tbuckley/cabot-search huggingface dataset:
DNase I-Like Endonuclease in Rat Kidney Cortex That Is Activated during Ischemia/Reperfusion Injury
Authors: Alexei G. Basnakian, Norishi Ueda, Gur P. Kaushal, Marina V. Mikhailova, Sudhir V. Shah
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Ischemia/reperfusion is known to result in DNA fragmentation and cell death in kidney tubular epithelium, but the endonucleases responsible for this DNA damage have not been identified. DNA substrate gel analysis of extracts from normal rat kidney cortex revealed the presence of a DNase with an apparent molecular mass of 30 to 34 kD. This enzyme is not a dimer of the previously described nuclear 15-kD endonuclease in kidney cells. Partially purified DNase exhibited characteristics similar to those of rat DNase I. The DNase was able to digest circular DNA (endonuclease), required both Ca2+ and Mg2+ ions, and was inhibited by Zn2+ and by aurintricarboxylic acid; it was not inhibited by G-actin. Rat kidneys were subjected to 40 min of ischemia, followed by 0, 1, 4, 16, or 48 h of reperfusion. The activity of the DNase in cytosolic and nuclear extracts, the 200-bp ladder-generating activity, and 3′OH strand breaks in nuclear DNA were simultaneously increased after ischemia, during the first hours of reperfusion. Oxidative DNA damage, measured as 8-hydroxydeoxyguanosine content, did not coincide with endonuclease-generated DNA breaks. Oxidative DNA damage was increased during ischemia and gradually decreased during reperfusion. Phosphorothioated DNase I antisense oligodeoxynucleotide introduced into cultured NRK-52E rat kidney epithelial cells inhibited DNA fragmentation and attenuated cell death induced by hypoxia/reoxygenation in vitro. The data indicate that the DNase I-like endonuclease may contribute to DNA fragmentation in reperfused rat kidneys.
A better therapeutic profile for the combination of mitomycin-C, ifosfamide and cisplatin (MIC) in advanced non-small-cell lung cancer: A useful dose-schedule modification
Authors: L. Crinò, E. Corgan, S. Porrozzi, M.A. Palladino, S. Darwish, V. Minotti, A.M. Mosconi, M. Tonati
Journal: Annals of Oncology (1997)
Mutation in alpha 5(IV) collagen chain gene in nonfamilial hematuria.
Authors: K Kitagawa, K Nakanishi, K Iijima, H Nishio, Y Sado, K Sano, H Nakamura, N Yoshikawa
Journal: Journal of the American Society of Nephrology (1995)

Alport syndrome is an inherited disorder characterized by progressive nephritis with ultrastructural basket-weave changes of the glomerular basement membrane and neurosensory deafness. Mutations in the COL4A5 gene encoding the Type IV collagen alpha 5 chain have been reported to occur in patients with X-linked Alport syndrome. A girl with hematuric nephritis, characteristic basket-weave glomerular basement membrane changes, and abnormal expression of the Type IV collagen alpha 5 chain immunohistochemically, but no family history of nephritis, was identified. Mutation detection enhancement gel electrophoresis of the polymerase chain reaction-amplified exons of COL4A5 from this patient revealed a sequence variant in the exon 50 region. Sequence analysis of her polymerase chain reaction product demonstrated a single-base (C; nucleotide 4728 from the 5' end) deletion in exon 50. This novel mutation alters the reading frame and introduces a translation stop codon that would be expected to result in a noncollagenous domain with only 209, instead of the normal 229, amino acid residues. Gene tracking with restriction enzyme AfIIII demonstrated that her mother was normal. These findings represent a new mutation of the X-linked Alport syndrome in this patient and demonstrate that a COL4A5 gene mutation causes the abnormal expression of Type IV collagen alpha 5 chain protein.
Differential Expression of Neural Isozymes by Human Medulloblastomas and Gliomas and Neuroectodermal Cell Lines23
Authors: Paul M. Zeltzer, Sandra L. Schneider, Paul J. Marangos, Mark H. Zweig
Journal: JNCI Journal of the National Cancer Institute (1986)

Journal Article Differential Expression of Neural Isozymes by Human Medulloblastomas and Gliomas and Neuroectodermal Cell Lines Get access Paul M. Zeltzer, Paul M. Zeltzer Search for other works by this author on: Oxford Academic PubMed Google Scholar Sandra L. Schneider, Sandra L. Schneider Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul J. Marangos, Paul J. Marangos Search for other works by this author on: Oxford Academic PubMed Google Scholar Mark H. Zweig Mark H. Zweig Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 77, Issue 3, September 1986, Pages 625–631, https://doi.org/10.1093/jnci/77.3.625 Published: 01 September 1986 Article history Received: 02 August 1985 Revision received: 02 April 1986 Accepted: 28 April 1986 Published: 01 September 1986
Osteopenia in survivors of childhood cancer.
Authors: R. Nagarajan, S. R. Rose, M. M. Rutter, J. Correll, D. Kent, M. Kim, B. Schnell, K. C. Burns
Journal: Journal of Clinical Oncology (2010)

9089 Background: As childhood cancer rates continue to improve, long-term complications of therapy are becoming increasingly important. One complication of childhood cancer therapy is osteopenia. This may be due to the cancer itself or treatment related factors such as radiation therapy, specific chemotherapy drugs, and/or the use of steroids. Methods: Recently dual energy X-ray absorptiometry (DXA) scans have become a standard of care for patients at risk for osteopenia attending our long term follow-up clinic. Patients at risk included those with a history of leukemia, lymphoma, and CNS tumors. These patients had prolonged steroid exposure, specific radiation exposures (including total body), endocrinopathies, and/or intensive chemotherapy treatments. A retrospective review of medical records was performed. All patients in the clinic were diagnosed under the age of 21 and were at least 5 years out from diagnosis. Z score for age and gender were obtained from DXA. Patients were compared based on cancer diagnosis. Results: 207 survivors (98 female) had a DXA scan performed. Average age at cancer diagnosis was 7 years (0.5-19y) with DXA performed an average of 11 years (0-34y) after diagnosis. Leukemias (n=119, lymphoblastic leukemias (ALL); n=21, myeloid leukemias) and lymphomas (n=27, Hodgkin; n=20, NHL) were the most common diagnoses. Overall, nearly 19% of survivors (n=39) had Z-score below -1.0 with 7.7% (n=16) below -2.0. No significant differences were seen between males and females in terms of % with Z-score below -1.0 (16.7% vs. 21.2%) or below -2.0 (6.5% vs. 9.1%). Nearly 16% of ALL survivors had a Z-score under -1.0. Patients with ALL accounted for 50% (n=8) of Z-scores below -2, while patients with CNS tumors accounted for 25% (n=4) of this group. The distribution of Z-scores differed significantly across diagnostic groups (p=0.0025). Conclusions: A significant portion of survivors considered to be at risk for osteopenia were indeed found to have low Z-scores measured by DXA scans. This risk varied by diagnosis. Males and females appear to be equally affected. Early interventions such as an exercise program and dietary supplements may be warranted to prevent osteopenia in cancer survivors. No significant financial relationships to disclose.
Cardiotoxicity after doxorubicin and AZD2171, an oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor, in patients (pts) with breast cancer
Authors: N. Denduluri, A. W. Berman, U. Vatas, C. K. Chow, D. R. Rosing, S. M. Swain
Journal: Journal of Clinical Oncology (2007)

554 Background: AZD2171 selectively inhibits VEGFR 1,2,3. This trial examined the safety and efficacy of AZD2171 with anthracycline-containing therapy. Methods: Pts with previously untreated Stage IIB and III breast cancer received neoadjuvant AZD2171 (30mg) alone for one cycle (1 week) followed by daily AZD2171 and TAC chemotherapy with docetaxel (T), doxorubicin 50 mg/m 2 (A) cyclophosphamide (C) for 6 cycles (Cy) every 3 weeks. Pts underwent breast surgery after completing neoadjuvant therapy. Eligible pts had left ventricular ejection fraction (EF) = 50%, and no uncontrolled HTN or cardiac history. Pts underwent electrocardiogram (EKG), and troponin first day (D) of every Cy and 24 hours after TAC as well as serial echocardiograms (echo). Cardiac stress MRI with dipyridamole was performed when pts had decreases in EF by echo. Results: Two pts received 2 Cy of AZD2171 alone, 9 Cy with TAC and AZD2171, and 1 Cy with TAC alone. Pt 1 and Pt 2 developed hypertension requiring medical therapy Cy4, D1 (148/97 mm Hg) and Cy2, D2 (169/93 mm Hg) respectively. Pt 1 had asymptomatic decrease in EF from 65% to 40% (grade 2) with global hypokinesis pre-Cy5 by echo. Troponin and EKG were negative for acute ischemia. Cardiac stress MRI was normal and EF returned to 60% within 48 hours. The pt continued therapy and pre-Cy7 EF was 51% by echo. Cumulative A dose received was 250mg/m 2 pre-Cy7. AZD2171 was held while Cy7 TAC was continued. EF was 57% by echo 1 month after Cy7 TAC. Pt 2 had asymptomatic decrease in EF from 65% to 50% pre-Cy4 by echo with mild global hypokinesis. Troponin and EKG were negative for acute ischemia. Cardiac stress MRI showed EF of 56% with no ischemia. She continued AZD2171 and TAC. Pre-Cy5 EF was 35–40% (grade 3) with global hypokinesis. Troponin and EKG were negative. Cumulative dose of A received was 150mg/m 2 . AZD2171 and A were stopped; T and C were continued. EF normalized to 55% by cardiac stress MRI and echo within 21 days. Conclusion: Due to the systolic dysfunction that occurred with concurrent AZD2171 and doxorubicin administration, the study is closed. Future trials should administer AZD2171 and anthracyclines sequentially with stringent monitoring of blood pressure and ejection fraction. No significant financial relationships to disclose.
Calgb/Swog 80405: Phase III Trial of Irinotecan/5-Fu/Leucovorin (Folfiri) or Oxaliplatin/5-Fu/Leucovorin (Mfolfox6) with Bevacizumab (Bv) or Cetuximab (Cet) for Patients (Pts) with Expanded Ras Analyses Untreated Metastatic Adenocarcinoma of the Colon Or Rectum (Mcrc)
Authors: H. Lenz, D. Niedzwiecki, F. Innocenti, C. Blanke, M.R. Mahony, B.H. O'Neil, J.E. Shaw, B. Polite, H. Hochster, J. Atkins, R. Goldberg, R. Mayer, R.L. Schilsky, M. Bertagnolli, A. Venook
Journal: Annals of Oncology (2014)
Abstract 18061: Attenuated Aortic Dilatation, Not Increased Wall Stiffness Best Explains the Rise in Pulse Pressure in Women With Aging: Results From the Baltimore Longitudinal Study of Aging
Authors: Majd AlGhatrif, James B Strait, Chris Morrell, Marco Canepa, Jeanette Wright, Palchamy Elango, Angelo Scuteri, Samer S Najjar, Luigi Ferrucci, Edward G Lakatta
Journal: Circulation (2013)

BACKGROUND: While women have a greater increase in pulse pressure (PP) with aging, aortic pulse wave velocity (PWV), a direct measure of arterial stiffness, is not higher in women than men. We hypothesized that a slower increase in aortic root diameter (AoD), rather than greater arterial wall stiffening per se, best explains the rise of PP in women with aging compared to men. METHODS AND RESUTLS: A total of 257 men and 310 women from the Baltimore Longitudinal Study of Aging, aged 25 to 93 years, had 2-8 repeated measures of PP, PWV, and AoD by echocardiography between 1988 and 2013. Linear Mixed-effects (LME) models were used to examine the longitudinal changes in PP, PWV, and AoD indexed to BSA. Age was expressed as First-age (age at entry), and Time (follow up time), to differentiate cross-sectional differences from longitudinal changes over time. Model-predicted values were plotted to illustrate concurrent trajectories of PP, PWV, and AoD (Fig. 1). Men had a pronounced acceleration in PWV increase, but a deceleration in PP increase with age beyond the 5 th decade [β= 0.21, P= 0.0004, and β= - 0.12, P= 0.0419, for (Time х First-age 2 ) in PWV and PP, respectively]; note the changes of the solid line’s slope in Fig.1A, B. On the other hand, women had an acceleration in PWV increase with age [β= 0.19, P= 0.0318, for Time х First-age] concordant with a steady increase in PP [β= 4.7, P&lt; .0001, for Time]. These trajectories resulted in a higher PWV, but a lower PP in men than women beyond the 5 th decade (Fig 1A, B). The dissociation between PP and PWV longitudinal changes in men was accompanied by a steeper increase in AoD in men than women resulting in greater AoD in men beyond the 5 th decade (β=0.04, P= 0.0146) (Fig1C). CONCLUSION: The greater acceleration in AoD in men likely offsets the effect of elevated arterial stiffness blunting the increases in pulse pressure; lesser AoD dilatation in women potentially leaves arterial wall stiffness unopposed, giving rise to a greater increase in PP in women with aging.
Thrombin increases clusterin mRNA in glomerular epithelial and mesangial cells.
Authors: N J Laping, B A Olson, B Short, C R Albrightson
Journal: Journal of the American Society of Nephrology (1997)

Clusterin, a multifunctional protein with complement blocking activity, and fibrin, a product of thrombin's enzymatic activity, are present in the kidney during acute and chronic renal failure. The role of thrombin in regulating clusterin mRNA in the kidney is not known. The effect of thrombin on clusterin mRNA expression was examined in rat glomerular mesangial and glomerular epithelial cells, and cultured human renal proximal tubular epithelial cells by northern blot. Thrombin (10(-8) M) increased clusterin mRNA levels two- to fourfold in glomerular mesangial, glomerular epithelial, and proximal tubule epithelial cells. This was a specific effect of thrombin receptor activation because peptides corresponding to the tethered ligand of the thrombin receptor were also able to increase clusterin mRNA levels. Epidermal growth factor, insulin-like growth factor-1, and transforming growth factor-beta 1 had little or no effect on clusterin mRNA levels. The protein kinase C inhibitor RO-32-0432 (1 microM) inhibited the thrombin-induced increase in clusterin mRNA, suggesting that thrombin receptor activation may regulate renal clusterin mRNA levels through protein kinase C.
Octreotide for advanced hepatocellular cancer revisited: Final data of a meta-analysis approach based on single patient data
Authors: G. Treiber, B. O'Neil, D. Dimitroulopoulos, C. Lersch, R. Plentz, G. Becker, G. Verset
Journal: Journal of Clinical Oncology (2008)

15508 Background: Octreotide as systemic treatment for locally advanced or metastatic hepatocellular cancer (HCC) has revealed conflictive results. Methods: To estimate a potential benefit of octreotide in HCC, we performed a meta-analysis of individual patient data from previous trials. Studies had to meet the following criteria: established diagnosis of advanced HCC; data published fully or as an abstract at major meetings; prospective design; treatment with octreotide (30 mg LAR, given im every 4 weeks), and reporting overall survival (OS), being the primary outcome measure for this analysis. Secondary outcome measures were TTP and 3-month-RR (RECIST). Results: 13 trials could be identified. Authors provided structured data questionnaires of 8 studies (2 with placebo/tamoxifen controls). 5 groups did not respond or declined permission to analyse their data. 315 patients had received octreotide and 116 patients were controls. Out of 431 patients, OS as the primary outcome measure could be retrieved from 399 patients, 3-mo RR from 305, and TTP from 209 individuals. For all pts., median OS was 24 weeks (32 vs 16 for Child A vs B/C, p<0.0001 respectively) and median TTP was 12 weeks, differences between controls and octreotide were NS. At 3 months, disease stabilisation (DS=SD + PR) had occured in 77/315 patients (24.4%). If patients were stratified as of whether DS had been observed at 3 months or not, median OS resulted in 38.4 vs 24.9 wks (p=0.0003, logrank test); and in 21.4 wks for controls (pts. with DS vs controls: HR 0.46, 95%-CI: 0.30–0.70). Pts. with DS and Child A status had an even better median OS than those with Child B or C (46.4 vs 28.6 wks, p<0.01). OS was also significantly associated with TTP and RR at 3 months (p<0.0001, each), as well as with baseline serum AFP, bilirubine, alkaline phosphatase, albumin; further with ECOG Performance status, tumor grading, presence of portal vein infiltration, CLIP/Okuda scores (p<0.001, each). Conclusions: In general, survival due to advanced HCC is around 5–6 months with or without octreotide treatment. Our results however imply, that patients achieving disease stabilisation at 3 months of octreotide treatment (NNT=4) will benefit from continued treatment, especially those with preserved liver function. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis
A controlled evaluation of recent approaches to biochemical modulation or enhancement of 5-fluorouracil therapy in colorectal carcinoma.
Authors: T R Buroker, C G Moertel, T R Fleming, L K Everson, S A Cullinan, J E Krook, J A Mailliard, R F Marschke, D J Klaassen, J A Laurie
Journal: Journal of Clinical Oncology (1985)

Three hundred thirty-five previously untreated patients with advanced colorectal carcinoma were randomly assigned to treatment with 5-fluorouracil (5-FU) alone, 5-FU plus N-(phosphonacetyl)-L-aspartic acid (PALA), 5-FU plus high-dose thymidine, 5-FU plus levamisole, or 5-FU plus methyl CCNU, vincristine, and streptozotocin (MOF-Strept). Dosages were designed to produce definite toxicity in the majority of patients, although the nature of dose-limiting reactions varied considerably among regimens. 5-FU alone and 5-FU plus levamisole produced mucocutaneous reactions, diarrhea, and leukopenia; 5-FU plus PALA produced primarily mucocutaneous reactions and diarrhea; 5-FU plus thymidine produced leukopenia with occasional neurotoxicity and hypotension; and MOF-Strept produced substantial nausea and vomiting with both thrombocytopenia and leukopenia. Objective response rates among patients with measurable disease varied from 12% (5-FU plus PALA) to 34% (MOF-Strept), but none of the regimens were significantly superior to 5-FU alone. Both interval to progression and survival were comparable among the five regimens with no reasonable chance that any combination regimen could produce as much as a 50% improvement when compared with 5-FU alone. Whereas we observed definite modulation of 5-FU dose--toxicity relationships, particularly with the thymidine and PALA combinations, this did not result in a detectable improvement in therapeutic effect. None of the combination regimens, administered in the dosages and schedules we used, can be recommended as standard therapy of advanced colorectal carcinoma.
Coumarin plus cimetidine: yet another angle for therapy of renal cell carcinoma.
Authors: J M Kirkwood, M S Ernstoff
Journal: Journal of Clinical Oncology (1987)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1987.5.6.836 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3585440 Coumarin plus cimetidine: yet another angle for therapy of renal cell carcinoma. J M KirkwoodxJ M KirkwoodSearch for articles by this author , M S ErnstoffxM S ErnstoffSearch for articles by this author https://doi.org/10.1200/JCO.1987.5.6.836 PDF "Coumarin plus cimetidine: yet another angle for therapy of renal cell carcinoma.." Journal of Clinical Oncology, 5(6), pp. 836–837© 1987 by American Society of Clinical Oncology
Heterotransplantation of Two Human Lymphoid Cell Lines Transformed &lt;italic&gt;In Vitro&lt;/italic&gt; by Epstein-Barr Virus
Authors: D. R. Deal, P. Gerber, F. V. Chisari
Journal: JNCI Journal of the National Cancer Institute (1971)

The in vivo biologic activity of 2 human lymphoid cell lines (AV1 and JQ), established after in vitro transformation by Epstein-Barr virus (EBV), was studied. (BALB/c × A/HeN)F1 mice, in the first 24 hours of life, were pretreated with rabbit antilymphocyte serum and then given intraperitoneal injections of varying doses of living cells. Of 30 mice that received 1 × 107-108 AV1 cells, 28 developed tumors and died; but, of 40 mice given lower doses, none died. JQ cells caused fatal tumors at a dose as low as 5 × 106. There was gross tumor involvement of all intra-abdominal organs, retroperitoneal structures, and surrounding muscular areas. Microscopically, all organs except the heart were invaded by very aggressive, undifferentiated lymphoid cells. Negative controls consisted of buffy-coat lymphocytes from 2 donors without serologic evidence of previous EBV infection. One of these seronegative donors contributed the cells from which the in vitro EBV-transformed cell line AV1 was established. We conclude that EBV can cause human lymphocytes to grow in an uncontrolled and highly invasive manner in a heterologous host. Possibly the EBV genome is necessary for the heterotransplantability of most, but possibly not all, continuous human lymphoid cell lines.
Treatment of ovarian cancer patients with malignant ascites using the trifunctional antibody catumaxomab: Results of a phase II/III study
Authors: S. L. Parsons, E. Kutarska, P. Koralewski, M. Gore, P. Wimberger, A. Burges, M. A. Stroehlein, A. Lahr, M. Jaeger, M. M. Heiss
Journal: Journal of Clinical Oncology (2007)

5520 Background: Malignant ascites in ovarian carcinoma patients (pts.) is associated with a poor prognosis and reduced quality of life. Catumaxomab (anti-EpCAM × anti-CD3) is known to effectively eliminate tumor cells within ascites by simultaneously activating T cells and Fc gamma-receptor positive cells and redirecting them against the tumor. Methods: A total of 129 ovarian cancer pts. with recurrent symptomatic malignant ascites containing EpCAM+ tumor cells were enrolled in the study; 85 were randomized to treatment with catumaxomab (paracentesis plus intraperitoneal infusions of 10, 20, 50 and 150 μg for 11 days), and 44 to the control arm (paracentesis alone). The primary endpoint was puncture free survival (time to first need for paracentesis after treatment or time to death, which ever occurred first). Results: Pts. characteristics were well balanced in both arms. Median puncture free survival was 52 days for catumaxomab vs. 11 days for control (p&lt;0.0001) whereas the median time to first need for paracentesis was 71 days vs. 11 days l (p&lt;0.0001). There was a pronounced decrease of tumor cell load accompanied by a distinct increase of leukocyte count during catumaxomab treatment within the ascites fluid. Overall and progression free survival data suggest longer survival for catumaxomab-treated pts. compared to control. Follow-up data will be presented. The most frequent AEs were symptoms related to cytokine release (pyrexia, nausea, vomiting). These were generally mild to moderate in intensity, and fully reversible. Transient increases in liver enzymes and bilirubin, and transient WBC abnormalities such as leukocytosis, neutrophilia and a decrease in peripheral lymphocyte were regularly observed as abnormal laboratory values but rarely considered clinically significant. Conclusions: Intraperitoneal therapy with catumaxomab resulted in a significant and clinically relevant improvement of puncture-free survival time, tumor cell load, and time to first need for puncture compared to the control group of best available treatment. The safety profile reflects catumaxomabs mode of action and reveals a low and acceptable toxicity. No significant financial relationships to disclose.