tbuckley/cabot-search huggingface dataset:
Abstract P225: Effect of Weight Loss Strategies on Serum Uric Acid in Cancer Patients in the Spirit Study
Authors: Jiun-ruey Hu, Hsin-Chieh Yeh, Noel T Mueller, Lawrence J Appel, Edgar R Miller, Stephen P Juraschek
Journal: Circulation (2020)

Introduction: Obesity is strongly associated with elevated serum uric acid (SUA), a hypothesized mediator of cardiovascular disease. In observational studies, weight loss is associated with lower SUA. However, trial evidence on weight loss and SUA is lacking. Hypothesis: We hypothesized that in a randomized, controlled setting, intentional weight loss would reduce SUA. Methods: The Survivorship Promotion In Reducing IGF-1 Trial (SPIRIT) was a three-arm, parallel trial of overweight or obese adult cancer survivors that compared the effects of a coach-directed weight loss intervention or metformin to self-directed weight loss (ref) on insulin growth factor-1 (IGF-1) over a 1-year period. Participants in the coach-directed arm underwent behavioral-based telephonic coaching with web-based support to promote healthy lifestyle and weight loss, targeting a 5% weight loss in the first 6 months. Participants assigned metformin received up to 2,000 mg daily. In our study, SUA was measured in specimens collected at baseline, 3-months, 6-months, and 12-months. Results: There were 121 participants, with a mean age of 60 years (standard deviation [SD]: 9), and a mean body mass index (BMI) of 35 kg/m 2 (SD: 5). Compared to the self-directed group, coach-directed weight loss reduced BMI by 0.6 kg/m 2 (95% CI: 0.1, 1.1) and metformin reduced BMI by 0.9 kg/m 2 (95% CI: 0.4, 1.5) over 12 months. However, compared to the self-directed group, coach-directed weight loss significantly increased SUA by 0.3 mg/dL (95% CI: 0.1, 0.6) over 12 months, while metformin did not significantly affect SUA (0.2 mg/dL; 95% CI: -0.04, 0.5). The increase observed with the coach-directed weight loss intervention occurred primarily within the first 3 months of the intervention (Figure). Conclusions: Contrary to our expectations, intentional weight loss increased SUA in the short-term. These results question weight loss as a strategy for SUA reduction. Studies testing the long-term effects of weight loss on SUA are needed.
Abstract CS1-2: Emerging Therapies for HER2 Positive Breast Cancer
Authors: S Modi
Journal: Cancer Research (2020)

Abstract HER2 targeted therapies have had a significant impact in improving clinical outcomes and survival for patients with HER2 positive breast cancer. However, new therapies for patients with refractory disease are still needed. Based on a greater understanding of the biology and mechanisms of resistance, a new generation of HER2 agents is evolving. Here we provide an overview of promising novel therapies, both proven and in development, for the treatment of refractory HER2 positive breast cancer. This will include a review of antibody drug conjugates, tyrosine kinase inhibitors, immune strategies as well as future combination therapies. Citation Format: S Modi. Emerging Therapies for HER2 Positive Breast Cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr CS1-2.
Abstract P525: The Effect of Weight Loss Combined With Aerobic Exercise Training on Arterial Stiffness: Results From the PREVAIL Pilot Study
Authors: Damon L Swift, Joshua E McGee, Marie C Clunan, Anna C Huff, Briceida G Osborne, Nicole R Gniewek, Taylor T Brown, Colleen Bucher, Robert Carels, Joseph A Houmard, Walter Pories, Laura Matarese
Journal: Circulation (2020)

Objective: The OPTIFAST diet has known effects for weight loss, but little data exists on the effects of the diet on arterial stiffness. Methods: Overweight and obese (BMI: 34.5 + 4.0) adults (N=17) participated in a 10-week OPTIFAST™ weight loss program and supervised aerobic exercise training (50%-75% VO 2 max). The diet consisted of OPTIFAST meal replacement products with a goal of reducing total caloric intake to 800 kcals/day and attending a weekly weight management class. Aerobic exercise was performed 3 times per week and the exercise volume was progressed from 300 to 700 MET mins. per week at an intensity of 50%-75% VO2 max. The goal of study participants was to achieve a 7% weight loss. Carotid-to-femoral pulse wave velocity, blood pressure (aortic and brachial), vascular age, augmentation index and blood samples were measured in the morning after an overnight fast at baseline and follow-up. A paired t-test was performed to evaluate the change in outcomes variables. Results: The mean percent weight loss in the sample was 9.0% (-8.5 kg), with 83.3% of participants achieving 7% weight loss (94.1% achieving ≥5%). The adherence to the exercise program was 94.9% and attendance in the weight loss classes was 81.8%. There was a reduction in pulse wave velocity (-0.44 m/s, p=0.030), aortic systolic blood pressure (-10.5 mmHg, p&lt;0.001), aortic diastolic blood pressure (-7.8 mmHg, p&lt;0.001), brachial systolic blood pressure (-11.2 mmHg , p&lt;0.001), brachial diastolic blood pressure (-7.7 mmHg, p&lt;0.001), vascular age (-13.4 yrs., p=0.008), resting heart rate (-4.7 bpm, p=0.005), and augmentation index (-7.5%, p=0.008) after the intervention. Change in resting heart rate from the intervention was associated with improvements in augmentation index (r=0.60, p=0.010) and approached significance for pulse wave velocity (r=0.45, p=0.07). Weight loss was associated with reduction in augmentation index (r= 0.56, p=0.02), but not change in PWV (r=-0.07, p=0.78). Changes in other cardiometabolic risk factors (e.g. glucose, insulin, lipids, and body fat) were not associated with improvements in arterial stiffness or blood pressure measures (all ps&gt;0.05). Discussion: A hypo-caloric dietary program in combination with aerobic exercise training improves arterial stiffness, aortic blood pressure, and brachial blood pressure in overweight and obese adults An important limitation of the present study is that we cannot separate the health benefits of the diet from the exercise.
Relapse free survival in a prospective cohort of hormone receptor/Her2neu defined breast cancer patients
Authors: H. G. Kaplan, J. A. Malmgren, M. K. Atwood
Journal: Journal of Clinical Oncology (2007)

21003 Background: Adjuvant trastuzumab for Her2/neu (Her2) positive breast cancer (BC) is now standard treatment. We describe hormone receptor (HR)/Her2/neu defined phenotypic BC subgroups and evaluate recurrence risk prior to widespread use of adjuvant trastuzumab. Methods: A prospective cohort of patients at our institution diagnosed with primary BC between 1998 and 2003 were categorized by HR and Her2 status into ER+/PR+/Her2- (HR+/Her2-) (N=1114), ER+/PR+/Her2+ (TP) (N=134), ER-/PR-/Her2- (TN) (N=176), and ER-/PR-/Her2+ (HR-/Her2+) (N=91) (n= 1550). Patients with discordant ER/PR status (n=262) or equivocal IHC Her2 results were excluded (n=179). Clinical variables including age, race, TNM stage, histologic type and detection method were chart abstracted and vital and disease status were updated annually. The endpoint was disease recurrence; local, regional, distant, or combination. Average length of follow up was 7 years and relapse free survival (RFS) was calculated using Kaplan-Meier procedures with Cox proportional hazards modeling for risk and 95% confidence intervals (CI). Results: Mean patient age at diagnosis was 57, ranging from 21–94 years. Compared to HR+/Her2- and TP patients, TN and HR-/Her2+ patients were significantly more likely to be younger, higher TNM stage, higher histologic grade and patient vs. mammography detected. Disease recurrence was 24% in HR-/Her2+ patients, 16% in TN patients, 8.4% in TP patients, and 3.3% in HR+/Her2- patients (Pearson chi square = 101.56, p&lt;.001). Excluding TNM stage IV patients (n=35), RFS at five years was in rank order HR+/Her2- (95%), TP (89%), TN (84%), HR-/Her2+ (76%) (log rank test = 53.14, p&lt;.001). When adjuvant trastuzumab treated patients (n=34) were removed from the analysis the 5 year RFS only changed in the HR-/Her2+ group to 73%. In a model adjusted for age, race, menopause, TNM stage and treatment using HR+/Her2- patients as the reference group, recurrence risk was 1.98 for TP (95% CI = 1.02 to 3.84), 2.32 for TN (95% CI = 1.32 to 4.08), and 4.25 for HR-/Her2+ patients (95% CI = 2.33, 7.75). Conclusions: All three subgroups had significantly worse RFS compared to HR+/Her2- patients. Even though TN and HR-/Her2+ share many poor prognostic characteristics, HR- /Her2+ BC had the highest risk of recurrence. No significant financial relationships to disclose.
Cell-free DNA analysis reveals POLR1D-mediated resistance to bevacizumab in colorectal cancer
Authors: Qing Zhou, Samantha O. Perakis, Peter Ulz, Sumitra Mohan, Jakob M. Riedl, Emina Talakic, Sigurd Lax, Martin Tötsch, Gerald Hoefler, Thomas Bauernhofer, Martin Pichler, Armin Gerger, Jochen B. Geigl, Ellen Heitzer, Michael R. Speicher
Journal: Genome Medicine (2020)

Abstract Background Bevacizumab, a monoclonal antibody against soluble VEGFA, is an approved and commonly administered anti-angiogenic drug in patients with metastasized colorectal cancer (mCRC). The survival benefit of anti-VEGF therapy in mCRC patients is limited to a few months, and acquired resistance mechanisms are largely unknown. Here, we employed whole-genome sequencing of plasma DNA to evaluate the tumor genome of patients undergoing treatment with bevacizumab to determine novel aberrations associated with resistance. Methods Using longitudinal plasma analyses, we studied the evolution of tumor genomes in a mCRC cohort ( n = 150) and conducted analyses of CRC cases from The Cancer Genome Atlas (TCGA) database ( n = 619) to identify associations between genomic aberrations and clinical features. We employed whole-genome sequencing to identify the most frequently occurring focal somatic copy number alterations (SCNAs). Using the TCGA data as a comparative and supporting dataset, we defined the minimally amplified overlapping region and studied the mechanistic consequences of copy number gain of the involved genes in this segment. In addition, we established an in vitro cell model and conducted downstream gene expression and cell viability assays to confirm our findings from the patient dataset. Results We observed a recurrent focal amplification (8.7% of cases) on chromosome 13q12.2. Analysis of CRC cases from the TCGA database suggested that this amplicon is associated with more advanced stages. We confirmed that this 13q12.2 amplicon frequently emerges later during the clinical course of disease. After defining the minimally amplified region, we observed that the amplification and expression of one gene, POLR1D , impacted cell proliferation and resulted in upregulation of VEGFA , an important regulator of angiogenesis which has been implicated in the resistance to bevacizumab treatment. In fact, in several patients, we observed the emergence of this 13q12.2 amplicon under bevacizumab treatment, which was invariably associated with therapy resistance. Conclusions Non-invasive analyses of cell-free DNA from patients undergoing treatment with bevacizumab enabled the tracking of evolving tumor genomes and helped identify a recurrent focal SCNA of clinical relevance. Here, we describe a novel resistance mechanism against a widely applied treatment in patients with mCRC which will impact the clinical management of patients.
Intensified treatment might improve survival in small cell lung cancer (SCLC) limited disease (LD). The STING study
Authors: O. Brodin, G. Wagenius
Journal: Journal of Clinical Oncology (2007)

18167 Background: Intensified treatment in SCLC is not used, in spite of 19% improved 2-year survival from high dose or dose densified treatment according to a comprehension of 20 randomised studies. (Annals of Oncology 13:1519, 2002). What would happen if both the doses were increased, one further drug was given and dose density increased? Methods: A standard (ST) and an intensified treatment (INT) schedule were given in a phase II study in which 42 patients were included, 18 of which with LD. Patients up to 75 were included. The ST consisted of 6 courses of carboplatin, 5 AUC and etoposide 100 mg/m 2 iv day 1–3 with 3 weeks interval. Thoracic radiotherapy was given 1.5 Gy bid to 45 Gy in patients with LD, starting concommitantly with course two. INT consisted of carboplatin 6 AUC, etoposide 120 mg/m 2 and ifosfamide 5,000 mg/m 2 course 1 and 3,000 mg/m 2 in courses 2–6. Treatment was given with 2 weeks interval, which was possible by the addition of filgrastim. Radiotherapy was given in the same way as in the ST. Results: There was more problems with trombocytopenia and fatigue in the INT arm but not more problems with leucopenia. Two year survival in the ST was 4/11 (37 %) and in the INT 5/7 (72%). We now also have reached 5 year survival and there are 3/11 (27%) survivors in the ST and 4/7 (57%) in the INT. One further patient with limited disease, not included in the study was also treated according to the INT schedule and she has now reached two year survival, thus 6/8 patients treated according to that schedule are 2 year survivors. Concerning extensive disease patients there was 0/13 ST and 2/11 (18%) surviving 2 years and no 5 year survivors. Conclusion: There were too few patients with LD in this study to prove a superiority of INT, however, we consider the results very promising. The INT treatment is possible to give to patients up to 75 years and the toxicity is feasible. INT earns further studies in SCLC. We plan to start a phase III study with the same treatment arms in patients with LD during the spring 2007 and would like to get in contact with other groups that might be interested to participate, who could contact ola.brodinkarolinska.se. No significant financial relationships to disclose.
EGFR is frequently hyperexpressed in human malignant peripheral nerve sheath tumors (MPNST) and is preferentially localized in high grade areas
Authors: J. Emile, S. Tabone, R. Bahleda, P. Terrier, Y. Bieche, A. Beauchet, M. Terrier-Lacombe, A. Lemoine, F. Penault-Llorca, A. Le Cesne
Journal: Journal of Clinical Oncology (2007)

21105 Background: MPNST are highly malignant Schwann cell neoplasms that are generally resistant to conventional radiation and chemotherapy. Mouse models and in vitro data suggest that epidermal growth factor receptor (EGFR) expression is implicated in malignant transformation of Schwann cells. Methods: MPNST samples from 52 patients were studied for EGFR, Ki67, neurofibromin, p53 and survivin expression by immunohistochemistry and for EGFR amplification by in situ hybridization. Results were correlated with clinical data. EGFR RNA were also quantified by RT-PCR in 20 other MPNST and 14 cutaneous neurofibroma samples. Results: Half of the patients had a neurofibromatosis type 1 (NF1), and their age was lower at diagnosis (19 versus 27 years, P=0.04). EGFR expression was detected in 86% of MPNST, and was more frequent in NF1 (95% versus 75%). The staining of tumor cells was heterogeneous in several cases, and closely associated with high grade, Ki67 high and p53 positive areas. MPNST expressed a higher level of EGFR transcripts than neurofibromas. The five year survival was 33%, and NF1 status was the only prognostic factor in multivariate analysis. Conclusion: Our data suggest that EGFR may become a target for new therapies in MPNST, in particular in NF1-associated MPNSTs. No significant financial relationships to disclose.
メトトレキサートの効果が不十分な患者におけるトシリズマブ追加またはトシリズマブ単独療法への切り替え: 2年間の関節リウマチを対象とした無作為化対照戦略試験(ACT-RAY)の24週間にわたる徴候的および構造的結果
Authors: Dougados Maxime, Kissel Karsten, Sheeran Tom, Tak Paul P, Conaghan Philip G, Mola Emilio Martin, Schett Georg, Amital Howard, Navarro-Sarabia Federico, Hou Antony, Bernasconi Corrado, Huizinga Twj
Journal: Annals of the Rheumatic Diseases (2013)
Real-time ultrasound elastography for monitoring tumor response to neoadjuvant chemotherapy in primary breast cancer
Authors: H. Bando, M. Ishii, E. Tohno, E. Ueno
Journal: Journal of Clinical Oncology (2007)

14023 Background: Response to neoadjuvant treatment is vital to predict a patient’s long-term survival. Precise detection of residual tumor cells after neoadjuvant chemotherapy would allow a better cosmetic results avoiding over surgery and reduce second operation due to positive margin status. Moreover, accurate prediction of pathological CR will yield no surgical intervention in certain population. Recently, a new generation of ultrasound platforms with real-time freehand elastography that enables the imaging of elasticity of the lesion by using the extended combined autocorrelation method (CAM) has become available. We are currently applying this technology to our patients with primary breast cancer in an attempt to assess response to neoadjuvant chemotherapy in comparison with MRI, conventional ultrasound and pathological findings. Methods: A total of 38 patients with primary breast cancer who underwent neoadjuvant chemotherapy and following surgical resection From May 2005 to Dec 2006 were included in this study. Board certified radiologists assessed the tumor response by MRI, US and US Elastography prior to surgery. Positive predictive value (PPV), and negative predictive value (NPV) for pathological CR (pCR) was assessed. Tsukuba Elastography score was applied for the assessment of Elastography. Results: 11/38 patients (28.9%) achieved a pCR in breast to neoadjuvant chemotherapy while no patients demonstrated progressive disease. The PPV for pCR of MRI and US was 54.5% and 36.3% respectively. The NPV of MRI and US was both 90.9%. None of the residual tumor mass with score 4 or 5 cases diagnosed by Elastography achieved pCR. When residual tumor image was detected by US, pCR was present in all 4 cases with score 1 or 2 Elatography. If the cut-off line is determined between score 3 and 4, the PPV and NPV for pCR by Elastography was 100% and 66.6% respectively. Conclusions: Elastography is easy to perform and it can provide an inexpensive, non-invasive, real-time tool for assessment of response to neoadjuvant chemotherapy among patients with primary breast cancer. In particular, Elastography might more effectively diagnose pathological CR. More patients are needed to evaluate the sensitivity and specificity of this new technology. No significant financial relationships to disclose.
IgE cross-reactivity between Pas n 1 of Bahia grass pollen and other group 1 grass pollen allergens [Conference Abstract]
Authors: Janet Davies, T. Dang, Astrid Voskamp, Mark Biondo, Michelle Phung, Jennifer Rolland, Robyn O'Hehir
Journal: Allergy (2010)

Background The subtropical Bahia grass (Paspalum notatum) is an important source of pollen allergens with an extended season of pollination and wide distribution in warmer climates. The immunological relationship between pollen allergens of Bahia grass and temperate grasses is unresolved. Methods Serum IgE reactivity of grass pollen-allergic patients with Bahia, Ryegrass and Bermuda grass pollen extracts and their purified group 1 allergens, Pas n 1, Lol p 1 and Cyn d 1, were compared by immunoblotting, ELISA, inhibition ELISA, basophil activation by flow cytometry and molecular modeling. Results Differences in antibody recognition of allergenic components between Bahia grass and Ryegrass pollen were observed by immunoblotting. Eight grass pollen-allergic patients from a temperate region showed greater serum IgE reactivity with Ryegrass pollen than Bahia grass by ELISA. For seven of these sera, Ryegrass pollen inhibited IgE reactivity with Bahia grass pollen but not the converse. For 51 sera from grass pollen-allergic patients in this temperate region, IgE reactivity with Lol p 1 was greater than Pas n 1 or Cyn d 1. IgE reactivity with Lol p 1 was not inhibited by Pas n 1 or Cyn d 1, but Pas n 1 IgE reactivity was inhibited by Lol p 1. Two group 1 grass pollen allergen-specific mAb distinguished between temperate and subtropical grass pollens. Basophil activation for three patients tested was greater by Ryegrass pollen than Bahia or Bermuda grass, and by Lol p 1 than Pas n 1 or Cyn d 1. In contrast, two patients from a subtropical region had higher serum IgE reactivity with Bahia grass pollen than Ryegrass and Bahia grass pollen inhibited IgE reactivity with Ryegrass. A structural model of Pas n 1 showed amino acids implicated in IgE epitopes of other group 1 allergens were juxtaposed on the surface. Conclusion Allergens from subtropical Bahia grass pollen, including Pas n 1, share antigenic determinants with temperate grass pollen allergens, but patients exhibit higher serum IgE reactivity to their locally predominant grass pollen. Basophil activation by Bahia grass pollen and Pas n 1 in patients from a temperate climate indicates clinically relevant cross-sensitization between temperate and subtropical grass pollens.
Covid-19: UK records first death, as world’s cases exceed 100 000
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Firmly established transplantable C3H/HeJ mammary carcinomas can be inhibited by host challenge with Vibrio cholerae neuraminidase (VCN) treated tumor cells. The effect is totally immunospecific, even VCN-treated tumors bearing shared mammary tumor virus (MTV) antigen cannot induce the regression. Thus, VCN is capable of increasing the immunogenicity of the private, unique-unshared tumor antigens on mammary carcinomas; VCN is incapable of increasing the immunogenicity of the shared MTV associated tumor antigen.
Effect of smoking on imatinib pharmacokinetics
Authors: N. P. van Erp, H. Gelderblom, M. van Glabbeke, A. van Oosterom, J. Verweij, H. Guchelaar, B. Peng, I. Judson
Journal: Journal of Clinical Oncology (2007)

2573 Background: Smoking is a potent inducer of the cytochrome P450 1A2 isoenzyme (CYP1A2) and may therefore effect the pharmacokinetics (PK) of drugs metabolized by CYP1A2. Indeed, clinical studies with erlotinib (metabolized by CYP3A4 and also partly by CYP1A2) have shown a major increase in erlotinib clearance in smokers versus non-smokers. The effect of smoking on the PK of imatinib, which is also metabolized by CYP3A4 and partly by CYP1A2, is unknown. We aimed to study the effect of smoking on imatinib PK in order to explain a part of the interpatient variation. Methods: The effect of smoking on the PK parameters was analyzed in 34 patients with gastro-intestinal stromal tumors or soft tissue sarcoma included in the EORTC-STBSG phase I and phase II trials. This cohort included 9 smokers and 25 non-smokers. The daily smoking habits of the study patients were retrieved retrospectively from the patient’s record. PK parameters assessed with NONMEM, version V were clearance (Cl), distribution volume (V), elimination half life (T1/2) and the dose standardized area under the concentration curve (AUC). We considered a 40% reduction in imatinib exposure clinically relevant and this study is adequately powered to detect this difference. Results: The mean PK parameters in the smokers versus the non-smokers group ± SD were: Cl; 9.6 ± 5.5 L/h vs 9.2 ± 4.6 L/h, V; 216.5 ± 114.3 L vs 207.0 ± 116.9 L, T1/2; 16.1 ± 6.0 h vs 16.5 ± 6.0 h, AUC; 133.6 ± 71.0 ng.h/ml.mg vs 142.3 ± 84.0 ng.h/ml.mg. There was no significant difference in PK parameters observed between the smokers and the non- smokers. Conclusion: This retrospective study suggest that the PK of imatinib was not affected by smoking and therefore does not explain the large variation in imatinib PK. No significant financial relationships to disclose.