tbuckley/cabot-search huggingface dataset:
Phase II open-label study to investigate efficacy and safety of PTK787/ZK 222584 orally administered once daily at 1,250 mg as second-line monotherapy in patients (pts) with stage IIIB or stage IV non-small cell lung cancer (NSCLC)
Authors: T. C. Gauler, B. Fischer, J. Soria, V. Gounant, F. Griesinger, H. Krissel, D. Laurent, W. E. Eberhardt
Journal: Journal of Clinical Oncology (2006)

7195 Background: Overexpression of vascular endothelial growth factor receptor (VEGF-R 1–3) in NSCLC is associated with poor prognosis and shorter overall survival. PTK787/ZK 222584 (PTK/ZK), a novel, oral, anti-angiogenic compound blocks tyrosine kinase signaling from all VEGF receptors. Methods: A prospective, single-arm, multi-center, proof-of-principle phase-II study to investigate both efficacy and safety of PTK/ ZK in patients with stage IIIB/IV NSCLC who received prior first line treatment with a platinum based chemotherapy regimen. All pts were relapsed/refractory as determined by available imaging. All pts were planned to receive 1,250 mg of PTK/ZK once daily (qd) for continuous treatment until disease progression or unacceptable toxicities. Response evaluation is based on RECIST criteria. Disease stabilization of at least 12 weeks based on CT/MRI-imaging was defined as clinically relevant drug activity. All pts had dynamic contrast enhanced MRI investigations for additional efficacy analysis and serum asservations for serum proteomic analysis. Results: To date, 56 pts have been enrolled. PTK/ZK is generally well tolerated. Most frequent adverse events (AEs) are nausea and vomiting. One pt developed interstitial lung disease (ILD) and in one pt with tracheal stent a fatal lung bleeding occurred. No other unexpected serious AEs have been reported. Maximum response for 48 evaluated pts include one pt with a partial response (PR) (2%), 27 pts with stable disease (SD) (56%), (disease control rate 58%), and 20 pts with progressive disease (PD) (42%). The pt with PR has responded for over 20 weeks. 15 pts have SD for at least 12 weeks; 5 pts of these had SD for at least 28 weeks. Conclusions: These preliminary results suggest that second-line treatment with single-agent PTK/ZK is generally safe and well tolerated. In pts with refractory disease in stage IIIB/IV NSCLC, a considerably high rate of disease control could be achieved in this study. The study is currently recruiting for twice daily (bid) treatment. [Table: see text]
Multiple Genetic Trajectories to Extreme Abiotic Stress Adaptation in Arctic Brassicaceae
Authors: Siri Birkeland, A Lovisa S Gustafsson, Anne K Brysting, Christian Brochmann, Michael D Nowak
Journal: Molecular Biology and Evolution (2020)

Extreme environments offer powerful opportunities to study how different organisms have adapted to similar selection pressures at the molecular level. Arctic plants have adapted to some of the coldest and driest biomes on Earth and typically possess suites of similar morphological and physiological adaptations to extremes in light and temperature. Here, we compare patterns of molecular evolution in three Brassicaceae species that have independently colonized the Arctic and present some of the first genetic evidence for plant adaptations to the Arctic environment. By testing for positive selection and identifying convergent substitutions in orthologous gene alignments for a total of 15 Brassicaceae species, we find that positive selection has been acting on different genes, but similar functional pathways in the three Arctic lineages. The positively selected gene sets identified in the three Arctic species showed convergent functional profiles associated with extreme abiotic stress characteristic of the Arctic. However, there was little evidence for independently fixed mutations at the same sites and for positive selection acting on the same genes. The three species appear to have evolved similar suites of adaptations by modifying different components in similar stress response pathways, implying that there could be many genetic trajectories for adaptation to the Arctic environment. By identifying candidate genes and functional pathways potentially involved in Arctic adaptation, our results provide a framework for future studies aimed at testing for the existence of a functional syndrome of Arctic adaptation in the Brassicaceae and perhaps flowering plants in general.
IMPDH1/YB-1 Positive Feedback Loop Assembles Cytoophidia and Represents a Therapeutic Target in Metastatic Tumors
Authors: Hailong Ruan, Zhengshuai Song, Qi Cao, Dong Ni, Tianbo Xu, Keshan Wang, Lin Bao, Junwei Tong, Haibing Xiao, Wen Xiao, Gong Cheng, Zhiyong Xiong, Huageng Liang, Di Liu, Liang Wang, Tredan Olivier, Boyle Helen Jane, Hongmei Yang, Xiaoping Zhang, Ke Chen
Journal: Molecular Therapy (2020)

Recently, cytoophidium, a nonmembrane-bound intracellular polymeric structure, has been shown to exist in various organisms, including tumor tissues, but its function and mechanism have not yet been examined. Examination of cytoophidia-assembled gene inosine monophosphate dehydrogenase (IMPDH) and cytidine triphosphate synthetase (CTPS) mRNA levels showed that only IMPDH1 levels were significantly higher in the clear cell renal cell carcinoma (ccRCC). IMPDH1 was positively correlated with the metastasis-related gene Y-box binding protein 1 (YB-1) and served as an independent prognostic factor in ccRCC. Kaplan-Meier analysis indicated that patients with tumors that expressed high IMPDH1 levels had a shorter overall survival (OS) and disease-free survival (DFS). Furthermore, detection of cytoophidia by immunofluorescence staining in ccRCC tissues showed that IMPDH1-assembled cytoophidia are positively associated with tumor metastasis. Mechanistically, IMPDH1 and YB-1 formed an autoregulatory positive feedback loop: IMPDH1 maintained YB-1 protein stabilization; YB-1 induced IMPDH1 expression by binding to the IMPDH1 promoter motif. Functionally, IMPDH1-assembled cytoophidia physically interacted with YB-1 and translocated YB-1 into the cell nucleus, thus correlating with ccRCC metastasis. Our findings provide the first solid theoretical rationale for targeting the IMPDH1/YB-1 axis to improve metastatic renal cancer treatment.
Increased levels of RbBP6 suggest an involvement in the tumorigenesis of breast cancer
Authors: Zodwa Dlamini, Zukile Mbita
Journal: Cancer Research (2007)

2018  Background: Human RbBP6 has three isoforms and has been implicated in the induction of apoptosis in cancer cells. RbBP6 may play a role in splicing and processing of mRNA as well as ubiquitination of important cellular proteins such as p53 and pRb.  Aim: This study was aimed at elucidating the possible role of RbBP6 in breast cancer and apoptosis, its localization and expression).  Methodology: Paraffin-embedded sections of normal and malignant intraductal and infiltrating duct carcinomas were utilized for in situ hybridization and immunocytochemistry studies. RNA probes were synthesized and labelled using Digoxigenin for colorimetric and fluorescent detection during the in situ hybridization (ISH) technique for localization. Real time quantitative RT-PCR was performed to determine the expression levels of RbBP6 mRNA in MCF 7 cell line (non-aggressive) using the Biorad MJ Mini Personal Thermal Cycler Results were analyzed by relative quantification and melting curves using Mini-Opticon 3.1 software.  Results:In situ hybridization as well as immunocytochemistry showed substantial upregulation of RbBP6 within the malignant tissue sections of intraductal, infiltrating duct and fatty tissue carcinomas compared to normal breast sections. The RbBp6 showed cytoplasmic localization in tumors as well as normal tissues. The results of the quantitative RT-PCR also showed the upregulation of the RbBP6 in MCF7 cells as compared to normal fibroblasts.  Conclusion: Increased levels of RbBP6 in breast cancer could suggest an involvement in the carcinogenesis of breast tumors.
Genomic and Transcriptomic Characterization of Natural Killer T Cell Lymphoma
Authors: Jie Xiong, Bo-Wen Cui, Nan Wang, Yu-Ting Dai, Hao Zhang, Chao-Fu Wang, Hui-Juan Zhong, Shu Cheng, Bin-Shen Ou-Yang, Yu Hu, Xi Zhang, Bin Xu, Wen-Bin Qian, Rong Tao, Feng Yan, Jian-Da Hu, Ming Hou, Xue-Jun Ma, Xin Wang, Yuan-Hua Liu, Zun-Min Zhu, Xiao-Bin Huang, Li Liu, Chong-Yang Wu, Li Huang, Yun-Feng Shen, Rui-Bin Huang, Jing-Yan Xu, Chun Wang, De-Pei Wu, Li Yu, Jian-Feng Li, Peng-Peng Xu, Li Wang, Jin-Yan Huang, Sai-Juan Chen, Wei-Li Zhao
Journal: Cancer Cell (2020)

Natural killer/T cell lymphoma (NKTCL) is an aggressive and heterogeneous entity of non-Hodgkin lymphoma, strongly associated with Epstein-Barr virus (EBV) infection. To identify molecular subtypes of NKTCL based on genomic structural alterations and EBV sequences, we performed multi-omics study on 128 biopsy samples of newly diagnosed NKTCL and defined three prominent subtypes, which differ significantly in cell of origin, EBV gene expression, transcriptional signatures, and responses to asparaginase-based regimens and targeted therapy. Our findings thus identify molecular networks of EBV-associated pathogenesis and suggest potential clinical strategies on NKTCL.
Final results of a large collaborative, hospital-based quality improvement study aimed at the implementation of interventions for the psychosocial care of adult cancer patients (HUCARE project).
Authors: Rodolfo Passalacqua, Caterina Caminiti, Mario Annunziata, Claudia Borreani, Francesca Diodati, Daniele Fagnani, Luciano Isa, Silvia Filiberti, Maria Grazia Ollari, Jessica Saleri
Journal: Journal of Clinical Oncology (2012)

9120 Background: Incorporating psychosocial research into practice is challenging. Aim of this study is to assess the feasibility and effectiveness in real life of interventions which have been tested in RCTs and have demonstrated to improve pts psychosocial conditions Methods: This is an implementation study of five EBM interventions conducted in 28 centers. We adopted the model of Pronovost (BMJ 2008), which includes context analysis to identify local barriers; introduction of the interventions, and evaluation of how many pts receive the recommended interventions. Primary EPs: degree of implementation detected in a blinded fashion by external personnel. Interventions included: 1) EBM communication courses for doctors and nurses; 2) use of a question prompt list (QPL) for all pts; 3) creation of the Point of Information and Support (PIS) in the ward (J Clin Oncol 27:1794-99,2009); 4) identification of a referring nurse (RN) for informing and educating pts; 5) screening of distress and social needs. Results: In December 2008, 28 eligible centers applied to participate. 27 are evaluable and 1 is too early. 156 oncologists and 401 nurses attended the 3 days training course. A QPL was subjected to cross-cultural adaptation, yielding the first validated Italian QPL (BMC Health Serv Res 2010). 24 centers (89%) have successfully implemented the intervention; 3 centers failed for various reasons: internal conflicts of the staff, poor motivation, etc. Main results for each intervention are shown in the table. Conclusions: A successful implementation of EBM measure was obtained in the vast majority of oncology centers and yields to significant changes in the delivery of psychosocial care. Project funded by the Italian Ministry of Health and Lombardia Region. [Table: see text]
Surgical and non-surgical treatment of pulmonary metastases of soft tissue sarcomas
Authors: J. P. Sade, M. Chacon, J. M. O′Connor, C. Pupareli, M. Varela, R. D. Chacon
Journal: Journal of Clinical Oncology (2006)

9582 Background: Several reports have shown a prolonged survival after surgery for lung metastases from soft tissue sarcomas (STS). This finding is in contrast with the results from chemotherapy. We performed a retrospective analysis to determine the impact of surgical and non surgical treatment in terms of time to progression (TTP) and disease specific survival (DSS). Methods: A review of 144 patients (pts) with STS treated at a single institution (december 1994-february 2005) was performed. Median age: 45 years old, female 53%. Extremity was the primary site in 54 pts and leiomyosarcoma was the most common histologic type (24%). In 42 pts pulmonary metastases were synchronous. The median disease free interval (DFI) was 11 months. Surgical treatment on the lung lesions was performed in 48 pts (group A), while 96 received medical treatment (group B). Results: Surgery was R0 in 90% of group A pts with only 4 lobectomies and 36 metastasectomies. Nine pts (19%) in this group received neo or adyuvant chemotherapy. The median TTP was 11 months (2–107) and 21 pts (44%) relapse in the lung (8 lung + other site). At the time of this analysis 13 pts (27%) are NED, with a DSS of 24 months for the surgical group. 28% remain alive at 5 years. In a univariate analysis only the number of lung metastases (1 vs 2 or more) was significant for DSS (p=0.05). Group B was treated primarily with chemotherapy being doxorubicin the most common drug used (89%). The RR was 23% with a median TTP of 3 months and a DSS of 12 months (1–98). Conclusions: The present results are similar with previous reports in terms of overall survival. Paliative chemotherapy showed modest activity and surgical treatment remains the only curative treatment modality for pts with lung metastases from STS. No significant financial relationships to disclose.
Second-hit APC mutation in a familial adamantinomatous craniopharyngioma
Authors: Alexander Gorelyshev, Nadia Mazerkina, Olga Medvedeva, Evgeny Vasilyev, Vasily Petrov, Marina Ryzhova, Sergey Gorelyshev, Anatoly Tiulpakov
Journal: Neuro-Oncology (2020)
ASSOCIATIONS OF DIABETES AND HYPERTENSION WITH LEFT VENTRICULAR MASS-THE JACKSON HEART STUDY
Authors: Arsalan Hamid, Wondwosen K. Yimer, Adebamike A. Oshunbade, Daisuke Kamimura, Donald Clark, Ervin Fox, Yuan-I Min, Paul Muntner, Daichi Shimbo, Ambarish Pandey, Amil M. Shah, Robert John Mentz, Daniel Jones, Alain Bertoni, John Hall, Adolfo Correa, Javed Butler, Michael Hall
Journal: Journal of the American College of Cardiology (2020)
Comparative evaluation of capecitabine or infusional leucovorin/5-fluorouracil (LV/5-FU) with or without oxaliplatin (Ox) for stage III colon cancer (CC): A pooled analysis of individual patient data from four randomized controlled trials.
Authors: Weijing Sun, Hans-Joachim Schmoll, Michael O'Connell, Thomas H. Cartwright, Christopher Twelves, Edward McKenna, Wasif M. Saif, Luen F. Lee, Greg Yothers, Daniel G. Haller
Journal: Journal of Clinical Oncology (2012)

3525 Background: A fluoropyrimidine + Ox is the standard of care for stage III CC but a fluoropyrimidine alone is recommended for selected patients in several practice guidelines. We assessed efficacy and safety of adjuvant capecitabine ± Ox vs. LV/5-FU ± Ox across a population of stage III CC patients enrolled in four trials. Methods: N = 5,819 patients from NSABP C-08, XELOXA, X-ACT, and AVANT were pooled and analyzed; bevacizumab-treated patients were excluded. Endpoints were disease-free survival (DFS, primary), relapse-free survival (RFS), overall survival (OS), and safety. Multivariate Cox regression analyses (MVA) controlled for age, gender, T, and N stage. Results: Patient demographics and disease characteristics (except lymph nodes examined) were well balanced across groups. The number of patients receiving capecitabine and LV/5-FU were 1,942 and 3,877, respectively. Median follow-up was shorter in NSABP C-08 and AVANT (36 and 50 months) vs. XELOXA and X-ACT (83 and 74 months). Five-year DFS was 62.8% for capecitabine ± Ox and LV/5-FU ± Ox. The capecitabine by Ox interaction was significant for OS with a trend for DFS and RFS; likely due to improved outcomes with capecitabine alone and similar outcomes for capecitabine or LV/5-FU + Ox. Serious adverse event (AE) rates were similar for LV/5-FU- and capecitabine-based therapy (16% vs. 20%, respectively). Overall, treatment-related grade 3/4 AEs were more common with LV/5-FU (59% vs. 47%). Treatment-related grade 3/4 AEs of interest included peripheral sensory neuropathy (5% vs. &lt; 1%), diarrhea (12% vs. 15%), febrile neutropenia (2% vs. &lt; 1%), and hand–foot syndrome (&lt; 1% vs. 12%). Conclusions: Adjuvant capecitabine ± Ox and LV/5-FU ± Ox show comparableefficacy benefits for the treatment of stage III CC; further supporting capecitabine or LV/5-FU-based regimens as standard options for the adjuvant therapy of stage III CC. [Table: see text]
Hepatic intra-arterial infusion (HAI) for liver metastases in pretreated metastatic breast cancer patients
Authors: C. Zanon, M. Airoldi, F. Pedani
Journal: Journal of Clinical Oncology (2006)

10579 Background: Breast cancer patients (pts) with liver metastases have a poor prognosis. HAI has been frequently used for liver metastases from colorectal cancer, with better response and possibly survival than with intravenous administration. We evaluated the activity of HAI in pretreated breast cancer patients with liver metastases only. Methods: From December 2001 to October 2005 thirty patients previously treated with anthracyclines, taxanes and vinorelbine were enrolled. Median age 58 years (44–68) and median PS 1 (0–2). Eight patients (27%) had 5 or more liver nodes, seventeen (57%) had 5 to 10 metastases and five (16%) more than 10 nodes. Eighteen patients received 2 previous lines of chemotherapy (67 %), eleven 3 lines (30%) and one (3%) three lines and one cicle of high dose chemotherapy followed by ABMT. Seventeen pts received prior hormonotherapy. Two patients had been submitted to liver metastasectomy. Patients underwent percutaneous implantation of an arterial hepatic port-a-cath. HAI regimen administered on days 1–3 every 4 weeks, consisted of cisplatin 10 mg/sqm bid, mitomycin-C 1 mg/sqm bid, 5-fluorouracil 1000 mg/sqm 72 hours continuous infusion. Results: On an intent-to-treat analysis, four pts had CR (13%) with a duration of responses of 12, 18, 24 and 36 months. Fourteen pts (47%) had PR with a median duration of 7 months. Six patients had stable disease (20%) with a median duration of 3 months. Six patients (20%) had PD. Responses were more frequent in patients with PS 0 (10/13, 77%) and in patients treated with 2 previous lines of chemotherapy (13/18, 72%) than 3 or more (5/12, 42%). Median survival for the whole population was 11.8 months (5–44; 95% CI, 10.0 to 13.9). For pts with CR or PR and those who had SD, median survival was 16 months (10–44) and 10 months (8–18), respectively. No treatment-related death occurred. Grade 3–4 neutropenia in 7 % of pts. Grade 4 thrombocytopenia and grade 3 anemia 3 % of patients. Most frequent G3 non-haematologic toxicities were nausea and vomiting (3%) and alopecia (3%). We observed 2 dislodgements of catheter (7%), 3 cases (10%) of gastroduodenal ulcers, neither cases of thrombosis, nor sclerosing cholangitis. Conclusions: This intra-arterial regimen seems active in this patient population, with a very good safety profile. No significant financial relationships to disclose.
Identification of novel melanoma gene expression signatures using a Bayesian approach to filter out gene expression noise from normal tissues.
Authors: David A. Liebner, Jeffrey Parvin, Kun Huang
Journal: Journal of Clinical Oncology (2012)

e19053 Background: Identification of pertinent gene expression signatures may be confounded by failure to account for admixture of tumor specimens with normal tissue. We propose a novel method for filtering out gene expression “noise” from normal tissues in a set of melanoma samples derived from the NCBI Gene Expression Omnibus (GEO) public database. Methods: Using customized software implemented in MATLAB, we performed a preliminary search of GEO using the query term “melanoma”. We manually identified 695 clinical samples within 19 different gene expression studies (median 43 samples per series). Gene expression results were merged across different platforms using rank normalization for the target gene of the respective probes. Standardized gene expression signatures for 36 normal tissues were identified in GEO (GSE2361). We performed a modified sparse Bayesian factor regression analysis that incorporated signatures of normal tissues. Additional regression allowed for discovery of latent factors characteristic of melanoma subtypes. Pathway analysis was performed using Ingenuity Pathway Analysis (IPA) on characteristic genes for inferred melanoma-specific latent factors. Results: Normal tissue contributed significantly to the reported gene expression profiles, explaining a median of 11.5% of specimen variability (range 1.3-55.0%). In a subset analysis of 40 primary or in situ melanoma lesions versus 16 metastatic lesions (GSE7553), primary lesions were more likely contaminated with genes characteristic of normal skin (p&lt;0.001). The top 5 latent factors explained a median of 17.0% of residual sample variance (range 0.6-64%). On IPA analysis, latent factor 1 was strongly associated with dermatologic disease (p = 7.46 e-36), latent factor 2 was associated with inflammatory response (p = 9.71e-25), and latent factor 3 was associated with upregulation of the MITF transcription factor regulation (p = 4.16e-19). Conclusions: Appropriate methods that filter out normal tissue contamination of melanoma specimens can improve our understanding of gene expression patterns in melanoma subtypes, and potentially improve future translational studies.
Resource-rational analysis versus resource-rational humans
Authors: Dobromir Rahnev
Journal: Behavioral and Brain Sciences (2020)

Abstract Lieder and Griffiths advocate for resource-rational analysis as a methodological device employed by the experimenter. However, at times this methodological device appears to morph into the substantive claim that humans are actually resource-rational. Such morphing is problematic; the methodological approach used by the experimenter and claims about the nature of human behavior ought to be kept completely separate.