tbuckley/cabot-search huggingface dataset:
PLK-1 interacts with RASSF1C and regulates its expression by a phosphorylation dependent mechanism
Authors: MT Ling, KL Fung, X Wang, YC Wong
Journal: Cancer Research (2007)

5197  Polo-like kinase-1 (Plk1) belongs to the polo-like kinase protein family which regulates mitotic progression and its activities was recently showed to be regulated by progressive phosphorylation at Ser137 and Thr210 during the cell cycle. One of its major roles during mitosis is to promote the mitotic spindle formation through direct interaction and phosphorylation of proteins involved in microtubule organization and assembly. Here, we report that Plk1 interacts with the 1C isoform of the RASSF1 protein family. RASSF1C, like RASSF1A, was recently showed to bind to and regulate microtubule stability. Although ectopic expression of the wild-type Plk1 failed to affect the expression of RASSF1C, the dominant active Plk1 mutants (T210D or S137D) significantly downregulated RASSF1C protein level. Meanwhile, a further downregulation of the RASSF1C protein was observed when a double mutant (T210D+S137D) was expressed, suggesting that the effect of Plk1 on RASSF1C depends on the kinase activities of Plk1. Interestingly, while Plk1 can also interact with RASSF1A, expression of either the wild-type or dominant active mutants did not affect the RASSF1A protein level. Taken together, our result demonstrated the microtubule regulator RASSF1C as a novel target of Plk1.
Lack of Susceptibility of F344 Rats to Mammary Tumor Induction by Topically Applied Fluorenylacetohydroxamic Acids and Their Acetates 2
Authors: D. Malejka-Giganti, R. E. Rydell
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Lack of Susceptibility of F344 Rats to Mammary Tumor Induction by Topically Applied Fluorenylacetohydroxamic Acids and Their Acetates Get access D. Malejka-Giganti, D. Malejka-Giganti 4 4Address reprint requests to Dr. Malejka-Giganti at Veterans Administration Hospital, 54th St. and 48th Ave. South, Minneapolis, Minn. 55417. Search for other works by this author on: Oxford Academic PubMed Google Scholar R. E. Rydell R. E. Rydell Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 2, February 1978, Pages 433–435, https://doi.org/10.1093/jnci/60.2.433 Published: 01 February 1978 Article history Received: 05 July 1977 Accepted: 26 September 1977 Published: 01 February 1978
Phase I study combining an IGFR inhibitor (IMC-A12) and an mTOR inhibitor (temsirolimus) in patients with solid tumors or lymphoma
Authors: A. Naing, P. LoRusso, G. Mills, D. Berry, L. Doyle, E. Rohren, A. Burger, H. Chen, N. L. Busaidy, R. Kurzrock
Journal: Journal of Clinical Oncology (2009)

e14535 Background: IMC-A12 is a fully humanized IgG1/ lambda monoclonal antibody directed at the type I Insulin-Like Growth Factor Receptor (IGF-IR). Temsirolimus, an ester of the macrocyclic immunosuppressive agent sirolimus, is a cytostatic cell cycle inhibitor, which specifically inhibits the mammalian target of rapamycin (mTOR). A paradoxical increase in AKT activation by an mTOR inhibitor through an IGF-1R-dependent mechanism may compromise the therapeutic effect of mTOR inhibitors. Hence we evaluated the combination of temsirolimus and IMC-A12. Methods: This standard “3+3” design used a fixed dose of 25 mg IV weekly of temsirolimus with an escalating weekly dose of IV IMC-A12 at 3 mg/kg, 4 mg/kg and 6 mg/kg with no intrapatient dose escalation. The goal of this study is to define the MTD and to evaluate the biologic effects and metabolic activity of IMC-A12 and temsirolimus, individually and in combination. Patients with advanced solid tumors and lymphoma are eligible. No history of diabetes is allowed in dose escalation cohorts. Results: To date, 11 patients (4 males and 7 females, median age 47) with various solid tumor histologies have been enrolled across 3 dose cohorts with the current dose cohort at 6 mg/kg weekly IV of IMC-A12 and 25 mg weekly IV of temsirolimus. The MTD has not been determined. The most common grade 1 and grade 2 toxicities have been dysgeusia (n=5), fatigue (n=5), hyperglycemia (n=6), hypertriglyceridemia (n=6), leucopenia (n=4), mucositis (n=4), and ocular flashes of light (n=3). No grade 3 or 4 toxicity lasted more than 7 days (nausea n=1; vomiting n=1; thrombocytopenia n=1). Two patients (metastatic prostate cancer and metastatic breast cancer) demonstrated prolonged stable disease for 4 and 6 months, respectively. Conclusions: Preliminary data suggest that the combination is well tolerated and that it warrants further investigation. The expansion phase of this study will evaluate the biologic effects and metabolic activity of IMC-A12 and temsirolimus, individually and in combination, through the use of RPPA (Reverse Phase Protein Assays) and PET scans. [Table: see text]
Trusts have been set “impossible task” to balance books, say NHS leaders
Authors: Adrian O’Dowd
Journal: BMJ (2016)

NHS trusts have been set an “impossible task” of staying in the black in the current climate of growing demand and small increases in NHS funding, MPs have been told.

Despite a relatively large boost in NHS funding for the coming year it was likely that trusts would struggle after that, NHS staff and organisation representative bodies told the parliamentary health committee during an evidence session on 8 March.

During the session for their inquiry into the effects of the comprehensive spending review1 on health and social care, MPs were told that the net deficit for the provider sector over the first three quarters of …
Absence of Stainable Iron From Preneoplastic and Neoplastic Lesions in Rat Liver With 8-Hydroxyquinoline-Induced Siderosis
Authors: Gary M. Williams, Richard S. Yamamoto
Journal: JNCI Journal of the National Cancer Institute (1972)

Detailed comparative studies were conducted on the progressive increase in stainable iron deposition in normal, preneoplastic, and neoplastic tissues of rats fed diets containing 8-hydroxyquinoline (HQ), with or without further supplements of iron as ferrous gluconate (FG). As previously reported, HQ induced hepatic iron deposition and this was enhanced by FG at all time points. However, even very minimal liver lesions induced by the hepatocarcinogens diethylnitrosamine or N-2-fluorenylacetamide, barely recognizable by standard hematoxylin and eosin staining techniques, stood out clearly because they did not accumulate stainable iron like the adjoining hepatocytes. Hepatic hyperplastic and neoplastic lesions of increasing severity seen during continuing carcinogen treatment characteristically did not exhibit siderosis. Thus iron stains in the livers of rats fed HQ and FG permit the sensitive and reliable detection of early hyperplastic or neoplastic lesions. Rats ingesting HQ in addition to the carcinogens had a lower incidence of hepatic malignancy.
Association of HLA-DM polymorphism with the production of antiphospholipid antibodies
Authors: M L Sanchez
Journal: Annals of the Rheumatic Diseases (2004)

To investigate whether variation in the HLA-DM gene is important in producing a group of pathogenic autoantibodies-antiphospholipid antibodies (aPL)-on the basis that HLA class II restricted antigen presentation is involved in the production of aPL.HLA-DMA and DMB polymorphisms were genotyped by polymerase chain reaction combined with restriction enzyme digestion in 51 white patients with primary antiphospholipid syndrome (APS), 82 with systemic lupus erythematosus (SLE) (42 with APS and 40 without APS), and 109 healthy white controls. The association with the aPL profile was examined.The distribution of DMA alleles in APS patients and in patients with APS associated with SLE was significantly different from that in controls by 4x2 chi(2) test with 3 degrees of freedom (p = 0.035 and 0.011, respectively), but it was not different between SLE patients without APS and controls. The allelic distribution of DMA was also different between patients with IgG class anticardiolipin antibody or those with lupus anticoagulant (LA) and controls (p = 0.012 and 0.007, respectively) and between patients with and without LA among SLE patients (p = 0.035). All these differences included the increase in DMA*0102 in the former groups.The results suggest that HLA-DMA*0102 or its linked gene(s) form one of the genetic risks for the production of aPL.
Malignant pleural mesothelioma: Inter-observer variability in the assessment of tumor response classification
Authors: J. L. Ogarek, S. G. Armato, A. Starkey, N. J. Vogelzang, H. L. Kindler, H. Macmahon
Journal: Journal of Clinical Oncology (2004)

7194 Background: Measurement of tumor thickness on the computed tomography (CT) scans of patients with malignant pleural mesothelioma (MPM) is tedious, and measurement consistency across sequential CT scans remains a significant clinical challenge. This study documents inter-observer variability in the tumor response classification of MPM. Methods: Three observers familiar with the clinical measurement protocol analyzed 22 CT scans from different MPM patients. Given previously measured baseline CT scans, observers measured tumor thickness in follow-up scans through a computer interface that allowed for the side-by-side viewing of the two scans. Observers made tumor thickness measurements in the follow-up scans during each of two independent sessions that differed in the manner in which baseline scan measurements were presented. One session visually displayed baseline measurements as line segments superimposed across the measurement sites on the baseline scan, while the other session used a written report of baseline measurements without a visual aid. Tumor response classification was determined from the differences in summed measurements between the two scans of each patient in accordance with RECIST guidelines. Results: 88% of pair-wise comparisons among the three observers exhibited concordant tumor response classifications using the visual aid; a 79% concordance rate was obtained based on the written report only. Statistically significant differences in summed measurement differences were observed for two of the three pair-wise observer comparisons based on the written report (p<0.05), while no statistically significant differences between observers were observed when follow-up measurements were based on the visual aid. Conclusions: This study documents the degree of inter-observer variability that exists in MPM tumor response classification. This variability may be reduced with a computer interface that presents a visual aid of baseline scan measurements. Incorporation of this interface into ongoing clinical trials is anticipated. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration R2 Technology, Inc. R2 Technology, Inc.
Folate-scan in subjects with suspected metastatic renal cell carcinoma
Authors: F. Naveed, R. Fisher, J. S. Engel, J. Lu, P. Low, R. J. Amato
Journal: Journal of Clinical Oncology (2004)

4751 Background: The folate receptor (FR) is overexpressed by different cancer types, including renal cell carcinoma. A folate-targeted imaging agent (EC20) could provide an alternative means of selecting folate receptor-positive (FR+) patients that may benefit from folate-targeted therapies. Methods: 40 subjects with known metastatic renal cell carcinoma were enrolled into the study and increased uptake of Folate-Scan in tumors was correlated with the immunohistochemical (IHC) staining. Formalin-fixed, paraffin-embedded tissue samples, primary and metastatic sites were analyzed for the folate receptor by an IHC assay. Three lesions were identified as target lesions on the subject's conventional image. Mid-thigh to head anterior and posterior planar images were then obtained 1 –2 hours following EC20 administration. SPECT images of the region known to contain the index lesion(s) as identified by the subject's CT or MRI were obtained immediately after acquisition of the planar images. The amount of FS uptake in the tumors were coded as no uptake, mild uptake, or marked uptake. Results: 29 out of the 40 subjects who have been scanned, data is available. 22 (74%) of the subjects were Folate-Scan positive, 15 (52%) of the subjects were positive on both the IHC and the Folate-Scan and 7(24%) were positive on the Folate-Scan with negative IHC. Of the 112 lesions identified on CT and evaluated on Folate-Scan, 69 lesions (61%) were positive for Folate-Scan uptake (mild or marked uptake of FolateScan), 43 lesions (38%) did not show any Folate-Scan uptake. Data suggest that larger lesions show mild or marked uptake of Folate-Scan whereas smaller lesions show little or no uptake of Folate-Scan. Conclusions: Primary tumors are not always folate receptor positive. It is difficult to obtain a current tissue sample from a metastatic site which has proven to be more positive. Folate-Scan is a non-invasive procedure that can identify folate receptors in recurrent or metastatic disease without the need for biopsy. The entire body can be scanned in real time which would prevent the need for biopsies in patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Endocyte, Inc.
Genetic Determinants of Morphological Differentiation in Hybrid Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Francis Wiener, Alisfair Cochran, George Klein, Henry Harris
Journal: JNCI Journal of the National Cancer Institute (1972)

A hybrid cell line was produced by fusing a fibroblastic L-cell derivative with a lymphocytic cell from a highly malignant, virus-induced lymphoma. The hybrid cells were fibroblasfic and initially had a chromosome constitution corresponding closely to the sum of the 2 parental chromosome sets. This hybrid line maintained an extremely low level of tumorigenicity during prolonged cultivation in vitro. Occasional tumors were, however, produced by the growth in vivo of segregant cells from which variable numbers of chromosomes had been eliminated. These segregant tumors permitted a study of the effects of chromosome loss on the morphology of the hybrid tumors. Where chromosome loss was not extensive, the tumors, like the hybrid line in vitro, were usually fibroblastic, though some were cytologically intermediate and some were composed of 2 populations of cells, one fibroblastic and the other lymphocytic. When a drastic loss of chromosomes occurred, lymphocytic morphology was completely restored in the hybrid tumor. Thus apparently, in fibroblastic hybrid cells, the genetic determinants of lymphocytic differentiation are not lost but are carried cryptically over long periods (if not indefinitely) of cultivation. When extensive chromosome loss eliminates the genetic determinants of fibroblastic differentiation, the determinants of lymphocytic differentiation may reassert themselves. The significance of these findings for current models of differentiation is discussed.
A 2 Step Approach To Myeloablative Haploidentical Hematopoietic Stem Cell Transplantation (HSCT): Low Non-Relapse Related Mortality (NRM) and High Overall Survival (OS) Rates Confirmed In Second Generation Trial
Authors: Dolores Grosso, Onder Alpdogan, Matthew Carabasi, Joanne Filicko-O'Hara, Margaret Kasner, Ubaldo Martinez, William O'Hara, John L. Wagner, Mark Weiss, Neal Flomenberg
Journal: Blood (2013)
The oncologic impact of pancreatic fistula after pancreatectomy in patients with pancreatic cancer.
Authors: Manabu Kawai, Yoshiaki Murakami, Seiko Hirono, Ken-Ichi Okada, Fuyuhiko Motoi, Michiaki Unno, Masayuki Sho, Yoshiyuki Nakajima, Kenichiro Uemura, Sohei Satoi, A-Hon Kwon, Ippei Matsumoto, Sadaki Asari, Goro Honda, Masanao Kurata, Hiroki Yamaue
Journal: Journal of Clinical Oncology (2015)

426 Background: There is a few reports that evaluates the association between pancreatic and long-term survival after pancreatectomy in patients with pancreatic cancer. The aim of this study was to elucidate the oncological impact of pancreatic fistula (PF) on long-term survival after pancreatectomy in patients with pancreatic cancer by performing a survey of high volume centers for pancreatic resection in Japan. Methods: Between January 2001 and December 2012, 1,369 patients who underwent pancreatectomy for pancreatic cancer at 7 high-volume centers in Japan were retrospectively reviewed. Results: Pancreatic fistula(PF) occurred in 320 of 1,369 patients (23.5%), and these were classified based ISGPF as follows; grade A in 10.2%, grade B in 10.7%, and grade C in 2.6% of the patients. Median survival time (MST) in no fistula/grade A, grade B and grade C were 24.0, 26.3 and 11.0 months, respectively. MST in grade B PF was similar with that in no fistula/grade A. However, patients with grade C PF had a significantly poorer survival than those without (P&lt;0.001). In the multivariate cox proportional hazard analysis, grade C PF was detected as an independent prognostic factor after pancreatectomy for pancreatic cancer (hazard ratio (HR) 2.15; 95% confidence interval (CI) 1.40-3.29; P&lt; 0.001). Conclusions: Grade C PF adversely affects long-term survival of patients with pancreatic cancer undergoing pancreatectomy, although patients with grade B PF have similar prognosis with no fistula/grade A. Postoperative management to prevent grade C PF is important to improve prognosis in patients with pancreatic cancer undergoing pancreatectomy.
FOXO3a predicts for survival and its phosphorylated form is downregulated following mTOR or MEK inhibitor therapy in Hepatocellular Carcinoma
Authors: M. Teo, H. T. Huynh, S. W. Hee, Y. P. Phoon, R. Quek, P. Wang, H. C. Toh
Journal: Journal of Clinical Oncology (2007)

4538 Background: Hepatocellular carcinoma (HCC) is an aggressive cancer endemic in Asia with few effective treatments. We hypothesize that FOXO3a may be a potential prognostic marker in HCC and analyze the effects of targeted therapy acting on the PI3K/AKT pathway, of which FOXO3a is downstream. PI3K activates serine/threonine protein kinase AKT, causing FOXO3a phosphorylation and its nuclear translocation, promoting apoptosis. Tumor suppressor, promyelocytic leukemia (PML), inactivates nuclear phosphorylated AKT (pAKT). mTOR, also of the P13K/AKT pathway, is dysregulated in many cancers. PI3K is an effector of RAS, which controls downstream mitogen-activated protein kinase kinase/extracellular regulated kinase (MEK/ERK) pathway. AZD6244 is a selective inhibitor of MEK1/2. RAD001 (Everolimus) specifically inhibits mTOR. Avastin (bevacizumab) is an anti-angiogenic agent. These therapies have shown clinical efficacy in various cancers, including preliminary results with either RAD001 or avastin treatment in HCC. Method: We analyzed FOXO3a status in 91 stage I and II HCC patients using relative real-time PCR and immunoblotting analysis. Using a primary human HCC xenograft SCID mouse model, we examined tumor efficacy and molecular effects of AZD6244, RAD001 and Avastin treatment. Results: The median survival of the high FOXO3a-expressing group (2-fold increased expression vs normal, &gt;2.0, n=16) was 27 months versus 95 months for the low expressing group (2-fold decreased expression vs normal, &lt;0.5, n=58) (p=0.037). Pearson correlation analysis indicated a positive correlation between FOXO3a and PML (n=46, correlation=0.533, p&lt;0.001). Immunoblotting results for 8 random HCC samples reveal increased levels of pFOXO3a (Ser253) in all tumor tissue compared to adjacent normal. Treatment of HCC xenograft mice with AZD6244 or RAD001 caused significant tumor shrinkage and reduced levels of pAKT (Ser308) and pFOXO3a (Ser318). Avastin had cytostatic effects and unchanged levels of pFOXO3a (Ser318). Conclusion: FOXO3a predicts for overall survival in HCC. A positive correlation is established between FOXO3a and PML. AZD6244 and RAD001 can induce tumor regression via the AKT-FOXO3a pathway in HCC xenografts. No significant financial relationships to disclose.
The Treatment of Advanced Gastric Cancer: In Search of the Right Combination
Authors: Matthew H. Kulke
Journal: Journal of Clinical Oncology (2000)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.14.2645 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10894862 The Treatment of Advanced Gastric Cancer: In Search of the Right Combination Matthew H. Kulke, MDxMatthew H. KulkeSearch for articles by this author Show More Dana-Farber Cancer Institute, Boston, MA https://doi.org/10.1200/JCO.2000.18.14.2645 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Managing Chronic Kidney Disease in Older People
Authors: Steven Jay Rosansky
Journal: JAMA (2016)

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Pharmacokinetic and Pharmacodynamic Characterization of Graspa Versus Native L-Asparaginase in Combination with Cooprall Chemotherapy in a Phase 3 Randomized Trial for the Treatment of Patients with Relapsed Acute Lymphoblastic Leukemia (NCT01518517)
Authors: Xavier Thomas, Yves Bertrand, Andre Baruchel, Nicolas Blin, Emmanuelle Tavernier, Stephane Ducassou, Norbert Vey, Virginie Gandemer, Victoria Cacheux, Francoise Mazingue, Emmanuel Raffoux, Genevieve Plat, Jose Fernandes, Maryline Poiree, Luc Fornecker, Jean-Louis Stephan, Mathilde Hunault, Anne Auvrignon, Thibault Leguay, Stephane Lepretre, Alina Ferster, Isabelle Pellier, Emmanuel Plouvier, Claudine Schmitt, Cecile Bonin, Yann Godfrin, Iman El Hariry
Journal: Blood (2015)
Effects of enteral polymeric diet on gut microbiota in children with Crohn's disease
Authors: Chloé Guinet-Charpentier, Patricia Lepage, Alain Morali, Mathias Chamaillard, Laurent Peyrin-Biroulet
Journal: Gut (2016)

We read with great interest the article by Wu et al 1 showing that the impact of diet on the composition of the gut microbiota was milder than its impact on metabolites produced by the gut microbiota, in healthy humans. Enteral nutrition is an effective treatment to manage active Crohn's disease (CD) in children.2 CD is known to be associated with gut microbial dysbiosis that is characterised by decreased diversity and imbalances in the intestinal microbiome. Recent evidence indicates that exclusive enteral nutrition (EEN) may affect gut microbiota in children with CD,3 but it remains elusive whether the aforementioned changes may occur independently of disease flares. We thus studied the impact of either EEN with Modulen (EXCL-MOD) or partial enteral nutrition (PEN) with Modulen (MOD) IBD on the bacterial composition of the gut microbiota from children with CD during either remission or active phase.

In this single-centre, prospective, observational cohort study, 34 children followed at Nancy University Children Hospital …