tbuckley/cabot-search huggingface dataset:
[<sup>18</sup>F]Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET)/Computed Tomography (CT) in Suspected Recurrent Breast Cancer: A Prospective Comparative Study of Dual-Time-Point FDG-PET/CT, Contrast-Enhanced CT, and Bone Scintigraphy
Authors: Malene Grubbe Hildebrandt, Oke Gerke, Christina Baun, Kirsten Falch, Jeanette Ansholm Hansen, Ziba Ahangarani Farahani, Henrik Petersen, Lisbet Brønsro Larsen, Sandra Duvnjak, Inguna Buskevica, Selma Bektas, Katrine Søe, Anne Marie Bak Jylling, Marianne Ewertz, Abass Alavi, Poul Flemming Høilund-Carlsen
Journal: Journal of Clinical Oncology (2016)

To prospectively investigate the diagnostic accuracy of [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) with dual-time-point imaging, contrast-enhanced CT (ceCT), and bone scintigraphy (BS) in patients with suspected breast cancer recurrence.One hundred women with suspected recurrence of breast cancer underwent 1-hour and 3-hour FDG-PET/CT, ceCT, and BS within approximately 10 days. The study was powered to estimate the precision of the individual imaging tests. Images were visually interpreted using a four-point assessment scale, and readers were blinded to other test results. The reference standard was biopsy along with treatment decisions and clinical follow-up (median, 17 months).FDG-PET/CT resulted in no false negatives and fewer false positives than the other imaging techniques. Accuracy of results were similar for 1-hour and 3-hour FDG-PET/CT. For distant recurrence, the area under the receiver operating curve was 0.99 (95% CI, 0.97 to 1) for FDG-PET/CT, 0.84 (95% CI, 0.73 to 0.94) for ceCT, and 0.86 (95% CI, 0.77 to 0.94) for the combined ceCT+BS. Of 100 patients, 22 (22%) were verified with distant recurrence, and 18 of these had bone involvement. Nineteen patients (19%) had local recurrence only. In exploratory analyses, diagnostic accuracy of FDG-PET/CT was better than ceCT alone or ceCT combined with BS in diagnosing distant, bone, and local recurrence, shown by a greater area under the receiver operating curve and higher sensitivity, specificity, and superior likelihood ratios.FDG-PET/CT was accurate in diagnosing recurrence in breast cancer patients. It allowed for distant recurrence to be correctly ruled out and resulted in only a small number of false-positive cases. Exploratory findings suggest that FDG-PET/CT has greater accuracy than conventional imaging technologies in this patient group.
First Genome-Wide Mutational Map of Macaques a Boon for Evolutionary Studies
Authors: Joseph Caspermeyer
Journal: Molecular Biology and Evolution (2016)

Scientists have long used comparative animal studies to better understand the nuances of human evolution, from making diverse body plans to the emergence of entirely powerful and unique features structures, including the human brain. Now, in a new study appearing in the advanced online edition of Molecular Biology and Evolution, corresponding authors Perdomo-Sabogal et al. (2016) have explored the global gene regulator GABPa to better understand its influence as a master switch. Their work honed in on human-specific DNA regions potentially contributing to human evolution in key functions including cell energy, division and death, and diseases ranging from brain disorders to diabetes. Many of the GABPa gene regulatory sites were found to be significantly enriched at genes important for brain, central nervous system and spinal cord functions that are unique to humans, an area ripe for future research, and GABPa deficits linked to Alzheimer’s and Parkinson diseases, breast cancer, and autism. GABPa exerts its profound genomic influence by a tandem repeat of four highly conserved DNA letters. The GGAA consensus motif is found to control genes in all primates, mice, dogs, and cows, underscoring its importance in these animals. By performing ChIP-Seq experiments in a human cell line, the group found that GABPa exercises its influence across the genome at 11,619 putative GABPa binding sites representing nearly 4,000 genes. Through a tour de force sequence comparison of the human GABPa binding sites with similar sequences from 34 mammals, they identified 224 GABPa binding sites unique to humans. Comparing chimpanzee, macaque, and human cell lines and mutating the GGAA sequence to more ancestral states to determine how these changes affected GABPa function, they further narrowed down their function. For instance, when the human GABPa binding sites were introduced into primate cells, gene expression was increased up to five times in 17 out of 18 cases, indicating that a recent human mutation in GABPa resulted in higher gene expression and forces behind the evolution of novel, uniquely human functions. “Mutations that cause changes in the regulation of gene activities are one of the major factors in shaping species during evolution,” said corresponding author Robert Querfurth. “Our study demonstrates how, out of the millions of DNA regions, in which we differ from other apes, we can sift out those that, in response to a specific regulatory protein, cause gene activity changes in human cells. In this set, we find genes involved in brain and breast development and also in diseases like Alzheimer’s and Parkinson’s.”
Efficacy and Safety of APO866 in Patients With Refractory or Relapsed Cutaneous T-Cell Lymphoma
Authors: Simone M. Goldinger, Sharon Gobbi Bischof, Regina Fink-Puches, Claus-Detlev Klemke, Brigitte Dréno, Martine Bagot, Reinhard Dummer
Journal: JAMA Dermatology (2016)

analyses: Clark level (II-III and unknown or IV-V), thickness (≤0.75 mm or 0.76-1 mm), tumor-infiltrating lymphocytes (present or absent), and mitoses (present or absent).For lesions in which an individual characteristic was not reported, the characteristic was recorded as unknown.Only patients with known mitotic rate data were included in the regression analyses (n = 698). 5Histologic subtype was not included in the previous analysis, thus providing the basis for this reanalysis.This study was approved, with a waiver for patient informed consent, by the Institutional Review Board of the University of Pennsylvania. Results |In our new prognostic model inclusive of histologic subtype, univariable analysis identified nodular melanoma (OR, 3.80) and acral lentiginous melanoma (ALM) (OR, 8.17) (P = .01for both) as factors significantly associated with SLN positivity.By multivariable logistic regression analysis, ALM remained a factor significantly associated with SLN positivity (OR, 16.02; P = .004),as did increased Clark level (OR, 3.04; P = .02)and mitotic rate of 1 mm 2 or more (OR, 6.04; P = .01).Sentinel lymph node positivity was found in 2 of 10 patients (20%) with ALM, 5 of 48 patients (10%) with nodular melanoma, 14 of 534 patients (3%) with superficial spreading melanoma, and none of 37 patients with lentigo maligna melanoma.Of the patients in the group with ALM, 9 of 10 (90%) were non-Hispanic white and 1 of 10 (10%) was Hispanic white.Nine of the 10 ALM lesions were found on the foot and 1 ALM lesion was found on the hand.Thickness (OR, 2.22; P = .09)and nodular melanoma (OR, 2.48; P = .09)showed a trend toward, but did not reach, statistical significance in our model (Table ).Discussion | The reanalysis found that the histologic subtype of ALM as well as mitoses and Clark level IV-V were independent predictors of SLN positivity.This finding is limited, however, by the relatively small number of patients (n = 10) with ALM in the cohort on which the reanalysis was done.The finding of ALM as a predictor of SLN metastasis should be further confirmed in other studies.Although the rate of SLN positivity was low for the study cohort of patients with thin melanomas (3.7%), a subset of patients can be identified with appreciable rates of nodal metastasis, who can be stratified for risk by the Clark level, mitotic rate, and histologic subtype of their melanoma.Further study of these factors can help guide clinical decision-making in patients with thin melanomas.
Potential molecular prognostic factors in non-small cell lung cancer (NSCLC) patients treated with gefitinib
Authors: C. Polowy, J. Coon, V. Villaflor, W. Leslie, I. Lukic, G. Kanevsky, M. Gale, I. Stewart, P. Bonomi
Journal: Journal of Clinical Oncology (2004)

7089 Background: Phase II studies have shown that gefitinib produces a 10% response rate in previously treated patients(pts) with NSCLC. Little is known about the relationship between molecular profiles and NSCLC response to gefitinib. The goal of this study was to assess IHC for EGFR, IGFR, VEGF expression and FISH for EGFR amplification as predictors of response to gefitinib. Methods:A total of 143 consecutive pts were enrolled in the Expanded Access Trial; seven pts died prior to starting gefitinib; one withdrew consent before treatment. Only pts who had > 1 week of therapy were included in the analysis. Results:126 pts(64 female, 62 male, median age 68, 67 adenocarcinomas/59 others) received gefitinib; median follow-up was 169 days. Overall response rate was 5.6%(1CR,6PR) and 24 pts(19%) had stable disease(SD). Median Kaplan-Meier survival and progression-free interval (PFI) were 172 and 59 days, respectively. The Fisher's Exact Test was used to evaluate associations. A greater proportion of pts with adenocarcinoma responded or had stable disease(p=.08). Of the 126 pts treated, 52 had tissue available for molecular profiles. None of the 28 pts who lacked expression of EGFR by IHC responded to gefitinib compared to 5 responses (CR+PR) in the 24 patients with EGFR positive tumors (p<.02). Median PFI for pts with and without EGFR expression was 102 and 75 days, respectively (Log-Rank p=.2563). For 21/50 pts with both EGFR expression and chromosome copy 7 number (FISH ≥2.5, five (24%) responded (CR+PR) compared to 0% of the 29 other pts (p<.001). 11 pts had EGFR amplification by FISH (≥1.5,Vysis SpectrumOrange-LSI EGFR probe) which was associated with EGFR expression (p=.064), and adenocarcinoma (p<.09).There was a positive association between EGFR expression and IGFR expression (p<.09) Conclusions:Defining molecular profiles for response to gefitinib is still at an early stage. Detectable EGFR expression and chromosome 7 copy number may have predictive value for response in pts treated with gefitinib. The association between EGFR expression IGFR expression in this small study suggests that further investigation of molecular markers is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb AstraZeneca
Population pharmacokinetics and pharmacodynamics of irinotecan (CPT-11) and active metabolite SN-38 during phase I trials
Authors: G G Chabot, D Abigerges, G Catimel, S Culine, M de Forni, J M Extra, M Mahjoubi, P Hérait, J P Armand, R Bugat
Journal: Annals of Oncology (1995)
Detoxification recidivism among urban American Indian alcoholics
Authors: D R Kivlahan, R D Walker, D M Donovan, H D Mischke
Journal: American Journal of Psychiatry (1985)

Fifty urban American Indians were interviewed during admission to a free-standing medical detoxification unit. From the year before the interview through 2 years of follow-up, this sample averaged 44.6 detoxification admissions and 64.1 days in other inpatient treatment and had no significant change in the number of annual detoxification admissions. At follow-up all but three subjects reported recent alcohol dependence symptoms or episodic alcohol abuse. these patients continued to experience serious alcohol-related problems despite repeated treatment in both medical detoxification and inpatient rehabilitation settings. These findings emphasize the need for more innovative and effective alternatives to the existing revolving door process.
Maternity care varies widely across England, report shows
Authors: Jacqui Wise
Journal: BMJ (2016)

Maternity units in England show considerable variation in practice, with emergency caesarean rates ranging from 8% to 15%, a report from the Royal College of Obstetricians and Gynaecologists shows.

The report, Patterns of Maternity Care in English NHS Trusts 2013/14 ,1 found that 55% of first time mothers had some form of intervention during labour and delivery. Rates of unassisted vaginal delivery among primiparous women ranged from 33% to 62% within individual NHS trusts, after adjusting for clinical and demographic factors. The rates of instrumental delivery ranged from 19% to 29%, and episiotomy rates ranged from 29% to 44%.

The mean …
Abstract 278: Domain-specific Roles for GRK2 in Cardiac Hypertrophy and Heart Failure
Authors: Sarah M Schumacher, Erhe Gao, J. Kurt Chuprun, Walter J. Koch
Journal: Circulation Research (2016)

During heart failure (HF), cardiac levels and activity of the G protein-coupled receptor (GPCR) kinase (GRK) GRK2 are elevated and contribute to adverse remodeling and contractile dysfunction, while inhibition via a carboxyl-terminal peptide, βARKct, enhances heart function and can prevent HF. Mounting evidence supports the idea of a dynamic “interactome” in which GRK2 can uncouple GPCRs via novel protein-protein interactions. Several GRK2 interacting partners are important for adaptive and maladaptive myocyte growth; therefore, an understanding of domain-specific interactions with signaling and regulatory molecules could lead to novel targets for HF therapy. For instance, GRK2 contains a putative amino-terminal R egulator of G protein S ignaling (RGS) domain (βARKrgs) that directly interacts with Gαq and inhibits signaling. Previously, our lab investigated cardiac-specific transgenic expression of a fragment of this RGS domain (βARKnt), that did not reduce acute hypertrophy after pressure overload or demonstrate RGS activity in vivo against Gαq-mediated signaling. In contrast, βARKnt induced hypertrophy and elevated β-adrenergic receptor (βAR) density without altering agonist-induced contractility or adenylyl cyclase activity, due to a compensatory increase in GRK2 activity. Importantly, βAR downregulation in response to chronic agonist administration was attenuated by βARKnt expression, indicating a novel regulation of βAR receptor density. Herein, we investigated the effect of βARKnt expression during chronic pressure overload post trans-aortic constriction (TAC). Echocardiographic analysis revealed increased posterior wall thickness and left-ventricular mass 4 weeks post-TAC compared to non-transgenic littermate controls. Importantly, despite enhanced hypertrophy, the progression to HF was inhibited in βARKnt mice 14 weeks post-TAC. Histological analysis of interstitial fibrosis and cross-sectional area is underway to determine alterations in maladaptive remodeling. Further, cardiomyocyte signaling and βARKnt protein-binding partners are a focus, since our data indicate that βARKnt-mediated regulation of βAR density may provide a novel means of cardioprotection during pressure-overload induced HF.
Breast Cancer
Authors: Robert W. Carlson, D. Craig Allred, Benjamin O. Anderson, Harold J. Burstein, W. Bradford Carter, Stephen B. Edge, John K. Erban, William B. Farrar, Lori J. Goldstein, William J. Gradishar, Daniel F. Hayes, Clifford A. Hudis, Mohammad Jahanzeb, Krystyna Kiel, Britt-Marie Ljung, P. Kelly Marcom, Ingrid A. Mayer, Beryl McCormick, Lisle M. Nabell, Lori J. Pierce, Elizabeth C. Reed, Mary Lou Smith, George Somlo, Richard L. Theriault, Neal S. Topham, John H. Ward, Eric P. Winer, Antonio C. Wolff
Journal: Journal of the National Comprehensive Cancer Network (2009)

NCCN Categories of Evidence and ConsensusCategory 1: The recommendation is based on high-level evidence (e.g., randomized controlled trials) and there is uniform NCCN consensus.Category 2A: The recommendation is based on lower-level evidence and there is uniform NCCN consensus.Category 2B: The recommendation is based on lower-level evidence and there is nonuniform NCCN consensus (but no major disagreement).Category 3: The recommendation is based on any level of evidence but reflects major disagreement.All recommendations are category 2A unless otherwise noted.The Breast Cancer Clinical Practice Guidelines presented here are the work of the members of the NCCN Breast Cancer Clinical Practice Guidelines Panel.Categories of evidence were assessed and are noted on the algorithms and in the text.Although not explicitly stated at every decision point of the Guidelines, patient participation in prospective clinical trials is the preferred option of treatment for all stages of breast cancer.The full breast cancer guidelines are not printed in this issue of JNCCN, but can be accessed online at www.nccn.org.
Phenotypic Expression of Drug Resistance in Hybrid Cells 2
Authors: Morgan Harris
Journal: JNCI Journal of the National Cancer Institute (1973)

Patterns of phenotypic expression have been examined for two drug resistance markers originating by de novo variation in clonal lines of Chinese hamster cells. Sublines sensitive and resistant to cytosine arabinoside (ara-C) and vinblastine sulfate (VEL) were derived by selection from mass populations with the two inhibitors. Clonal derivatives of these lines were used to construct hybrids by spontaneous fusion in mixed cultures; the resulting hybrids were isolated in HAT medium without selective pressure on ara-C or VEL markers. Hybrids and parental lines were assayed by plating efficiency tests for resistance to VEL and ara-C. The results show that VEL resistance is expressed as a dominant or codominant characteristic, while resistance to ara-C is uniformly recessive. No cross-resistance or interaction between the two markers was observed. A variable factor in different lots of serum conditioned the toxicity of VEL; this effect was absent with ara-C.
Prevalence and Clinical Outcomes for Patients with Met Protein Expression in Patients with Non-Small Cell Lung Cancer in Europe: Results from the European Thoracic Oncology Platform Lungscape Project
Authors: L. Bubendorf, O. Dafni, V. Tischler, S. Finn, W. Biernat, E. Verbeken, H. Hager, N. Murtra, E. Thunnissen, D. Nonaka, A. Warth, E.J. Speel, S. Savic, M. Martorell, Z. Tsourti, K. Schulze, A. Das-Gupta, K.M. Kerr, S. Peters, R.A. Stahel
Journal: Annals of Oncology (2014)
Screening for Gonorrhea, Chlamydia, and Hepatitis B
Authors: Audrey Tanksley, Adam S. Cifu
Journal: JAMA (2016)

The incidence of STIs is increasing, and these infections cause significant health and economic burden.1 The Centers for Disease Control and Prevention (CDC) reported that an estimated 1.4 million new cases of chlamydia and 350 000 cases of gonorrhea occurred in 2014.2 The highest-risk age group is between 15 and 29 years, but cases are seen at every age. Adding to the burden of the diseases, many infections are undiagnosed and untreated, potentially leading to late-term complications such as pelvic inflammatory disease, neonatal illness, and infertility. The CDC estimates that approximately 24 000 US women develop infertility related to STIs.3 Between 700 000 and 2.2 million people in the United States are infected with hepatitis B.4 Left untreated, 15% to 25% of these people will die of hepatic decompensation or hepatocellular carcinoma. Screening and early diagnosis have the potential to decrease both the complications and transmission of gonorrhea, chlamydia, and hepatitis B
Design and interpretation of clinical trials that evaluate agents that may offer protection from the toxic effects of cancer chemotherapy.
Authors: K A Phillips, I F Tannock
Journal: Journal of Clinical Oncology (1998)

PURPOSE To review the features of randomized clinical trials (RCTs) used in the development of agents that may protect against chemotherapy-induced toxicities, including trials of the cardioprotective agent dexrazoxane, hematologic growth factors, and amifostine; to suggest recommendations based on information gained from such trials and improvements in the design of ongoing and future trials. METHODS Critical review of reports of RCTs obtained from a Medline search, references from these articles, and review of trials listed in the physician data query (PDQ) clinical trials data base. RESULTS Several of the phase III trials did not use a format of comparing widely accepted strategies of chemotherapy with and without a protective agent. Instead, patients in the control arms of some of the trials have been exposed to more prolonged use or increased dosage of toxic chemotherapy that placed them at greater risk of the toxicity the protective agent was designed to prevent (eg, cardiotoxicity in trials of dexrazoxane, myelosuppression or thrombocytopenia in trials of growth factors). CONCLUSION RCTs have shown clear evidence of biologic activity for the protective agents, but this does not imply therapeutic benefit as compared with alternative strategies such as avoidance of prolonged use of cardiotoxic agents or use of standard doses of chemotherapy. Ongoing and future trials of protective agents should be modified to avoid undue risk to patients.
Estimating survival probability in stage III melanoma: A multivariable individualized patient risk assessment nomogram
Authors: D. G. Coit, C. Qin Zhou, A. Patel, K. Panageas
Journal: Journal of Clinical Oncology (2006)

8020 Background: Recent revisions in the AJCC staging system have increased its complexity without comparable improvement in prognostic accuracy for patients with Stage III melanoma. Furthermore, there remains significant prognostic heterogeneity, even within Stages IIIA, IIIB, and IIIC. The current study was undertaken to develop a model for individual patient risk assessment, both to facilitate patient care, and to help define prognostically homogeneous patient populations for entry into clinical trials. Methods: Patients with AJCC Stage III melanoma were identified from a prospective single institution database. Overall survival was calculated from the date of Stage III to last followup. A multivariate Cox model of independent prognostic factors was developed, and a multivariable individualized patient risk assessment nomogram was built from that model. Results: Among 1,064 patients with Stage III melanoma, 535 have died, at a median followup of 44 months. Independent predictors of overall survival are shown in the table. Individual patient three and five year survival was predicted by incorporating all eight variables into a prognostic nomogram. The nomogram was superior to the AJCC Staging system in predicting outcome in Stage III melanoma patients. Conclusions: Individual patient risk assessment is more accurate than traditional AJCC staging in predicting outcome in Stage III melanoma. This approach, which can be easily incorporated into a handheld computing environment, offers potential advantages for both patient care and clinical research, and should be explored in the next iteration of the AJCC staging system. [Table: see text] No significant financial relationships to disclose.
Development and analysis of patient-derived xenograft mouse models in intravascular large B-cell lymphoma
Authors: K Shimada, S Shimada, K Sugimoto, M Nakatochi, M Suguro, A Hirakawa, T D Hocking, I Takeuchi, T Tokunaga, Y Takagi, A Sakamoto, T Aoki, T Naoe, S Nakamura, F Hayakawa, M Seto, A Tomita, H Kiyoi
Journal: Leukemia (2016)