tbuckley/cabot-search huggingface dataset:
Increased enzyme activity of indoleamine 2,3-dioxygenase (IDO) in tumor cells facilitates immune escape and leads to enhanced metastases
Authors: Irmgard Kronberger, Birgit Troster, Klaus Laimer, Dietmar Fuchs, Petra Obexer, Raimund Margreiter, Albert Amberger, Gerald Brandacher
Journal: Cancer Research (2007)

225  Purpose: Indoleamine 2,3-dioxygenase (IDO) is activated by IFN-γ and via local tryptophan depletion modulates T-cell function and promotes immune tolerance. IDO has been demonstrated to be critically involved in maternal tolerance and recent attention has turned towards its role in immune evasion of certain tumors. However, if IDO expression is involved in tumorigenesis and tumor growth control still remains controversial.  Material and Methods: Murine CT26 colon adenocarcinoma cells were transfected with the human IDO gene and stably expressing cells (CT26-IDO+ and CT26-vector control) were then injected subcutaneously into BALB/c mice. Macroscopic tumor growth was assessed after 12 days. Concentrations of kynurenine and tryptophan in culture supernatants and serum were analyzed by HPLC. Kynurenine to tryptophan ratio (kyn/trp) was calculated to estimate IDO-activity. IDO gene expression in cell lines and tumor tissue was assessed by quantitative PCR and Western blot analysis.  Results: CT26-IDO+ cells exhibit high IDO enzyme activity as determined by HPLC and expressed as the kynurenine to tryptophan ratio (μmol/mmol) after 24 hours. In vivo, IDO activity (kyn/trp) determined in serum of tumor bearing mice was significantly higher (75.25±10.21µmol/mmol) in animals with CT26-IDO+ tumors as compared to 37.29±7.85µmol/mmol in animals with IDO negative tumors. All mice developed clinically evident tumors after six days, as confirmed by histology. Tumor size of CT26-IDO+ tumors was significantly smaller than that of CT26 vector controls (136.2 ± 28.46 mm3 vs. 237.0 ± 63.02 mm3). However, only mice with CT26-IDO+ tumors developed peritoneal carcinosis, malignant aszites and distant metastases, whereas mice with CT26-IDO negative tumors showed locally restricted tumor growth.  Conclusion: This is the first preclinical model to demonstrate that IDO expression by colorectal tumor cells significantly contributes to disease progression, frequency of metastases and overall survival. Interfering with the IDO pathway by the use of IDO inhibitors might add a novel tool in the panel of cancer therapeutics and may enhance T cell-dependent antitumor immunitiy.
Psycho-oncological screening followed by risk adjusted psychological intervention in patients with newly diagnosed or relapsing cancer
Authors: Meinolf Karthaus, S Schulte-Martini, C Scherb, E Kuhlmann, N Pfeil, K Tagizadeh, M Trapp
Journal: Cancer Research (2007)

37  Breaking news in cancer patients often has to be supported by psychological help. Although this need itself is not new, it remains unclear who and how many patients really need this kind of supportive care, since patients may react in very different ways. Some patients show high risk profiles for anxious reactions or depressions after breaking bad news and should therefore be detected for interventions. Need for pycho-oncological intervention was screened with a simple 14-point item test (HADS). A scoring of  21 was assumed to describe high-risk patients. Pts considered to be at low risk, did not receive further psychotherapeutically intervention. Patients detected to be at medium or high risk received further psychological intervention and support. The aim of the trial was to evaluate efficacy of psychological support in patients being confronted with newly diagnosed cancer or relapse of cancer >1 year after a primary curative approach of their cancer disease. The trial was in accordance with local ethics.  Patients and Methods: We evaluated psycho-oncological interventions in tertiary cancer within a two year period (07/04 to 07/06). Out of a total of 611 cancer patients, 63 pts had a newly diagnosis of cancer or a relapse of >1 year since primary diagnosis or therapy and signed informed consent. Out of these, most pts had breast cancer (33%), colon cancer (33%) or ovarian-cancer (9.5%). Patients assumed to be at low risk had a mean score of 6,97 (SD 3.71) prior and 7,03 (SD4.97) after the end of cancer therapy. In this group of low risk pts there was no further psychological intervention. In pts detected with a medium risk (15-21) mean HADS score prior therapy was 16.63 (SD 1.38) and fell down during cancer treatment and supportive psychotherapeutically intervention to 13.58 post therapy (SD 6.16). Pts with the highest risk at diagnosis had a mean of 28.25 (SD 4.41) and decreased to a mean HADS of 16.83 (SD 4.84) at the end of cancer therapy while being under supportive psychotherapeutically care. Mean number of psychotherapeutic sessions were 3.86/patient with a mean duration of intervention time of 1.38 h.  Conclusion: Pts with a HADS   Supported by Carina Foundation
Acute myeloid leukemia induces protumoral p16INK4a-driven senescence in the bone marrow microenvironment
Authors: Amina M. Abdul-Aziz, Yu Sun, Charlotte Hellmich, Christopher R. Marlein, Jayna Mistry, Eoghan Forde, Rachel E. Piddock, Manar S. Shafat, Adam Morfakis, Tarang Mehta, Federica Di Palma, Iain Macaulay, Christopher J. Ingham, Anna Haestier, Angela Collins, Judith Campisi, Kristian M. Bowles, Stuart A. Rushworth
Journal: Blood (2018)
Abstract 17455: Impact of a Novel Protocol for Atrial Fibrillation Management for Outpatient Gastrointestinal Endoscopic Procedures
Authors: Joseph Longino, Ashish Chadda, Matthew Kalscheur, Anne Rikkers, Deepak Gopal, Jennifer Wright
Journal: Circulation (2017)

Introduction: Atrial fibrillation (AF) may result in procedure cancellations and emergency department (ED) referrals for patients presenting for outpatient GI endoscopic procedures. Such cancellati...
EXTH-25. DIANHYDROGALACTITOL (VAL-083) REDUCES GLIOBLASTOMA TUMOR GROWTH IN VIVO, UPON BEVACIZUMAB-INDUCED HYPOXIA
Authors: Anna Golebiewska, Anais Oudin, Anne Steino, Simone Niclou, Dennis Brown, Jeffrey Bacha
Journal: Neuro-Oncology (2018)

Standard-of-care for glioblastoma (GBM) includes surgery, radiation and temozolomide. Nearly all tumors recur and 5-year survival is less than 3%. Unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for temozolomide-resistance. Second-line treatment with bevacizumab has not only failed to improve survival, but has also been shown to induce intratumor hypoxia, which is implicated in increased chemoresistance. VAL-083 is a bi-functional DNA-targeting agent that readily crosses the blood-brain barrier. VAL-083 targets N7-guanine, causing DNA double-strand breaks and cancer cell-death in GBM cancer stem cells (CSCs) and non-CSCs, independent of MGMT. We have previously shown that bevacizumab treatment upregulates expression of glucose transporters GLUT-1/GLUT-3 on GBM cells. We hypothesized that, based on its unique monosaccharide backbone structure, VAL-083 may benefit from bevacizumab-induced GLUT transporter upregulation leading to enhanced VAL-083 uptake and anti-tumor activity. Methods: To investigate the in vivo anti-tumor effect of VAL-083+bevacizumab, we used a orthotopic patient-derived xenograft GBM model. All mice carried MGMT-unmethylated, temozolomide-resistant recurrent T16 GBM tumors as detected by MRI 35 days post-implantation. Mice were grouped into control, bevacizumab, VAL-083, and VAL-083+bevacizmab. Tumor progression was measured by MRI on days 49 and 56, and tumor growth rate was calculated for the entire study (day 35 vs. 56) and for the last 7 days (day 49 vs. 56). Results: Tumors were significantly smaller in VAL-083-treated mice both compared to control (-83%, p<0.001) and compared to bevacizumab-treated (-75%, p<0.001) mice. Additionally, analysis of tumor growth in-time showed significantly reduced tumor growth rate for VAL-083+bevacizumab compared to VAL-083 alone (p<0.01). Conclusions: These results show strong in vivo anti-tumor efficacy of VAL-083 against MGMT-unmethylated, temozolomide-resistant recurrent GBM. This effect was further augmented in combination with bevacizumab, providing rationale of clinical investigation in combination with bevacizumab in the treatment of GBM.
Moving Precision Oncology Forward Amid Myths and Misconceptions—Reply
Authors: John Marquart, Emerson Y. Chen, Vinay Prasad
Journal: JAMA Oncology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
EXTH-52. USE OF A PHOSPHOLIPID BINDING MARCKS MIMETIC FOR TARGETED KILLING OF GLIOBLASTOMA CELLS
Authors: Nicholas Eustace, Jason Warram, Hayley Widden, Joshua Anderson, Patricia Hicks, Rune Troelsgaard, William Placzek, Anita Hjelmeland, Yancey Gillespie, Christopher Willey
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) like most cancers harbors frequent mutations in phospholipid signaling that contributes to many of the hallmarks of cancer, including immune suppression from the externalization of phosphatidylserine (PS) in viable cells, to pro-growth, survival and invasive signaling resulting from mutations in phosphoinositide (PI) metabolizing enzymes like phosphoinositide 3-kinase p110α (PIK3CA). We evaluated the therapeutic potential of using a PS and phosphatidylinositol 4,5-bisphosphate (PIP2) binding peptide derived from Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) effector domain (ED) to suppress GBM growth. The conjugation of a cell penetrating trans-activator of transcription (TAT) sequence to MARCKS ED (TAT-ED) was found to have potent dose-dependent cytotoxicity to GBM patient-derived xenografts (PDX) at low micromolar doses, 20 times greater than the unconjugated ED peptide while remaining nontoxic to normal human astrocytes. A Cy7 labeled TAT-ED showed substantial punctate accumulations at the plasma membrane of GBM but only rarely on NHA’s. Quantification of the TAT-ED uptake using the Xcyto10 image cytometer showed TAT-ED accumulates to greater levels in the cytoplasm and nucleus of GBM, poorly penetrates into the nucleus of NHA’s, and revealed high levels of TAT-ED was associated with DNA hypoploidy. TAT-ED was equally cytotoxic to PDX neurospheres and adherent cells and found to trigger a rapid and sustained rise in intracellular calcium, with the appearance of a unique annexin V positive bleb, preceding a caspase-independent cell death and simultaneous annexin V positivity and membrane permeability. In vivo bio distribution studies revealed TAT-ED crosses the blood-brain barrier concentrating in the periventricular region of tumor naive mice or in intracranial tumors. Kinomic and mRNA pathway analysis suggests TAT-ED activates PKC, NRD2 and MAPK pathway, while inhibiting ephrin receptors and SRC family kinases. Overall, this study finds TAT-ED to have both selective and potent therapeutic effects against GBM.
Marine n−3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer
Authors: JoAnn E. Manson, Nancy R. Cook, I-Min Lee, William Christen, Shari S. Bassuk, Samia Mora, Heike Gibson, Christine M. Albert, David Gordon, Trisha Copeland, Denise D’Agostino, Georgina Friedenberg, Claire Ridge, Vadim Bubes, Edward L. Giovannucci, Walter C. Willett, Julie E. Buring
Journal: New England Journal of Medicine (2018)

Higher intake of marine n−3 (also called omega-3) fatty acids has been associated with reduced risks of cardiovascular disease and cancer in several observational studies. Whether supplementation with n−3 fatty acids has such effects in general populations at usual risk for these end points is unclear.
Further Lessons in Pneumocystis Pneumonia Prophylaxis—Reply
Authors: Jaclyn LoPiccolo, Seema A. Mehta, Evan J. Lipson
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
MNGI-14. LOSS OF HISTONE H3K27me3 IDENTIFIES A SUBSET OF MENINGIOMAS WITH INCREASED RISK OF RECURRENCE
Authors: Leah M Katz, Thomas Hielscher, Benjamin Liechty, Joshua Silverman, David Zagzag, Rajeev Sen, Peter Wu, John Golfinos, David Reuss, Marian Neidert, Hans-Georg Wirsching, Peter Baumgarten, Christel Herold-Mende, Wolfgang Wick, Patrick Harter, Michael Weller, Andreas von Deimling, Matija Snuderl, Chandra Sen, Felix Sahm
Journal: Neuro-Oncology (2018)

Epigenetic patterns on the level of DNA methylation have already shown to separate clinically relevant subgroups of meningiomas. Based on a reference set (Sahm et al., Lancet Oncol 2017), an epigenetic meningioma classifier employing DNA methylation patterns is made available through molecularneurpathology.org. We now set out to identify prognostic implications of epigenetic modification on the proteome level, particularly modifications of histones. First focus was on H3K27 trimethylation (H3K27me3). H3K27me3 was assessed by immunohistochemistry on 232 meningiomas. In 194 cases, trimethylation was detected in tumor cells. In 25 cases, staining was limited to vessels while all tumor cells were negative. Finally, 13 cases yielded equivocal staining patterns. Reduced abundance of H3K27me3 in cases with staining limited to vessels was confirmed by mass spectrometry on a subset of cases. Lack of staining for H3K27me3 in all tumor cells was significantly associated with more rapid progression (p=0.009). In line, H3K27me3 negative cases were associated with a DNA methylation pattern of the more aggressive types among the recently introduced DNA methylation groups. Also, NF2 and SUFU mutations were enriched among cases with lack of H3K27me3 in tumor cells (p<0.0001 and p=0.029, respectively). H3K27me3 staining pattern added significant prognostic insight in WHO grade II cases and in the compound subset of WHO grade I and II cases (p=0.04 and p=0.007, respectively). However, it did not further stratify within WHO grade III cases. Collectively, this data indicate that epigenetic modifications beyond DNA methylation are involved in the aggressiveness of meningioma. It also suggests that H3K27me3 immunohistochemistry might be a useful adjunct in meningioma diagnostics, particularly for cases with WHO grade II histology or at the borderline between WHO grade I and II. Ongoing studies evaluate the role of histone marks other than H3K27me3 and consequences on the proteomic composition of meningioma cells by high-throughput mass spectrometry.
Abstract 17900: Sarcomere Gene Mutations in Left Ventricular Noncompaction
Authors: Asami Takasaki, Yukiko Hata, Keiichi Hirono, Nakaoka Hideyuki, Keijiro Ibuki, Sayaka Ozawa, Naoki Yoshimura, Naoki Nishida, Fukiko Ichida
Journal: Circulation (2014)

Introduction: Left ventricular noncompaction (LVNC) is a primary cardiomyopathy with heterogeneous genetic origins, however, the genetic basis of disease in a large proportion of patients with LVNC is still unresolved. We evaluated the potential clinical impact of genetic analysis of sarcomere genes in patients with LVNC. Methods: We investigated 93 Japanese LVNC patients, including 23 familial cases, for mutations of genes encoded sarcomeric proteins including myosin binding protein C (MYBPC3), β-myosin heavy chain (MYH7), α-tropomyosin (TPM1), cardiac troponin T (TNNT2), α-cardiac actin (ACTC) and cardiac troponin I (TNNI3). Of these 49 were infants and 44 were juvenile cases. Results: We identified 28 sarcomeric gene mutations in 32 patients (34%) including 17 infants and 15 juvenile cases . These mutations were distributed among 5 genes, 12 in MYH7 and 9 in MYBPC3, 3 in TPM1, 2 in TNNT2, and 2 in ACTC1. Nineteen (68%) of the mutations were novel, affected conserved amino acid residues and were predict...
Abstract 11907: The Association of Life’s Simple 7 Health Metrics and Incident Non-Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis
Authors: Oluseye Ogunmoroti, Norrina B Allen, Erin D Michos, Tatjana Rundek, Jamal Rana, Ron Blankstein, Roger S Blumenthal, Mary Cushman, Michael J Blaha, Emir Veledar, Khurram Nasir
Journal: Circulation (2015)

Introduction: The American Heart Association (AHA) introduced the Life’s Simple 7 (LS7) health metrics to assess and promote cardiovascular health and wellness. Favorable LS7 status is associated with reduced risk of cardiovascular and all-cause mortality. We assessed the association between the LS7 health metrics and non-cardiovascular disease (non-CVD). Methods: 6,814 participants (mean age 62 ±10 years, females 53%) from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed for a median of 10.2 years. Each component of the LS7 metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood pressure and blood glucose) was categorized into 3 according to AHA criteria and assigned points, ideal (2), intermediate (1) and poor (0). The LS7 health index, created from the metrics, was categorized into 3 levels based on total number of points achieved, ideal (11-14), intermediate (9-10) and poor (0-8). Cox proportional hazard ratios and incidence rate per 1000 person-years were calculated for hospital ICD-9 diagnoses of cancer, chronic kidney disease (CKD), pneumonia, chronic obstructive pulmonary disease (COPD), dementia and hip fracture. Analyses were adjusted for age, race/ethnicity, and socioeconomic status. Results: Overall all non-CVD event rates were lower with improving LS7 health status (Figure 1). In multivariable adjusted models (Table 1), with the poor category of the LS7 health index as reference, individuals in the ideal category had a lower hazard for non-CVD events, 21% lower for cancer (95% CI 0.64-0.98), 62% lower for CKD (95% CI 0.27-0.53), 45% lower for pneumonia (95% CI 0.39-0.78) and 48% lower for COPD (95% CI 0.31-0.85). Conclusion: The LS7 health index may identify vulnerability for multiple chronic conditions beyond CVD. These results suggest the implications of achieving the AHA’s national goal of ideal LS7 health metrics are favorable, as it will reduce the burden of many diseases as well as health care costs.
Growth inhibition and chemo-sensitizing effects for 5-fluorouracil or irinotecan by cetuximab in human gastric and colon cancer cells
Authors: Kun-Huei Yeh, Shiou-Hwei Yeh, Joeu-Pei Wan, Chien-Shing Lin, Yee-Wah Chiang, Jui-Chueh Lin, Ying-Chun Shen, Ann-Lii Cheng
Journal: Cancer Research (2006)

1230  The decision for treating breast cancer patients with the anti-Her-2/neu monoclonal antibody Herceptin either as single agent or in conjunction with cytotoxic drugs is based upon the detection of Her-2/neu (erbB-2) gene amplification and/or overexpression. Using low Her-2/neu-expressing MCF-7 human breast cancer cells engineered to overexpress the growth factor Heregulin (HRG), a combinatorial ligand for the Her-2/-3/-4 network, the present study was performed to investigate whether: a) Ligand-induced transactivation of Her-2/neu can affect breast cancer cell sensitivity to chemotherapy and b) Herceptin treatment may trigger a Receptor-Enhanced Chemosensitivity (REC) effect when combined with chemotherapy in the absence of Her-2/neu overexpression. HRG-overexpressing MCF-7 cells were > 10 fold resistant to the alkylating agent cisplatin (CDDP), while Herceptin co-exposure completely reversed HRG-promoted CDDP resistance. The nature of the interaction between Herceptin and CDDP, as assessed by anchorage-dependent proliferation, soft-agar colony formation and apoptotic cell death assays, was found to be synergistic in HRG-overexpressing MCF-7 cells with antagonism occurring in matched control cells. This synergistic effect of Herceptin in HRG overexpressors also occurred with the taxane paclitaxel (PTX) and the vinca alkaloid vincristine (VCR), while additive interactions occurred with the fluoropyrimidine 5-Fluorouracil (5-FU). Herceptin treatment significantly prevented down-stream activation of the anti-apoptotic and proliferative transduction cascades PI-3’K ◊ AKT and MEK1/2 ◊ ERK1/2 MAPK, and efficiently inhibited HRG-induced hyper-Tyrosine (Tyr)-phosphorylation of Her-2/neu and Her-3 receptors as determined by immunoblotting and Phospho-Receptor Tyr-Kinase proteome arrays. Herceptin co-exposure was ineffective in enhancing chemotherapy efficacy against MCF-7 cells forced to overexpress a structural deletion mutant of HRG that is not secreted into the extracellular media. Therefore, Herceptin-induced REC, in the absence of Her-2/neu overexpression, appears to occur through the blockade of HRG autocrine actions on the Tyr-kinase activity of Her-2/neu and Her-3. These findings support the notion that a combined examination of HRG expression and/or activation status of Her-2/neu should define a much larger population of breast cancer patients for whom treatment with Herceptin in combination with chemotherapy will be more efficient, yet in the absence of Her-2/neu overexpression.
Neoadjuvant Crizotinib in Resectable Locally Advanced Non–Small Cell Lung Cancer with ALK Rearrangement
Authors: Chao Zhang, Shao-lei Li, Qiang Nie, Song Dong, Yang Shao, Xue-ning Yang, Yi-long Wu, Yue Yang, Wen-zhao Zhong
Journal: Journal of Thoracic Oncology (2018)