bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of high-fat diet and/or body weight on mammary tumor leptin and apoptosis signaling pathways in MMTV-TGF-α mice
Authors: Dogan Soner , Hu Xin , Zhang Yan , Maihle Nita J , Grande Joseph P , Cleary Margot P 
Published: December 2007

Abstract
Introduction
Obesity is a risk factor for postmenopausal breast cancer and is associated with shortened mammary tumor (MT) latency in MMTV-TGF-α mice with dietary-induced obesity. One link between obesity and breast cancer is the adipokine, leptin. Here, the focus is on diet-induced obesity and MT and mammary fat pad (MFP) leptin and apoptotic signaling proteins.

Methods
MMTV-TGF-α mice were fed low-fat or high-fat diets from 10 to 85 weeks of age. High-Fat mice were divided into Obesity-Prone and Obesity-Resistant groups based on final body weights. Mice were followed to assess MT development and obtain serum, MFP, and MT.

Results
Incidence of palpable MTs was significantly different: Obesity-Prone > Obesity-Resistant > Low-Fat. Serum leptin was significantly higher in Obesity-Prone compared with Obesity-Resistant and Low-Fat mice. Low-Fat mice had higher MFP and MT ObRb (leptin receptor) protein and Jak2 (Janus kinase 2) protein and mRNA levels in comparison with High-Fat mice regardless of body weight. Leptin (mRNA) and pSTAT3 (phosphorylated signal transducer and activator of transcription 3) (mRNA and protein) also were higher in MTs from Low-Fat versus High-Fat mice. Expression of MT and MFP pro-apoptotic proteins was higher in Low-Fat versus High-Fat mice.

Conclusion
These results confirm a connection between body weight and MT development and between body weight and serum leptin levels. However, diet impacts MT and MFP leptin and apoptosis signaling proteins independently of body weight.
Changeovers of vasoactive drug infusion pumps: impact of a quality improvement program
Authors: Argaud Laurent , Cour Martin , Martin Olivier , Saint-Denis Marc , Ferry Tristan , Goyatton Agnes , Robert Dominique 
Published: December 2007

Abstract
Background
Hemodynamic instability following the changeover of vasoactive infusion pump (CVIP) is a common problem in the intensive care unit. Several empiric methods are used to achieve CVIP. We hypothesized that the variation in these procedures could generate some morbidity. We sought to assess the effects of the standardization of practice, as a quality improvement program, on the CVIP-induced incidents.

Materials and methods
We performed a prospective before-and-after intervention study including all adult patients with a diagnosis of cardiovascular failure who received a continuous infusion of vasoactive drugs or inotropic drugs. After a baseline preimplementation period (phase 1), a standardized 'quick change method' of CVIP using two syringe drivers was implemented in our intensive care unit (phase 2). Endpoints (rate and distribution of incidents: variations of systolic blood pressure >20 mmHg or heart rate >20 beats/min, and arrhythmias) were registered in both 3-month phases.

Results
We studied a total of 913 CVIP events (phase 1, 435 events; phase 2, 478 events) from 43 patients. Patient characteristics were not significantly different among phases, with a majority of the patients having septic shock. The frequency of incidents was significantly (P < 0.0001) reduced in phase 2 (5.9%, n = 28) versus phase 1 (17.8%, n = 78). This effect was observed whichever catecholamine was used. More than 98% of incidents were blood pressure variations, with a similar distribution of the nature of incidents in both phases.

Conclusion
The present study illustrates that adverse events are common following CVIP, and illustrates the positive impact of a quality improvement program to enhance inpatient safety related to this current process of care.
Health-Related Quality of Life Results in Pathologic Stage C Prostate Cancer From a Southwest Oncology Group Trial Comparing Radical Prostatectomy Alone With Radical Prostatectomy Plus Radiation Therapy
Authors: Moinpour Carol M. , Hayden Katherine A. , Unger Joseph M. , Thompson Ian M. , Redman Mary W. , Canby-Hagino Edith D. , Higgins Betsy A. , Sullivan Jerry W. , Lemmon Dianne , Breslin Sheila , Crawford E. David 
Published: December 2007

Purpose To compare short- and long-term effects of adjuvant treatment versus observation after surgery on health-related quality of life (HRQL) of prostate cancer patients. Patients and Methods The Southwest Oncology Group (SWOG) intergroup trial compared radical prostatectomy (RP) plus observation versus RP plus adjuvant radiation therapy (RT). Two-hundred seventeen of 425 therapeutic trial patients were eligible and registered to the HRQL study. Patients completed the SWOG Quality of Life Questionnaire (emotional, physical, social, and role function; general symptom status; treatment/disease-specific symptoms; and global HRQL [GHRQL]) at baseline, 6 weeks, 6 months, and annually for 5 years. Prespecified outcomes were three genitourinary symptoms (bowel function tenderness, frequent urination, and erectile dysfunction [ED]) and measures of physical and emotional function. Adjustments were made for the baseline score. Results Patients receiving adjuvant RT reported worse bowel function (through approximately 2 years) and worse urinary function. There were no statistically significant differences for ED. GHRQL was initially worse for the RP+RT arm but improved over time and was better at the end of the period than the GHRQL reported for RP alone (treatment arm × time interaction, P = .0004). Symptom distress was significantly worse for the RP+RT arm compared with the RP alone arm, but the treatment arms did not differ with respect to other general measures of HRQL. Conclusion The addition of RT to surgery resulted in more frequent urination, as well as early report of more bowel dysfunction, although bowel function differences disappeared over the 5-year period. The addition of RT did not negatively impact ED.
Taxane-Based Combinations As Adjuvant Chemotherapy of Early Breast Cancer: A Meta-Analysis of Randomized Trials
Authors: De Laurentiis Michele , Cancello Giuseppe , D'Agostino Diego , Giuliano Mario , Giordano Antonio , Montagna Emilia , Lauria Rossella , Forestieri Valeria , Esposito Angela , Silvestro Lucrezia , Pennacchio Roberta , Criscitiello Carmen , Montanino Agnese , Limite Gennaro , Bianco Angelo Raffaele , De Placido Sabino 
Published: December 2007

PurposeWe conducted a meta-analysis of randomized trials that evaluated the efficacy of incorporating taxanes into anthracycline-based regimens for early breast cancer (EBC). We aimed to determine whether this approach improves disease-free survival (DFS) and overall survival (OS) and whether benefits are maintained across relevant patient subgroups.MethodsStudies were retrieved by searching the PubMed database and the proceedings of major conferences. We extracted hazard ratios (HR) and 95% CIs for DFS and OS from each trial and obtained pooled estimates using an inverse-variance model.ResultsThirteen studies were included in the meta-analysis (N = 22,903 patients). The pooled HR estimate was 0.83 (95% CI, 0.79 to 0.87; P < .00001) for DFS and 0.85 (95% CI, 0.79 to 0.91; P < .00001) for OS. Risk reduction was not influenced by the type of taxane, by estrogen receptor (ER) expression, by the number of axillary metastases (N1 to 3 v N4+), or by the patient's age/menopausal status. Sensitivity analysis showed that taxanes given in combination with anthracyclines, unlike sequential administration, did not significantly improve OS. However, the test for interaction showed that HR did not differ between the two schedules (P = .54). Taxane administration resulted in an absolute 5-year risk reduction of 5% for DFS and 3% for OS.ConclusionThe addition of a taxane to an anthracycline-based regimen improves the DFS and OS of high-risk EBC patients. The DFS benefit was independent of ER expression, degree of nodal involvement, type of taxane, age/menopausal status of patient, and administration schedule.
Effect of BRCA1/2 Mutations on Long-Term Survival of Patients With Invasive Ovarian Cancer: The National Israeli Study of Ovarian Cancer
Authors: Chetrit Angela , Hirsh-Yechezkel Galit , Ben-David Yehuda , Lubin Flora , Friedman Eitan , Sadetzki Siegal 
Published: December 2007

Purpose To evaluate the long-term survival of ovarian cancer (OvC) patients in total and by BRCA1/2 mutation status. Patients and Methods In a nationwide case-control study on OvC conducted in Israel between 1994 and 1999, 779 Jewish women with epithelial invasive OvC were tested for the three Ashkenazi Jewish founder mutations in BRCA1 (185delAG; 5382insC) and BRCA2 (6174delT) genes and followed for survival up to 2003. Of the 605 women of Ashkenazi origin, 213 (35.2%) carried a mutation in the BRCA1/2 genes. Clinical characteristics were abstracted from the patients' medical records. The Kaplan-Meier method, log-rank tests, and stepwise Cox regression model were used for survival analyses. Results The 5-year survival rate for the entire group was 39%. Median survival for carriers was significantly longer than for noncarriers (53.7 v 37.9 months, respectively; P = .002). This differential survival was pronounced among women diagnosed at stages III to IV (5-year survival rates of 38.1% and 24.5% for carriers and noncarriers, respectively; P < .001) and for women with poor grade (45.4% v 31.5%, for carriers and noncarriers, respectively; P < .001). These results remained significant after controlling for age at diagnosis, grade, and morphology. This benefit in prognosis was seen for both BRCA1 and BRCA2 carriers compared with noncarriers. During the study period (median follow-up, 6.2 years), being a BRCA1/2 mutation carrier decreased the mortality rate by 28%. Conclusion This study confirms that, among Ashkenazi OvC patients, BRCA1/2 mutations are associated with improved long-term survival. This may be due to distinct clinical behavior and/or to a better response to chemotherapy.
Phase II Clinical Trial of Bevacizumab and Low-Dose Metronomic Oral Cyclophosphamide in Recurrent Ovarian Cancer: A Trial of the California, Chicago, and Princess Margaret Hospital Phase II Consortia
Authors: Garcia Agustin A. , Hirte Hal , Fleming Gini , Yang Dongyun , Tsao-Wei Denice D. , Roman Lynda , Groshen Susan , Swenson Steve , Markland Frank , Gandara David , Scudder Sidney , Morgan Robert , Chen Helen , Lenz Heinz-Josef , Oza Amit M. 
Published: December 2007

Purpose Vascular endothelial growth factor (VEGF) plays an important role in the biology of ovarian cancer (OC). Inhibitors of VEGF suppress tumor growth in OC models. Metronomic chemotherapy, defined as frequent administration of low doses of cytotoxic chemotherapy, suppresses tumor growth, possibly by inhibiting angiogenesis. A phase II trial was conducted to evaluate the antitumor activity and adverse effects of bevacizumab and metronomic oral cyclophosphamide in women with recurrent OC. Patients and Methods Patients with measurable disease and prior treatment with a platinum-containing regimen were eligible. Up to two different regimens for recurrent disease were allowed. Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks and oral cyclophosphamide 50 mg/d. The primary end point was progression-free survival at 6 months. Plasma levels of VEGF, E-selectin, and thrombospondin-1 were obtained serially. Results Seventy patients were enrolled. The probability of being alive and progression free at 6 months was 56% (± 6% SE). A partial response was achieved in 17 patients (24%). Median time to progression and survival were 7.2 and 16.9 months, respectively. The most common serious toxicities were hypertension, fatigue, and pain. Bevacizumab-related toxicities included four episodes of gastrointestinal perforation or fistula, two episodes each of CNS ischemia and pulmonary hypertension, and one episode each of gastrointestinal bleeding and wound healing complication. There were three treatment-related deaths. Levels of VEGF, E-selectin, and thrombospondin-1 were not associated with clinical outcome. Conclusion The combination of bevacizumab and metronomic cyclophosphamide is active in recurrent OC. Further study of this combination is warranted.
Survival for Patients With Invasive Cutaneous Melanoma Among Ethnic Groups: The Effects of Socioeconomic Status and Treatment
Authors: Zell Jason A. , Cinar Pelin , Mobasher Mehrdad , Ziogas Argyrios , Meyskens Frank L. , Anton-Culver Hoda 
Published: December 2007

PurposeAlthough uncommon, melanoma is associated with poor survival characteristics among African Americans and Hispanics compared with non-Hispanic whites (NHWs). Low socioeconomic status (SES) is also associated with poor survival among patients with melanoma, but it is not known whether this is because of SES itself or because of treatment disparities. We set out to determine this by using the large, population-based California Cancer Registry (CCR) database as a model.Patients and MethodsWe conducted a case-only analysis of CCR data (1993 to 2003), including a descriptive analysis of relevant clinical variables and SES. The SES variable used has been derived from principle component analysis of census block-level CCR data that was linked to census data to address seven indicators of SES. Univariate analyses of overall survival (OS) were conducted using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazard ratios (HRs).ResultsA total of 39,049 incident patient cases of cutaneous melanoma, including 36,694 in NHWs; 127 in African Americans; 1,996 in Hispanics; and 262 in Asian-Americans, were analyzed. Higher SES was associated with an early stage at presentation (P < .0001), with treatment with surgery (P = .0005), and with prolonged survival (P < .0001). After adjustments for age, sex, histology, American Joint Committee on Cancer stage, anatomic site, treatment, and SES, a statistically significant increased risk of death was observed for African Americans compared with NHWs (HR, 1.60; 95% CI, 1.17 to 2.18); no survival differences were noted for Asians or Hispanics compared with NHWs in the adjusted analysis.ConclusionLow SES independently predicts poor outcome among patients with cutaneous melanoma. However, the poor OS observed for African American patients with melanoma is not explained by differences in treatment or SES.
Age and Comorbidity As Independent Prognostic Factors in the Treatment of Non–Small-Cell Lung Cancer: A Review of National Cancer Institute of Canada Clinical Trials Group Trials
Authors: Asmis Timothy R. , Ding Keyue , Seymour Lesley , Shepherd Frances A. , Leighl Natasha B. , Winton Tim L. , Whitehead Marlo , Spaans Johanna N. , Graham Barbara C. , Goss Glenwood D. 
Published: December 2007

Purpose This study analyzed patients enrolled in two large, prospectively randomized trials of systemic chemotherapy (adjuvant/palliative setting) for non–small-cell lung Cancer (NSCLC). The main objective was to determine if age and/or the burden of chronic medical conditions (comorbidity) are independent predictors of survival, treatment delivery, and toxicity. Patients and Methods Baseline comorbid conditions were scored using the Charlson comorbidity index (CCI), a validated measure of patient comorbidity that is weighted according to the influence of comorbidity on overall mortality. The CCI score (CCIS) was correlated with demographic data,(ie, age, sex, race), performance status (PS), histology, cancer stage, patient weight, hemoglobin, alkaline phosphatase, lactate dehydrogenase, outcomes of chemotherapy delivery (ie, type, total dose, and dose intensity), survival, and response. Results A total of 1,255 patients were included in this analysis. The median age was 61 years (range, 34 to 89 years); 34% of patients were elderly (at least 65 years of age); and 31% had comorbid conditions at randomization. Twenty-five percent of patients had a CCIS of 1, whereas 6% had a CCIS of 2 or greater. Elderly patients were more likely to have a CCIS equal to or greater than 1 compared with younger patients (42% v 26%; P < .0001), as were male patients (35% v 21%; P < .0001) and patients with squamous histology (36% v 29%; P = .001). Although age did not influence overall survival, the CCIS appeared prognostic (CCIS 1 v 0; hazard ratio 1.28; 95%CI, 1.09 to 1.5; P = .003). Conclusion In these large, randomized trials, the presence of comorbid conditions (CCIS ≥ 1), rather than age more than 65 years, was associated with poorer survival.
Outcomes for Elderly, Advanced-Stage Non–Small-Cell Lung Cancer Patients Treated With Bevacizumab in Combination With Carboplatin and Paclitaxel: Analysis of Eastern Cooperative Oncology Group Trial 4599
Authors: Ramalingam Suresh S. , Dahlberg Suzanne E. , Langer Corey J. , Gray Robert , Belani Chandra P. , Brahmer Julie R. , Sandler Alan B. , Schiller Joan H. , Johnson David H. 
Published: December 2007

Purpose Fit elderly patients with advanced non–small-cell lung cancer (NSCLC) benefit from platinum-based, two-drug chemotherapy. Bevacizumab (B) in combination with carboplatin (C) and paclitaxel (P) improves survival for advanced, nonsquamous NSCLC, as evidenced in Eastern Cooperative Oncology Group (ECOG) 4599. We conducted a subset analysis of ECOG 4599 to determine the outcome for elderly patients. Patients and Methods ECOG 4599 randomly assigned patients with advanced nonsquamous NSCLC to PC or to PCB. We analyzed outcome in patients who were at least 70 years of age at the time of study entry. Patient characteristics, efficacy, and toxicity data were compared between PC and PCB for the elderly. Outcomes for elderly and younger patients (< 70 years) treated with PCB were also compared. Results Among elderly patients (n = 224; 26%), there was a trend towards higher response rate (29% v 17%; P = .067) and progression-free survival (5.9 v 4.9 months; P = .063) with PCB compared with PC, although overall survival (PCB = 11.3 months; PC = 12.1 months; P = .4) was similar. Grade 3 to 5 toxicities occurred in 87% of elderly patients with PCB versus 61% with PC (P < .001), with seven treatment-related deaths in the PCB arm compared with two with PC. Elderly patients had higher incidence of grade 3 to 5 neutropenia, bleeding, and proteinuria with PCB compared with younger patients. Conclusion In elderly NSCLC patients, PCB was associated with a higher degree of toxicity, but no obvious improvement in survival compared with PC. Data from this unplanned, retrospective analysis justify prospective evaluation of the therapeutic index of PCB regimen in elderly patients.
BRCA1 p.Val1688del Is a Deleterious Mutation That Recurs in Breast and Ovarian Cancer Families From Northeast Italy
Authors: Malacrida Sandro , Agata Simona , Callegaro Monia , Casella Cinzia , Barana Daniela , Scaini Maria C. , Manoukian Siranoush , Oliani Cristina , Radice Paolo , Barile Monica , Menin Chiara , D'Andrea Emma , Montagna Marco 
Published: December 2007

Purpose A growing number of sequence changes of unknown clinical significance are being identified in the BRCA1 gene. However, these variants cannot be used for identification and surveillance of at-risk individuals unless their pathogenic role can be demonstrated. The frequency of these variants makes research on this subject a relevant topic in the field of predisposition to breast and ovarian cancers. Herein, we investigate the pathogenicity of the BRCA1 p.Val1688del (c.5181_5183delGTT) variant, which recurs in our population. Patients and Methods Recent studies have drawn attention to different strategies that, if considered singly, do not usually provide sufficient power to firmly state for or against causality, thus forcing to a re-evaluation of the literature on each specific variant. To increase the power of our study, we used a recently described strategy that integrates data from multiple independent evidences. By this approach, we analyzed data from the comprehensive study of 12 breast/ovarian cancer families carrying p.Val1688del. Results We succeeded in integrating five independent evidences of disease causality including segregation, tumor pathology, and evolutionary and epidemiologic data. Under this model, we obtained a final score of 349,000:1 in favor of disease causality. This result largely matches established cutoffs, and thus is readily translatable into a clear clinical message. Conclusion We show that p.Val1688del is a pathogenic mutation deriving from a common founder. Notably, this study alone increases by 15% the number of BRCA1-positive families in our patients’ cohort, thus substantially contributing to explain many of the families wherein prediction of a BRCA1 mutation contrasted with the absence of a molecular recognizable defect.
Long-Term Outcome of Complete Cytogenetic Responders After Imatinib 400 mg in Late Chronic Phase, Philadelphia-Positive Chronic Myeloid Leukemia: The GIMEMA Working Party on CML
Authors: Palandri Francesca , Iacobucci Ilaria , Martinelli Giovanni , Amabile Marilina , Poerio Angela , Testoni Nicoletta , Soverini Simona , Castagnetti Fausto , De Vivo Antonio , Breccia Massimo , Specchia Giorgina , Abruzzese Elisabetta , Martino Bruno , Cilloni Daniela , Saglio Giuseppe , Pane Fabrizio , Liberati Anna Marina , Rosti Gianantonio , Baccarani Michele 
Published: December 2007

Purpose Imatinib mesylate (IM) has rapidly become the front-line treatment of Philadelphia-positive (Ph-pos) chronic myeloid leukemia, but the number of patients who were treated and are being treated with IM second-line is still substantial. Patients and Methods We have monitored and analyzed the cytogenetic and molecular response to IM 400 mg/d in a cohort of 277 late chronic phase (LCP) patients who were resistant or intolerant to interferon-α and were observed for 48 to 79 months (median, 72 months). Results One hundred fifty-three patients (55%) achieved a complete cytogenetic response (CCgR). Seventy-seven percent of them were still in CCgR after 5 years. The rate of response loss did not increase over time. The 6-year progression-free survival and overall survival of these 153 complete cytogenetic responders were 90% and 91%, respectively. Molecular response was less than major in 21%, major in 78%, and complete in one patient only. Conclusion These data confirm that, in LCP the CCgR rate to IM is 50% to 60%, and show that CCgR is stable and is associated with a prolonged survival, even if leukemia continues to be molecularly detectable.