tbuckley/cabot-search huggingface dataset:
Risk of Bilateral Renal Cell Cancer
Authors: Fredrik Wiklund, Steinar Tretli, Toni K. Choueiri, Sabina Signoretti, Katja Fall, Hans-Olov Adami
Journal: Journal of Clinical Oncology (2009)

The risk of developing bilateral kidney cancer has not been adequately defined in any large, population-based study with long-term follow-up to our knowledge.We estimated the risk of metachronous bilateral renal cell cancer in patients diagnosed with unilateral kidney cancer, as recorded in the nationwide cancer registries of Norway and Sweden. Altogether 28,642 patients were followed for an average of 4.4 years. The standardized incidence ratio--the ratio of the observed number of bilateral cancers to the number expected on the basis of the incidence in the Norwegian and Swedish population at large--was used as a measure of relative risk. We used multivariate Poisson regression to separate the effects of the explanatory variables.A synchronous bilateral renal cell cancer was reported in 86 patients. A total of 112 metachronous bilateral cancers were recorded during 126,493 person-years of follow-up compared with 35.8 expected, yielding an overall relative risk (RR) of 3.1 (95% CI, 2.6 to 3.8) and a cumulative incidence of 0.8% after 20 or more years of follow-up. In the multivariate analyses, risk increased monotonically with younger age at first diagnosis (P for trend < .001); compared with patients who were 60 years or older, those younger than 40 years were at a 17-fold higher risk (RR = 17.4; 95% CI, 10.1 to 29.8). We also found a modest but statistically significant decreasing trend with increasing duration of follow-up.The risk of metachronous bilateral renal cell cancer is drastically higher among patients first affected at a young age, suggesting a subset of early onset renal cell cancer with a strong genetic component.
Two-Year Outcome of a Combination of Weight Loss Therapies for Type 2 Diabetes
Authors: J. Bruce Redmon, Kristell P. Reck, Susan K. Raatz, Joyce E. Swanson, Christine A. Kwong, Hong Ji, William Thomas, John P. Bantle
Journal: Diabetes Care (2005)

OBJECTIVE—To evaluate the effects over 2 years of a weight loss program combining several weight loss strategies on weight loss and diabetes control in overweight subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 59 overweight or obese individuals with type 2 diabetes were randomly assigned to either a combination therapy weight loss program for 2 years (C therapy) or a standard therapy weight loss program for 1 year followed by a combination therapy weight loss program in the 2nd year (S/C therapy). C therapy combined the use of meal replacement products, repetitive intermittent low-calorie-diet weeks, and pharmacologic therapy with sibutramine. Outcome measures included changes in weight, glycemic control, plasma lipids, blood pressure, and body composition over 2 years. RESULTS—A total of 48 participants (23 in the C therapy group and 25 in the S/C therapy group) completed 2 years of study. After 2 years, the C therapy group had weight loss of 4.6 ± 1.2 kg (P &amp;lt; 0.001) and a decrease in HbA1c of 0.5 ± 0.3% (P = 0.08) from baseline. At 2 years, the C therapy group had significant reductions in BMI, fat mass, lean body mass, and systolic blood pressure. The S/C therapy group showed changes in weight and HbA1c in year 2 of the study that were similar to those demonstrated by the C therapy group in year 1. CONCLUSIONS—This combination weight loss program resulted in significant weight loss and improved diabetes control over a 2-year period in overweight subjects with type 2 diabetes.
Potential Utility of an Expression Array Signature for Predicting Anthracycline Responsiveness or Resistance
Authors: Michael F. Press, Michael A. Gordon, Dennis J. Slamon
Journal: Journal of Clinical Oncology (2011)

Breast cancers, like other malignancies, are heterogeneous in terms of their molecular genetic alterations, gene expression patterns, clinical outcomes, and response to various therapies. This complexity has been characterized with various methods including expression array analyses, which have been used to define breast cancer subtypes according to identified predominant patterns of gene expression (Table 1). These subclasses are correlated with clinical outcomes and, therefore, represent prognostic markers (Table 1). However, therapeutic decision making is now being primarily based on the status of individual predictive markers such as estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2). These markers are used to select patients for treatment with specific therapies including antiestrogens, HER2-targeted agents, and/or chemotherapeutics. RNA array analyses permit characterization of expression of individual markers on a gene-by-gene basis and allow for analyses of combinations of gene expression across the entire genome. This has allowed for correlation of various expression patterns with responsiveness to any of a number of administered therapies. Although it had been expected that such detailed analyses across the entire range of known genes would reveal clear patterns of gene expression closely associated with specific responses to particular treatments, this goal has remained largely elusive.
Tumor Site–Specific Silencing of <i>NF-κB p65</i> by Targeted Hollow Gold Nanosphere–Mediated Photothermal Transfection
Authors: Wei Lu, Guodong Zhang, Rui Zhang, Leo G. Flores, Qian Huang, Juri G. Gelovani, Chun Li
Journal: Cancer Research (2010)

Abstract NF-κB transcription factor is a critical regulator of the expression of genes involved in tumor formation and progression. Successful RNA interference (RNAi) therapeutics targeting NF-κB is challenged by small interfering RNA (siRNA) delivery systems, which can render targeted in vivo delivery, efficient endolysosomal escape, and dynamic control over activation of RNAi. Here, we report near-IR (NIR) light–inducible NF-κB downregulation through folate receptor–targeted hollow gold nanospheres carrying siRNA recognizing NF-κB p65 subunit. Using micro–positron emission tomography/computed tomography imaging, the targeted nanoconstructs exhibited significantly higher tumor uptake in nude mice bearing HeLa cervical cancer xenografts than nontargeted nanoparticles following i.v. administration. Mediated by hollow gold nanospheres, controllable cytoplasmic delivery of siRNA was obtained on NIR light irradiation through photothermal effect. Efficient downregulation of NF-κB p65 was achieved only in tumors irradiated with NIR light but not in nonirradiated tumors grown in the same mice. Liver, spleen, kidney, and lung were not affected by the treatments, in spite of significant uptake of the siRNA nanoparticles in these organs. We term this mode of action “photothermal transfection.” Combined treatments with p65 siRNA photothermal transfection and irinotecan caused substantially enhanced tumor apoptosis and significant tumor growth delay compared with other treatment regimens. Therefore, photothermal transfection of NF-κB p65 siRNA could effectively sensitize the tumor to chemotherapeutic agents. Because NIR light can penetrate the skin and be delivered with high spatiotemporal control, therapeutic RNAi may benefit from this novel transfection strategy while avoiding unwanted side effect. Cancer Res; 70(8); 3177–88. ©2010 AACR.
Antibody-mediated suppression of grafted lymphoma. IV. Influence of time of tumor residency in vivo and tumor size upon the effectiveness of suppression by syngeneic antibody.
Authors: H S Shin, J S Economou, G R Pasternack, R J Johnson, M L Hayden
Journal: The Journal of Experimental Medicine (1976)

In the suppression of the growth of a mouse lymphoma 6C3HED by antibody, the effectiveness of antibody in suppressing growing or established tumor cells and comparable number of freshly injected tumor cells is quantitatively similar. The effectiveness of antibody diminishes markedly when the number of tumor cells per mouse reaches the level of 10(6) due to the development of a macrophage shortage. At the 10(5) tumor cells level, antibody-mediated suppression takes place in an optimal manner and between 10(5) and 10(4) tumor cell numbers, the amount of antibody required to suppress 50% of the tumor cells is directly proportional to the number of tumor cells suppressed.
<i>CD14</i>polymorphisms, microbial exposure and allergic diseases: a systematic review of gene-environment interactions
Authors: M. Y. Z. Lau, S. C. Dharmage, J. A. Burgess, A. J. Lowe, C. J. Lodge, B. Campbell, M. C. Matheson
Journal: Allergy (2014)

Asthma and allergy may develop as a result of interactions between environmental factors and the genetic characteristics of an individual. This review aims to summarize the available evidence for, and potential effects of, an interaction between polymorphisms of the CD14 gene and exposure to microbes on the risk of asthma and allergic diseases. We searched PubMed, MEDLINE and Global Health databases, finding 12 articles which met inclusion criteria. Most studies reported a significant interaction between CD14 polymorphisms and microbial exposure. When stratified by age at microbial exposure (early life vs adult life), there was evidence of a protective effect of gene–environment interaction against atopy in children, but not adults. We also found different effects of interaction depending on the type of microbial exposures. There was no strong evidence for asthma and eczema. Future studies should consider a three-way interaction between CD14 gene polymorphisms, microbial exposures and the age of exposure.
High-Dose Granulocyte-Macrophage Colony-Stimulating Factor-Producing Vaccines Impair the Immune Response through the Recruitment of Myeloid Suppressor Cells
Authors: Paolo Serafini, Rebecca Carbley, Kimberly A. Noonan, Gladys Tan, Vincenzo Bronte, Ivan Borrello
Journal: Cancer Research (2004)

Abstract Tumor vaccines have shown promise in early clinical trials. Among them, tumor cells genetically engineered to secrete biologically active granulocyte-macrophage colony-stimulating factor (GM-CSF) can generate a systemic antitumor immune response. Although the minimal required GM-CSF dose produced by modified tumor cells to achieve a measurable antitumor effect is well known, no data examined whether an upper therapeutic limit may exist for this vaccination strategy. Because recent data demonstrate an immunosuppressive effect of GM-CSF produced by growing tumors, we thus sought to determine whether high GM-CSF doses administered in a vaccine formulation could impair antitumor immunity. Using a vaccine strategy involving a GM-CSF-producing bystander cell line (B78H1-GM) admixed with autologous tumor, we assessed the impact of varying doses of GM-CSF while maintaining a constant antigen dose. Our results defined a threshold above which a GM-CSF-based vaccine not only lost its efficacy, but more importantly for its clinical implications resulted in substantial immunosuppression in vivo. Above this threshold, GM-CSF induced Gr1+/CD11b+ myeloid suppressor cells that substantially impaired antigen-specific T-cell responses and adversely affected antitumor immune responses in vivo. The dual effects of GM-CSF are mediated by the systemic and not local concentration of this cytokine. Myeloid suppressor cell-induced immunosuppression is mediated by nitric oxide production via inducible nitric oxide synthase (iNOS) because the specific iNOS inhibitor, l-NMMA, restored antigen-specific T-cell responsiveness in vitro. Taken together, our data demonstrated the negative impact of supra-therapeutic vaccine doses of GM-CSF and underscored the importance of identifying these critical variables in an effort to increase the therapeutic efficacy of tumor vaccines.
A phase II study of lenalidomide in platinum-sensitive recurrent ovarian carcinoma
Authors: F. Selle, E. Sevin, I. Ray-Coquard, V. Mari, D. Berton-Rigaud, L. Favier, M. Fabbro, A. Lesoin, A. Lortholary, E. Pujade-Lauraine
Journal: Annals of Oncology (2014)
Identification of Overexpression and Amplification of <i>ABCF2</i> in Clear Cell Ovarian Adenocarcinomas by cDNA Microarray Analyses
Authors: Hiroshi Tsuda, Yoichi M. Ito, Yasuo Ohashi, Kwong-Kwok Wong, Yasunori Hashiguchi, William R. Welch, Ross S. Berkowitz, Michael J. Birrer, Samuel C. Mok
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Patients with ovarian clear cell adenocarcinoma generally have a poor response to combination chemotherapy and have overall poorer prognosis than patients with other histologic types of ovarian cancer. Genetic changes in this group of cancer have not been thoroughly explored. Identification of these changes may provide us new therapeutic targets to treat this disease. Experimental Design: Genomic and expression array analyses were applied on 30 clear cell ovarian cancer cases and 19 serous cases using a 10,816-element cDNA microarray platform. Further validation and clinical correlation studies were done on differentially expressed genes that are related to chemoresistance. Results: Based on array analyses, 12 genes showed a significant increase in DNA and mRNA copy number and 5 genes showed a significant decrease in DNA and RNA copy number in clear cell tumors compared with those in the serous type. One of the genes was ABCF2, which belongs to the ATP-binding cassette gene superfamily and has been shown to amplify in other tumor types. Validation studies were done using real-time quantitative PCR and immunohistochemistry. The results showed significantly higher ABCF2 DNA and mRNA copy number and protein levels in clear cell cases compared with those in serous cases. Furthermore, in 20 clear cell cases with chemoresponse data available, ABCF2 cytoplasmic staining was significantly higher in nonresponders than that in the responders (60.0% versus 28.5%; P = 0.0002). Conclusions: These data suggest that ABCF2 protein may be a prognostic marker for ovarian clear cell ovarian adenocarcinoma.
Factitial Weber-Christian Syndrome
Authors: A. Bernard Ackerman
Journal: JAMA (1966)

A unique psychocutaneous syndrome characterized by relapsing febrile nodular nonsuppurative panniculitis was seen in a teenage girl. Her disease, thought to be Weber-Christian syndrome clinically and pathologically, was eventually discovered to be caused by self-injections of milk. The bizarre pattern of typical factitial dermatitis is easily recognized, but exceptional cases may closely resemble authentic disease. Although factitial dermatitis may be associated with many different psychiatric conditions, the highest suspicion should be reserved for the hysterical personality. The characteristic behavior of the hysterical personality can alert the clinician to the possibility of factitial dermatitis.
VH mutation status and VDJ rearrangement structure in mantle cell lymphoma: correlation with genomic aberrations, clinical characteristics, and outcome
Authors: Dirk Kienle, Alexander Kröber, Tiemo Katzenberger, German Ott, Elke Leupolt, Thomas F. E. Barth, Peter Möller, Axel Benner, Annett Habermann, Hans Konrad Müller-Hermelink, Martin Bentz, Peter Lichter, Hartmut Döhner, Stephan Stilgenbauer
Journal: Blood (2003)
Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128
Authors: Yogita K Adlakha, Neeru Saini
Journal: Molecular Cancer (2014)

MicroRNAs, the non-coding single-stranded RNA of 19-25 nucleotides are emerging as robust players of gene regulation. Plethora of evidences support that the ability of microRNAs to regulate several genes of a pathway or even multiple cross talking pathways have significant impact on a complex regulatory network and ultimately the physiological processes and diseases. Brain being a complex organ with several cell types, expresses more distinct miRNAs than any other tissues. This review aims to discuss about the microRNAs in brain development, function and their dysfunction in brain tumors. We also provide a comprehensive summary of targets of brain specific and brain enriched miRNAs that contribute to the diversity and plasticity of the brain. In particular, we uncover recent findings on miRNA-128, a brain-enriched microRNA that is induced during neuronal differentiation and whose aberrant expression has been reported in several cancers. This review describes the wide spectrum of targets of miRNA-128 that have been identified till date with potential roles in apoptosis, angiogenesis, proliferation, cholesterol metabolism, self renewal, invasion and cancer progression and how this knowledge might be exploited for the development of future miRNA-128 based therapies for the treatment of cancer as well as metabolic diseases.
Erratum: Corrigendum: Germline KRAS mutations cause Noonan syndrome
Authors: Suzanne Schubbert, Martin Zenker, Sara L Rowe, Silke Böll, Cornelia Klein, Gideon Bollag, Ineke van der Burgt, Luciana Musante, Vera Kalscheuer, Lars-Erik Wehner, Hoa Nguyen, Brian West, Kam Y J Zhang, Erik Sistermans, Anita Rauch, Charlotte M Niemeyer, Kevin Shannon, Christian P Kratz
Journal: Nature Genetics (2006)
Turning Point for Colorectal Cancer Clinical Trials
Authors: Neal J. Meropol
Journal: Journal of Clinical Oncology (2006)

The recent introduction of therapeutic antibodies for the treatment of patients with colorectal cancer has garnered welldeserved attention and excitement. 1-4 However, it is notable that traditional cytotoxics remain the backbone of systemic therapy for this disease. The benefits of both bevacizumab and cetuximab are augmented by concurrent administration of chemotherapy. 2,3 In fact, both of these targeted therapeutics may be appropriately viewed as chemotherapy sensitizers. Therefore, efforts to refine understanding and optimize the clinical use of available cytotoxics remain important. In this issue, Goldberg et al 5 report outcomes for a subset of patients enrolled onto North Central Cancer Treatment Group trial9741,aNorthAmericanintergroupstudyofinitialtherapyfor patientswithmetastaticcolorectalcancer.Thelatestdatafromthis rich clinical resource continue to answer relevant clinical questions, while highlighting those that remain. In addition, the design andconductofthistrialillustratehowtheworldofclinicalresearch in colorectal cancer has evolved over the past decade. North Central Cancer Treatment Group trial 9741 was the first phase III cooperative group study to move beyond the question of how best to deliver fluorouracil (FU). 6 It was designed at a time when irinotecan and oxaliplatin were new to our armamentarium. Whereas irinotecan was commercially available at the initiation of this trial, oxaliplatin was not. The study began as a six-arm trial. Bolus FU/leucovorin (LV) was the control arm, with two irinotecan plus FU/LV schedules, two oxaliplatin plus FU/LV schedules, and a nonfluoropyrimidine irinotecan plus oxaliplatin arm. 7 After the study was initiated, emerging data showed improved survival for irinotecan/FU/LV compared with FU/LV, and a new standard treatment for patients with metastatic colorectal cancer was established. Consequently, the FU/LV control arm was deleted. In addition, the arms containing a daily times five bolus schedule of FU/LV with either oxaliplatin or irinotecan, which were regimens that had not undergone extensive previous clinical testing, proved too toxic and were also discontinued. The initial inclusionofthesearmsrepresentedanewlevelofconfidencebythe GI intergroup in the ability to successfully monitor toxicity in real time and react rapidly with appropriate protocol modification if needed. Thus, 9741 was reduced to the following three arms: weekly irinotecan/FU/LV (IFL), biweekly oxaliplatin/bolus plus infusional FU/LV (FOLFOX4), and 3-weekly irinotecan plus oxaliplatin. Approximately 1 year after the three-arm design was
Whole-Body Dual-Modality PET/CT and Whole-Body MRI for Tumor Staging in Oncology
Authors: Gerald Antoch, Florian M Vogt, Lutz S Freudenberg, Fridun Nazaradeh, Susanne C Goehde, Jörg Barkhausen, Gerlinde Dahmen, Andreas Bockisch, Jörg F Debatin, Stefan G Ruehm
Journal: JAMA (2003)

ContextDeciding on the appropriate therapy for patients with malignant diseases mandates accurate tumor staging with whole-body coverage. Magnetic resonance imaging (MRI) and a combined modality including positron emission tomography (PET) and computed tomography (CT) provide whole-body tumor staging in a single session.ObjectiveTo determine the staging accuracies of both whole-body PET/CT and whole-body MRI for different malignant diseases.Design, Setting, and PatientsProspective, blinded, investigator-initiated study of 98 patients (mean age, 58 years; range, 27-94 years) with various oncological diseases who underwent back-to-back whole-body glucose analog [18F]-fluorodeoxyglucose–PET/CT and whole-body MRI for tumor staging. The study was conducted at a university hospital from December 2001 through October 2002 and had a mean follow-up of 273 days (range, 75-515 days). The images were evaluated by 2 different, blinded reader teams. The diagnostic accuracies of the 2 imaging procedures were compared.Main Outcome MeasuresCorrect classification of the primary tumor, regional lymph nodes, and distant metastasis (overall TNM stage) using whole-body PET/CT and whole-body MRI. Secondary outcome measures were accurate assessment of T-stage, N-stage, and M-stage by the 2 imaging procedures.ResultsOf 98 patients, the overall TNM stage was correctly determined in 75 with PET/CT (77%; 95% confidence interval [CI], 67%-85%) and in 53 with MRI (54%; 95% CI, 44%-64%) (P&lt;.001). Compared with MRI, PET/CT had a direct impact on patient management in 12 patients. Results from MRI changed the therapy regimen in 2 patients compared with PET/CT. Separate assessment of T-stage (with pathological verification) in 46 patients revealed PET/CT to be accurate in 37 (80%; 95% CI, 66%-91%) and MRI to be accurate in 24 (52%; 95% CI, 37%-67%) (P&lt;.001). Of 98 patients, N-stage was correctly determined in 91 patients with PET/CT (93%; 95% CI, 86%-97%) and in 77 patients with MRI (79%; 95% CI, 69%-86%) (P = .001). Both imaging procedures showed a similar performance in detecting distant metastases.ConclusionsThe feasibility and diagnostic accuracy of the whole-body staging strategies of PET/CT and MRI are established. Superior performance in overall TNM staging suggests the use of [18F]-fluorodeoxyglucose–PET/CT as a possible first-line modality for whole-body tumor staging.