tbuckley/cabot-search huggingface dataset:
Multi-symptom asthma (MSA) and comorbidities in a cohort of Italian young asthmatic subjects
Authors: Stefania La Grutta, Sara Maio, Sandra Baldacci, Sonia Cerrai, Giuseppe Sarno, Francesco Di Pede, Francesco Pistelli, Laura Carrozzi, Giovanni Viegi
Journal: European Respiratory Journal (2013)

MSA was used as indication of disease severity in adult cross-sectional surveys. Aim of our study was to investigate the characteristics of multi-symptom asthma score (MSAs) in a longitudinal survey. A cohort of subjects living in Pisa, Central Italy, was selected, based on subjects included in the IMCA study (2007-2011) who had participated as children either in PISA1 (1985-1988) or PISA2 (1991-1993) previous surveys, making at least two points of data collection available for each subject. All subjects completed self-administered questionnaires on past and current respiratory symptoms, concomitant allergic disease, personal information, smoke/pets exposure, health care utilization, comorbidities. MSAs was defined as reporting ‘‘physician-diagnosed asthma’’,‘‘asthma medication’’,‘‘attacks of shortness of breath’’ last 12 months and at least one additional respiratory symptom. The demographic characteristics included 143 children (M=58%;11.7±3.4yr - PISA1), 179 adolescents (M=55%; 15.9±4.4yr - PISA2), 186 adults (M=56.5%; 34.3±6.2yr - IMCA). MSAs was present in 2.7%, 3.2% and 2,2% of PISA1, PISA2 and IMCA subjects, respectively. 20,7%, 28.5% and 20,7% of asthmatics reported MSAs, despite use of asthma medication, in PISA1, PISA2 and IMCA, respectively. MSAs was associated with rhinitis (p
Activation of MMP-2 by endometrial cancer cells in vitro is enhanced by LPA
Authors: L. R. Boyd, E. V. Ariztia, D. A. Fishman
Journal: Journal of Clinical Oncology (2007)

16047 Background: Matrix metalloproteinases (MMPs) are responsible for the breakdown of extracellular matrix components, and are important in the metastatic phenotype. HEC-1A is an endometrial cancer cell line, derived from a moderately-differentiated tumor. These cells do not produce MMP-2, an important mediator of invasive behavior. We sought to: evaluate if HEC-1A cells have the capacity to activate proMMP-2 if given the proenzyme exogenously; and determine if the addition of lysophosphatidic acid (LPA), a known activator of MMPs in other cancers, would further enhance this conversion. Methods: HEC-1A cells were maintained per known protocols. Conditioned media from HT1080 chondrosarcoma cells, a source of proMMP-2, was added to HEC-1A cells. Cells were also treated with 0.1, 1.0 and 10uM LPA. Conditioned media from the cells was analyzed for the presence of MMP-2 and its proenzyme utilizing gelatin zymography. Cellular invasion through collagen matrix was quantified using a modified Boyden chamber assay. Migration was evaluated using a wound healing assay with quantification of wound closure at 48 hours. Proliferation was assessed following cell culture for 48 hours using an MTS tetrazolium salt/phenazine methosulfate assay. Results: HEC-1A cells activated exogenous proMMP-2 to MMP-2, as confirmed by gelatin zymography. This occurred in both the presence and absence of LPA. Invasion of HEC-1A cells treated with proMMP-2 was significantly increased as compared to controls (p &lt; .001). LPA increased invasion in cells with and without exogenous proMMP-2, with the most invasive cells being those treated with both LPA and exogenous proMMP-2. The addition of both exogenous MMP-2 and LPA significantly increased cellular migration as quantified using the wound healing assay (p &lt; .001). Cellular proliferation was significantly increased with LPA vs. controls. The addition of proMMP-2 did not lead to a significant difference in proliferation. Conclusions: HEC-1A cells can convert exogenous proMMP-2 to its active form, and in doing so exhibit a more invasive phenotype. LPA serves to further increase these behaviors. This may reflect the tumor microenvironment, with endometrial cancer cells responding to bioactive lipids and proenzymes secreted by the surrounding stroma. No significant financial relationships to disclose.
Decline in the use of erythropoiesis-stimulating agents: Long-term effects of regulation, reimbursement, and unfavorable data.
Authors: M. A. Mirza, M. D. Newton, R. Sager, S. Kurian, J. Abraham
Journal: Journal of Clinical Oncology (2010)

e13158 Background: The use of erythropoiesis-stimulating agents (ESAs) for the treatment of anemia in cancer patients underwent a rapid increase in the 1990s and early 2000s. At their peak, they were used in nearly half of all U.S. cancer patients to increase hemoglobin concentrations, reduce the need for blood transfusions, and increase quality of life. In the past 3 years however, the publication of data calling the safety of these agents into question has resulted in increased regulation of ESAs. We examine the impact these events have had on the use of ESAs at our institution. Methods: A retrospective review of 3,289 cancer patients treated at West Virginia University (inpatients and outpatients) between 2004 and 2008 was initiated. The data collected was primarily for epogen (epoetin alpha) only as this was the institutional preferred formulary agent. The data extracted was the number of patients per month using epoetin alpha as dispensed by the pharmacy. The number of patients using epoetin alpha per month was plotted against time. We associated data points to specific milestone events that could have influenced the use of ESAs (guideline updates, regulatory changes, and studies showing detrimental effect of ESA use in cancer patients). Results: We observed a long-term downward trend in the use of ESAs at our institution. The peak of use occurred in March 2006, when 129 patients received epoetin alpha. A reduction in use of approximately 30% was observed in association with the publication of Bohlius' meta- analysis in May 2006 indicating possible increased thromboembolic risk. Other reductions in use were observed in temporal association with the suspension of the DAHANCA H&N trial in December 2006, addition of FDA black box warning in March 2007, CMS National Coverage Policy change in July 2007, and FDA labeling changes in 2007 and 2008. The cumulative effect of these events resulted in a decline in use of 89% at our institution, with only 14 patients receiving ESAs in June 2008, the last month of our analysis. Conclusions: Unfavorable safety data and increased regulation of ESAs have resulted in a substantial decline in the use of these agents at our institution. No significant financial relationships to disclose.
Randomized phase II study of proteinase 3-derived PR1 vaccine and GM-CSF with or without peg-interferon alfa-2b to eradicate minimal residual disease in chronic myeloid leukemia
Authors: A. Quintas-Cardama, H. M. Kantarjian, E. Wieder, J. Molldrem, J. E. Cortes
Journal: Journal of Clinical Oncology (2008)

22043 Background: Imatinib (IM) induces complete molecular responses in a minority of patients (pts) with chronic myeloid leukemia (CML). CML is responsive to T-cell-mediated immunity. The PR1 peptide (VLQELNVTV) is a leukemia-associated antigen presented on HLA-A2 to cytotoxic T lymphocytes (CTL) that preferentially kills leukemia progenitors. Methods: We evaluated the activity of PR1 vaccine (2 mg) with GM-CSF (0.6 mg) and Montanide ISA-51 given subcutaneously to pts with CML on IM in complete cytogenetic response with stable residual molecular disease. Pts were randomized to receive pegylated interferon alfa (PEG-IFN-α; 0.5 μg/kg) with each vaccination. PR1 was administered on weeks 0, 3, 6, and 18. Immune responses were assessed by PR1/HLA-A2 tetramer staining and molecular responses by quantitative PCR in peripheral blood before study entry, prior to each vaccination, and every 3 months thereafter. Results: 4 of the 20 planned HLA-A2+ pts have been accrued. Pt 1 (on IM 600 mg/d for 85 months) and 2 (on IM 800 mg/d for 72 months) received PR1 vaccine+PEG-IFN-α and Pts 3 and 4 (both on IM 400 mg/d, for 43 and 37 months, respectively) received PR1 vaccine alone. BCR- ABL1/ABL1 ratios prior to vaccination were 0.99, 0.79, 0.52, and 0.10, respectively. The median follow-up is 8.5 months (range, 4–11). All pts had mild elevations of BCR-ABL1 transcripts after the first vaccine, followed by steady decline in transcript levels in Pt 1 (>1- log), Pt 2 (<1-log) and Pt 3 (<1-log). Toxicity was limited to grade 1–2 injection site reactions except for Pt 2, in whom PEG-IFN-α was discontinued after 4 mos due to behavioral changes. Immune responses were elicited in Pts 1 (PR1 vaccine+PEG-IFN-α), and 3 (PR1 vaccine). Data on differentiation phenotype, T cell receptor (TCR-alpha-beta) gene usage, TCR avidity, and peptide-induced CTL cytokine secretion profile of PR1-CTLs compared to overall CTL population and CTL with specificity for the HLA-A2-restricted NLV peptide from CMV at each time point after PR1 will be presented. Conclusions: PR1 vaccine in pts with CML in CCyR with stable or rising levels of BCR-ABL1 transcripts on IM induces specific immune responses and ongoing improvement of molecular response. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration The Vaccine Company The Vaccine Company The Vaccine Company
Control of chemotherapy-induced diarrhea with the synthetic enkephalin BW942C: a randomized trial with placebo in patients receiving cisplatin.
Authors: M G Kris, R J Gralla, R A Clark, L B Tyson, S Groshen
Journal: Journal of Clinical Oncology (1988)

Diarrhea commonly occurs following the administration of cisplatin. BW942C, a pentapeptide, is a synthetic enkephalin shown to control castor oil-induced and traveler's diarrhea. To assess the safety and efficacy of BW942C in controlling diarrhea caused by cisplatin, 30 adults with lung cancer who had already experienced diarrhea (three or more loose bowel movements) during the 24-hour period following a prior cisplatin administration were randomized to receive either BW942C or placebo during the next cisplatin course. All patients received a concomitant antiemetic regimen including metoclopramide, dexamethasone, and lorazepam during all courses. Patients administered BW942C experienced less diarrhea (27% v 67%, P = .02). Twenty-seven percent of patients given the pentapeptide had loose bowel movements as opposed to 93% who received placebo (P = .0002). There were no significant differences in the incidence and degree of vomiting and other treatment-related side effects observed between the placebo and treatment groups. We conclude that oral BW942C is more effective than placebo in controlling diarrhea following cisplatin chemotherapy.
Is genetic testing being performed by the proband's close relatives? An assessment in hereditary breast and ovarian cancer (HBOC) Spanish families
Authors: J. Sanz, J. Balmaña, O. Díez, M. Baiget, M. C. Alonso
Journal: Journal of Clinical Oncology (2004)

9660 Background: After a mutation is identified in a HBOC family, uptake of genetic testing among the relatives stratifies their cancer risk and impacts their clinical management. Pursuing genetic testing may depend on whether positive results are consistently disclosed by the proband to their relatives, as well as demographic, psychological and cultural factors. In order to assess the participation of members of BRCA1/2 Spanish families, we described the frequency of genetic testing among first (FDR) and second-degree relatives (SDR) of BRCA1/2 probands. We also analyzed and to analyze the clinical and demographic features of probands and family members that may be associated with performing genetic testing. Methods: We analyzed 248 FDR and SDR belonging to 34 BRCA1/2 families. Clinical and demographic features of the individuals undergoing testing were collected in a personal interview, such as gender, being affected by cancer, having children, being the proband's offspring or a sibling, having a FDR affected by cancer, probands' educational level and age at cancer diagnosis. Logistic regression was used to determine independent variables associated with uptake of genetic testing. Results: Genetic testing was performed in 83 (69%) of 120 FDR and 38 (30%) of 128 SDR, p< .0001. Median time for genetic testing after result's disclosure to the proband was 3 months for FDR and 5 months for SDR. Among FDR, male were less likely than women to undergo testing (OR 0.14, 95%CI: 0.05–0.38). Among SDR, individuals younger than 45 compared to those who were older (OR 4.81, 95%CI: 1.9–12.2), and a high educational level of the proband compared to low (OR 3.66, 95%CI: 1.5–8.9) were independently associated with performing testing. Conclusions: Genetic testing is being performed by a high percentage of FDR and a relatively low percentage of SDR in BRCA1/2 Spanish families. The reasons why male FDR, SDR older than 45 years, and SDR of probands with a low educational level undergo genetic testing less frequently should be addressed in future studies and develop genetic counseling strategies to improve these rates. No significant financial relationships to disclose.
Organ preservation for patients treated with induction chemotherapy (IC) followed by radiation therapy (RT) or chemoradiation (CRT) for advanced stage squamous cell carcinoma of the larynx (SCCL)
Authors: B. A. Guadagnolo, R. B. Tishler, M. R. Posner, L. Weeks, L. J. Wirth, C. M. Norris, C. A. Sullivan, L. Goguen, P. M. Busse, R. I. Haddad
Journal: Journal of Clinical Oncology (2004)

5600 Background: We reviewed the charts of patients with laryngeal cancer treated with IC and definitive RT or CRT to determine the rates of overall organ preservation and function. Methods: Between September 1995 and December 2001, 29 patients with stage III (45%) and IV (55%) SCCL, were treated with IC and definitive RT or CRT on one of seven consecutive trials. The median age at diagnosis was 54 years (range 38–74). 55% had clinically node-positive disease. 55% and 45% had T3 and T4 tumors, respectively. All received 3 cycles of IC with a platinum-based regimen. QD RT was given to 48%, BID RT to 45%, and concomitant boost (CB) RT to 7%. CRT was given with carboplatin (28%) or docetaxel (28%). Those treated with BID RT did not receive CRT. Results: Median follow-up is 52 months (range 17–85). Overall survival is 66%. Relapse occurred in12 (41%) patients, and 6 underwent salvage laryngectomy (5 Stage III, 1 Stage IV). Of the entire cohort, 59% (17/29) are alive at last follow-up with an anatomically intact larynx, and 48% (14/29) are alive with a functional larynx. Detailed information on g-tube placement/removal was available for 23 patients. Median time with G-tube was 12 months (range, 1–50 months), and 15/23 (65%) had g-tube for 6 months or longer. 23 of all 29 patients (79%) retained an anatomically intact larynx, but 30% (7/23) did not resume their pre-treatment swallowing mechanics and airway protection. Overall rate of functional organ preservation, regardless of survival was, 55% (16/29). The 7/29 patients (26%) who retained a non-functional larynx required permanent g-tube or were unable to return to pretreatment oral intake capability. Nine of 13 with T4 SCCL (69%) compared to 7 of 16 (44%) T3 SCCL retained a functional larynx. Conclusions: The rate of larynx preservation is high, but toxicity remains significant with combined modality therapy. Advanced stage was not an indicator of poor outcome. Half of all patients were alive, able to retain their larynx, and return to pretreatment function. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis
Expression of nuclear splicing factors in ovarian cancer: correlations
Authors: E. Stickeler, S. Iborra, M. Jaeger, D. Watermann, M. Hirschfeld, G. Gitsch, A. zur Hausen
Journal: Journal of Clinical Oncology (2008)

16550 Background: Alternative splicing represents an important nuclear mechanism in the post-transcriptional regulation of gene expression, which is frequently altered during tumorigenesis. Previously, we have described marked changes in alternative splicing of the CD44 gene in ovarian and breast cancer. We described also a specific induction of some splicing factors during tumor development. In the present study we have focussed on the expression profiles of different splicing factors, including classical SR proteins, Tra2β, Tra2α, Y-Box, ASF SF2 and FAK in normal and malignant ovarian tissue as well as metastasis to evaluate their expression pattern in regards to tumor development. Methods: We investigated expression levels of the different splicing factors in 15 normal tissue samples, 19 primary tumors and 24 metastatic samples of patients diagnosed with ovarian using quantified RT-PCR analysis. Results: The analysis revealed a marked and specific induction of Tra2-beta, Y-Box, SRp55, SRp30 and FAK in primary tumors as well as metastasis in comparison to physiological tissue samples (p<0.01). However, in our patienit cohort no induction was seen for the other investigated splicing factors ASF SF2, SRp40 and Tra2α. Conclusions: Our results suggest a specific induction of distinct splicing factors in ovarian cancer tumorigenesist. The involvement of Tra2-beta, Y-Box, SRp55, SRp30 and FAK in exon recognition and alternative splicing may be important for gene regulation of alternatively spliced genes like CD44 with potential functional consequences in this tumor type leading to tumor progression and metastasis. No significant financial relationships to disclose.
Predictors of renal function in nephron sparing surgery for renal cell carcinoma in solitary kidneys
Authors: M. Wosnitzer, D. J. Lee, A. J. Hirsch, J. M. McKiernan
Journal: Journal of Clinical Oncology (2009)

e16045 Background: Partial nephrectomy (PN) is an effective option for the treatment of renal cell carcinoma (RCC) in patients who need to preserve renal function. However, the oncologic safety and functional outcome after PN in solitary kidneys have not been fully examined. We assessed the outcomes after PN, and evaluated predictors of post-operative renal function. Methods: A retrospective analysis of the Columbia Urologic Oncology database found 1327 patients were treated for RCC from 1988 - 2008, of whom 38 consecutive patients underwent PN on a solitary kidney. Glomerular filtration rate (GFR) was estimated with the Modification of Diet in Renal Disease (MDRD) equation. Severe chronic kidney disease (CKD) and renal failure were defined as GFR of 15–30 cc/min/1.73m2 and GFR&lt;15, respectively. Cox proportional hazards regression methods were used. Results: The study group included 30 men and 8 women with unilateral RCC. The mean age was 63.2 years (range 35–83). The mean estimated blood loss was 465cc, the mean tumor diameter was 3.9cm, and 6 (17%) of the patients had a positive surgical margin. 9 patients (30%) had recurrence of RCC at a mean of 23 months postoperatively. Recurrence occurred in the kidneys of 4 patients, lung in 3 patients, bone in 3 patients, and the ipsilateral adrenal gland in one patient. The mean preoperative GFR was 55.6, and the GFR decreased postoperatively by an average of 14.2%. No patients required postoperative hemodialysis. Preoperative GFR (HR=1.01, p&lt;0.01) and the volume of kidney removed (HR=0.93, p=0.01) were associated with severe CKD and renal failure on a univariate Cox regression analysis, but were not independent predictors after adjusting for age, race, tumor stage and grade. Preoperative GFR, volume removed, age, tumor stage or grade were not independent predictors of RCC recurrence. Conclusions: PN in solitary kidneys pose difficult challenges for surgical and clinical management. Nephron sparing surgery for the treatment of RCC is feasible with acceptable morbidity and renal function outcome. The volume of renal parenchyma removed and the preoperative GFR are associated with renal function loss several months after surgery, and may be useful in predicting long-term renal function. No significant financial relationships to disclose.
Clinical characteristics of patients with hereditary breast and ovarian cancer syndrome.
Authors: A. Ravipati, S. Kizilbash, W. Ducaine, L. Dohany, I. A. Jaiyesimi, D. Zakalik
Journal: Journal of Clinical Oncology (2010)

e12024 Background: The hereditary breast-ovarian cancer syndrome accounts for an estimated 10%-15% of breast cancer diagnosed in the United States each year. BRCA1 and 2 genes account for the majority of inherited breast and ovarian cancers. Identification of BRCA1 and 2 mutation carriers is an important focus in the prevention and early detection of breast and ovarian cancer. This study describes the clinical characteristics of patients with BRCA1 and BRCA2 mutation at a community-based hospital. Methods: A retrospective review was conducted of all women with BRCA1/2 mutation that were managed at the cancer genetics clinic at our institution from 2005-2008. Results: 145 patients were evaluated. 100 patients (69%) had a BRCA1, 45 (31%) had BRCA2. 84 patients had breast cancer. The majority of patients (90%) had a diagnosis of infiltrating ductal carcinoma, 7.1% had infiltrating lobular carcinoma. 63.6% had ductal carcinoma-in-situ and only 3% had lobular carcinoma in situ. 45.2% were ER positive, 30% were PR positive and only 5.4% were HER2/neu positive. The most common mutation sequence was 5385insC affecting 14.5% of the population. BRCA1 carriers when compared to BRCA2 carriers developed breast cancer at significantly younger age (39.8 vs. 47.2 years, p = 0.0008). No significant association was found between breast cancer pathology and BRCA mutation status. When compared to BRCA1, patients with BRCA2 mutation were more likely to be ER positive (28.2% vs. 73.9%; p = 0.0005) and PR positive (16.2% vs. 52.2%, p = 0.0031). Overall 40% of the patients underwent prophylactic mastectomy and 40% underwent prophylactic bilateral salpingo-oophorectomy. Conclusions: Based on our experience, patients with BRCA2 carriers are significantly older than patients with BRCA1. BRCA2 carriers are also more likely to be ER and PR positive. A significant proportion (40%) of our population elected to undergo risk-reducing surgeries. No significant financial relationships to disclose.