tbuckley/cabot-search huggingface dataset:
A Molecular Classification of Papillary Renal Cell Carcinoma
Authors: Ximing J. Yang, Min-Han Tan, Hyung L. Kim, Jonathon A. Ditlev, Mark W. Betten, Carolina E. Png, Eric J. Kort, Kunihiko Futami, Kyle A. Furge, Masayuki Takahashi, Hiro-omi Kanayama, Puay Hoon Tan, Bin Sing Teh, Chunyan Luan, Kim Wang, Michael Pins, Maria Tretiakova, John Anema, Richard Kahnoski, Theresa Nicol, Walter Stadler, Nicholas G. Vogelzang, Robert Amato, David Seligson, Robert Figlin, Arie Belldegrun, Craig G. Rogers, Bin Tean Teh
Journal: Cancer Research (2005)

Abstract Despite the moderate incidence of papillary renal cell carcinoma (PRCC), there is a disproportionately limited understanding of its underlying genetic programs. There is no effective therapy for metastatic PRCC, and patients are often excluded from kidney cancer trials. A morphologic classification of PRCC into type 1 and 2 tumors has been recently proposed, but its biological relevance remains uncertain. We studied the gene expression profiles of 34 cases of PRCC using Affymetrix HGU133 Plus 2.0 arrays (54,675 probe sets) using both unsupervised and supervised analyses. Comparative genomic microarray analysis was used to infer cytogenetic aberrations, and pathways were ranked with a curated database. Expression of selected genes was validated by immunohistochemistry in 34 samples with 15 independent tumors. We identified two highly distinct molecular PRCC subclasses with morphologic correlation. The first class, with excellent survival, corresponded to three histologic subtypes: type 1, low-grade type 2, and mixed type 1/low-grade type 2 tumors. The second class, with poor survival, corresponded to high-grade type 2 tumors (n = 11). Dysregulation of G1-S and G2-M checkpoint genes were found in class 1 and 2 tumors, respectively, alongside characteristic chromosomal aberrations. We identified a seven-transcript predictor that classified samples on cross-validation with 97% accuracy. Immunohistochemistry confirmed high expression of cytokeratin 7 in class 1 tumors and of topoisomerase IIα in class 2 tumors. We report two molecular subclasses of PRCC, which are biologically and clinically distinct and may be readily distinguished in a clinical setting.
Alterations in Gemin5 Expression Contribute to Alternative mRNA Splicing Patterns and Tumor Cell Motility
Authors: Jong Heun Lee, Christine E. Horak, Chand Khanna, Zhaojing Meng, Li Rong Yu, Timothy D. Veenstra, Patricia S. Steeg
Journal: Cancer Research (2008)

Abstract The role of Gemin5 in alternative mRNA splicing, tumor cell motility, and proteomic instability was investigated. Isotope Capture Affinity Tag proteomic analysis was conducted on MDA-MB-435 tumor cells transfected with either a control vector (C-100) or the Nm23-H1 metastasis suppressor (H1-177). Ingenuity pathway analysis revealed that RNA posttranscriptional processing was the most prominent class of differentially expressed proteins. Within this category, overexpression of Acinus1, Poly(a) binding protein, HNRPA2B1, Bop1, and Gemin5 was confirmed in less metastatic H1-177 cells. Overexpression of the latter four proteins was also observed in the lower metastatic antisense Ezrin transfectant of a murine osteosarcoma model system, confirming the general relevance of the trends. Gemin5, a component of the spliceosomal complex, was chosen for further study. Analysis of global mRNA splicing by SpliceArray chips revealed that 16 genes were differentially spliced in C-100 compared with H1-177 cells; transient transfection of gemin5 into C-100 cells restored the splice pattern to that of H1-177 cells. Alternative splicing patterns for the engulfment and cell motility 1 and thrombospondin 4 genes were confirmed by semiquantitative reverse transcription-PCR. Gemin5 overexpression coordinately reduced C-100 cell motility by 50%, and siRNA-mediated reduction of Gemin5 expression increased the motility of H1-177 cells by 2-fold (P &amp;lt; 0.004). The data provide the first demonstration that alterations in the expression of a spliceosome protein can effect both specific splicing events and tumor cell motility. The data also show that changes in mRNA splicing patterns accompany metastatic progression, which may contribute to proteome instability. [Cancer Res 2008;68(3):639–44]
Risk of Colorectal Cancer After Diagnosis of Endometrial Cancer: A Population-Based Study
Authors: Harminder Singh, Zoann Nugent, Alain Demers, Piotr M. Czaykowski, Salaheddin M. Mahmud
Journal: Journal of Clinical Oncology (2013)

Purpose Site-specific risk of colorectal cancer (CRC) among survivors of endometrial cancer (EC) is not known. The objective of the present study was to assess the risk of CRC (overall and subsite specific) among EC survivors. Methods A historical cohort study was performed by linking the Manitoba Cancer Registry and the Manitoba Health administrative databases. Each subject diagnosed with EC as her first cancer between 1987 and 2008 was age matched with up to five women with no history of invasive cancer on the index date (date of EC diagnosis). All subjects were followed up to the date of diagnosis of CRC or another cancer, death, migration, or study end point (December 31, 2009). Competing-risk proportional hazards models were used to compare the CRC incidence rates with adjustment for age, history of lower gastrointestinal endoscopy, and socioeconomic status. There were three mutually exclusive (and competing) outcomes: CRC, another primary cancer, and death. Results A total of 3,115 women with EC and 15,084 without EC were followed up for a total of 145,502 person-years. Women diagnosed with EC at age ≤ 50 years had an increased risk of being diagnosed with CRC (all CRC: hazard ratio [HR] = 4.41; 95% CI, 1.47 to 13.26; right-sided CRC: HR = 7.48; 95% CI, 1.29 to 43.28). There was no increased risk of all CRC among women 51 to 65 years of age or those older than 65 years at the time of EC diagnosis. However, women 51 to 65 years of age at EC diagnosis had an increased risk of right-sided CRC (HR = 2.30; 95% CI, 1.05 to 5.01). Conclusion This study suggests young women (age ≤ 50 years) with EC are at increased risk of CRC; risk of right-sided CRC is also increased in women 51 to 65 years old at EC diagnosis.
The Somatosensory Link in Fibromyalgia: Functional Connectivity of the Primary Somatosensory Cortex Is Altered by Sustained Pain and Is Associated With Clinical/Autonomic Dysfunction
Authors: Jieun Kim, Marco L. Loggia, Christine M. Cahalan, Richard E. Harris, Florian Beissner, Ronald G. Garcia, Hyungjun Kim, Riccardo Barbieri, Ajay D. Wasan, Robert R. Edwards, Vitaly Napadow
Journal: Arthritis & Rheumatology (2015)

Objective Fibromyalgia (FM) is a chronic functional pain syndrome characterized by widespread pain, significant pain catastrophizing, sympathovagal dysfunction, and amplified temporal summation for evoked pain. While several studies have demonstrated altered resting brain connectivity in FM, studies have not specifically probed the somatosensory system and its role in both somatic and nonsomatic FM symptoms. Our objective was to evaluate resting primary somatosensory cortex (S1) connectivity and to explore how sustained, evoked deep tissue pain modulates this connectivity. Methods We acquired functional magnetic resonance imaging and electrocardiography data on FM patients and healthy controls during rest (the rest phase) and during sustained mechanical pressure–induced pain over the lower leg (the pain phase). Functional connectivity associated with different S1 subregions was calculated, while S1 leg connectivity (representation of the leg in the primary somatosensory cortex) was contrasted between the rest phase and the pain phase and was correlated with clinically relevant measures in FM. Results During the rest phase, FM patients showed decreased connectivity between multiple ipsilateral and cross‐hemispheric S1 subregions, which was correlated with clinical pain severity. Compared to the rest phase, the pain phase produced increased S1 leg connectivity to the bilateral anterior insula in FM patients, but not in healthy controls. Moreover, in FM patients, sustained pain–altered S1 leg connectivity to the anterior insula was correlated with clinical/behavioral pain measures and autonomic responses. Conclusion Our study demonstrates that both somatic and nonsomatic dysfunction in FM, including clinical pain, pain catastrophizing, autonomic dysfunction, and amplified temporal summation, are closely linked with the degree to which evoked deep tissue pain alters S1 connectivity to salience/affective pain‐processing regions. Additionally, diminished connectivity between S1 subregions during the rest phase in FM may result from ongoing widespread clinical pain.
Early Response Evaluation in Malignant Pleural Mesothelioma by Positron Emission Tomography With [<sup>18</sup>F]Fluorodeoxyglucose
Authors: Giovanni L. Ceresoli, Arturo Chiti, Paolo A. Zucali, Marcello Rodari, Romano F. Lutman, Silvia Salamina, Matteo Incarbone, Marco Alloisio, Armando Santoro
Journal: Journal of Clinical Oncology (2006)

Response evaluation with conventional criteria based on computed tomography (CT) is particularly challenging in malignant pleural mesothelioma (MPM) due to its diffuse pattern of growth. There is growing evidence that therapy-induced changes in tumor [(18)F]fluorodeoxyglucose (FDG) uptake as measured by positron emission tomography (PET) may predict response and patient outcome early in the course of treatment.Patients with histologically proven MPM, not candidates to curative surgery, scheduled to undergo palliative chemotherapy with a pemetrexed-based regimen were eligible for this study. Patients were evaluated by FDG-PET and CT at baseline and after two cycles of therapy. A decrease of 25% or more in tumor FDG uptake as measured by standardized uptake value was defined as a metabolic response (MR). Best overall response from CT scans was determined according to previously published criteria.Twenty-two patients were included in the study, and 20 were assessable for early metabolic response with FDG-PET. Of these, eight were classified as responders (40%) and 12 as nonresponders (60%). Early MR was significantly correlated to median time-to-tumor progression (TTP) with a median TTP for metabolic responders of 14 months versus 7 months for nonresponders (P = .02). No correlation was found between TTP and radiologic response evaluated by CT. Patients with a MR had a trend toward longer overall survival.The use of MR evaluated by FDG-PET in the assessment of treatment efficacy in MPM appears promising. Our observations need to be validated in a larger prospective series.
Intratumoral <i>COX-2</i> Gene Expression Is a Predictive Factor for Colorectal Cancer Response to Fluoropyrimidine-Based Chemotherapy
Authors: Kazumi Uchida, Sylke Schneider, Ji Min Yochim, Hidekazu Kuramochi, Kazuhiko Hayashi, Ken Takasaki, Dongyun Yang, Kathleen D. Danenberg, Peter V. Danenberg
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Cyclooxygenase-2 (COX-2) is generally elevated in tumors compared with normal tissue and apparently has an important role in tumor development. A number of studies have found high expression of COX-2 to be an unfavorable prognostic factor for overall survival in several cancers. However, the influence of COX-2 expression levels on tumor response to chemotherapy has been relatively little studied. The purpose of this study was to ascertain if COX-2 gene expression is associated with tumor response in the clinical treatment of colorectal cancer with the fluoropyrimidine-based therapy S-1. Experimental Design: Patients with advanced (stage IV) colorectal cancer were treated with S-1 twice daily based on the patient's body surface area (BSA; BSA &amp;lt; 1.25 m2, 80 mg/d; 1.25 m2 ≤ BSA &amp;lt; 1.5 m2, 100 mg/d; BSA ≥ 1.5 m2, 120 mg/d) for 28 days followed by a 2-week period rest. mRNA was isolated from paraffin-embedded pretreatment primary tumor specimens and expression levels of COX-2 relative to β-actin as the internal reference gene were measured using a quantitative reverse transcription-PCR (Taqman) system. Results: The overall response rate in a group of 44 patients treated with S-1 was 40.9%. Sufficient tumor tissue was available from 40 of these patients for COX-2 mRNA quantitation. COX-2 gene expression was significantly lower in the responding tumors compared with the nonresponders (P = 0.012, Wilcoxon test). Patients with COX-2 values above the cutoff value of 3.28 × 10−3 had a significantly shorter survival than those with COX-2 gene expressions below the cutoff value (adjusted P = 0.031). Conclusions: Intratumoral COX-2 gene expression is associated with likelihood of response to chemotherapy with S-1 and is a prognostic factor for survival of patients after the start of S-1 chemotherapy.
Rosiglitazone Decreases C-Reactive Protein to a Greater Extent Relative to Glyburide and Metformin Over 4 Years Despite Greater Weight Gain
Authors: Steven E. Kahn, Steven M. Haffner, Giancarlo Viberti, William H. Herman, John M. Lachin, Barbara G. Kravitz, Dahong Yu, Gitanjali Paul, Rury R. Holman, Bernard Zinman
Journal: Diabetes Care (2009)

OBJECTIVE C-reactive protein (CRP) is closely associated with obesity and cardiovascular disease in both diabetic and nondiabetic populations. In the short term, commonly prescribed antidiabetic agents have different effects on CRP; however, the long-term effects of those agents are unknown. RESEARCH DESIGN AND METHODS In A Diabetes Outcome Progression Trial (ADOPT), we examined the long-term effects of rosiglitazone, glyburide, and metformin on CRP and the relationship among CRP, weight, and glycemic variables in 904 subjects over 4 years. RESULTS Baseline CRP was significantly correlated with homeostasis model assessment of insulin resistance (HOMA-IR), A1C, BMI, waist circumference, and waist-to-hip ratio. CRP reduction was greater in the rosiglitazone group by −47.6% relative to glyburide and by −30.5% relative to metformin at 48 months. Mean weight gain from baseline (at 48 months) was 5.6 kg with rosiglitazone, 1.8 kg with glyburide, and −2.8 kg with metformin. The change in CRP from baseline to 12 months was correlated positively with change in BMI in glyburide (r = 0.18) and metformin (r = 0.20) groups but not in the rosiglitazone (r = −0.05, NS) group. However, there was no longer a significant correlation between change in CRP and change in HOMA-IR, A1C, or waist-to-hip ratio in any of the three treatment groups. CONCLUSIONS Rosiglitazone treatment was associated with durable reductions in CRP independent of changes in insulin sensitivity, A1C, and weight gain. CRP in the glyburide and metformin groups was positively associated with changes in weight, but this was not the case with rosiglitazone.
More than 40% of cancer patients not seen by specialist in two weeks
Authors: Rebecca Coombes
Journal: BMJ (2005)

More than 40% of patients who go on to receive a diagnosis of cancer are not having their referrals classed as “urgent” by their GPs, with the result that they are not being seen by a specialist within two weeks, a report from the National Audit Office says.

In a survey in 2004 of 4000 patients in England with breast, lung, bowel, or prostate cancer—a repeat of a poll carried out in 2000—the watchdog body found that some types of patient are likely to be referred more quickly than others.

Patients with breast cancer were seen the quickest, with 70% seeing a specialist within two weeks. …
PPAD remains a credible candidate for inducing autoimmunity in rheumatoid arthritis: comment on the article by Konig <i>et al</i>
Authors: Anne-Marie Quirke, Karin Lundberg, Jan Potempa, Ted R Mikuls, Patrick J Venables
Journal: Annals of the Rheumatic Diseases (2014)

There is accumulating evidence that periodontitis is linked to rheumatoid arthritis (RA) and that this may be due to the pathogen Porphyromonas gingivalis possessing a peptidyl arginine deiminase (PPAD). This apparently unique bacterial enzyme is capable of producing citrullinated bacterial or host proteins which could break tolerance leading to the generation of autoantibodies in RA.1 We have previously shown that PPAD is autocitrullinated and there is an increased antibody response to PPAD in RA, which was due to reactions with autocitrullinated epitopes on the PPAD molecule.2 We were therefore interested to read the article by Konig et al 3 in which they confirm our findings that full-length recombinant PPAD is autocitrullinated, but showed that a truncated and secreted form of PPAD purified from supernatants of P. gingivalis cultures was not autocitrullinated. From this they concluded that autocitrullination was a feature of cloning, which would not occur in nature. However, growing bacteria in culture is not natural either. In vivo , at the site of infection, bacteria would be lysed …
Evaluation of an Alternate Dosing Strategy for Cisplatin in Patients With Extreme Body Surface Area Values
Authors: Walter J. Loos, Felix E. de Jongh, Alex Sparreboom, Ronald de Wit, Desiree M. van Boven-van Zomeren, Gerrit Stoter, Kees Nooter, Jaap Verweij
Journal: Journal of Clinical Oncology (2006)

Purpose The majority of cytotoxic drugs for adults are dosed based on body surface area (BSA), aiming to reduce interpatient variability in drug exposure. We prospectively studied the usefulness of BSA-based dosing of cisplatin in patients at extremes of BSA values. Patients and Methods Patients were randomly assigned to receive a fixed dose of cisplatin in course 1, and a BSA-adjusted dose in course 2, or vice versa. The fixed dose was based on the average BSA for males and females, while extremes were set at BSA values exceeding the average ± 1 standard deviation. Subsequently, we retrospectively analyzed data from a normal population. Results In 25 patients assessable for both courses, the use of a fixed dose of cisplatin resulted in reduced exposure to unbound platinum in patients at the upper extremes of BSA (P = .003) and higher exposures in patients at the lower extremes (P = .009), as compared with exposures following the BSA-adjusted dose. Although clearance was related to BSA (R 2 = 0.44; P &lt; .001), only a small reduction in interpatient variability in clearance after correction for BSA was achieved (20.8% v 17.1%). In the retrospective analysis, compared with the average patient, the clearance of unbound platinum in patients with a BSA value ≤ 1.65 m 2 was 16% slower (P &lt; .001), while an 18% faster clearance (P &lt; .001) was observed in patients with a BSA value ≥ 2.05 m 2 . Conclusion Unless better predictors for platinum clearance are identified, fixed-dose regimens per BSA cluster (≤ 1.65 m 2 ; 1.66 m 2 to 2.04 m 2 ; ≥ 2.05 m 2 ) are recommended.
The 6-year trajectory of non-traumatic knee symptoms (including patellofemoral pain) in adolescents and young adults in general practice: a study of clinical predictors
Authors: M Kastelein, P A J Luijsterburg, E M Heintjes, M van Middelkoop, J A N Verhaar, B W Koes, S M A Bierma-Zeinstra
Journal: British Journal of Sports Medicine (2014)

Aims (1) To assess the 1-year and 6-year courses of non-traumatic knee symptoms in adolescents and young adults presenting in general practice. (2) To identify prognostic factors for persistent knee symptoms at 1-year follow-up. Methods Adolescents and young adults (12–35 years; n=172) with non-traumatic knee symptoms were included in the cohort study by their general practitioner (GP) and followed for 6 years. Multivariable logistic regression analysis was used to identify prognostic factors for persistent knee symptoms at 1-year follow-up and the area under the receiver operating curve (AUC) was calculated. Results Persistent knee symptoms in patients receiving a GP diagnosis of unspecified knee symptoms were reported by 41% of the patients at 1-year follow-up and by 19% of the available patients at 6-year follow-up. Patients receiving a GP diagnosis of patellofemoral pain syndrome had the worse prognosis, with 40% reporting persistent knee symptoms at 6-year follow-up. Prognostic factors associated with persistent knee symptoms at 1-year follow-up were BMI &gt;25, low/middle education level, bilateral symptoms and self-reported absence of crepitus of the knee (AUC 0.80) for patients receiving a GP diagnosis of unspecified knee symptoms. For patients receiving a GP diagnosis of patellofemoral pain syndrome, prognostic factors were low/middle education level, poor health, having bilateral symptoms and self-report of a swollen knee (AUC 0.76). Conclusions The prognosis of non-traumatic knee symptoms in adolescents and young adults in general practice is not as good as was previously assumed. Several prognostic factors collected at baseline were associated with persistent knee symptoms at follow-up. However, the results should be replicated in another larger study.
Abbreviated Chemotherapy With Fludarabine Followed by Tositumomab and Iodine I 131 Tositumomab for Untreated Follicular Lymphoma
Authors: John P. Leonard, Morton Coleman, Lale Kostakoglu, Amy Chadburn, Ethel Cesarman, Richard R. Furman, Michael W. Schuster, Ruben Niesvizky, Daniel Muss, Jennifer Fiore, Stewart Kroll, George Tidmarsh, Shankar Vallabhajosula, Stanley J. Goldsmith
Journal: Journal of Clinical Oncology (2005)

To evaluate the safety and efficacy of a sequential chemotherapy plus radioimmunotherapy (RIT) regimen in previously untreated follicular non-Hodgkin's lymphoma.Thirty-five patients received an abbreviated course (three cycles) of fludarabine followed 6 to 8 weeks later by tositumomab and iodine I 131 tositumomab.After fludarabine, 31 (89%) of 35 patients responded, with three (9%) of 31 patients achieving a complete response (CR). After the full regimen of fludarabine and iodine I 131 tositumomab, all 35 patients responded; 30 (86%) of 35 patients achieved CR, and five (14%) of 35 achieved partial response. After a median follow-up of 58 months, the median progression-free survival (PFS) had not been reached (95% CI, 27 months to not reached), but it will be at least 48 months. The 5-year estimated PFS rate is 60%. Baseline Follicular Lymphoma International Prognostic Index (FLIPI) was significantly associated (P = .003) with PFS. Five of six patients with more than 25% bone marrow involvement at baseline achieved adequate bone marrow cytoreduction to receive standard-dose iodine I 131 tositumomab. Ten (77%) of 13 patients with baseline bone marrow Bcl-2 positivity demonstrated molecular remissions at month 12. Toxicities were manageable and principally hematologic. Two (6%) of 35 patients developed human antimurine antibodies (HAMA) after RIT.Use of abbreviated fludarabine before iodine I 131 tositumomab can reduce bone marrow involvement, when needed, to allow the use of RIT and can suppress HAMA responses. This sequential treatment regimen is highly effective as front-line therapy for follicular lymphoma, particularly for low- or intermediate-risk FLIPI patients.