tbuckley/cabot-search huggingface dataset:
The analysis of sHLA-G antigen blood serum concentration levels during radical therapy for gynecological malignancies.
Authors: Krzysztof Koper, Lukasz Wicherek, Zbigniew Kojs, Agnieszka Chamier-Cieminska, Krzysztof Roszkowski
Journal: Journal of Clinical Oncology (2015)

e22192 Background: HLA-G is a non-classic major histocompatibility antigen (MHC) class Ib. The suppressive properties of HLA-G play an important role in escape from immune surveillance, a phenomenon of fundamental importance for the development of various types of cancer. The expression of HLA-G is involved in the development of malignant melanoma, ovarian, cervical and other types of cancers. It can be released into the extracellular space in a soluble form (sHLA-G) that retains biological activity. Methods: 215 patients with gynecological malignancies were included in this study. The blood serum levels of soluble HLA-G were measured prior to radical treatment: surgery and chemotherapy in ovarian cancer patients, radiochemiotherapy in patients with cervical cancer, and surgery followed by radiotherapy for those suffering from endometrial cancer. Long-term outcomes were observed. The patients were divided into three groups according to overall survival time. In the first group, OS was less than 2 years. The second group consisted of patients with OS more than 2 but less than 5 years. The third group included patients with OS of more than 5 years. Results: The highest sHLA-G blood serum concentration levels were found in the group of patients with the shortest overall survival time. There were statistically significant differences in OSbetween the three cohorts. We observed median levels of sHLA-G concentration as follows: 15.58U/l in the first group, 13.33U/l in the second, and 10.63U /l in the third group. Conclusions: As a predictor of overall patient survival time, the HLA-G blood serum concentration level seems to be a useful diagnostic biomarker in cancer cases. Additionally, HLA-G can serve as a potential therapeutic target in the treatment of cancer patients.
Abstract 4209: Inhibitory activity of lichen secondary metabolite, physciosporin, against lung cancer cell motility
Authors: Yi Yang, Young Hyun Yu, Hyung-Ho Ha, Kyung-Hwa Lee, Kyung-Sub Moon, Kyung Keun Kim, Hangun Kim
Journal: Cancer Research (2017)

Abstract Lichens produce various unique chemicals that can be used for pharmaceutical purposes. To screen for novel lichen secondary metabolites showing inhibitory activity against lung cancer cell motility, we tested acetone extracts of 13 lichen samples collected in Chile. Physciosporin, isolated from Pseudocyphellaria coriacea (Hook f. &amp; Taylor) D.J. Galloway &amp; P. James, was identified as an effective compound and showed significant inhibitory activity in migration and invasion assays against human lung cancer cells. Physciosporin treatment reduced both protein and mRNA levels of N-cadherin with concomitant decreases in the levels of epithelial-mesenchymal transition markers such as snail and twist. Physciosporin also suppressed KITENIN (KAI1 C-terminal interacting tetraspanin)-mediated AP-1 activity in both the absence and presence of epidermal growth factor stimulation. Quantitative real-time PCR analysis showed that the expression of the metastasis suppressor gene, KAI1, was increased while that of the metastasis enhancer gene, KITENIN, was dramatically decreased by physciosporin. Particularly, the activity of 3'-untranslated region of KITENIN was decreased by physciosporin. Moreover, Cdc42 and Rac1 activities were decreased by physciosporin. These results demonstrated that the lichen secondary metabolite, physciosporin, inhibits lung cancer cell motility through novel mechanisms of action. Citation Format: Yi Yang, Young Hyun Yu, Hyung-Ho Ha, Kyung-Hwa Lee, Kyung-Sub Moon, Kyung Keun Kim, Hangun Kim. Inhibitory activity of lichen secondary metabolite, physciosporin, against lung cancer cell motility [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4209. doi:10.1158/1538-7445.AM2017-4209
Abstract 1765: Molecular and immunological characterization of non-small cell lung cancer harboring cMET alterations
Authors: Maria Saigi, Carolina Pereira, Eva Pros, Elisabeth Brambilla, Ernest Nadal, Montse Sánchez-Céspedes
Journal: Cancer Research (2017)

Abstract Purpose: To explore the correlation between the expression of immunological biomarkers in a subset of NSCLC tumors presenting cMET activation. Methods: We retrospectively reviewed 200 tumor samples from a cohort of patients diagnosed with NSCLC in 3 different hospitals, from Spain and France. cMET activation was defined by the presence of one or more of the following criteria: 1- cMET mutations inducing exon 14 skipping (METex14), 2- cMET amplification, assessed by FISH 3- cMET overexpression, assessed by immunohistochemistry (IHC). METex14 mutations were determined by genomic sequencing and RT-PCR. FISH was interpreted according to Capuzzo scoring system, considering 5 or more gene copies as the mean value for positive amplification. Concurrent genetic alterations in EGFR and ERBB2 tyrosine kinase receptors were also determined. PD-L1 expression and density of tumoral infiltrating CD8+ lymphocytes were assessed by IHC. Statistical correlation analysis was performed by Chi-square and Fisher’s exact test. Results: METex14, cMET amplification and cMET overexpression were detected in 2%, 7.8% and 31% of tumors, respectively. Histological subtypes included: 70% adenocarcinoma, 20% squamous cell carcinoma, 8% large cell, 2% pulmonary sarcomatoid. Curiously, one of the METex14 adenocarcinoma was concurrent with ERBB2 amplification. Those tumors harbouring METex14 or cMET amplification were correlated with positivity for PD-L1 expression (p = 0.02). However, this association was not observed in cMET overexpressed tumors. Conclusions: We observed a direct correlation between PD-L1 positivity and METex14 or cMET amplification. Functional analysis and a large cohort of tumors are required to better characterize the potential role of cMET pathway in the regulation of PD-L1 expression. Citation Format: Maria Saigi, Carolina Pereira, Eva Pros, Elisabeth Brambilla, Ernest Nadal, Montse Sánchez-Céspedes. Molecular and immunological characterization of non-small cell lung cancer harboring cMET alterations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1765. doi:10.1158/1538-7445.AM2017-1765
Abstract 4386: Identification of clinically relevant colon cancer genes predictve of improved relapse free survival
Authors: Marie J. Parsons
Journal: Cancer Research (2017)

Abstract Colorectal cancer (CRC) is the third most common cancer worldwide, affecting over 15,000 individuals in Australia each year. While CRC is often detected at a stage where resection of the primary tumour is possible, approximately 50% will relapse and die from metastatic disease. Prognostication is mainly determined by tumour depth (T), lymph node stage (N) and the extent of cancer spread (M). However, clinical outcomes of patients with the same TNM stage can be heterogeneous. Therefore, there is a need to identify markers to better predict prognosis and stratify patients for treatment regimes. A panel of 113 candidate CRC genes were identified as significantly mutated in whole genome and whole exome sequencing studies from 361 MSS colon cancers and 63 CRC cell lines. Custom amplicon panels for target enrichment were designed for use with the HaloPlexTM target enrichment system. Sample libraries were prepared for 274 patients with stage II/III CRC using the automated Bravo liquid handling platform followed by next-generation sequencing (NGS) on the Illumina Next-Seq 500. Analysis of the 113 candidate genes identified 31 genes recurrently mutated above 10 percent in our discovery cohort. We identified 4 genes previously reported as colon cancer genes (APC 68%, TP53 60%, KRAS 30% and PIK3CA 20%), confirming APC, TP53 and KRAS as the most frequently mutated genes in CRC. To identify novel and clinically relevant genes, the 31 genes in our discovery cohort were tested for association with clinical features of CRC. In the discovery cohort, 24/31 genes were significantly associated with right sided CRC, 10/31 with mucinous CRC, 9/31 with stage II CRC and 7/31 with improved relapse free survival (RFS). Of these significantly associated genes, 10/24 genes were validated as significantly associated with right sided colon cancer, 3/9 with stage II and 3/10 with mucinous CRC in the validation cohort. Five of these genes were selected for further investigation as they were significantly associated with improved RFS, together with one or more clinical feature of CRC. Identification of novel recurrently mutated genes is key to a better understanding of the molecular mechanisms of CRC and development of novel therapeutics. Citation Format: Marie J. Parsons. Identification of clinically relevant colon cancer genes predictve of improved relapse free survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4386. doi:10.1158/1538-7445.AM2017-4386
Abstract 4788: Abraxane eliminates cancer stem cells in triple-negative breast cancers
Authors: Hebao Yuan, Hongwei Guo, Feng Li, Joseph Burnett, Miao He, Nathan Truchan, Ila Myers, Duxin Sun
Journal: Cancer Research (2017)

Abstract Triple-negative breast cancer (TNBC) represents about 20 percent of all breast cancers, with a poorer survival rate and being associated with high-grade tumors and the least favorable prognosis. Due to the absence of hormone receptors and Her2 receptor, no targeted therapy is available and chemotherapy is the standard treatment for TNBC patient. Paclitaxel is a widely used chemotherapy drug for various cancers with severe side effects due to its solvent. Abraxane is an albumin-bound nanoparticle of paclitaxel with less severe side effects. Here we investigated whether cancer stem cells (CSCs) in TNBC response differentially to abraxane and paclitaxel both in cell culture and xenograft mouse models. Using a series of human TNBC cell lines, we showed that there is no difference between solvent-based paclitaxel and abraxane in vitro in term of efficacy and eliminating cancer stem cells using MTS assay, mammosphere formation assay, and flow analysis of cancer stem cells. Interestingly, we demonstrated that abraxane shows superior efficacy than solvent-based paclitaxel in human SUM149 xenograft NOD SCID mouse model in adjuvant treatment. More important, we demonstrated that abraxane eliminates cancer stem cells in xenograft NOD SCID mouse model in advanced treatment, while solvent-based paclitaxel increases cancer stem cells. Cell uptake assay indicated that TNBC cells take more abraxane than solvent-based paclitaxel, which partially attributes to its superior efficacy in xenograft mouse models. Taken together, our data confirmed that abraxane is superior to solvent-based paclitaxel and may be a better option for TNBC patients in adjuvant or metastatic treatment. Citation Format: Hebao Yuan, Hongwei Guo, Feng Li, Joseph Burnett, Miao He, Nathan Truchan, Ila Myers, Duxin Sun. Abraxane eliminates cancer stem cells in triple-negative breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4788. doi:10.1158/1538-7445.AM2017-4788
Abstract 3118: Histological subtypes correlate with distinct genetic abnormalities in defining therapeutic targets in medulloblastoma
Authors: Samuel Gelnick, Anubhav G. Amin, Molly Gordon, Raphael Salles Scortegagna de Medeiros, Nelci Zanon, Raj Murali, Meena Jhanwar-Uniyal
Journal: Cancer Research (2017)

Abstract Medulloblastoma (MB) is the most common primary pediatric malignant brain tumor. Genetic classification and distinct histologic subtypes defines MB into 4 groups: classic (WNT), sonic hedgehog (Shh), group 3 and group 4. In addition, recent studies have provided evidence that p53 abnormalities is seen in various sub-groups of MB and that p53-mutated SHH MBs commonly harbor genetic anomalies including MYCN and GLI2 amplifications, which confers drug resistance. Here, we test the hypothesis that specific immunohistological markers, their correlation with the amplification of the oncogene MYC, and abnormalities in tumor suppressor gene p53, may define their metastatic potential. Materials and Methods: Immunohistological analysis of MB tumors (n=41) was evaluated for the expression of glioma transcription factor 1 (GLI-1), Grb2-associated binding protein 1 (GAB-1), natriuretic peptide receptor (NPR), voltage-gated potassium channel (KV1) and mutant p53. FISH analysis was performed to determine MYC amplification or iso- P53. p53-mutant MB cell line was used to investigate the signaling pathway leading to proliferation, migration, and drug resistance using HDAC (LBH-589) and PI3K/mTOR (BKM-120/rapamycin) inhibitors. Results: we showed that: 1) GAB-1 was highly expressed in the Shh group (82%) and KV1 expression was evenly distributed in all subtypes; 2) No obvious correlation with expression of GLI-1, GAB-1, NPR, or KV1 with metastasis was seen; 3) Analysis of loss of p53 and overexpression of MYC varied in each subtype; 4) Combined Treatment with LBH-589 and BKM-120 reduced cell proliferation, migration and S-phase entry, however, MB cells were resistant to BKM -120 treatments, while LBH-589 caused massive apoptosis; 5) Tumor formation was suppressed by BKM-120 given with mTOR inhibitors. Conclusion: the result of this study suggests that expression of GLI-1, GAB-1, NPR, KV1 and p53 was important in defining the subgroups of MB, although their metastatic potential remains to be understood. MB cells shows reduced cell proliferation, cell cycle and migration, when treated with HDAC inhibitor LBH-589, however these cells display complete drug resistance to PI3K inhibitors. Citation Format: Samuel Gelnick, Anubhav G. Amin, Molly Gordon, Raphael Salles Scortegagna de Medeiros, Nelci Zanon, Raj Murali, Meena Jhanwar-Uniyal. Histological subtypes correlate with distinct genetic abnormalities in defining therapeutic targets in medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3118. doi:10.1158/1538-7445.AM2017-3118
Abstract 4447: Analysis of small RNA-seq data for differential expression of small noncoding RNAs in human colorectal cancer
Authors: Srinivas V. Koduru, Amit K. Tiwari, Sprague W. Hazard, Milind K. Mahajan, Dino J. Ravnic
Journal: Cancer Research (2017)

Abstract Background: Cancer is a major cause of deaths worldwide, despite improved healthcare and technologies. Recent advancements in genome sequencing have led to the rapid study of the whole transcriptome and small RNAs with their biological functions. Non-coding RNAs (ncRNAs) play an important role in biological processes that greatly impact biomarker development for diagnosis, prognosis, and therapy. Non-coding RNAs such as microRNAs (miRNA), Piwi-interacting-RNAs (piRNAs), small nuclear/nucleolar RNAs (sn/snoRNAs) have recently been studied to understand their biology and pathology. Results: In the present study, we used eight matched colorectal patient tissue samples (benign, tumor, and metastasis) small RNA sequencing data remapped for various small RNA annotation. We identified aberrant expression of 13 miRs in tumor and metastasis specimens [tumor vs benign group (19 miRs) and metastasis vs benign group (38 miRs)] of which five were upregulated, and eight were downregulated, during disease progression. We also investigated pathway analysis on abbarent expression of miRNAs, which showed majority of miRs involved in the colon other types of cancers. Further analysis of piRNAs revealed that six piRNAs in tumor vs benign and 24 in metastasis vs benign samples (commonly in both groups, only two piRNAs). Additionally, we examined other types of small RNAs [sn/snoRNAs, mt_rRNA, misc_RNA, nonsense mediated decay (NMD) and rRNA], we identified 15 in tumor vs benign and 104 metastasis vs benign and only four in commonly expressed. Conclusion: In summary, our results identified multiple sncRNAs during colorectal cancer progression which needs to be further validated and can be used for prognosis, diagnosis, and therapeutic potentials. Citation Format: Srinivas V. Koduru, Amit K. Tiwari, Sprague W. Hazard, Milind K. Mahajan, Dino J. Ravnic. Analysis of small RNA-seq data for differential expression of small noncoding RNAs in human colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4447. doi:10.1158/1538-7445.AM2017-4447
Abstract LB-312: Breast cancer targeting by theranostic gold nanorods
Authors: Samir V. Jenkins, Zeid A. Nima, Kieng B. Vang, Dmitry Nedosekin, Vladimir P. Zharov, Robert J. Griffin, Alexandru S. Biris, Ruud P. Dings
Journal: Cancer Research (2017)

Abstract An ongoing need for new cancer therapeutics exists, especially ones that specifically home and target triple negative breast cancer (TNBC) tumors. Because TNBC does not express estrogen, progesterone, or Her2/Neu receptors, another target must be used for advanced drug delivery strategies. Here, we engineered a nanodrug delivery system consisting of silver-coated gold nanorods targeting EpCAM and loaded with doxorubicin. This novel nanodrug system, EpCAM-AuNR/Ag/Dox, was found to specifically target EpCAM-expressing tumor cells compared to low EpCAM-expressing tumors. Namely, the system had an inhibiting cell viability effective dose (ED50) of 3μM on 4T1 cells and an ED50 of 110μM for MDA-MD-231 cells. Flow cytometry indicated that 4T1 cells, on average, express two orders of magnitude more EpCAM than MDA-MD-231 cells, which correlates with our ED50 findings. Moreover, due to its thin silver coating, the AuNR/Ag allowed for detection by surface-enhanced Raman spectroscopy (SERS) and photoacoustics (PA). Analysis by both imaging detection techniques showed that the targeted nanodrug system was taken up by EpCAM-expressing cells and tumors at significantly higher rates than untargeted nanoparticles (p&amp;lt;0.05). In conclusion, our novel approach establishes a plasmonically-active nanodrug therapeutic system for TNBC and, potentially, a delivery system with improved multimodal imaging capability for other clinically approved chemotherapeutics with dose-limiting toxicities, such as platinum-based or taxane-based therapies. Citation Format: Samir V. Jenkins, Zeid A. Nima, Kieng B. Vang, Dmitry Nedosekin, Vladimir P. Zharov, Robert J. Griffin, Alexandru S. Biris, Ruud P. Dings. Breast cancer targeting by theranostic gold nanorods [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-312. doi:10.1158/1538-7445.AM2017-LB-312
Abstract 5042: Defining an optimal single time point sampling strategy representative of overall capecitabine pharmacokinetics
Authors: Stephen Welch, Wendy Teft, John Lenehan, Rommel Tirona, Karen Lumsden, Eric Winquist, Richard B. Kim
Journal: Cancer Research (2017)

Abstract Background: Capecitabine is an oral chemotherapy pro-drug used to treat advanced colorectal cancer. Patients may experience hand-foot syndrome and diarrhea, among other side effects, that affect quality of life and may necessitate dose modification or discontinuation. There is significant regional variation in capecitabine tolerability, related to a myriad of factors including pharmacogenomics, dietary and cultural differences. Capecitabine dose modification, when necessary, is empirical based on toxicity suggesting a personalized dosing approach might better optimize therapy. Objective: In phase I of a personalized dosing approach, our objective was to define an optimal time point for blood sampling that best represented overall exposure of capecitabine and its metabolites. Methods: A single-arm prospective pharmacokinetic cohort study of patients with advanced or metastatic colorectal cancer prescribed capecitabine monotherapy was done. Blood samples were collected pre-dose and at timed intervals between 0 and 8 hours post-dose. Plasma concentration of capecitabine and its major metabolites, 5'-deoxy-5-fluorocytidine (5'-DFCR) and 5'-deoxy-5-fluorouracil (5'-DFUR), were measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results: 26 patients were enrolled; 65% were male and 42.3% had metastatic disease. Mean capecitabine dose was 2854 ± 944 mg. Hand-foot symptoms (60%), fatigue (53%) and diarrhea (30%) were the most common adverse drug reactions. Dose normalized mean (SD) AUC0-8h for capecitabine, 5’-DFCR and 5’-DFUR were 6.74 (3.0), 4.19 (1.5) and 6.33 (2.8) ng/ml*h, respectively. Spearman correlation between dose normalized concentrations and AUC at each blood draw was performed. The best estimated time points for capecitabine, 5’-DFCR and 5’-DFUR were 1.5, 2 and 2 hours with r2 values of 0.6 (p &amp;lt;0.01), 0.64 (p &amp;lt;0.001) and 0.51 (p &amp;lt;0.01), respectively. There was a significant correlation seen between capecitabine AUC and need for subsequent dose reduction (p&amp;lt;0.05). Conclusions: Blood samples obtained between 1.5 and 2 hours post-dose provide the best estimate of capecitabine exposure. Further pharmacokinetic analysis in this cohort is ongoing. This blood draw strategy will be used in a larger trial intended to develop a personalized capecitabine dosing algorithm. Citation Format: Stephen Welch, Wendy Teft, John Lenehan, Rommel Tirona, Karen Lumsden, Eric Winquist, Richard B. Kim. Defining an optimal single time point sampling strategy representative of overall capecitabine pharmacokinetics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5042. doi:10.1158/1538-7445.AM2017-5042
Interactional Dysfunction of the Social Brain in a Paradigmatic Relational Disorder
Authors: Michael J. Minzenberg
Journal: JAMA Psychiatry (2017)

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 Psychiatry 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 Psychiatry journal