comprehensively and quantitatively summarize the evidence for the use of CTC to predict patients' clinical outcome. Methods: Fifty-three studies enrolling 5,433 patients were reviewed. Correlation of CTC status with tumor-node-metastasis disease stage and patients' overall (OS) and progression-free (PFS) survival was assessed by means of association statistics and meta-analysis, respectively. Results: CTC status correlated with both tumor-node-metastasis stage (stage I, 32%; stage II, 41.7%; stage III, 41.1%; stage IV, 47.4%; Ptrend &amp;lt; 0.0001) and survival (OS: hazard ratio, 2.42; 95% confidence interval, 1.7-3.45, P &amp;lt; 0.0001; PFS: hazard ratio, 2.45; 95% confidence interval, 1.78-3.38; P &amp;lt; 0.0001). However, statistical heterogeneity was significant for both OS and PFS, likely underscoring the wide variability in study design. Furthermore, CTC positivity rates in early stages were higher and in the metastatic setting were lower than expected, which indicates an unsatisfactory accuracy of currently available CTC detection assays. Conclusions: Our findings suggest that CTC might have a clinically valuable prognostic power in patients with melanoma. However, the heterogeneity of the studies thus far published warrants caution not to overestimate the favorable results of pooled data.
Cells Deficient in the FANC/BRCA Pathway Are Hypersensitive to Plasma Levels of Formaldehyde
Authors: John R. Ridpath, Ayumi Nakamura, Keizo Tano, April M. Luke, Eiichiro Sonoda, Hiroshi Arakawa, Jean-Marie Buerstedde, David A.F. Gillespie, Julian E. Sale, Mitsuyoshi Yamazoe, Douglas K. Bishop, Minoru Takata, Shunichi Takeda, Masami Watanabe, James A. Swenberg, Jun Nakamura
Journal: Cancer Research (2007)

Abstract Formaldehyde is an aliphatic monoaldehyde and is a highly reactive environmental human carcinogen. Whereas humans are continuously exposed to exogenous formaldehyde, this reactive aldehyde is a naturally occurring biological compound that is present in human plasma at concentrations ranging from 13 to 97 μmol/L. It has been well documented that DNA-protein crosslinks (DPC) likely play an important role with regard to the genotoxicity and carcinogenicity of formaldehyde. However, little is known about which DNA damage response pathways are essential for cells to counteract formaldehyde. In the present study, we first assessed the DNA damage response to plasma levels of formaldehyde using chicken DT40 cells with targeted mutations in various DNA repair genes. Here, we show that the hypersensitivity to formaldehyde is detected in DT40 mutants deficient in the BRCA/FANC pathway, homologous recombination, or translesion DNA synthesis. In addition, FANCD2-deficient DT40 cells are hypersensitive to acetaldehyde, but not to acrolein, crotonaldehyde, glyoxal, and methylglyoxal. Human cells deficient in FANCC and FANCG are also hypersensitive to plasma levels of formaldehyde. These results indicate that the BRCA/FANC pathway is essential to counteract DPCs caused by aliphatic monoaldehydes. Based on the results obtained in the present study, we are currently proposing that endogenous formaldehyde might have an effect on highly proliferating cells, such as bone marrow cells, as well as an etiology of cancer in Fanconi anemia patients. [Cancer Res 2007;67(23):11117–22]
Relation Between Hospital Intra-Aortic Balloon Counterpulsation Volume and Mortality in Acute Myocardial Infarction Complicated by Cardiogenic Shock
Authors: Edmond W. Chen, John G. Canto, Lori S. Parsons, Eric D. Peterson, Katherine A. Littrell, Nathan R. Every, C. Michael Gibson, Judith S. Hochman, E. Magnus Ohman, Morris Cheeks, Hal V. Barron
Journal: Circulation (2003)

Background— Increasing evidence suggests an inverse relationship between outcome and the total number of invasive cardiac procedures performed at a given hospital. The purpose of the present study was to determine if a similar relationship exists between the number of intra-aortic balloon counterpulsation (IABP) procedures performed at a given hospital per year and the in-hospital mortality rate of patients with acute myocardial infarction complicated by cardiogenic shock. Methods and Results— We analyzed data of 12 730 patients at 750 hospitals enrolled in the National Registry of Myocardial Infarction 2 from 1994 to 1998. The hospitals were divided into tertiles (low–, intermediate–, and high–IABP volume hospitals) according to the number of IABPs performed at the given hospital per year. The median number of IABPs performed per hospital per year was 3.4, 12.7, and 37.4 IABPs at low-, intermediate-, and high-volume hospitals, respectively. Of those patients who underwent IABP, there were only minor differences in baseline patient characteristics between the 3 groups. Crude mortality rate decreased with increasing IABP volume: 65.4%, lowest volume tertile; 54.1%, intermediate volume tertile; and 50.6%, highest volume tertile ( P for trend &lt;0.001). This mortality difference represented 150 fewer deaths per 1000 patients treated at the high IABP hospitals. In the multivariate analysis, high hospital IABP volume for patients with acute myocardial infarction was associated with lower mortality (OR=0.71, 95% CI=0.56 to 0.90), independent of baseline patient characteristics, hospital factors, treatment, and procedures such as PTCA. Conclusions— Among the myocardial infarction patients with cardiogenic shock who underwent IABP placement, mortality rate was significantly lower at high–IABP volume hospitals compared with low–IABP volume hospitals.