tbuckley/cabot-search huggingface dataset:
Autocrine VEGFR1 and VEGFR2 signaling promotes survival in human glioblastoma models in vitro and in vivo
Authors: Emese Szabo, Hannah Schneider, Katharina Seystahl, Elisabeth Jane Rushing, Frank Herting, K. Michael Weidner, Michael Weller
Journal: Neuro-Oncology (2016)

Although the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) system has become a prime target for antiangiogenic treatment, its biological role in glioblastoma beyond angiogenesis has remained controversial. Using neutralizing antibodies to VEGF or placental growth factor (PlGF) or the tyrosine kinase inhibitor, cediranib, or lentiviral gene silencing, we delineated autocrine signaling in glioma cell lines. The in vivo effects of VEGFR1 and VEGFR2 depletion were evaluated in orthotopic glioma xenograft models. VEGFR1 and VEGFR2 modulated glioma cell clonogenicity, viability, and invasiveness in vitro in an autocrine, cell–line-specific manner. VEGFR1 silencing promoted mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling, whereas VEGFR2 silencing resulted in cell-type dependent activation of the protein kinase B (PKB)/AKT and MAPK/ERK pathways. These responses may represent specific escape mechanisms from VEGFR inhibition. The survival of orthotopic glioma-bearing mice was prolonged upon VEGFR1 silencing in the LNT-229, LN-308, and U87MG models and upon VEGFR2 silencing in LN-308 and U87MG. Disruption of VEGFR1 and VEGFR2 signaling was associated with decreased tumor size, increased tumor necrosis, or loss of matrix metalloproteinase 9 (MMP9) immunoreactivity. Neutralizing VEGF and PlGF by specific antibodies was superior to either antibody treatment alone in the VEGFR1-dependent LNT-229 model. Differential dependence on autocrine signaling through VEGFR1 and VEGFR2 suggests a need for biomarker–stratified VEGF(R)-based therapeutic approaches to glioblastoma.
Effect of Dietary Alfalfa, Pectin, and Wheat Bran on Azoxymethane- or Methylnitrosourea-Induced Colon Carcinogenesis in F344 Rats&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: K Watanabe, B S Reddy, J H Weisburger, D Kritchevsky
Journal: JNCI Journal of the National Cancer Institute (1979)

The effect of dietary alfalfa, pectin, and wheat bran on colon carcinogenesis was studied in female inbred F344 rats. Weanling rats were fed semipurified diets containing 0 or 15% alfalfa, pectin, or wheat bran. At 7 weeks of age, all animals except controls were given azoxymethane (AOM) sc at a dose rate of 8 mg/kg body weight/week for 10 weeks or methylnitrosourea (MNU) intrarectally at a dose rate of 2 mg/rat twice a week for 3 weeks. The AOM-treated group was autopsied 40 weeks and the MNU-treated group 30 weeks after the first injection of the carcinogen. No tumors were observed in the colon or other organs of untreated rats fed the various diets. The animals fed the alfalfa diet and treated with MNU had a higher incidence of colon tumors than did those fed the control diet or the diets containing pectin or wheat bran. The incidence of MNU-induced colon tumors did not differ between the animals fed the control diet or the diets containing pectin or wheat bran. However, the incidence of AOM-induced colon tumors in rats fed diets containing pectin or wheat bran was lower than that in rats fed the control diet or the alfalfa diet. These results thus indicate that the effect of fiber in colon carcinogenesis depends on the type of fiber and, possibly, the fiber's mode of action.
Analysis of a phase I pharmacokinetic (PK)/food effect study of AT-101 in patients with advanced solid tumors
Authors: H. C. Pitot, D. Mould, J. Maleski, L. Leopold
Journal: Journal of Clinical Oncology (2009)

2557 Background: AT-101 is an oral, pan-Bcl-2 inhibitor (Bcl-2, Bcl-XL, Bcl-W, Mcl-1). Overexpression of Bcl-2 family proteins is common in human cancers. AT-101 activity as a single agent as well as in combination with docetaxel has been reported. The ongoing Phase 1 study of AT-101 as a single agent was expanded to include a cohort of patients to determine the PK of AT-101 in fed and fasted states. Methods: Twelve patients (pts) were enrolled and randomized into cohorts of six pts each. Cohort A received AT-101 (80 mg) orally on day 1 on an empty stomach (fasted) and again on day 8 with a high fat high calorie breakfast (fed), per FDA guidelines. Cohort B received AT-101 on day 1 fed and on day 8 fasted. Preliminary plasma concentration time data for AT-101 from 10 patients administered 80 mg orally were evaluated using noncompartmental analysis. Log transformed peak concentration (C max ) and exposure (AUC) were compared the between fed and fasted groups with the fasted group as the reference treatment. Results: Preliminary PK results from the first 10 pts are shown in the Table. For AUC and C max , the effect of food resulted in an approximately 42% and 5% increase, respectively. However the confidence intervals were not wholly outside the 80–125% intervals. Conclusions: These data indicate that food may increase AT-101 exposure in terms of AUC and C max . Updated results from all 12 pts will be presented at the meeting. Based on our preliminary results, it is recommended that AT-101 be taken at least an hour (or more) before or after food. [Table: see text] [Table: see text]
ATPS-52A PRE-CLINICAL COMBINATORIAL STRATEGY TO TARGET THE JAK/STAT AND EGFR PATHWAYS IN GBM
Authors: H. Artee Luchman, Katharine Jensen, Jiqing Zhang, Samuel Weiss
Journal: Neuro-Oncology (2015)

Glioblastoma multiforme (GBM), characterized by an aggressive clinical course, therapeutic resistance and striking molecular heterogeneity, remains incurable. A large number GBMs have EGFR alterations and, despite poor clinical translation to date, EGFR inhibition remains of therapeutic relevance. Recent evidence, from our group and others, indicates that JAK2/STAT3 pathway is an important mediator of tumor cell survival, growth, and invasion in GBM. Interestingly, EGFR inhibition leads to activation of survival-signalling pathways such as STAT3, diminishing effectiveness of EGFR inhibition. We investigated the efficacy of a novel JAK2 inhibitor, pacritinib, in brain tumour initiating cell (BTIC) lines to evaluate potential use in the treatment of GBM patients. In a Phase III study of patients with myelofibrosis, pacritinib demonstrated manageable toxicity and clinically and statistically improved patient spleen volume and patient reported outcomes. Pacritinib results in on-target JAK2/STAT3 inhibition at 1-2 µM and dramatically reduces BTIC proliferation, regardless of endogenous MGMT promoter methylation or EGFR, PTEN, and TP53 mutational status. Pacritinib in combination with temozolomide prolongs survival, over either drug alone, in orthopically xenografted NOD-SCID. We are testing the hypothesis that concurrent inhibition of JAK/STAT and EGFR signalling may be an effective, clinically relevant therapeutic, strategy for GBM. We examined the in vitro actions of pacritinib on BTICs, in combination with three clinically approved EGFR inhibitors, erlotinib, afatinib and lapatinib and are investigating other clinically relevant EGFR inhibitors for GBM. Combinatorial treatment with pacritinib and EGFR inhibitors shows striking responses, with lowered IC50s and BTIC viability. The combinatorial actions of EGFR and STAT3 inhibition were particularly effective in BTIC lines with EGFR activating vIII and missense point mutations. On target activity was demonstrated with reduced phospho-EGFR, phospho-STAT3 and effectors of both pathways. Current studies are aimed at investigating the combined actions of Pacritinib and EGFR inhibitors, over single agents, in orthotopic xenograft animal survival.
Commonly Measured Clinical Variables Are Not Associated With Burden of Complications in Long-standing Type 1 Diabetes: Results From the Canadian Study of Longevity in Diabetes
Authors: Alanna Weisman, Randy Rovinski, Mohammed A. Farooqi, Leif E. Lovblom, Elise M. Halpern, Genevieve Boulet, Devrim Eldelekli, Hillary A. Keenan, Michael H. Brent, Narinder Paul, Vera Bril, David Z. Cherney, Bruce A. Perkins
Journal: Diabetes Care (2016)

Twenty-five percent of individuals with long-standing type 1 diabetes (T1D) are resistant to complications, and this is not entirely explained by superior glycemic control (1–4). Although associations between clinical variables and individual complications have been comprehensively examined (1–4), analysis of total complication burden may detect previously unrecognized associations.

The Canadian Study of Longevity in Diabetes actively recruited 325 individuals who had T1D for 50 or more years (5). Subjects completed a questionnaire, and recent laboratory tests and eye reports were provided by primary care physicians and eye specialists, respectively.

Nephropathy was defined by an albumin-to-creatinine ratio of >2 mg/mmol for participants on an ACE inhibitor or angiotensin receptor blocker (ARB) or >3.4 mg/mmol for participants not on an ACE inhibitor or ARB. Symptomatic neuropathy was defined by a score ≥3 on the Michigan Neuropathy Screening Instrument (MNSI) questionnaire component. Retinopathy was defined by documentation of nonproliferative or proliferative retinopathy in the eye specialist report. Coronary artery disease was defined by self-reported …
A Randomized Phase II Trial of Three Novel Regimens for Relapsed/ Refractory Acute Myeloid Leukemia (AML) Demonstrates Encouraging Results with a Flavopiridol-Based Regimen: Results of Eastern Cooperative Oncology Group (ECOG) Trial E1906
Authors: Mark R. Litzow, Xin Victoria Wang, Martin P. Carroll, Judith E. Karp, Rhett Ketterling, Scott H. Kaufmann, Hillard M. Lazarus, Selina M. Luger, Elisabeth M. Paietta, Jacob M. Rowe, Jessica K Altman, Keith W Pratz, E. Randolph Broun, Martin S. Tallman
Journal: Blood (2014)
Correlation Between Concanavalin A Agglutinability and Cytotoxic Sensitivity to Antiserum Against Tumor-Associated Antigen in Rat Fibrosarcoma Cells
Authors: Tetsuya Moriuchi, Eiki Gotohda, Takao Kodama, Masuo Hosokawa, Hiroshi Kobayashi
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Correlation Between Concanavalin A Agglutinability and Cytotoxic Sensitivity to Antiserum Against Tumor-Associated Antigen in Rat Fibrosarcoma Cells Get access Tetsuya Moriuchi, Tetsuya Moriuchi 2Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Sapporo, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Eiki Gotohda, Eiki Gotohda 2Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Sapporo, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Takao Kodama, Takao Kodama 2Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Sapporo, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Masuo Hosokawa, Masuo Hosokawa 2Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Sapporo, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Hiroshi Kobayashi Hiroshi Kobayashi 2Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Sapporo, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 62, Issue 3, March 1979, Pages 579–583, https://doi.org/10.1093/jnci/62.3.579 Published: 01 March 1979 Article history Received: 18 April 1978 Accepted: 14 September 1978 Published: 01 March 1979
Can we really treat patients older than age 70 with a chemotherapy doublet for non-small cell lung cancer (NSCLC)?
Authors: M. G. Zauderer, C. S. Sima, B. Korc-Grodzicki, M. G. Kris, L. M. Krug
Journal: Journal of Clinical Oncology (2011)

7546 Background: A recent randomized trial showed that patients over 70 years old with advanced lung cancer achieved superior survival with platinum doublet therapy compared to single-agent therapy (Quoix et al., ASCO 2010). However, not all elderly can tolerate this treatment. We need metrics to identify appropriate patients for doublet chemotherapy. A cancer-specific geriatric assessment (CGA) is in development (Hurria et al., ASCO 2010) but is not yet disease, stage, or regimen specific. We retrospectively evaluated the toxicities and outcomes of elderly patients with metastatic NSCLC to help refine the CGA for further prospective study in lung cancer. Methods: We reviewed records for 70 consecutive patients age 70 or older with metastatic NSCLC treated at our center from 1/2008 through 12/2009 with first-line cytotoxic chemotherapy. Results: Patient characteristics: median age 75 (range 70-92); median Karnofsky performance status (KPS) 80% (range 60-90%); median albumin 3.6 (range 2.1-4.7, 39%<3.5); dependent in activities of daily living (ADLs) 6% and instrumental ADLs (iADLs) 9%. Treatment: 80% doublet therapy (64% platinum doublet); 40% completed 4 cycles without dose reduction. Toxicity: 44% hospitalized; 6% grade 4 hematologic toxicity; 39% grade 3/4 non-hematologic toxicity. KPS was not associated with toxicity or hospitalization. Albumin <3.5 was associated with grade 3/4 hematologic toxicity (p=0.02). Dependence in ADLs and iADLS as well as albumin <3.5 were associated with shorter survival (p<0.001, p=0.02, p=0.02). Doublet therapy had a higher risk of hospitalization (p=0.02) while platinum doublets had improved median survival (11 vs 8 months, p=0.005), but this is confounded by patient selection. Conclusions: Many in this cohort experienced significant toxicity and 44% required hospitalization. Yet, others tolerated therapy well and possibly derived benefit from platinum treatment. Physician assessment of KPS was not predictive of treatment tolerance. Therefore, we plan to prospectively assess a version of the CGA including factors such as albumin, ADL/iADL dependence, and “get up and go” functional status to identify who will best tolerate doublet chemotherapy.
Exome sequencing reveals recurrent germ line variants in patients with familial Waldenström macroglobulinemia
Authors: Aldo M. Roccaro, Antonio Sacco, Jiantao Shi, Marco Chiarini, Adriana Perilla-Glen, Salomon Manier, Siobhan Glavey, Yosra Aljawai, Yuji Mishima, Yawara Kawano, Michele Moschetta, Mick Correll, Ma. Reina Improgo, Jennifer R. Brown, Luisa Imberti, Giuseppe Rossi, Jorge J. Castillo, Steven P. Treon, Matthew L. Freedman, Eliezer M. Van Allen, Winston Hide, Elaine Hiller, Irene Rainville, Irene M. Ghobrial
Journal: Blood (2016)
A comparison of traditional and symptom-checklist-based histories
Authors: C E Climent, R Plutchik, H Estrada, L F Gaviria, W Arévalo
Journal: American Journal of Psychiatry (1975)

The authors compared the results of independent evaluations of 96 patients, each of whom was given a traditional psychiatric interview, resulting in a narrative report, and a structured interview based on a self-report questionnaire, resulting in a standardized report. Although the latter method produced a higher frequency of report of all symptoms, the overall accuracy of diagnoses was similar for the two methods. The authors enumerate the potential benefits of the use of standardized histories.
A novel Rab27a mutation binds melanophilin, but not Munc13-4, causing immunodeficiency without albinism
Authors: Petra Netter, Sanny K. Chan, Pinaki P. Banerjee, Linda Monaco-Shawver, Lenora M. Noroski, Imelda C. Hanson, Lisa R. Forbes, Emily M. Mace, Javier Chinen, H. Bobby Gaspar, Patrick Sleiman, Hakon Hakonarson, Christoph Klein, Mohammad S. Ehlayel, Jordan S. Orange
Journal: Journal of Allergy and Clinical Immunology (2016)
Abstract 3807: Capsazepine attenuates JAK/STAT3 signaling pathway, proliferation, survival of prostate carcinoma DU145 cells through induction of the protein tyrosine phosphatase epsilon (PTP-epsilon)
Authors: Jong Hyun Lee, Chulwon Kim, Seok-Geun Lee, Junhee Lee, Jung-woo Lee, Kwang Seok Ahn
Journal: Cancer Research (2015)

Abstract Constitutive activation of signal transducers and activators of transcription (STAT) 3 is a major distinguishing feature of various human cancer cells and its activation leads to survival, proliferation, and metastasis of tumor cells. Whether the anti-proliferative, pro-apoptotic, and anti-invasive effects of capsazepine (Capz), a synthetic analog of capsaicin, are linked to its capability to inhibit STAT3 activation was investigated. We found that Capz suppressed both constitutive and IL-6-inducible STAT3 activation in human prostate carcinoma cells. Capz also suppressed nuclear translocation and DNA binding activity of STAT3. The suppression was mediated through the inhibition of activation of the upstream kinases JAK1/2 and c-Src. Treatment with the protein tyrosine phosphatase (PTP) inhibitor pervanadate treatment reversed the Capz-induced down-regulation of STAT3, thereby suggesting the involvement of a PTP. Capz induced the expression of PTPϵ protein and mRNA. Moreover, knockdown of PTPϵ by small interfering RNA suppressed the induction of PTPϵ, reversed the inhibition of STAT3 activation, suggesting the critical role of PTPϵ in its possible mechanism of action. Capz downregulated the expression of STAT3-regulated proliferative, antiapoptotic, angiogenetic, and metastatic gene products; and this correlated with suppression of cell proliferation and invasion, the accumulation of cells in sub-G1 phase of cell cycle, and induction of apoptosis. Overexpression of phosphorylated STAT3 led to the attenuation of Capz-mediated cleavage of PARP as compared to the control. Thus, overall, our results suggest that Capz is a novel inhibitor of STAT3 activation and thus may have a potential in negative regulation of growth, metastasis, and angiogenesis of tumor cells. Citation Format: Jong Hyun Lee, Chulwon Kim, Seok-Geun Lee, Junhee Lee, Jung-woo Lee, Kwang Seok Ahn. Capsazepine attenuates JAK/STAT3 signaling pathway, proliferation, survival of prostate carcinoma DU145 cells through induction of the protein tyrosine phosphatase epsilon (PTP-epsilon). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3807. doi:10.1158/1538-7445.AM2015-3807
Chronic Pain Management in Cancer Survivors
Authors: Natalie Moryl, Nessa Coyle, Samuel Essandoh, Paul Glare
Journal: Journal of the National Comprehensive Cancer Network (2010)

The problem of pain in cancer survivors is attracting increased attention. Although comprehensive information about the prevalence of persistent pain in the cancer survivor population is currently lacking, it is known to depend on the type of cancer, comorbid conditions, and the initial pain management. Epidemiologic studies generally categorize pain in patients with cancer as either pain directly caused by the neoplastic process or related phenomena, pain occurring as a complication of anticancer treatment, or pain unrelated to the neoplastic process, caused by debility or concurrent disorders. This article focuses on pain syndromes in cancer survivors and the safe use of opioid therapy in this population when its ongoing use is part of the pain management plan. The use of physical therapy, rehabilitation therapy, and cognitive behavioral therapy, which are all extremely important aspects of pain management in the cancer survivor, are briefly mentioned.
Gastrin Protection Against Chemically Induced Gastric Adenocarcinomas in Wistar Rats: Histopathology of the Glandular Stomach and Incidence of Gastric Adenocarcinoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Masaharu Tatsuta, M.D., Hisako Yamamura, B.S., Haruo Taniguchi, M.D., Hiroshi Tamura, M.D.
Journal: JNCI Journal of the National Cancer Institute (1982)

The effects of gastrin on the histopathology of the glandular stomach and on the incidence of gastric carcinoma induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in inbred Wistar (W) rats. Prolonged administration of gastrin after treatment with MNNG significantly reduced the incidence of adenocarcinomas of the glandular stomach. In addition, atypical glandular proliferations were significantly less frequent and were smaller, and the incidence of marked mucosal atrophy was significantly reduced in both the antral and oxyntic gland mucosae. Both atypical glandular hyperplasia and mucosal atrophy are precursors of gastric cancers; prolonged administration of gastrin to rats after treatment with MNNG suppressed development of precursors of gastric cancer and so prevented development of gastric cancers.
John Alexander-Williams
Authors: M. Alexander-Williams
Journal: BMJ (2015)

John Alexander-Williams gained his reputation as world class surgeon and was highly respected as a leading authority on diseases of the gut. His masterly ability in the operating theatre and his brilliance as an orator and teacher led to numerous appointments as visiting professor in academic departments of surgery throughout the world. He delivered scores of lectures and scientific presentations. Junior surgeons and research fellows from around the world flocked to work with him in the Department of Surgery at Birmingham General Hospital.

Alexander-Williams w as attracted to any aspect of disease connected to the gastrointestinal tract. He was part of the team of researchers who initially linked the bacterium Clostridium difficile to a life threatening infection of the large bowel.

He gained respect not only for his …
Demonstration and Immunochemical Characterization of Carcinoembryonic Antigen in Human Pancreatic Juice 2 3
Authors: R. P. McCabe, H. Z. Kupchik, C. A. Saravis, S. A. Broitman, J. A. Gregg, N. Zamcheck
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Demonstration and Immunochemical Characterization of Carcinoembryonic Antigen in Human Pancreatic Juice Get access R. P. McCabe, R. P. McCabe Search for other works by this author on: Oxford Academic PubMed Google Scholar H. Z. Kupchik, H. Z. Kupchik Search for other works by this author on: Oxford Academic PubMed Google Scholar C. A. Saravis, C. A. Saravis Search for other works by this author on: Oxford Academic PubMed Google Scholar S. A. Broitman, S. A. Broitman Search for other works by this author on: Oxford Academic PubMed Google Scholar J. A. Gregg, J. A. Gregg Search for other works by this author on: Oxford Academic PubMed Google Scholar N. Zamcheck N. Zamcheck Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 5, May 1976, Pages 885–889, https://doi.org/10.1093/jnci/56.5.885 Published: 01 May 1976 Article history Received: 27 May 1975 Accepted: 25 November 1975 Published: 01 May 1976
Differential inhibitory noradrenergic responses to clonidine in 25 depressed patients and 25 normal control subjects
Authors: L J Siever, T W Uhde, D C Jimerson, C R Lake, E R Silberman, R M Post, D L Murphy
Journal: American Journal of Psychiatry (1984)

The authors measured plasma 3-methoxy-4-hydroxyphenylglycol (MHPG), plasma norepinephrine, blood pressure, and heart rate responses to the alpha 2-adrenergic agonist clonidine in 25 depressed patients and 25 normal control subjects. In the control subjects clonidine reduced plasma norepinephrine, blood pressure, and heart rate significantly more than placebo. In the depressed patients clonidine reduced blood pressure and the percent fall in plasma norepinephrine but not plasma MHPG or heart rate significantly more than placebo. The absolute and percent reductions in plasma MHPG and heart rate following clonidine were significantly less than in control subjects. These results raise the possibility that the sensitivity of the alpha 2-adrenergic receptors inhibitory to noradrenergic output may be reduced in depression.