tbuckley/cabot-search huggingface dataset:
First-cycle blood counts and subsequent neutropenia, dose reduction, or delay in early-stage breast cancer therapy.
Authors: J H Silber, M Fridman, R S DiPaola, M H Erder, M V Pauly, K R Fox
Journal: Journal of Clinical Oncology (1998)

PURPOSE If patients could be ranked according to their projected need for supportive care therapy, then more efficient and less costly treatment algorithms might be developed. This work reports on the construction of a model of neutropenia, dose reduction, or delay that rank-orders patients according to their need for costly supportive care such as granulocyte growth factors. PATIENTS AND METHODS A case series and consecutive sample of patients treated for breast cancer were studied. Patients had received standard-dose adjuvant chemotherapy for early-stage nonmetastatic breast cancer and were treated by four medical oncologists. Using 95 patients and validated with 80 additional patients, development models were constructed to predict one or more of the following events: neutropenia (absolute neutrophil count [ANC] &lt; or = 250/microL), dose reduction &gt; or = 15% of that scheduled, or treatment delay &gt; or = 7 days. Two approaches to modeling were attempted. The pretreatment approach used only pretreatment predictors such as chemotherapy regimen and radiation history; the conditional approach included, in addition, blood count information obtained in the first cycle of treatment. RESULTS The pretreatment model was unsuccessful at predicting neutropenia, dose reduction, or delay (c-statistic = 0.63). Conditional models were good predictors of subsequent events after cycle 1 (c-statistic = 0.87 and 0.78 for development and validation samples, respectively). The depth of the first-cycle ANC was an excellent predictor of events in subsequent cycles (P = .0001 to .004). Chemotherapy plus radiation also increased the risk of subsequent events (P = .0011 to .0901). Decline in hemoglobin (HGB) level during the first cycle of therapy was a significant predictor of events in the development study (P = .0074 and .0015), and although the trend was similar in the validation study, HGB decline failed to reach statistical significance. CONCLUSION It is possible to rank patients according to their need of supportive care based on blood counts observed in the first cycle of therapy. Such rankings may aid in the choice of appropriate supportive care for patients with early-stage breast cancer.
Final clinical, pharmacokinetic and pharmacodynamic results of the phase I study of the novel poly(ADP-ribose)polymerase (PARP) inhibitor, AG014699, in combination with temozolomide
Authors: ER Plummer, M Middleton, R Wilson, J Evans, C Jones, A Olson, AV Boddy, NJ Curtin, R Kaufman, A Harris, P Johnston, Newell, L Robson, R Dewji, AH Calvert
Journal: Clinical Cancer Research (2005)
Add-Aspirin trial: A phase III, double blind, placebo-controlled, randomized trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common nonmetastatic solid tumors.
Authors: Ruth E Langley, Richard H. Wilson, Alistair E. Ring, Howard Gordon Kynaston, David A. Cameron, Christopher Coyle, Duncan Charles Gilbert, Carlo Patrono, Sam Rowley, Claire Murphy, David Adlam, Richard Hubner, Tim Iveson, Robert J Steele, Anne L. Thomas, Timothy J Underwood, Janusz Jankowski, Sudeep Gupta, Conjeevaram S Pramesh, Mahesh Parmar
Journal: Journal of Clinical Oncology (2014)

TPS1617 Background: Pre-clinical data demonstrate that aspirin inhibits tumour growth and prevents metastases. Meta-analyses of individual patient data from randomized trials evaluating cardiovascular (CV) effects of aspirin show reduced metastases and cancer deaths for those on aspirin. Toxicity concerns have limited aspirin use as a primary anti-cancer prevention agent. In the adjuvant setting, the risk:benefit ratio differs, with higher morbidity and mortality from recurrence potentially outweighing risks. Aspirin, an inexpensive drug with a potential therapeutic role in several common cancers, could have a large impact on the global cancer burden. The Add-Aspirin trial investigates if aspirin use after curative treatment for non-metastatic solid tumours prevents recurrence and prolongs survival. Methods: Add-Aspirin is a double blind, placebo-controlled, multicentre, international trial. Eligible participants (n=9,920) from the UK and India will have had potentially curative treatment for non-metastatic cancer. There are 4 separate tumour cohorts – breast (BC), colorectal (CRC), gastro-oesophageal (GOC) and prostate cancer (PC). Following an 8 week active run-in period of aspirin 100mg daily to assess adherence and tolerability, participants are randomised to aspirin 100mg, 300mg or placebo daily for > 5 years. Each tumour specific cohort is individually powered and has a separate disease-specific primary outcome measure: BC (n = 3,100) invasive disease-free survival (DFS); CRC (n = 2,600) DFS; GOC (n = 2,100) overall survival (OS); and PC (n = 2,120) biochemical recurrence-free survival. Secondary outcome measures include adherence, toxicity and CV events. OS across the 4 cohorts is a co-primary outcome measure. Sub-studies include assessment of thromboxane B2 for compliance and methodological work to assess the utility of long-term passive follow up. Blood/tissue specimens collected at enrolment will allow tumour-specific mutations to be used as stratification factors. Recruitment will commence by May 2014. Funder CRUK; Sponsor University College UK. Clinical trial information: 2013-004398-28.
Outcomes of Percutaneous Coronary Intervention Performed at Offsite Versus Onsite Surgical Centers in the United Kingdom
Authors: Scot Garg, Simon G. Anderson, Keith Oldroyd, Colin Berry, Connor A. Emdin, Sanne A.E. Peters, Nick E.J. West, Damian Kelly, Kanarath Balachandran, John McDonald, Ravi Singh, Sen Devadathan, Simon Redwood, Peter F. Ludman, Kazem Rahimi, Mark Woodward
Journal: Journal of the American College of Cardiology (2015)
Is there a change in pulmonary function in patients with COPD and primary lung cancer treated with radiofrequency ablation (RFA)
Authors: Evangelos Skondras, Julia Beeson, Sundeep Kaul, Paras Dalal
Journal: European Respiratory Journal (2014)

Introduction   RFA is an increasingly popular treatment choice for non-operable lung tumours. Our aim was to evaluate changes in lung function after RFA in patients with COPD and primary lung cancer.   Method   This study looked at the first 20 consecutive lung cancer patients with COPD treated in our institution. All patients were approved by tumour board for RFA treatment.  Mean patient age was 74 years (range: 55-83). Male to female ratio 8:12.  The parameters that were used for statistical analysis were FEV1 and FVC.   Results   All patients had biopsy proven primary lung cancer (histology: 11 squamous, 5 adenocarcinomas and 5 mixed NSCLC subtypes - staging: 11 T1, 3 T2, 6 T4).  Spirometry was performed 1-4 months before treatment. The mean follow up spirometry was 14 months (range 10-36 months).  The mean (+SD) FEV1 pre and post ablation was 1.27 L (+0.38) and 1.16 L (+0.36). The mean FVC (+SD) pre and post ablation was 2.45 L (+0.86) and 2.15 L (+0.65).   Conclusion   There was a small decrease of the pulmonary function on medium / long term follow up (10+ months). This does not take into account acute clinical symptoms (including infection or exacerbation of COPD) at the time of lung function testing. In addition a proportion of the decline may have been secondary to the natural history of patients underlying COPD. These results are comparable to the stereotactic radiotherapy and other post-ablation reports.  RFA of primary lung cancer offers relative preservation of the lung function.
Brochial artery embolization in 110 patients with massive hemoptysis in Punjab, India
Authors: Jagdeep Whig, Bishav Mohan, Rajesh Mahajan, Harpreet Thind
Journal: European Respiratory Journal (2011)

Aims and objective:  BAE role has been established as an effective technique in the emergency treatment of life threatening hemoptysis. We report our experience with 110 cases that underwent BAE.   Material and methods:  Records of 110 consecutive patients (89 males and 21 females) from march 2005 to march 2010 with massive hemoptysis and who underwent BAE were retrospectively studied and analyzed.   Results:  The mean age of patients who underwent BAE was 46 years (range 19-80 years). 50% of patients presented with acute hemoptysis. The aetiology of hemoptysis included post tubercular bronchiectasis in 53 patients (48%), active pulmonary tuberculosis in 40 patients (36%), mycetoma in 11 patients (10%), pneumonia in 4 patients (6%), pulmonary embolism in 1 patient and unknown in 1 patient. Embolization was done with Polyvinyl alcohol Cook9s particles (size 300-750 micron) in 90 patients, coils in 6 patients and gel foam in 14 patients. Overall, 112 sessions of embolization were performed and average number of arteries embolized per patient was 3.5 Massive hemoptysis was successfully controlled in 102 patients but 10 patients had recurrence and were treated by re-embolization. 1 patient expired despite re-embolization. 3 patients were sent for lobectomy. The complication of BAE seen included perforation of bronchial artery (in two patients), transient chest pain (in 10 patients) and secondary infection in one patient.   Conclusion:  BAE is a safe and effective procedure for controlling massive hemoptysis and should be regarded as the first line treatment for patients presenting with massive hemoptysis. Multiple sites of non-bronchial collaterals causing hemoptysis are not unusual.
Vinblastine Versus Vinblastine Plus Oral Estramustine Phosphate for Patients With Hormone-Refractory Prostate Cancer: A Hoosier Oncology Group and Fox Chase Network Phase III Trial
Authors: Gary Hudes, Lawrence Einhorn, Eric Ross, Andrew Balsham, Patrick Loehrer, Harry Ramsey, John Sprandio, Michael Entmacher, William Dugan, Rafat Ansari, Frank Monaco, Mark Hanna, Bruce Roth
Journal: Journal of Clinical Oncology (1999)

To compare vinblastine versus the combination of vinblastine plus estramustine as treatment for patients with hormone-refractory prostate cancer (HRPC).A total of 201 patients with metastatic prostate cancer, progressive after hormonal therapy and antiandrogen withdrawal (if prior antiandrogen treatment), were randomized to receive vinblastine (V) 4 mg/m(2) by intravenous bolus weekly for 6 weeks followed by 2 weeks off, either alone or together with estramustine phosphate (EM-V) 600 mg/m(2) PO days 1 through 42, repeated every 8 weeks. Of 193 eligible patients, 98 received V, and 95 received EM-V.Overall survival trended in favor of EM-V but was not significantly different as determined by Kaplan-Meier analysis (P =.08). Median survival was 11.9 months for EM-V and 9.2 months for V. EM-V was superior to V for secondary end points of time to progression (P <. 001, stratified log rank test; median 3.7 v 2.2 months, respectively) and for proportion of patients with >/= 50% prostate-specific antigen (PSA) decline sustained for at least 3 monthly measurements (25.2% v 3.2%, respectively; P <.0001). Granulocytopenia was significantly less for EM-V compared with V (grade 2, 3, and 4 = 7%, 7%, and 1% v 27%, 18% and 9%, respectively; P <.0001); however, grade 2 or worse nausea (26% v 7%, respectively; P =.0002) and extremity edema (22% v 8%, respectively; P =.005) were more frequent for EM-V.Although overall survival was not significantly greater for the combination, EM-V was superior to V for time to progression and PSA improvement. These results encourage further study of estramustine-based antimicrotubule drug combinations in HRPC.
The long-acting β2-agonist formoterol re-establishes the anti-proliferative effect of glucocorticoids in asthmatic airway smooth muscle cells (ASMC)
Authors: Michael Roth, Jun Zhong, Chong S'ng, Michael Tamm
Journal: European Respiratory Journal (2011)

Background:  Asthma is characterized by an increased mass of ASMC which show increased proliferation in vitro. As previously reported, glucocorticoids do not have a significant anti-proliferative effect on ASMC of asthmatics while although their anti-inflammatory efficacy is maintained.   Methods:  We assessed whether the addition of the long-acting β2-agonist formoterol modifies the anti-proliferative efficacy of glucocorticoids (beclomethasone, budenoside, fluticasone). Primary human ASMC lines from asthmatics and controls were set up from bronchoscopic lung biopsies.   Results:  Serum deprived sub-confuent cells were stimulated by 5% serum with or without a single drug or combination for a further 48 and 72 hrs. Serum alone increased cell proliferation in healthy control cells by 65% (48 hrs) and 81% (72 hrs); a significantly higher proliferation response was seen in asthmatic ASMC (82% at 48 hrs; 123% at 72 hrs). In the presence of different glucocorticoids alone serum-induced proliferation was significantly reduced in healthy cells (max. 48%) but not in asthmatic ASMC. Treatment with formoterol alone reduced serum-induced proliferation by max. 24% at any time point, with no differences between asthmatic and healthy ASMC. When formoterol was combined with fluticasone a 78% reduction of ASMC proliferation was achieved.   Conclusions:  Our results show that the β2-agonist formoterol re-establishes the anti-proliferative effect of fluticasone in asthmatic airway smooth muscle cells. This synergistic action may exert an anti-remodeling effect on the asthmatic airway supporting the clinical benefit of combination therapy.
A conversation with Stuart Kornfeld
Authors: Ushma S. Neill
Journal: Journal of Clinical Investigation (2015)

of Medicine, is best known for his research in glycobiology, in particular his work describing pathways involved in oligosaccharide biosynthesis, processing, and maturation.These actions are critical in mediating proper folding and transport of proteins.Kornfeld (Figure 1) also discovered how lysosomal enzymes are routed from where they are produced to where they are needed in lysosomes, which help rid cells of macromolecules.See the full interview on the JCI website (http://www.jci.org/videos/cgms) for more of Kornfeld's stories about his first experiment, stuttering, and why St. Louis has such magnetism.JCI: Where did you grow up?Kornfeld: I grew up in St. Louis.My father was a dentist in private practice, but
Sentinel node biopsy in breast cancer
Authors: H. Thornton, M. Thomas, N Beechey-Newman, I S Fentiman, A E Young, J M. Dixon
Journal: BMJ (1999)

Editor—Careful consideration needs to be given to the implications for breast cancer patients from the use of the unevaluated technique of sentinel node biopsy.1 Ideally, clinical trials to refine this technique should have been done before its introduction into routine clinical practice by enthusiastic surgeons. Training courses and conferences on this topic must be timed to avoid encouraging premature introduction and wasting resources.

The possibility that sentinel node biopsy would avoid clearance of the axilla, with its attendant problems, could be seductive to both surgeons and patients. The technique holds promise of clearer prognosis and swifter assessment with minimum invasiveness. What then might the drawbacks be for patients? Consideration of the best total outcome for the patient must always be the overriding objective.

It might be useful to draw a parallel between the introduction of mammographic screening, which resulted in closer scrutiny of breast tissue, and the use of sentinel node biopsy. Screening caused the label “breast cancer” to be applied to borderline cases so that many women with non-invasive conditions which would never cause them problems in their lifetime carried the “cancer” label with all its drawbacks, emotional and financial. By the same token, closer scrutiny of the sentinel node will cause an upstaging of the disease. Techniques such as step sections, immunostaining, and polymerase chain reaction (which can detect 1 in 10 000 cancer cells) will inevitably mean that the label “metastatic” is applied more readily, with enormous implications for the women given that label.

Foucar commented on the surprising docility of patients about the pathologist’s monopoly on diagnostic terminology that links objective histopathological observations to clinical interventions.2 Classifications resulting from the use of sentinel node biopsy will not only give choice of therapy but change attitudes of mind. We will therefore need to implement Foucar’s recommendation to develop a new classification so that we do not transmit “more fear than knowledge into the clinical arena.”
Serum concentrations of vascular endothelial growth factor in collagen diseases
Authors: None Kikuchi, None Kubo, None Kadono, None Yazawa, None Ihn, None Tamaki
Journal: British Journal of Dermatology (1998)

Vascular endothelial growth factor (VEGF) is an angiogenic cytokine which has been reported to be important in the pathogenesis of rheumatoid arthritis (RA). In this study, the serum level of VEGF was measured using enzyme-linked immunosorbent assay in 17 patients with systemic lupus erythematosus, 49 patients with polymyositis/dermatomyositis (PM/DM), 40 patients with systemic lupus erythematosus, 49 patients with polymyositis/dermatomyositis (PM/DM), 40 patients with systemic sclerosis (SSc), 11 patients with RA and 20 control subjects. The VEGF level was 184 +/- 62 pg/mL (mean +/- SD) in the serum of normal individuals. The mean VEGF levels in the patients with PM/DM or RA were significantly higher than in the normal controls. In 21 of the 49 patients with PM/DM and nine of the 11 patients with RA, the serum VEGF level was considered to be elevated. In patients with SSc, those with diffuse cutaneous SSc showed elevated VEGF levels in comparison with normal controls. An elevated serum VEGF level was correlated with the frequency of lung fibrosis and reduced vital capacity in the patients with SSc.
Ectopic expression of PTTG1/securin promotes tumorigenesis in human embryonic kidney cells.
Authors: Tariq Hamid, Mohammed T Malik, Sham S Kakar
Journal: Molecular Cancer (2005)

Pituitary tumor transforming gene1 (PTTG1) is a novel oncogene that is expressed in most tumors. It encodes a protein that is primarily involved in the regulation of sister chromatid separation during cell division. The oncogenic potential of PTTG1 has been well characterized in the mouse, particularly mouse fibroblast (NIH3T3) cells, in which it induces cell proliferation, promotes tumor formation and angiogenesis. Human tumorigenesis is a complex and a multistep process often requiring concordant expression of a number of genes. Also due to differences between rodent and human cell biology it is difficult to extrapolate results from mouse models to humans. To determine if PTTG1 functions similarly as an oncogene in humans, we have characterized its effects on human embryonic kidney (HEK293) cells. We report that introduction of human PTTG1 into HEK293 cells through transfection with PTTG1 cDNA resulted in increased cell proliferation, anchorage-independent growth in soft agar, and formation of tumors after subcutaneous injection of nu/nu mice. Pathologic analysis revealed that these tumors were poorly differentiated. Both analysis of HEK293 cells transiently transfected with PTTG1 cDNA and analysis of tumors developed on injection of HEK293 cells that had been stably transfected with PTTG1 cDNA indicated significantly higher levels of secretion and expression of bFGF, VEGF and IL-8 compared to HEK293 cells transfected with pcDNA3.1 vector or uninvolved tissues collected from the mice. Mutation of the proline-rich motifs at the C-terminal of PTTG1 abolished its oncogenic properties. Mice injected with this mutated PTTG1 either did not form tumors or formed very small tumors. Taken together our results suggest that PTTG1 is a human oncogene that possesses the ability to promote tumorigenesis in human cells at least in part through the regulation of expression or secretion of bFGF, VEGF and IL-8. Our results demonstrate that PTTG1 is a potent human oncogene and has the ability to induce cellular transformation of human cells. Overexpression of PTTG1 in HEK293 cells leads to an increase in the secretion and expression of bFGF, VEGF and IL-8. Mutation of C-terminal proline-rich motifs abrogates the oncogenic function of PTTG1. To our knowledge, this is the first study demonstrating the importance of PTTG1 in human tumorigenesis.
Implication of a Chromosome 15q15.2 Locus in Regulating UBR1 and Predisposing Smokers to MGMT Methylation in Lung
Authors: Shuguang Leng, Guodong Wu, Leonard B. Collins, Cynthia L. Thomas, Carmen S. Tellez, Andrew R. Jauregui, Maria A. Picchi, Xiequn Zhang, Daniel E. Juri, Dhimant Desai, Shantu G. Amin, Richard E. Crowell, Christine A. Stidley, Yushi Liu, James A. Swenberg, Yong Lin, Marc G. Wathelet, Frank D. Gilliland, Steven A. Belinsky
Journal: Cancer Research (2015)

O(6)-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that protects cells from carcinogenic effects of alkylating agents; however, MGMT is silenced by promoter hypermethylation during carcinogenesis. A single-nucleotide polymorphism (SNP) in an enhancer in the MGMT promoter was previously identified to be highly significantly associated with risk for MGMT methylation in lung cancer and sputum from smokers. To further genetic investigations, a genome-wide association and replication study was conducted in two smoker cohorts to identify novel loci for MGMT methylation in sputum that were independent of the MGMT enhancer polymorphism. Two novel trans-acting loci (15q15.2 and 17q24.3) that were identified acted together with the enhancer SNP to empower risk prediction for MGMT methylation. We found that the predisposition to MGMT methylation arising from the 15q15.2 locus involved regulation of the ubiquitin protein ligase E3 component UBR1. UBR1 attenuation reduced turnover of MGMT protein and increased repair of O6-methylguanine in nitrosomethylurea-treated human bronchial epithelial cells, while also reducing MGMT promoter activity and abolishing MGMT induction. Overall, our results substantiate reduced gene transcription as a major mechanism for predisposition to MGMT methylation in the lungs of smokers, and support the importance of UBR1 in regulating MGMT homeostasis and DNA repair of alkylated DNA adducts in cells.
Habitual Violence : A Profile of 62 Men
Authors: GEORGE BACH-Y-RITA, ARTHUR VENO
Journal: American Journal of Psychiatry (1974)

The authors studied a group of 62 habitually violent patient/inmates from a prison population for life history and clinical variables. An extraordinarily high incidence of self-destructive behavior and self-mutilation was found as well as a high incidence of childhood pathology suggestive of deprivation and neurological impairment in the sepatients. The population was also found to be heterogeneous, differing on several significant variables.