tbuckley/cabot-search huggingface dataset:
Responses in renal cell cancer patients in phase I clinical trials: Drug activity or spontaneous remissions? A systematic review
Authors: M. Garcia-Martin, X. Garcia Del Muro, A. Montes, F. Cardenal, J. R. Germa-Lluch
Journal: Journal of Clinical Oncology (2004)

6061 Background: Renal cell cancer shows a particular behavior. These tumors show great heterogeneity, from aggressive forms to indolent ones. Less than 1% can experience a spontaneous regression and it has been described that about 6% of cases may respond to placebo. It is quite frequent to include these patients in phase I chemotherapy trials, where responses are found in approximately 4% of cases and these responses are not predictive to efficacy in further phase III. Methods: 58 novel targeted drug phase I clinical trials were systematically reviewed, between 2001–2003 publications and ASCO abstracts, 20 of them testing antiangiogenic drugs, in order to know the preliminary activity of these compounds in renal cell cancer, in terms of response rate. Combinations with well-known active drugs were excluded. Results: We found 134 cases of renal cell cancer. There were 7 partial responses (5.0%); three of them in a study with SU11248 (TKI anti VEGF, PDGF, FT-1), testing the drug in 4 renal cancer cases. Excluding this study, only 4 partial responses were seen in 130 patients (3.0%). These responses were seen in one patient (pt) treated with the farnesyl transferasa inhibitor R115777, one with PTK787 (TKI anti VEGF, PDGF, FT-1), 1 pt TKI anti EGFR, OSI-774 and 1 pt BAY 43–9006 (anti Raf kinase). Considering only antiangiogenic studies, one response was seen in 20 studies which included 66 renal cancer patients (2%); 6.0% if we consider SU11248. Conclusion: Renal cell cancers present sporadic responses in several new drugs phase I clinical trials, with an exception, SU11248. No other drug shows the same degree of interesting activity. Responses seen with other drugs excluding SU11248 could not be attributed to drug activity. No significant financial relationships to disclose.
Evaluation of Cepheid Xpert® BCR-ABL Monitor Assay in Three Italian Reference Centers for Monitoring of BCR-ABL Transcript Levels in CML Patients
Authors: Maria Teresa Bochicchio, Barbara Izzo, Enrico Gottardi, Biagio De Angelis, Roberta Lorenzatti, Claudia Venturi, Francesca Crasto, Caterina De Benedittis, Filomena Daraio, Emanuela Ottaviani, Alessandro Volpengo, Giuseppe Saglio, Fabrizio Pane, Giovanni Martinelli
Journal: Blood (2014)
The Distinctive MicroRNA Signature of Acute Myeloid Leukemia with Translocation t(8;16)(p11;p13)/MYST3-CREBBP Is Responsible for RET Overexpression and Is Regulated by Epigenetic Mechanisms
Authors: Marina Díaz-Beyá, Alfons Navarro, Tania Díaz, Gerardo Ferrer, Rut Tejero, Mireia Camós, Montserrat Torrebadell, Marta Pratcorona, Maria Rozman, Mariano Monzó, Jordi Esteve
Journal: Blood (2011)
Abstract 3793: Overexpression of A20 and activated-Src result in TRAIL resistance in oral cancer cells
Authors: Satoshi Hino, Tomohiro Hamakawa, Koh-ichi Nakashiro, Hiroyuki Hamakawa
Journal: Cancer Research (2015)

Abstract The 5-year survival rate for oral cancer patients is around 50%, and has remained unchanged for the last several decades. This poor survival rate is due to the delay in diagnosis, the high incidence of recurrence, and the difficulty of controlling metastases. It is considered that the acquisition of resistance to anoikis and apoptosis is an essential event to successfully metastasize. We have to withdraw these resistance of cancer cells to improve the survival ratio. In this study, we have used oral squamous cell carcinoma cell lines with and without distinct metastatic ability, and revealed the relationship between their anoikis and apoptosis sensitivity and the metastatic ability. At first we examined their sensitivity to anoikis by using the low attachment culture condition. There was no apparent relation between their metastatic potential and the sensitivity to anoikis. SAS cells which have no metastatic potency showed modest sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), whereas SAS-T5 cells and SAS-L1 cells, a clone with high metastatic potential showed robust resistance. Fas ligand (Anti-Fas/CD95 monoclonal antibody) showed the similar effects for apoptosis induction as well as TRAIL, but TNF-α had no effect in these cells. We confirmed that the expression levels and the localization of TRAIL receptors were not correlated with TRAIL sensitivity. We found that the mechanisms underlying the differences in these resistance to TRAIL was an activity of Src kinase and the basal levels of A20. Phosphorylated Src (Tyr 416), the active form, was upregulated in SAS-T5 and SAS-L1 cells compared to parental SAS cells. Src inhibitor PP2 suppressed cell proliferation in response to dependence on Src signaling. Downregulation of Src or A20 with siRNA made metastatic cells dissolve the resistance to TRAIL-induced apoptosis. These results suggest that combination therapy with TRAIL and some drug inhibiting Src kinase and /or A20 expression may be a treatment strategy for oral squamous cell carcinoma. Citation Format: Satoshi Hino, Tomohiro Hamakawa, Koh-ichi Nakashiro, Hiroyuki Hamakawa. Overexpression of A20 and activated-Src result in TRAIL resistance in oral cancer cells. [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 3793. doi:10.1158/1538-7445.AM2015-3793
Baseline comprehensive geriatric assessment (CGA) and prediction of toxicity in elderly non-small cell lung cancer (NSCLC) patients receiving chemotherapy.
Authors: A. Karampeazis, L. Vamvakas, S. Agelaki, A. Xyrafas, A. G. Pallis, E. S. Saloustros, Z. Giannousi, K. Kalbakis, D. Mavroudis, V. Georgoulias
Journal: Journal of Clinical Oncology (2011)

e19656 Background: Nearly 50% of NSCLC patients (pts) are age 70 or over but only a few of them receive treatment. The results of CGA for elderly NSCLC cancer pts receiving chemotherapy were analyzed to investigate the correlation between each CGA domain and development of severe toxicity. Methods: A total of 131 NSCLC pts ≥ 65 years with stage IIIb/IV disease were treated with either monotherapy of vinorelbine (n=3) or docetaxel (n=1) or pemetrexed (n=28) or gemcitabine (n=31) or erlotinib (n=36) or the gemcitabine plus docetaxel combination (n=32). At baseline, CGA was performed using the following instruments: Cumulative Illness Rating Scale-Geriatrics (CIRS-G), Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Mini-Mental State Examination (MMSE) and Geriatric Depression Score (GDS-15). Toxicity was scored using NCI-CTC v2. Results: Median age was 74 years (range 65-92). Treatment was 1st-line for 51% of pts. Single-agent treatment was administered to 65% of pts and 28% of pts received erlotinib. Performance status was 0 in 27%, 1 in 56% and 2 in 17% of pts. Median (range) baseline CGA scores were as follows: ADL 6, IADL 7 (0-8), CIRS-G 3.0 (0-24), grade 3-4 CIRS-G 0 (0-3), MMSE 28 (16-30), GDS 5 (0-13). Overall, grade 3-4 neutropenia occurred in 4% of pts, grade 2-3 anemia in 20%, grade 3-4 thrombocytopenia in 1% and any non-hematologic grade 3-4 toxicity in 6% of pts. None of the CGA scores were significantly associated with the occurrence of severe toxicity. Conclusions: Baseline CGA does not predict severe toxicity in elderly NCSLC pts receiving chemotherapy. Correlations between CGA domains and toxicity (p values shown). Neutropenia grade 3-4 Anemia grade 2-3 Thrombocytopenia grade 3-4 Any nonhematologic grade 3-4 IADL 7-8 vs <7 0.851 0.045 0.430 0.724 MMSE <24 vs ≥24 0.261 0.783 0.200 0.201 GDS ≤5 vs >5 0.999 0.638 0.999 0.433 CIRS-G grade 3-4 0 vs ≥1 0.999 0.802 0.364 0.703
Abstract 3372: Molecular characteristics of cancer-associated adipocytes in breast cancer
Authors: Hyeong-Gon Moon, Jiwoo Lee, Han-Byoel Lee, Han Suk Ryu, Wonshik Han, Dong-Young Noh
Journal: Cancer Research (2015)

Abstract Adipose tissue in the tumor microenvironment is now regarded to be an active player in cancer development and progression. Recent studies have suggested critical roles of the cancer-associated adipocytes in breast cancer proliferation and invasion. However, unlike the well-known cancer-associated fibroblasts, the molecular profiles of cancer-associated adipocytes are largely unknown. We studied the histo-morphologic changes in adipose tissue adjacent to the breast cancer cells in human tissues. Adipocytes had smaller fat droplets and often associated with immune cell infiltration. We investigated the changes of mRNA expression profiles of differentiated adipocytes when they were cultured with breast cancer cells (MCF-7 and MDA-MB-231) by using the NIH-3T3-L1 cell line. Indirect coculture with cancer cells resulted in significantly altered expression of genes involved in immune response, extracellular matrix remodeling, angiogenesis, metabolism, and apoptosis. IL6 and its downstream genes, transcription factors such as RUNX1, as well as PTX3 and TIMP1 were most unregulated genes. Increased secretion of IL6 was further validated in the culture media by ELISA. Also, the gene expression data showed that adipocytes cocultured with cancer cells showed decreased adipocyte-differentiation genes suggesting the cells underwent de-differentiation process. Microscopic examination of co-cultured adipocytes showed smaller fat droplets similar to human specimens. The co-cultured adipocytes showed different effect on cancer cells according to the molecular subtypes of the breast cancer cells. The conditioned media from co-cultured adipocytes resulted in increased proliferation of ER+ breast cancer cells, suggesting a subtype-dependent effect of co-cultured adipocytes in breast cancer. Our results suggest that cancer-associated adipocytes show increased expression of genes involved in immune response, extracellular matrix remodeling, angiogenesis, metabolism, and apoptosis. Futhermore, these cancer-associated adipocytes show features toward the preadipocyte state suggesting the possibility of de-differentiation of adipocyte under the influence of adjacent cancer cells. The functional impact of the cancer-associated adipocyte seem to vary according to the molecular subtype of epithelial cancer cells. Citation Format: Hyeong-Gon Moon, Jiwoo Lee, Han-Byoel Lee, Han Suk Ryu, Wonshik Han, Dong-Young Noh. Molecular characteristics of cancer-associated adipocytes in breast cancer. [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 3372. doi:10.1158/1538-7445.AM2015-3372
MRD Monitoring Using Minor-BCR-ABL1 Genomic Breakpoint in Childhood ALL Identifies a Subgroup with Distinct Biology and a Very Poor Prognosis
Authors: Lenka Hovorkova, Marketa Zaliova, Nicola C Venn, Walter Muskovic, Jodie E Giles, Jana Linhartova, Katerina Machova Polakova, Peter J Shaw, Rosemary Sutton, Jan Stary, Jan Trka, Jan Zuna
Journal: Blood (2015)
547. Untranslated Region Optimization Increases Transgene mRNA and Protein Levels, Resulting in Enhanced Therapeutic Efficacy of AAV Vector Gene Transfer In Vivo for Crigler-Najjar Syndrome
Authors: Giuseppe Ronzitti, Giulia Bortolussi, Fanny Collaud, Severine Charles, Andres Muro, Federico Mingozzi
Journal: Molecular Therapy (2015)

Optimization of the transgene expression cassette for adeno-associated virus (AAV) vector-mediated gene therapy has been mainly focused on the design of efficient promoter/enhancers and on the optimization of the transgene codon usage. Addition of intron sequences to expression cassette of a given transgene has also been shown to be beneficial in terms of expression levels. In an effort to develop a liver gene transfer approach to treat Crigler-Najjar (CN) syndrome, an autosomal recessive disorder caused by mutations in the UDP-glucuronosyltransferase 1 isotype A1 (UGT1A1) gene and associated with toxic accumulation of unconjugated bilirubin in serum, we designed several UGT1A1 transgene expression cassettes and we packaged them into serotype 8 AAV vectors. We first performed the codon optimization of the UGT1A1 wildtype (w.t.) cDNA following two algorithms (v1 and v2), which led to cDNAs with nucleotide sequences significantly different from each other (nucleotide sequence homology of 77.5% for v1 and 78.3% for v2 vs. w.t.). Surprisingly, the sequence with a codon adaptation index closer to that of w.t. (w.t.=0.76, v1=0.76, v2=0.96) thus predicted to be the least efficient in terms of expression, showed the best performance in vitro in human hepatocyte cell lines, both at the RNA and protein levels. These results were confirmed in vivo in Ugt1a1-/- mice, a model of CN syndrome, where gene transfer with the optimized UGT1A1 resulted in better reduction of total bilirubin in serum. Next, we analyzed the 5' untranslated region (UTR) of the expression cassette for sequences that may affect the efficacy of the transgene expression levels. Aside from the introduction of an optimized Kozak consensus sequence, the human beta2-globin (hBB2) intron sequence associated with the promoter revealed the presence of out of frame and in frame ATG codons before the start site of the UGT1A1 transgene. Removal of these cryptic ATGs from the intron sequence enhanced transgene expression, which resulted in stable, long-term correction of the disease phenotype following in vivo gene transfer. This demonstrated that the intron sequence optimization increases mRNA and protein levels in vitro and enhance the efficacy of the vector in vivo. Similar analysis was conducted in other common promoter/intron combinations used in AAV vector gene transfer. In conclusion, our results provide evidence that the combination of a potent liver specific promoter, codon optimization, and optimized untranslated region elements allow for decreasing the therapeutic dose of AAV vectors.
Guidelines to Help Prevent Peanut Allergy
Authors: Megan A. Moreno
Journal: JAMA Pediatrics (2017)

Guidelines to Help Prevent Peanut AllergyThe number of children with peanut allergy has increased dramatically over the past 20 years.Parents may be particularly concerned about peanut allergy because most food-related serious allergic reactions, such as anaphylaxis, a severe allergic reaction that includes breathing difficulties as well as fatal allergic reactions, are associated with peanuts.
PWE-023 A prospective quasi-experimental pilot study comparing percutaneous tibial nerve stimulation and biofeedback treatment on slow transit and idiopathic constipation
Authors: Y M Wright, J Ramjeet, C T Speakman
Journal: Gut (2010)

<h3>Introduction</h3> This quasi experimental pilot study compared percutaneous tibial nerve stimulation (PTNS) with biofeedback treatment to see whether PTNS is more effective for slow transit constipation (STC) and idiopathic constipation. <h3>Methods</h3> Ten female participants, 3 with STC and 7 with idiopathic constipation were recruited from gastroenterology clinics, with a mean age of 42.5 years (SD=7.0) and the patients were randomly allocated into two groups: one group had standard treatment (biofeedback) and the second group had PTNS. The following measures were recorded at baseline and after treatment: Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL), Hospital Anxiety and Depression Scale questionnaire (HADS), diary cards (constipation symptoms), anorectal physiology tests and a shape study (% colonic transit markers) for STC participants. The psychological measures were PAC-QOL and HADS questionnaires, the physiology measures were rectal sensation and rest and squeeze pressures and the symptom measures were diary cards. Descriptive statistics and a Wilcoxon matched pairs test looked at the within group data at baseline and after treatment. A Mann–Whitney U test was used to test for differences in the mean between the 2 groups. <h3>Result</h3> There were no differences found between the 2 treatment groups for all the diary cards, PAC-QOL, HADS and physiology tests measures (p value &lt;0.05). The Wilcoxon test showed that there was a significant difference within group (p=0.05) between baseline and after treatment for the PTNS group for the total constipation score (PAC-QOL). <h3>Conclusion</h3> This study indicates that PTNS significantly improves the total constipation quality of life score for slow transit and idiopathic constipation. Recommendations include carrying out a larger sample multi centre study in the future to see if PTNS is efficacious at improving constipation symptoms compared to biofeedback.
The Prognosis of Karyotypic Subgroups in Pediatric Acute Myeloid Leukemia Depends on the Alterations of KIT, MLL and FLT3 Genes: A Report from Japanese Childhood AML Cooperative Study Group.
Authors: Akira Shimada, Tomohiko Taki, Ken Tabuchi, Ryoji Hanada, Akio Tawa, Masahiro Tsuchida, Keizo Horibe, Ichiro Tsukimoto, Yasuhide Hayashi
Journal: Blood (2006)
Long-Term Safety and Efficacy of Single Administration of a Fixed Dose Pegfilgrastim (Neulasta) in Inducing Neutrophil Count Recovery after ABVD Chemotherapy in Patients with Hodgkin Lymphoma.
Authors: Anas Younes, Luis Fayad, Jorge Romaguera, Barbara Pro, Andre Goy, Nam Dang, Michael Wang
Journal: Blood (2004)
High dietary glycemic load and glycemic index increase risk of cardiovascular disease : A population-based follow-up study
Authors: Joline W. Beulens, Leonie de Bruijne, Ronald P. Stolk, Petra H. Peeters, Michiel L. Bots, Diederick E. Grobbee, Yvonne T. van der Schouw
Journal: Circulation (2007)
Abstract 2216: A novel G-quadruplex formed in the proximal P1 promoter of bcl-2 gene is a gene suppressor
Authors: Buket Onel, Megan Carver, Danzhou Yang
Journal: Cancer Research (2015)

Abstract Deregulation of bcl-2, an anti-apoptotic protein, is associated with several human diseases such as tumorigenesis, neurodegeneration, and autoimmune deficiencies. DNA G-quadruplex secondary structures that form in the G-rich proximal promoter regions have been found to play an important role in gene transcriptional regulation. We discovered a novel GC-rich sequence in the immediate proximal P1 promoter of the bcl-2 gene (bcl2P1Pu29), which forms a thermodynamically stable, intramolecular G-quadruplex (bcl2P1G4) that represses bcl-2 gene transcription. Dimethyl sulfate footprinting studies indicated that this bcl2 P1 promoter G-rich region forms G-quadruplexes under physiologically relevant ionic conditions. This was shown by clear DMS protection of guanine N7, which is characteristic of G-quadruplex formation. NMR spectroscopic study of bcl2P1Pu29 showed the formation of a well-defined major G-quadruplex structure under physiologically relevant ionic conditions, as evident by sharp peaks in the imino proton region. Interestingly, NMR data also indicated the presence of Watson-Crick base-pairing, suggesting a potential unique loop conformation. Circular dichroism (CD) studies suggested that bcl2P1G4 adopts parallel-stranded folding. Both NMR and CD data indicated a monomeric structure of bcl2P1G4 with high thermo-stability. Using a luciferase assay, we have shown that TMPyP4, a planar cationic G-quadruplex-interactive compound, significantly inhibits the promoter activity through this G-rich bcl-2 P1 promoter region, while TMPyP2, a positional isomer of TMPyP4 which is a poor G-quadruplex-interactive compound, did not show a significant effect. Our results suggest that this novel intramolecular G-quadruplex formed in the bcl-2 proximal promoter region appears to be a suppressor of gene transcription, which could be a potential molecular target for small molecules to modulate bcl-2 gene transcription. Citation Format: Buket Onel, Megan Carver, Danzhou Yang. A novel G-quadruplex formed in the proximal P1 promoter of bcl-2 gene is a gene suppressor. [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 2216. doi:10.1158/1538-7445.AM2015-2216
Abstract 960: Deregulation of the Hippo pathway in soft tissue sarcoma promotes FOXM1 expression and tumorigenesis
Authors: T.S. Karin Eisinger, Vera Mucaj, Kevin Biju, Michael Nakazawa, Mercy Gohil, Timothy Cash, Sam Yoon, Nicolas Skuli, Kyung Min park, Sharon Gerecht, Celeste Simon
Journal: Cancer Research (2015)

Abstract The genetic aberrations responsible for soft tissue sarcoma formation in adults are largely unknown, and targeted therapies are sorely needed for this complex and heterogeneous family of diseases. Here we report that that the Hippo pathway is deregulated in many soft tissue sarcomas, resulting in elevated expression of the effector molecule YAP. Based on data gathered from human sarcoma patients, we concluded that more than 40% of human sarcomas have lost one or more copies of upstream HIPPO pathway regulators including SAV1, LATS2, and NF2. Loss of these molecules deactivates the HIPPO pathway, permitting uncontrolled proliferation and growth. Expression of active YAP is the direct result of this copy number loss and we have found YAP to be elevated in primary human fibrosarscomas, liposarcomas, and pleomorphic tumors. Pharmacologic inhibition of YAP significantly impaired primary sarcomagenesis in a murine allograft model. Using a novel autochthonous mouse model and mechanistic analyses in human and murine sarcoma cells, we determined that YAP-dependent expression of the transcription factor, FOXM1, is necessary for sarcoma cell proliferation and tumorigenesis. FOXM1 expression is elevated in multiple human soft tissue sarcoma subtypes. Notably, FOXM1 directly interacts with the YAP transcriptional complex via TEAD1, resulting in co-regulation of numerous critical pro-proliferation targets that enhance sarcoma progression. Finally, pharmacologic inhibition of FOXM1 decreases tumor size in vivo, making FOXM1 an attractive therapeutic target for the treatment of sarcomas. Citation Format: T.S. Karin Eisinger, Vera Mucaj, Kevin Biju, Michael Nakazawa, Mercy Gohil, Timothy Cash, Sam Yoon, Nicolas Skuli, Kyung Min park, Sharon Gerecht, Celeste Simon. Deregulation of the Hippo pathway in soft tissue sarcoma promotes FOXM1 expression and tumorigenesis. [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 960. doi:10.1158/1538-7445.AM2015-960
ADCC Induced By Monoclonal Anti-CD20 Antibodies in a 3D Follicular Lymphoma model : Signaling and Spatial Localization
Authors: Christine Bezombes, Emilie Decaup, Cedric Rossi, Pauline Gravelle, Camille Laurent, Ariel Savina, Jean-Jacques Fournié, Christian Klein
Journal: Blood (2014)