tbuckley/cabot-search huggingface dataset:
Pregabalin (PGB) in treatment of oxaliplatin-induced neuropathy
Authors: I. Isufi, E. James, K. Keley, J. Peccerillo, M. W. Saif
Journal: Journal of Clinical Oncology (2009)

e15045 Background: Oxaliplatin is effective in many GI cancers, especially colorectal cancer (CRC); however, severe neuropathy develops frequently. PGB is a new antiepileptic drug approved as adjunctive therapy of partial seizures in adults, pain from diabetic neuropathy and post-herpetic neuralgia. PGB is structurally related to gabapentin, but unlike gabapentin, it is well absorbed (&gt; 90%) and its absorption is dose independent. In this study, we evaluated the role of PGB in reduction of oxaliplatin- induced neuropathy. Methods: From Nov 2006 to Dec 2008, a total of 23 pts (age range: 50–71 yrs; M:F = 14:9) with GI cancers were treated with PGB upon development of oxaliplatin-induced neuropathy &gt; G2 (NCI-CTC 3.0). Of these pts, 15 received FOLFOX for CRC, 2 EOX for gastric ca and 6 GemOx for pancreatic ca. Neurologic symptoms were evaluated prior PGB and then q 2 wks. PGB was started at 50mg PO tid, and if tolerated, dose was escalated by 50mg increments until symptoms improved up to a maximum of 150mg PO tid. Results: 5/23 pts (22%) were escalated to 150mg PO tid. 12 pts (52%) were escalated to 100mg tid, out of which 7 (58%) continued, 4 (33%) stopped due to no benefit and 1 (8%) stopped due to weight gain. 1/23 (4%) decided to follow 100mg bid. 5/23 (22%) could not be escalated above 50mg tid; 2 continued at this dose and 3 stopped due to CNS side effects. Onset of benefit was observed in 2 - 6 wks. In 3/23 pts (13%), neuropathy improved from G3 to G2, 2/23 (9%) from G3 to G1, 5/23 (22%) from G2 to G1, 6/23 (26%) remained stable at G2 and no pts remained at G3. Most pts continued PGB even beyond disease progression on oxaliplatin (15/23). Among those who continued (15), duration of therapy was 4 -24 months. The best benefit with PGB was seen at a dose of 150mg tid, followed by 100mg tid. The most common non-hematologic toxicities were dizziness (57%), headache (26%), somnolence (22%), dry mouth (17%), ataxia (17%), tremor (13%), peripheral edema (13%), weight gain (13%), blurred vision (13%) and constipation (9%). Hematologic toxicity (G1 thrombocytopenia) was seen in 1 pt (4%) but impact of chemotherapy could not be excluded. Conclusions: PGB significantly reduces the severity of oxaliplatin-induced neuropathy. Larger, placebo-controlled trials assessing safety and efficacy of oral PGB are warranted in pts treated with oxaliplatin. [Table: see text]
The discontinuity theory of immunity
Authors: Thomas Pradeu, Eric Vivier
Journal: Science Immunology (2016)

Some biological systems detect the rate of change in a stimulus rather than the stimulus itself only. We suggest that the immune system works in this way. According to the discontinuity theory of immunity, the immune system responds to sudden changes in antigenic stimulation and is rendered tolerant by slow or continuous stimulation. This basic principle, which is supported by recent data on immune checkpoints in viral infections, cancers, and allergies, can be seen as a unifying framework for diverse immune responses.
Abstract 4058: DNA damage and tumour burden in mouse colon is increased in response to carcinogen exposure after induction of chronic inflammation - a more disease relevant model of colitis-associated colorectal cancer
Authors: Tamsin RM Lannagan, Mark T. Mano, Richard J. Head, Trevor Lockett, Matthias Ernst, Leah J. Cosgrove
Journal: Cancer Research (2016)

Abstract Chronic inflammation (CI) such as inflammatory bowel disease increases the risk of developing colorectal cancer (CRC). Tumorigenesis is supported by inflammatory cytokines through increased cell proliferation and inhibiting apoptosis of neoplastic cells. The classic mouse model of colitis-associated CRC (CA-CRC) requires treatment with a mutagen (azoxymethane, AOM) followed by induction of inflammation through ingestion of a luminal irritant (dextran sulfate sodium, DSS). AOM is metabolized by colonic epithelium causing DNA damage through formation of mutagenic DNA adducts. Although the AOM + DSS model of CA-CRC is a valuable research model, it “reverses” events that take place in humans where CI typically precedes CRC. We hypothesise that CI sensitises colonic epithelium to DNA damage and predisposes the epithelium to neoplastic transformation. In order to investigate this we reversed the AOM + DSS model to more accurately represent the disease process in humans. Using two experimental approaches we treated wildtype (WT) mice with AOM alone or with DSS then AOM and collected colonic tissue after 6 and 48 hours (short-term) or colonic tumours (long-term). Tumour number and size were quantified. Immunohistochemistry was used to analyse DNA damage, apoptosis, and proliferation. Formation of the DNA adduct O6MeG was measured by a modified method of HPLC, and qPCR was used to analyse expression of DNA damage signalling pathway components. Compared with an AOM challenge alone, prior CI induction by DSS treatment increased DNA damage, reduced apoptosis, and increased tumour number and tumour size. This data reveals how prior CI modulates the colonic epithelial response to mutagen exposure in the short-term and how it promotes tumour formation in the long-term. In addition, this data demonstrates that the “reverse” model of CA-CRC can be successfully used as a more appropriate experimental framework to better understand the molecular mechanisms underpinning CA-CRC and will allow us to further investigate the relationship between prior CI, DNA damage, and tumour development. Citation Format: Tamsin RM Lannagan, Mark T. Mano, Richard J. Head, Trevor Lockett, Matthias Ernst, Leah J. Cosgrove. DNA damage and tumour burden in mouse colon is increased in response to carcinogen exposure after induction of chronic inflammation - a more disease relevant model of colitis-associated colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4058.
Beneficial and Adverse Effects of an LXR Agonist on Human Lipid and Lipoprotein Metabolism and Circulating Neutrophils
Authors: Todd G. Kirchgessner, Paul Sleph, Jacek Ostrowski, John Lupisella, Carol S. Ryan, Xiaoqin Liu, Gayani Fernando, Denise Grimm, Petia Shipkova, Rongan Zhang, Ricardo Garcia, Jun Zhu, Aiqing He, Harold Malone, Richard Martin, Kamelia Behnia, Zhaoqing Wang, Yu Chen Barrett, Robert J. Garmise, Long Yuan, Jane Zhang, Mohit D. Gandhi, Philip Wastall, Tong Li, Shuyan Du, Lisa Salvador, Raju Mohan, Glenn H. Cantor, Ellen Kick, John Lee, Robert J.A. Frost
Journal: Cell Metabolism (2016)
Maternal Obesity Affects Sociality of Offspring by Altering Gut Bacteria
Authors: Tracy Hampton
Journal: JAMA (2016)

According to recent findings, a maternal high-fat diet in mice resulted in impaired social behaviors in their offspring, deficits that were associated with gut microbiome dysbiosis and alterations in neural plasticity (Buffington SA et al. Cell. 2016;165[7]:1762-1775).
Cereblon (CRBN) Splicing Could Influence Response To IMiDs : A New PCR Strategy to Easily Detect and Semi-Quantify Loss Of The IMiDs Binding Domain
Authors: Audrey Ménard, Cyrille Touzeau, Anne Lok, Martine Amiot, Catherine Pellat-Deceunynck, Sophie Maiga, Florence Magrangeas, Stephane Minvielle, Nicolas Blin, Beatrice Mahe, Viviane Dubruille, Benoit Tessoulin, Maxime Halliez, Soraya Wuillème, Nelly Robillard, Philippe Moreau, Hervé Maisonneuve, Henry Jardel, Marie C. Bene, Philippe Moreau, Laurence Lodé
Journal: Blood (2013)
Abstract 1211: Killing cancer one cell at a time: Development and characterization of a novel antibody drug conjugate
Authors: Michael Xiao, Roger Chu, Jayson Pagaduan, Richard A. Robison, Kim L. O’Neill
Journal: Cancer Research (2016)

Abstract Thymidine Kinase 1 (TK1) is a protein that we have established to be present on the surface of cancer cells and absent on the surface of normal cells. Various methods have been used to confirm the presence of TK1 using localization methods such as scanning electron microscopy gold labeling, fluorescence imaging, and flow cytometry analysis. In this project, we explored the potential of using the TK1 marker as a therapeutic target by conjugating an anti-TK1 antibody to the toxin saporin, a ribosome inhibiting protein derived from the seeds of Saponaria officinalis. The toxin is widely used in the biological and neurological fields due to its stability and adaptability. An additional benefit to using this particular toxin is the inability of saporin to transverse the cell membrane without an antibody or other agent mediating internalization into the cell. We expressed a cysteine mutated form of saporin in the BL21(DE3) E. coli strain. Saporin from the expressed protein was subsequently isolated with a cation exchange cellulose column before verification on a non-reducing SDS-PAGE gel. A single band was observed at approximately 30 kD, indicating purity of the protein. After thiolation of the amine groups in the anti-TK1 antibody, the cysteine residues on the mutated saporin toxin was linked to the antibody through the formation of disulfide bonds. Further purification of the conjugate was achieved by eliminating unconjugated saporin and antibody, and high molecular weight aggregates using a Sephacryl S-200 column. Over 90% cancer cell death was observed in the Burkitt's Lymphoma Raji cell line when exposed to conjugate concentrations of 10 nM. Complete cell death was observed with exposure to 100 nM concentrations. In addition, there was a significant difference between the saporin conjugated treated and untreated samples (p &amp;lt; 0.001). Further tests are underway to determine the effectiveness of the conjugate in other cancer cell lines. These promising results suggest the use of saporin in an effective antibody drug conjugate therapeutic that could influence the way we treat cancer: a drug that will selectively target cancer cells. Citation Format: Michael Xiao, Roger Chu, Jayson Pagaduan, Richard A. Robison, Kim L. O’Neill. Killing cancer one cell at a time: Development and characterization of a novel antibody drug conjugate. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1211.
Second non-ocular tumors among survivors of retinoblastoma treated with proton therapy.
Authors: Roshan V Sethi, Helen Alice Shih, David Kim, Beow Y. Yeap, Kent Mouw, Karen Chayt Marcus, Eric Grabowski, Torunn I. Yock, Nancy Tarbell, Shizuo Mukai, Shannon M. MacDonald
Journal: Journal of Clinical Oncology (2013)

10018 Background: The leading cause of death for patients with hereditary retinoblastoma is second malignancy. Proton radiation allows for significant sparing of non-target tissue. We sought to determine the risk of second malignancy for the largest and oldest cohort of retinoblastoma patients treated with proton therapy. Methods: We performed a retrospective review of patients treated at the Massachusetts General Hospital (MGH) between 1986 and 2011. Results: Fifty-two patients were identified (see Table). Forty-four patients (85%) were hereditary survivors. Patients were followed for a median of 6.9 years from the start of radiation therapy (range, 11.3 months to 24.4 years). The median age at follow-up was 9.0 years (range, 31.3 months to 24.5 years). Fifteen patients had more than 10 years of follow-up from the start of radiation therapy, and 20 patients were more than 10 years old at last follow-up. With 417.2 person-years of follow-up, we identified one secondary malignancy, an osteosarcoma of the distal femur. The cumulative incidence of second tumor was 5% at 10 years. No radiation-associated malignancies were reported. Conclusions: Retinoblastoma is highly responsive to radiation. The central objection to the use of radiation—the risk of second malignancy—is founded on studies of patients treated with relatively non-conformal techniques. We present the first series of patients treated with the most conformal of current available modalities. While longer follow up is necessary, our preliminary data suggest that the risk of radiation-associated malignancy is minimal with proton therapy. [Table: see text]
The prognostic significance of tumor human papillomavirus status in patients with anal squamous cell carcinoma treated with combined chemoradiotherapy.
Authors: H. Yhim, E. Song, N. Lee, J. Hwang, H. Shim, I. Chung, H. Park, M. Park, C. Yim
Journal: Journal of Clinical Oncology (2010)

3658 Background: The prognostic relevance of tumor human papillomavirus (HPV) status in patients (pts) with anal squamous cell carcinoma (SCC) has not been elucidated. Methods: We conducted a multicenter, retrospective, observational study and consecutively enrolled pts with newly-diagnosed invasive anal SCC treated with combined chemoradiotherapy (CCRT) from 1998 to 2009. The pts with recurrent/metastatic cancer or positive serology test for HIV were excluded. Tumor HPV status was determined by HPV DNA chip analysis from paraffin-embedded tumor tissues at initial diagnosis. Results: 47 anal SCC pts treated with CCRT and with available paraffin-embedded tissues were identified. The median age was 65.0 (range, 44-90) years, 18 (38.3%) pts had regional nodal disease (N-pos), and mitomycin-containing regimen was used in 40 (85.1%). 35 (74.5%) pts were HPV positive and 31 (66.0%) were type 16 (HPV16-pos). After median follow-up of 51.7 months (range, 5.1-136.0), the 4-year progression-free survival (PFS) and overall survival (OS) were 47.0% (95% confidence interval [CI], 38.7-55.2) and 69.2% (95% CI, 61.2-77.2). Pts with HPV16-pos had better 4-year PFS (63.1% [53.1- 73.1] vs. 15.6% [5.6-25.7], p < 0.001) and OS (84.6% [76.2-93.0] vs. 39.8% [26.1-53.4], p = 0.008) than those without HPV type 16 (HPV16-neg). In multivariate analysis for PFS, N-pos (hazard ratio [HR], 2.97; 95% CI, 1.19-7.43) and HPV16-pos (HR, 0.30; 95% CI, 0.12-0.74) were independent prognostic factors for PFS. For OS, N-pos (HR, 4.58; 95% CI, 1.40-14.98) was the only independent prognostic factor. Comparing patterns of failure, time to loco- regional failure was statistically superior in pts with HPV16-pos over those with HPV16-neg (HR, 0.24; 95% CI, 0.08-0.72, p = 0.006), but time to systemic failure was not different (HR, 0.37; 95% CI, 0.11-1.27, p = 0.098). Conclusions: In pts with anal SCC treated with CCRT, tumor HPV16 status as well as nodal status was a strong independent prognostic factor for PFS. Further studies to define the prognostic relevance of HPV16 status are warranted, and HPV16 status should be considered as an important stratification factor in future trials in anal SCC. No significant financial relationships to disclose.
Abstract 4852: Multivalent peptoid conjugates suppress enzalutamide-resistant prostate cancer cellular proliferation
Authors: Yu Wang, Paul Levine, Dilani Dehigaspitiya, Adam Profit, Susan Logan, Keren Imberg-Kazdan, Kent Kirshenbaum, Michael Garabedian
Journal: Cancer Research (2016)

Abstract Development of resistance to latest anti-androgens treatment for advanced prostate cancer is a growing concern. New strategies to block androgen receptor (AR) function in castration resistant prostate cancer are therefore required. Here we report the characterization of a multivalent conjugate presenting two spatially defined bioactive ethisterone ligands as spatially defined pendant groups on a peptoid oligomer. The conjugate, termed Multivalent Peptoid Conjugate 6 (MPC6), suppressed the proliferation of multiple AR-expressing prostate cancer cell lines including those that failed to respond to enzalutamide and ARN509. The structure-activity relationships of MPC6 variants were evaluated, revealing that increased spacing between ethisterone moieties and changes in peptoid topology eliminated its anti-proliferative effect. Mechanistically, MPC6 blocked AR coactivator-peptide interaction, and decreased AR protein half-life. Pharmacological studies revealed that MPC6 was metabolically stable and displayed a low plasma clearance rate. Importantly, MPC6 treatment reduced tumor growth and decreased Ki67 and AR expression in mouse xenograft models of enzalutamide-resistant LNCaP-abl cells. Thus, MPC6 represents a new class of compounds with the potential to combat treatment-resistant prostate cancer. Citation Format: Yu Wang, Paul Levine, Dilani Dehigaspitiya, Adam Profit, Susan Logan, Keren Imberg-Kazdan, Kent Kirshenbaum, Michael Garabedian. Multivalent peptoid conjugates suppress enzalutamide-resistant prostate cancer cellular proliferation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4852.
Abstract 3471: Perceived role of family for Hispanic/Latino lung cancer patients: A qualitative study
Authors: Ana Motta-Moss, William Alago, Lorna Lin, Jane Akhuetie
Journal: Cancer Research (2016)

Abstract Healthcare decisions are not made by the patients alone, but rather the result of collaborative efforts between healthcare professionals and, more importantly, family members who become significant because of the various roles they perform throughout the process. The purpose of this study was to examine the role of family in the care of Hispanic/Latinos patients with lung cancer. Inconsistent expectations of the role of family affect how patients view family support throughout the diagnosis and treatment process. Therefore, it is important to examine what patients perceive to be an appropriate role for family members that assist in their healthcare. Twenty-four patients self-identified as Hispanic/Latino and treated at Memorial Sloan Kettering Cancer Center (MSKCC) for lung cancer stage I-IV participated in semi-structured face-to-face interviews. The four major themes of the role of family identified in this study include: general support, navigation of healthcare system, communications, and lack of family support. It is important to understand that family roles change as the patients’ needs change over the course of the disease. Nonetheless, identifying the various forms of support provided by family is essential to understanding the benefits of family presence in the diagnosis and treatment of lung cancer, particularly among Latinos. Citation Format: Ana Motta-Moss, William Alago, Lorna Lin, Jane Akhuetie. Perceived role of family for Hispanic/Latino lung cancer patients: A qualitative study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3471.
Abstract 1845: Development of a quantitative targeted RNA-Seq methodology for use in differential gene expression analysis
Authors: Eric Lader, Melanie Hussong, Matthew Fosbrink
Journal: Cancer Research (2016)

Abstract RNA Sequencing (RNA-Seq) uses the capabilities of Next Generation high-throughput sequencing (NGS) methods to provide insight into the transcriptome of a cell as it generates millions of reads. Whole transcriptome sequencing can be used to quantify gene expression on a transcriptome-wide scale, identify splice variants, quantify allele specific expression, and characterize fusion transcripts. Development of a highly reproducible and sensitive targeted quantitative sequencing method would aid in facilitating a deeper understanding and characterization of the roles of a specific set of genes, while enabling much higher sample throughput and significant cost savings relative to whole-transcriptome sequencing. In this study, we report a targeted RNA-Seq technology, QIAseq RNA, which makes use of several methodologies to deliver an extremely flexible, highly precise tool for characterizing gene expression. QIASeq RNA incorporates 12-base random molecular barcodes into each unique target strand which benefits quantifying gene expression in a given multiplexed sample. Counting the number of molecular tags allows one to determine the sequence coverage per target and adjust experimental conditions to use the read budget of any sequencing platform most efficiently. Using either the Illumina or Ion Torrent platforms, users can choose to multiplex up to 96 RNA samples from 12 to 1000-plex expression panels. No mRNA selection or rRNA removal or blocking is required. The entire protocol, from cDNA synthesis to finished library, which is ready for sequencing, can be accomplished in under one day. Custom assays for a specific target site can add the ability to distinguish between isoforms or identify allele specific expression. We explore the capabilities of this system by profiling large numbers of genes in a cell model system's response to small molecule treatment. Changes in gene expression by these treatments were measured by targeted RNA NGS, and fold-changes in gene expression due to chemical perturbation were characterized. Complex gene relationships in perturbed pathways were mapped using QIAGEN's Ingenuity Pathway Analysis (IPA) tool. The IPA tool also facilitated the elucidation of the impact of gene expression changes in the context of biological processes, molecular interactions, cellular phenotypes and disease. This article will provide application data for GRRC including a discussion of technical challenges faced when profiling large numbers of genes in a large cohort. Citation Format: Eric Lader, Melanie Hussong, Matthew Fosbrink. Development of a quantitative targeted RNA-Seq methodology for use in differential gene expression analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1845.
P0164 : Clinical significance of subclinical ascites in Korean patients with hepatitis B virus-related liver cirrhosis: A multicenter, retrospective study
Authors: S.Y. Yim, H. Ahn, J.-H. Lee, S.U. Kim, S.G. Kim, Y.S. Kim, J.H. Kim, W.H. Choe, T.Y. Kim, Y.K. Jung, S.J. Suh, K.T. Suk, Y.S. Seo, S.H. Um
Journal: Journal of Hepatology (2015)
3D Bioprinting: 3D Bioprinting Using a Templated Porous Bioink (Adv. Healthcare Mater. 14/2016)
Authors: James P. K. Armstrong, Madeline Burke, Benjamin M. Carter, Sean A. Davis, Adam W. Perriman
Journal: Advanced Healthcare Materials (2016)

A.W. Perriman and co-workers describe a new cell-containing hybrid bio-ink that allows the 3D printing of physiological architectures with templated micropores on page 1724. The printed constructs are then used in cartilage and bone tissue engineering, giving rise to well-distributed extracellular matrix components.