tbuckley/cabot-search huggingface dataset:
Paclitaxel/carboplatin versus single-agent carboplatin in patients with epithelial ovarian cancer and correlation to serum marker VEGF.
Authors: R. A. Malek, S. Amin
Journal: Journal of Clinical Oncology (2010)

e15546 Background: The superiority of a platinum and paclitaxel combination regimen over single-agent platinum remains the subject of debate. Overexpression of VEGF by ovarian cancer cells is a major mediator of angiogenesis and serum values may therefore serve as a prognostic tool. The aim of this study is to compare the standard chemotherapy protocol (paclitaxel/carboplatin) to single agent carboplatin as regard the response rate, progression-free survival (PFS) at 2 years; as well as prognostic value of different factors, namely: age, stage, grade, baseline CA-125 and serum VEGF at presentation. Methods: This study is a prospective nonrandomized study including 50 patients with established diagnosis of epithelial ovarian carcinoma attending Clinical Oncology department, Cairo University Hospital in the period from Jan 2006 to Dec 2007. After surgical staging, the patients received either paclitaxel 175 mg/m2 followed by carboplatin AUC 5 (Arm A) or single-agent carboplatin AUC 6 (Arm B) for 6 cycles. Serum sample was collected at baseline and serum VEGF was measured using ELISA technique. Results: At a median follow up period of 16.3 months, the median PFS was 10.8 months. About 60 % of patients showed no disease progression at 2 years. Comparing the two arms, the overall response rate was 88% in arm A versus 82.6% in arm B (p = 0.771). Mean PFS in arm A was 20.51 ± 2.99 compared to 25.14 ± 2.71 in arm B (p = 0.311) with an odds ratio 1.7 (95% CI 0.53-5.60). By analyzing the effect of different factors namely: age, performance status, parity, optimal surgery, stage, grade, baseline CA125, serum VEGF > 100 pg/mL and treatment received using multivariate analysis; it was found that the disease stage as well as optimal surgery showed the most statistically significant relation regarding outcome (p = 0.004 and 0.04 respectively). Neither the baseline CA125, serum VEGF nor treatment arm affected the outcome. Conclusions: Single-agent carboplatin is not inferior to Combination chemotherapy with paclitaxel and carboplatin regarding response rate and PFS at 2 years. Serum vascular endothelial growth factor at baseline seems to have no prognostic value with any correlation to either disease stage or outcome. No significant financial relationships to disclose.
Advancing the use of<i>Lactobacillus acidophilus</i>surface layer protein A for the treatment of intestinal disorders in humans
Authors: Bikash Sahay, Yong Ge, Natacha Colliou, Mojgan Zadeh, Chelsea Weiner, Ashley Mila, Jennifer L Owen, Mansour Mohamadzadeh
Journal: Gut Microbes (2015)

Intestinal immunity is subject to complex and fine-tuned regulation dictated by interactions of the resident microbial community and their gene products with host innate cells. Deterioration of this delicate process may result in devastating autoinflammatory diseases, including inflammatory bowel disease (IBD), which primarily comprises Crohn's disease (CD) and ulcerative colitis (UC). Efficacious interventions to regulate proinflammatory signals, which play critical roles in IBD, require further scientific investigation. We recently demonstrated that rebalancing intestinal immunity via the surface layer protein A (SlpA) from Lactobacillus acidophilus NCFM potentially represents a feasible therapeutic approach to restore intestinal homeostasis. To expand on these findings, we established a new method of purifying bacterial SlpA, a new SlpA-specific monoclonal antibody, and found no SlpA-associated toxicity in mice. Thus, these data may assist in our efforts to determine the immune regulatory efficacy of SlpA in humans.
Survival prediction in terminally ill cancer patients: Description and validation of a new predictive score
Authors: A. M. Jimenez Gordo, J. Feliu, J. Dominguez, R. Molina, J. C. Camara, A. Alonso, R. Madero, J. De Castro, E. Espinosa, M. Gonzalez-Baron
Journal: Journal of Clinical Oncology (2009)

9595 Background: Determining an accurate prognosis for terminally ill cancer patients is one of the biggest challenges that confronts a physician. Correct predictions can be done in only 20–40% of all cases. Although the current prognostic scales are helpful, they have significant limitations. Our objective consists of determining the potential indicators that influence the survival of these patients and develop and validate a new predictive model. Methods: A prospective, multicentric and observational study was conducted in 880 terminally ill cancer patients. At first, 40 clinical, demographic and laboratory variables were recorded in 406 patients. A forward stepwise regression method was applied for the multivariate survival analysis. Hence, a predictive model was constructed. Subsequent validation was performed in 474 patients. Results: Median age was 66.4 years (range 18–95). The median overall survival was 21 days in the first 406 patients studied and 19 days in the validation group. A prognostic model with 9 variables was constructed (age, ECOG, the amount of time between initial diagnosis up to being considered terminal phase, nauseas, anorexia, cognitive impairment, lymphocytes, LDH and albumin). Afterwards, to simplify the model, 4 variables that were considered more objective and with greater Odds ratio were selected and assigned one point per each prognostically poor category. We obtained a survival model that discriminates 3 prognostic categories: Good prognoses (score 0) with a median survival of 95 days (44–146), intermediate prognoses (score 1–2) with a median survival of 33 days (26.8–39.2) and bad prognoses (score 3–4) with a median survival of 15 days (11.1–18.9). In the validation group, median survival times were 60 (47.1–72.8), 27 (22.8–31.1) and 11 days (9.2–12.7) respectively. Conclusions: We propose a predictive score model that is objective and easy to use to help in accurately predicting life expectancy in terminally ill cancer patients. Its effectiveness has been validated in a group of independent centers. No significant financial relationships to disclose.
Phase I trial of gemcitabine (GEM) infused at fixed-dose rate (FDR) with high-dose docetaxel/melphalan/carboplatin (GEM-DMC) and autologous stem-cell transplant (ASCT)
Authors: Y. Nieto, J. Rifon, J. Perez-Calvo, A. Zafra, L. Zufia, A. Viudez, S. Viteri, O. Sayan, M. Hernandez, A. Aldaz
Journal: Journal of Clinical Oncology (2007)

17500 Background: More active ASCT regimens are needed. We combined GEM, which inhibits DNA damage repair, with the potent DMC regimen (BBMT 11:297–306,2005). GEM infusions at FDR of 10 mg/m 2 /min, targeting steady-state concentrations (Css) &lt;20 μM, which in vitro do not saturate its intracellular activation to GEM-triphosphate (GEM-TP), result in greater activity but more myelotoxicity than its usual short infusions. Methods: Pts with advanced, refractory tumors and normal organ function were eligible. Study endpoints: to define the maximum tolerated duration (MTD) of GEM at FDR with ASCT, dose-limiting toxicity (DLT) and regimen-related toxicity (RRT) of GEM-DMC, and pharmacokinetics (PK) of high-dose GEM and docetaxel. Daily GEM FDR infusions (d-5 to d-2) were extended in sequential cohorts (total length: 9 to 20 hr), followed on d-5 by docetaxel (350 mg/m 2 ), on d-4 to d-2 by melphalan (50 mg/m 2 /d) and carboplatin (333 mg/m 2 /d), and ASCT on d0. Results: 52 pts accrued (breast ca [N=31], Ewing's [5], germ-cell [4], lymphoma [4], Hodgkin's [3], sarcoma [5]), median age 40 (6–66), 3 median prior chemo regimens and 3 organs involved. GEM MTD: 5 hr/d x 4 (total 20 hr, 12 g/m 2 ). Neutrophils engrafted on d+8 (6–10) and platelets on d+11 (8–33). There were 3 non-RRT deaths (1 aspiration, 2 catheter-related sepsis). At the MTD (N=25), enteritis (20% G3) was DLT; all other RRT were = G3 and reversible (28% stomatitis, 8% ileus, 8% rash). The response rate was 97% (60% complete). At median follow-up of 18 (7–27) months, 58% EFS (median 22 mo) and 85% OS rates (median not reached). All pts had GEM Css &lt;20 μM. The infusion length correlated linearly with the AUC of GEM (r 2 = 0.65, p&lt;10 -5 ) but not with its clearance (r 2 =0.03) or t 1/2 (r 2 = 0.02). GEM AUC was associated with G3 RRT (p&lt;10 -3 ). The AUCs of GEM and GEM-TP (/10 6 mononuclear cells) correlated on d-5 (r 2 =0.5, p=0.01), but not on d-2 (r 2 = 0.05) due to late GEM-TP accumulation. Docetaxel had 3–4 fold higher AUC and peak levels and similar clearance compared to its standard-dose population PK. Conclusions: GEM-DMC, markedly extending GEM infusions at FDR, is tolerable and highly active, without saturating the activation of GEM to GEM-TP. High-dose GEM and docetaxel show adequate linear PK. No significant financial relationships to disclose.
MicroRNA-21 Aggravates Cyst Growth in a Model of Polycystic Kidney Disease
Authors: Ronak Lakhia, Sachin Hajarnis, Darren Williams, Karam Aboudehen, Matanel Yheskel, Chao Xing, Mark E. Hatley, Vicente E. Torres, Darren P. Wallace, Vishal Patel
Journal: Journal of the American Society of Nephrology (2015)

Autosomal dominant polycystic kidney disease (ADPKD), one of the most common monogenetic disorders, is characterized by kidney failure caused by bilateral renal cyst growth. MicroRNAs (miRs) have been implicated in numerous diseases, but the role of these noncoding RNAs in ADPKD pathogenesis is still poorly defined. Here, we investigated the role of miR-21, an oncogenic miR, in kidney cyst growth. We found that transcriptional activation of miR-21 is a common feature of murine PKD. Furthermore, compared with renal tubules from kidney samples of normal controls, cysts in kidney samples from patients with ADPKD had increased levels of miR-21. cAMP signaling, a key pathogenic pathway in PKD, transactivated miR-21 promoter in kidney cells and promoted miR-21 expression in cystic kidneys of mice. Genetic deletion of miR-21 attenuated cyst burden, reduced kidney injury, and improved survival of an orthologous model of ADPKD. RNA sequencing analysis and additional in vivo assays showed that miR-21 inhibits apoptosis of cyst epithelial cells, likely through direct repression of its target gene programmed cell death 4 . Thus, miR-21 functions downstream of the cAMP pathway and promotes disease progression in experimental PKD. Our results suggest that inhibiting miR-21 is a potential new therapeutic approach to slow cyst growth in PKD.
Important excess of cardiovascular mortality among breast cancer patients irradiated for inner quadrant tumors
Authors: C. Bouchardy, E. Rapiti, M. Usel, S. Balmer-Majno, G. Vlastos, I. Neyroud-Caspar, H. Verkooijen, V. Vinh-Hung
Journal: Journal of Clinical Oncology (2008)

584 Background: Radiation therapy of left breast has been associated with higher cardiovascular (CV) mortality due to higher cardiotoxicity. Because tumor location can also influence heart exposure, it could influence CV mortality linked to radiotherapy. This study aims to assess CV mortality in irradiated patients according to breast cancer laterality and location. Methods: From a population-based cancer registry, we identified all women who had been irradiated for a first primary node-negative breast cancer between 1980 and 2004. We compared CV mortality between patients with cancer in the inner quadrants (n=393) versus outer quadrant (n=852) by log-rank test and by Cox regression accounting for the main prognostic factors. For all patients who die from CV, we collected and compared data on radiotherapy type and dose according to quadrant and laterality by chi-square of heterogeneity. Results: The mean follow-up was 7.7 years. Out of 1,245 patients, 28 died because of CV disease. Patients with inner tumor had a more than doubled risk for CV mortality compared with patients with outer tumor (multi-adjusted Hazard Ratio: 2.3, 95%CI: 1.1–5.1, p=0.034). Patients with breast-conserving therapy for inner cancer who die from CV received higher dose to the breast (p=0.032) but similar internal mammary chain irradiation than those with outer quadrant. Breast laterality had no effect on CV mortality. Conclusions: This study reports a strong excess of CV mortality among patients irradiated for inner breast cancer probably linked to site of the boost and higher radiation exposure of the heart. No significant financial relationships to disclose.
Prognostic associations of 25OH vitamin D in NCIC CTG MA.21, a phase III adjuvant RCT of three chemotherapy regimens (EC/T, CEF, AC/T) in high-risk breast cancer (BC).
Authors: Ana Elisa Lohmann, Judy-Anne W. Chapman, Margot J. Burnell, Mark Norman Levine, Elena Tsvetkova, Kathleen I. Pritchard, Karen A. Gelmon, Patti O'Brien, Lei Han, Hope S. Rugo, Kathy S. Albain, Edith A. Perez, Theodore A. Vandenberg, Haji I. Chalchal, Ravinder Pal Singh Sawhney, Lois E. Shepherd, Pamela Jean Goodwin
Journal: Journal of Clinical Oncology (2014)

504 Background: Low vitamin D (VitD) has been associated with poor outcomes in BC. We examined in MA.21 the association of VitD blood levels with relapse-free-survival (RFS) in all patients, and in BC subtypes. Methods: Fasting blood was collected pre-chemotherapy in 935/2,104 ((44.4%) of subjects (blood collection was initiated part-way through the trial); serum was frozen at -80C and shipped on dry ice to Mount Sinai Hospital (Toronto); it was analyzed for Vit D (radioimmunoassay, Diasorin) 25(OH)D (nmol/L). VitD underwent a λ=0.5 Box-Cox transformation for analysis to reduce asymmetry; data were back-transformed for reporting. VitD was assessed as a transformed continuous factor, and by quartiles and IOM categories (<40, [40-50), [50-125), >125 nmol/L). Univariate and multivariate (mv) assessments were with Cox models, adjusted for treatment, stratification factors, and imbalances in who had VitD assessed. Results: Median age was 47.8 years; most patients were white (91.6%), premenopausal (69.4%) with good performance status (PS) 0-1 (99.9%). The majority presented with grade III (52%), HER2 neg (66.6%), HER2 missing (22.9%), ER pos (61.9%), T1-2 (89.4%), N+ (72.7%) BC. 52.1% underwent mastectomy and 74.3% received adjuvant radiotherapy. Compared to the full MA.21 population, those with VitD levels were marginally (but significantly) more likely to be white, PS 1 or 2, to have undergone mastectomy and to have ER+, HER2 neg tumors. Mean Vit D was 69.7 nmol/L [95% CI (68.1-71.3)] nmol/L. The majority (752/935 = 80.5%) had levels > 50nmol/L (20ng/ml), considered adequate by the Institute of Medicine (IOM). In adjusted mv analyses, (continuous) VitD was not associated with RFS (HR 0.98, 95% CI (0.93-1.03); p=0.36) or categorical variable (between quartiles, p=0.20-0.43; between IOM categories, p=0.33-0.78). There were no significant differences in mean VitD levels or association of VitD with RFS in tumor subtypes (ER+, HER2- / any ER, HER2+ / ER-, HER2-; p=0.14-0.50). Conclusions: There is no evidence that VitD was associated with RFS in MA.21; the majority of subjects had adequate VitD levels at study entry. Clinical trial information: NCT00014222.
A phase II study of cetuximab (C225) in combination with chemoradiation (CRT) in patients (pts) with stage III A/B non-small cell lung cancer (NSCLC): An interim report of the RTOG 0324 trial
Authors: G. Blumenschein, J. Moughan, W. Curran, F. Robert, F. Fossella, M. Werner-Wasik, P. Doescher, H. Choy, R. Komaki
Journal: Journal of Clinical Oncology (2007)

7531 Background: Cetuximab (C225) is a chimerized monoclonal antibody that targets the epidermal growth factor receptor (EGFR). NSCLC commonly expresses the EGFR, which is associated with aggressive tumor behavior and poor clinical outcome. Preclinical model systems demonstrate radiosensitization following molecular inhibition of EGFR signaling. Methods: We report a phase II trial testing the combination of C225 with CRT in unresectable stage III NSCLC with a planned sample size of 84 PTS. Eligibility criteria included Zubrod performance status (PS) = 1, weight loss = 5% over past 3 months, FEV 1 = 1.2 l, adequate hematologic, hepatic, and renal function. PTS received an initial dose of C225 (400 mg/m 2 ) on day 1 of week 1, then weekly doses of C225 (250 mg/m 2 ) until completion of therapy (weeks 2 –17). During week 2, patients started CRT (63 Gy/35 fractions) with weekly carboplatin (C) AUC 2 and paclitaxel (P) 45 mg/m 2 × 6 doses followed by C (AUC 6) and P (200 mg/m 2 ) × 2 cycles (weeks 12–17). Interim monitoring for severe (grade = 3) or excessive non-hematologic toxicities occurred after pts had been treated and followed for at least 90 days after RT. Primary endpoints include safety and compliance of concurrent C225 and CRT. Results: 93 pts were enrolled with 87 evaluable pts. Pts characteristics: 57% male, median age 64 years (range 42–85), 47% PS 0, 46% stage IIIA. Median follow-up is 14 months. Response rate is 62% (n=54) and 12 month overall survival (OS) is 68% (# at risk=56). Adverse events related to treatment include 20% (n=17) of pts with grade 4 hematologic toxicities and 7 pts who had grade 3 esophagitis. There was 1 infection related death, 1 death NOS, and 3 pts who died of pulmonary complications (adult respiratory distress syndrome, pneumonitis, and hypoxia). Conclusions: The combination of C225 with CRT is feasible. Further study will be needed to determine whether the addition C225 to CRT enhances toxicity or efficacy. Complete compliance and toxicity data along with 18 month OS will be reported. No significant financial relationships to disclose.
Evaluation of early sequential 18F-FDG PET imaging as a prognostic indicator and predictor of response to platinum and pemetrexed chemotherapy in malignant pleural mesothelioma (MPM)
Authors: J. D. O’Flaherty, C. Farrelly, M. Knox, D. Power, J. Lucey, K. O’Byrne
Journal: Journal of Clinical Oncology (2009)

e14534 Background: Recent evidence has suggested that baseline SUV and metabolic response measured on sequential PET scans early in the course of chemotherapy may predict for survival and response to chemotherapy. Methods: Patients with MPM suitable for platinum/pemetrexed chemotherapy were studied. Baseline pre-chemotherapy PET and CT scans were performed with a further PET scan before cycle 2. CT scans were repeated mid-treatment and at the end of 6 cycles. PET response was determined by measuring the change in the maximum and mean SUV, PET Vol (volume of tumor above SUV threshold of 3.5) and Total Lesion Glycolysis (TLG, calculated as PET Vol x SUV Max). Metabolic response (MR), as measured by a 25% drop in SUV Max, SUV Mean, PET Vol and TLG was compared to overall survival (OS) and to subsequent response to chemotherapy on CT. CT scans were read using Modified RECIST criteria and CT response was compared to OS. Results: 21 patients had baseline PET scans of whom 17 had a further PET before cycle 2. 19 patients had CT scans evaluable by Modified RECIST criteria. Baseline SUV Max and SUV Mean were found to predict for OS. Median survival was 17.2 months for patients with SUV Max less than 15 versus 6 months for those with SUV Max greater than 15 (p=0.0193). Median survival was 14.1 months for patients with SUV Mean less than 5 versus 6.5 months for those with SUV Mean greater than 5 (p=0.0681). MR defined by SUV Max, SUV Mean, PET Vol or TLG did not predict for OS. MR on PET correlated poorly with CT response with Kappa values of 0.01, 0.05, 0.15 and 0.31 for MR defined by SUV Max, PET Vol, SUV Mean and TLG respectively. CT response using Modified RECIST criteria correlated significantly with OS. Patients with partial response (PR), stable disease (SD) and progressive disease (PD) had median survivals of 25.6 months, 8.6 months and 4.6 months respectively (p=0.0072) Conclusions: MR measured by SUV Max, SUV Mean, PET Volume and TLG on early sequential PET scans did not correlate with CT assessed response to chemotherapy or OS. Baseline SUV Max &gt;15 and SUV Mean &gt;5 were indicative of poor prognosis. CT response as measured by Modified RECIST criteria correlated significantly with OS. No significant financial relationships to disclose.
Cutaneous Malignant Melanoma in Association With Other Skin Cancers
Authors: A C Green, M G O'Rourke
Journal: JNCI Journal of the National Cancer Institute (1985)

A case-control study of 232 cases of cutaneous malignant melanoma and 232 matched controls was performed to assess the association of the disease with nonmelanotic skin tumors--basal cell carcinomas, squamous cell carcinomas, and solar keratoses. There was a fourfold increase in risk of melanoma of all types when actinic tumors were present on the face. The risk was not restricted to the lentigo malignant melanoma class as might be expected but was significantly raised for superficial spreading melanoma and nodular melanoma as well (relative risk, 2.8; 95% confidence interval, 1.1-7.2). This relationship with lesions known to be associated with high-dose solar UV irradiation was supported by quantitative evidence that heavy sun exposure was associated with an increased risk of malignant melanoma.
Independent Impact of RV Involvement on In-Hospital Outcome of Patients With Takotsubo Syndrome
Authors: Rodolfo Citro, Eduardo Bossone, Guido Parodi, Fausto Rigo, Federico Nardi, Gennaro Provenza, Concetta Zito, Giuseppina Novo, Giovanni Vitale, Costantina Prota, Angelo Silverio, Olga Vriz, Antonello D’Andrea, Francesco Antonini-Canterin, Jorge Salerno-Uriarte, Federico Piscione
Journal: JACC. Cardiovascular imaging (2015)
Neoadjuvant Chemotherapy, Locally Advanced Breast Cancer, and Quality of Life
Authors: Kelly M. McMasters, Kelly K. Hunt
Journal: Journal of Clinical Oncology (1999)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.2.441 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10080583 Neoadjuvant Chemotherapy, Locally Advanced Breast Cancer, and Quality of Life Kelly M. McMastersxKelly M. McMastersSearch for articles by this author Kelly K. HuntxKelly K. HuntSearch for articles by this author Show More University of Louisville, James Graham Brown Cancer Center, Louisville, KYUniversity of Texas, M.D. Anderson Cancer Center, Houston, TX https://doi.org/10.1200/JCO.1999.17.2.441 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
Surgical Treatment of Acute Manifestations of Crohn's Disease during Pregnancy
Authors: J Hill Chm, A Clark, Na Scott
Journal: Journal of the Royal Society of Medicine (1997)

When requiring surgery, acute exacerbations of Crohn's disease in pregnancy have been reported to carry high maternal and fetal mortality. We report six cases. The women presented at 30, 28, 12, 11, 31 and 25 weeks' gestation and all proved to have intraperitoneal sepsis. In three, the acute symptoms were the first indication of Crohn's disease. All the women recovered and five had healthy babies; the other had a miscarriage when a colonic anastomosis dehisced. In pregnant women with Crohn's disease, the indications for surgery are the same as in non-pregnant patients. For acute manifestations we recommend removal of the source of the sepsis and exteriorization of the bowel ends.