tbuckley/cabot-search huggingface dataset:
Margaret McCartney: Nagging people is a futile exercise
Authors: Margaret McCartney
Journal: BMJ (2015)

We’re bossy and boring. Do more exercise! Take the stairs! Have you done your 30 minutes today? Exercise is promoted as a moral good, something to which responsible citizens should be enslaved, or at least devoted.

We are all urged to exercise regularly to save the NHS money in the long term, to stop us getting fat, getting diabetes, Alzheimer’s disease, depression—and from infarcting our myocardiums. We are repeatedly told of a host of diseases that we might experience if we dare not clothe ourselves in Lycra and step up to the treadmill. In short, we are oppressed by medical do-gooders, nagging us to do more and guilt tripping us into going to the gym.

Doctors are not immune to …
Endoscopic ultrasonography for pancreatic cystic lesions: let’s enhance it
Authors: Marcin Polkowski
Journal: Endoscopy (2015)

Pancreatic cysts[*] are associated with the risk of malignancy; however, recent data suggest that this risk has been overstated. As estimated in a model that takes into account the prevalence of pancreatic cyst in the US adult population and the annual number of cancers attributable to cystic precursors, the risk that an incidental cyst is malignant at the time of diagnosis is only 0.01 %. Moreover, the risk remains low (0.25 %) even under the extreme assumption that all pancreatic malignancies develop from cystic precursors [1]. This low baseline risk is modified by several factors, such as cyst size, presence of mural nodules or solid component, concomitant dilatation of the pancreatic duct, and possibly other, less well-established, predictors of malignancy [1]. Current guidelines recommend resection of cysts with risk factors and surveillance of those without [1] [2] [3]. Unfortunately, the strategies to stratify the risk have a low positive predictive value (PPV) and only 25 % of individuals who meet the criteria for resection have high grade dysplasia (HGD) or invasive carcinoma in the resected specimen (collectively referred to here as “malignancy”) [4]. The remaining 75 % undergo major surgery associated with significant mortality (2 % at high volume centers and 6 % overall), only to discover that their cyst had low malignant potential [1]. Some may find this risk acceptable because resection of a potentially malignant cyst prevents its future malignant transformation; however, the overall risk of developing carcinoma during surveillance is relatively low, between 0.24 % and 0.7 % per year, and most likely lower for cysts without HGD [1].
Abstract MP55: Electrocardiographic versus Echocardiographic Left Ventricular Hypertrophy in Prediction of Congestive Heart Failure in the Elderly
Authors: Mohamed Faher Almahmoud, Elsayed Soliman, Waqas Qureshi, Wesley T O'Neal
Journal: Circulation (2015)

Background: Left ventricular hypertrophy (LVH) is an established risk factor for congestive heart failure (HF) and is a component of the Framingham HF Risk Score (FHFRS). Whether LVH detected by electrocardiogram (ECG-LVH) is equally predictive of HF as LVH detected by echocardiography (Echo-LVH) is unclear. Methods: This analysis included 4,543 participants (85% white; 41% male) aged 65 years or older from the Cardiovascular Health Study (CHS) who were free of HF and major intraventricular conduction defects at baseline. Adjudicated incident HF was identified during a median follow-up of 12 years. ECG-LVH was defined by the sex-specific Cornell voltage criteria. Echo-LVH was defined from the observed left ventricular (LV) mass compared with the sex-specific predicted LV mass values. Cox proportional hazard regression was used to compute hazard ratios (HR) and 95% confidence intervals (95%CI) for the association between ECG-LVH and Echo-LVH with incident HF, separately. Models were adjusted for age, sex, ...
A single-arm phase II trial to evaluate the combination of cetuximab plus docetaxel, cisplatin, and 5-fluorouracil (TPF) as induction chemotherapy (IC) in patients (pts) with unresectable SCCHN
Authors: R. Mesia, S. Vázquez, J. J. Grau, J. A. García-Sáenz, C. Bayona, J. C. Galceran, A. Irigoyen, A. Lozano, M. Mañós, J. J. Cruz
Journal: Journal of Clinical Oncology (2009)

6015 Background: TPF combination is the new standard IC. Adding cetuximab to PF chemotherapy is superior to PF alone in metastatic disease. We incorporated cetuximab into IC with TPF and subsequent radiotherapy (RT) in unresectable SCCHN. Methods: Phase II trial conducted in 7 Spanish hospitals. Previously untreated pts aged 18–70 yrs, ECOG PS 0–1 with unresectable SCCHN were eligible. Induction comprised T 75mg/m 2 day 1, P 75mg/m 2 day 1, F 750mg/m 2 days 1–5, and cetuximab 250mg/m 2 days 1, 8, and 15 (initial dose 400mg/m 2 on cycle (C) 1, day 1), repeated every 21 days x 4 C, with prophylactic antibiotics and G-CSF support. Subsequently, pts received accelerated RT with a concomitant boost (69.9Gy) and cetuximab 250mg/m 2 weekly. The primary endpoint was the objective response rate (RR) to cetuximab TPF as neoadjuvant therapy. Simon's optimal two-stage design was used to calculate the sample size of 49 evaluable pts. Results: 50 pts were enrolled: median age 54 yrs (33–68); 44 male; all stage IV (T4=31, N2–3=40). Primary sites were: oropharynx, 23; hypopharynx, 16; oral cavity, 5; larynx, 4.41(82%) pts received all 4 cycles of cetuximab TPF; 47 pts received ≥2 C and were evaluable for response using RECIST. 3 pts received &lt;2 C (2 deaths from intercurrent disease and febrile neutropenia, 1 secondary neoplasm diagnosed). The table shows RR. Serious grade 3/4 adverse events (AEs) were: neutropenia 24%; neutropenic fever 20%; infection 6%; thrombocytopenia 4%; diarrhea 12%; hepatotoxicity 4%; hypomagnesemia 2%. Grade 3 AEs were: nausea/vomiting 2%; mucositis 6%; renal failure 4%; asthenia 4%; rash 4%; hypotension 4%. There were 2 AE-related deaths (febrile neutropenia and hepatic insufficiency). Conclusions: The addition of cetuximab to TPF IC in pts with unresectable SCCHN yields a high RR, mainly CR, potentially prolonging survival. Cetuximab TPF combination should be given to pts with good PS with specialized support provided. [Table: see text] [Table: see text]
Pseudoprogression (PsPr) after concurrent radiotherapy (RT) and temozolomide (TMZ) for newly diagnosed glioblastoma multiforme (GBM)
Authors: J. L. Clarke, L. E. Abrey, S. Karimi, A. B. Lassman
Journal: Journal of Clinical Oncology (2008)

2025 Background: Increased contrast enhancement on brain imaging following chemoradiotherapy is often interpreted as progression of disease (PD). However, there is growing evidence that radiographic and even clinical worsening may result from effects of therapy, i.e. PsPr, rather than from true PD. Methods: 80 patients (pts) with GBM were treated in an IRB-approved phase 2 clinical trial with concurrent RT and TMZ followed by adjuvant TMZ. MRI was performed post-RT. PsPr was defined as increased contrast enhancement on the initial post-RT MRI scan that improved without changing chemotherapy, or as histologically documented necrosis. True PD was defined as continued progression on subsequent scans, or histologically documented viable tumor. MR perfusion imaging with relative cerebral blood volume (rCBV) and FDG PET imaging were collected in subsets of patients. Results: There were 33 pts with increased enhancement on the initial post-RT MRI; 8 (24%) had PsPr, 17 (52%) had true PD, and 8 (24%) discontinued TMZ (PsPr vs. true PD unknown). Of the 8 pts with PsPr, 2 had MR perfusion scans; both demonstrated increased rather than decreased rCBV. Two others had FDG PET scans; both showed hyper- rather than hypometabolism. Of the 17 patients with true PD, 5 had MR perfusion scans: 4 had increased rCBV and 1 had decreased rCBV; none had PET scans. The single patient with histologically documented PsPr had at the time of surgery, after 2 cycles of adjuvant TMZ, both increased rCBV and hypermetabolic PET scan; perfusion imaging was not performed with his first post-RT MRI. 6 of the 8 pts with PsPr were clinically worse at their post-RT visit; 7 of the 17 with true PD were clinically worse. Conclusions: At least 24% of our pts with increased contrast enhancement post-RT had PsPr; the incidence could be as high as 48% if all 8 pts who discontinued TMZ for a worsening scan actually had PsPr. MR perfusion, FDG PET, and clinical status were not predictive of PsPr versus true PD. It may be reasonable to consider findings on the post-RT MRI as a new baseline, rather than an assessment of response to chemo-RT, because of the high (24–48%) risk of PsPr. This approach would also minimize the likelihood of overestimating the benefits of second-line treatment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Schering-Plough Schering-Plough
Combination gemcitabine and cisplatin for recurrent ovarian cancer
Authors: D. L. Richardson, K. Kim, L. G. Seamon, D. M. O'Malley, L. A. Eaton, D. E. Cohn, L. J. Copeland, J. M. Fowler
Journal: Journal of Clinical Oncology (2007)

16037 Background: Recent evidence suggests gemcitabine combined with a platinum drug is active in recurrent ovarian cancer. In an effort to decrease dose-limiting myelosuppression associated with gemcitabine plus carboplatin, cisplatin can be substituted for carboplatin. Our objective is to describe a single institutional experience with day 1 and day 15 (D1/15) gemcitabine (1000 mg/m 2 ) and cisplatin (30 mg/m 2 ) for the treatment of recurrent ovarian cancer. Methods: A retrospective chart review was performed of all patients with recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer who were treated with gemcitabine and cisplatin from 8/2001 through 8/2006 at a single institution. Sixty-seven patients met inclusion criteria. Results: The median number of prior chemotherapy regimens was 2 (range 1–6). The median platinum-free treatment interval was 10 months (range 0–40). While 34 (51%) patients were platinum sensitive, 24 (36%) patients were platinum resistant, and 9 patients (13%) were platinum refractory. Patients were treated with a median of 6 cycles (range 1–31) of gemcitabine plus cisplatin. Fifteen (22%) patients had a complete clinical response with a median progression free survival (PFS) of 16 months (range 5–40); 15 (22%) patients had a partial clinical response (median PFS 6 months, range 2–15). Stable disease was noted in 19 patients, with a median PFS of 24 months (range 4–36). Three (38%) out of eight patients with refractory ovarian cancer had a complete clinical response, and 1 patient had a partial response. Non-hematologic toxicities were most common, occurring in 23% of the patient population (neuropathy, fatigue and pain). Grade 3 and 4 hematologic toxicities were rare, occurring in less than 10% of patients. Conclusions: Gemcitabine plus cisplatin (D1/15) is a well tolerated and active regimen in patients with recurrent ovarian cancer, regardless of previous response to platinum-based chemotherapy. No significant financial relationships to disclose.
Characterization of the Retinoid Binding Properties of the Major Fusion Products Present in Acute Promyelocytic Leukemia Cells
Authors: Laura Benedetti, Arthur A. Levin, Bianca M. Scicchitano, Francesco Grignani, Gary Allenby, Daniela Diverio, Francesco Lo Coco, Giuseppe Avvisati, Martin Ruthardt, Sergio Adamo, Pier Giuseppe Pelicci, Clara Nervi
Journal: Blood (1997)
Integrated FDG-PET/CT for initial staging of breast cancer
Authors: Q. J. Khan, A. P. O’Dea, R. Dusing, P. Sharma, S. M. Roling, C. J. Fabian, B. F. Kimler
Journal: Journal of Clinical Oncology (2007)

558 Background: Integrated FDG-PET/CT improves the diagnostic accuracy of staging of some cancers. The value of FDG-PET/CT in initial staging of breast cancer for detection of distant metastases has not been defined. Methods: Retrospective analysis of 83 consecutive women at the University of Kansas Medical Center who had a FDG-PET/CT from Jan 2005 to July 2006, at the time of initial diagnosis of invasive breast cancer. Women with symptoms suspicious for metastatic disease were excluded. Radiographic reports and patient charts were reviewed. All suspicious CT scans were re-read by a single radiologist who was blinded to the PET results. All suspicious scans were confirmed either by a biopsy or follow-up scans according to the discretion of the treating physician. Results: Median age was 52. 23 (28%) cancers were stage I, 44 (53%) stage II and 16 (19%) were stage III. 15/83 (18%) women had a suspicious FDG-PET/CT. Only 2 of these 15 women were confirmed to have metastatic disease, while 13 (16 %) had a false positive (FP) scan. In 5 women where both CT and PET were suspicious, 2 were true positives (TP) whereas 3 were FP. All 3 women who had suspicious PET but a non-suspicious CT were FP. All 7 women who had a non-suspicious PET and a suspicious CT were FP. PET influenced the CT classification by the radiologist in 5 (6%) women. 71/83 (86%) women had a negative or a non-suspicious CT. 3 women had lesions classified as non-suspicious with the help of a negative PET, two had lesions classified as suspicious with the help of a positive PET and seven had suspicious lesions on CT regardless of the PET. FDG-PET/CT resulted in unnecessary follow-up scans in eleven women, and unnecessary biopsies in two. One TP had metastatic bone disease. The other TP had a solitary liver metastasis detected by FDG-PET/CT which was resected and she has no evidence of disease after two years of follow-up. Conclusions: Given the high false positive rate and overall low incidence of metastases, routine use of FDG- PET/CT in asymptomatic women diagnosed with invasive breast cancer cannot be recommended. No significant financial relationships to disclose.
Detection of Antigenically Distinctive Components of Mouse Melanoma S912
Authors: Peter Abramoff, Harry Chinchinian, John W. Saunders
Journal: JNCI Journal of the National Cancer Institute (1959)

Antiserums were produced in White Rock and New Hampshire Red cockerels against the S91 mouse melanoma and against tissues of normal mice of the inbred tumor-host strain (DBA/1). After absorption with normal mouse-tissue antigens, antiserums against the neoplasm showed significant precipitation titers of specific antibodies in reaction with the tumor antigen. Likewise, antiserums against normal mouse tissues precipitated normal tissue antigens after absorption with tumor antigen. It is clear, therefore, that the S91 melanoma and normal tissues of the host mouse strain possess distinctive antigenic components. In preliminary tests of a tumor of more recent origin, the B16 melanoma, similar antigenic differences between the neoplasm and tissues of its C57BL/6 host strain were observed.
Abstract P6-07-03: An exhaustive algorithm for detecting copy number aberrations and large structural variants in whole-genome mate-pair sequencing data
Authors: Yan W Asmann, Chen Wang, Brian M Necela, Xianfeng Chen, Jean-Pierre A Kocher, Matthew J Maurer, Thomas M Habermann, Susan L Slager, Andrew L Feldman, Anne J Novak, James R Cerhan, Edith A Perez, E  Aubrey Thompson
Journal: Cancer Research (2015)

Abstract Objectives and Rationale: Structural variants (SV) including large copy number aberrations (CNV), translocations, inversions, and large insertions and deletions (INDEL) play a critical role in tumorigenesis and progression. In fact, we now know that tumors can be categorized according to the size of mutations harbored. In several cancers, including ovarian and breast cancer, the large structural mutations, rather than single site mutations, play a dominate role in tumor etiology. Therefore, it's critical to implement reliable algorithm for the detection of structural variants in DNA sequencing data. Mate-pair sequencing is a protocol specifically implemented for detection of the whole-genome level structural variants. It requires less sequencing depth therefor is cost effective, and enables the detection of CNVs, translocations, and inversions simultaneously. However, so far there has been no reliable bioinformatics pipeline for the analyses of the mate-pair sequencing data. Methods: Our novel algorithm, the SnowShoes-SV, is an exhaustive search algorithm designed specifically for mate-pair DNA sequencing data analyses. It calls the SVs based on disconcordant read pairs. The false SVs are filtered according to the following criteria: (i) the number of the supporting read pairs; (ii) the lack of reads from control data that implicate SV at the same region; (iii) the mappability and uniqueness of the region based on data from the ENCODE project; (iv) consistencies of the mapping orientations of the supporting read pairs; (v) the similar sizes between sequencing library and the two end read clusters. Results: Using a set of samples previously genotyped by aCGH, the SnowShoes-SV successfully detected all known CNVs and other SVs. It also identified copy number neutral translocations and inversions previously not identified by aCGH. In addition, the algorithm nominated novel SVs which are to be validated by PCR. Conclusions: SnowShoes-SV is a highly sensitive and specific algorithm for SV detection from the mate-pair DNA sequencing data. Citation Format: Yan W Asmann, Chen Wang, Brian M Necela, Xianfeng Chen, Jean-Pierre A Kocher, Matthew J Maurer, Thomas M Habermann, Susan L Slager, Andrew L Feldman, Anne J Novak, James R Cerhan, Edith A Perez, E Aubrey Thompson. An exhaustive algorithm for detecting copy number aberrations and large structural variants in whole-genome mate-pair sequencing data [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-07-03.
Influence of triptolide on breast cancer apoptosis
Authors: Reginald Halaby, Kenneth Pamiloza, Devika Mahabier, Iqra Javeed, Maryam Hasani, Kelly Delgado, Evelyn Guevara
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

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Triptolide, a diterpenoid isolated from the Chinese herb Tripterygium wilfordii Hook.f, has shown antitumor activities in a broad range of solid tumors. However, little is known about the ability of triptolide to induce apoptosis in breast cancer cells. We investigated the effects of triptolide on MCF-7 breast adenocarcinoma cells, and found that it potently induced apoptosis in these cells. Apoptosis was monitored by using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay to measure cell viability; 4’,6-diamidino-2-phenylindole (DAPI) staining to detect chromatin condensation; and cell morphology. Triptolide induced apoptosis of MCF-7 cells in a concentration-dependent manner at very low (nM) concentrations. Utilization of the LysoTracker Green probe revealed that triptolide triggered an increase in the amount of lysosomes present in dying cells. A biochemical assay for lysosomal acid phosphatase showed that the activity of this enzyme increased in experimental cells compared to vehicle-treated cells. In conclusion, triptolide inhibits MCF-7 cell growth by inducing apoptosis and activating lysosomal enzymes. These results suggest that triptolide might be a natural alternative for the treatment of breast cancer. The identification of the mechanisms by which triptolide regulates apoptosis warrant further investigation.
Health care resource use (HRU) with nonplatinum chemotherapy for previously treated advanced ovarian cancer (aOC): Findings from SEER-Medicare data.
Authors: A. Parthan, S. K. Gao, A. Oglesby, A. H. Teitelbaum, R. Song, W. J. Langeberg, R. Borker
Journal: Journal of Clinical Oncology (2010)

e15539 Background: Real world HRU in second-line aOC has not been well quantified. The objective of this study was to assess HRU and treatment patterns in women with previously-treated aOC subsequently treated with nonplatinum chemotherapy (CT). Methods: A retrospective study was conducted using the SEER-Medicare linked dataset. The population included women ≥ 65 years who were diagnosed with incident, distant-stage aOC between 1993-2005 and who had ≥ 3 months of claims data before diagnosis. The study cohort included patients previously treated with platinum-based CT and re-treated following a ≥ 90 day treatment-free interval (TFI) with nonplatinum-based CT in 2000-2005. Patients were followed from the first claim for retreatment with a nonplatinum CT regimen until either death or the end of the claims data (12/31/2007). Measures of HRU included hospitalizations, outpatient visits, physician visits, hospice care, home health care, and skilled nursing facility (SNF) visits. Costs of each HRU event were estimated by summing all Medicare payments, primary insurer payments, patient copayments and deductibles for services in the claims files. Average healthcare costs per patient per event type (e.g., hospitalization) are calculated as total event cost per event divided by number of patients with the event. Results: 2,166 previously treated aOC patients subsequently received nonplatinum CT as second-line therapy. Mean age was 74.0 years (SD 5.6). The mean treatment duration in the non- platinum CT period was 317 days (SD 354). Paclitaxel and pegylated liposomal doxorubicin (PLD) were the most commonly used nonplatinum CT agents. Paclitaxel use declined from 38.1% to 30.0% while PLD use increased from 16.4% to 26.8% from 2000-2005. Rate of hospitalization was 1.3 per person-year. Mean hospitalization cost per patient was $10,466 (SD $10,846). Mean SNF and hospice care costs per patient were $7,416 (SD $6,907) and $6,955 (SD $11,416) respectively. Conclusions: Both paclitaxel and PLD were frequently used nonplatinum-based CTs in women with aOC who were previously treated with platinum-based agents. Hospitalization costs per patient were substantial. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen
Cell Sorting Enables iFISH Detection Of Low BCR-ABL Producing Stem Cells In CML Patients Beyond Deep Molecular Remission
Authors: Peter Buur van Kooten Niekerk, Charlotte Christie Petersen, Charlotte Guldborg Nyvold, Hans Beier Ommen, Anne Stidsholt Roug, Line Nederby, Peter Hokland, Eigil Kjeldsen
Journal: Blood (2013)
Infiltration of immune cells into cancer cell/stroma cell 3D microtissues
Authors: Stefan Koeck, Marit Zwierzina, Edith Lorenz, Gabriele Gamerith, Heinz Zwierzina, Arno Amann
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The pharmacological manipulation of the interaction between the immune system, fibroblasts and cancer cells has been proven to be a key target for cancer therapy. Based on our previously developed co-culture system, this work aims to develop an innovative 3D cell culture system