tbuckley/cabot-search huggingface dataset:
Reduced Cardiotoxicity and Preserved Antitumor Efficacy of Liposome-Encapsulated Doxorubicin and Cyclophosphamide Compared With Conventional Doxorubicin and Cyclophosphamide in a Randomized, Multicenter Trial of Metastatic Breast Cancer
Authors: Gerald Batist, Gopal Ramakrishnan, Chandra Sekhar Rao, Aruna Chandrasekharan, John Gutheil, Troy Guthrie, Pankaj Shah, Ali Khojasteh, Madhavan Krishnan Nair, Karen Hoelzer, Katherine Tkaczuk, Youn Choi Park, Lily W. Lee
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine whether Myocet (liposome-encapsulated doxorubicin; The Liposome Company, Elan Corporation, Princeton, NJ) in combination with cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing comparable antitumor efficacy in first-line treatment of metastatic breast cancer (MBC). PATIENTS AND METHODS: Two hundred ninety-seven patients with MBC and no prior chemotherapy for metastatic disease were randomized to receive either 60 mg/m 2 of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg/m 2 of cyclophosphamide (C), every 3 weeks until disease progression or unacceptable toxicity. Cardiotoxicity was defined by reductions in left-ventricular ejection fraction, assessed by serial multigated radionuclide angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization criteria), time to progression, and survival. RESULTS: Six percent of MC patients versus 21% (including five cases of CHF) of AC patients developed cardiotoxicity (P = .0002). Median cumulative doxorubicin dose at onset was more than 2,220 mg/m 2 for MC versus 480 mg/m 2 for AC (P = .0001, hazard ratio, 5.04). MC patients also experienced less grade 4 neutropenia. Antitumor efficacy of MC versus AC was comparable: objective response rates, 43% versus 43%; median time to progression, 5.1% versus 5.5 months; median time to treatment failure, 4.6 versus 4.4 months; and median survival, 19 versus 16 months. CONCLUSION: Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.
How Are You Feeling? Who Wants To Know? Patients’ and Oncologists’ Preferences for Discussing Health-Related Quality-of-Life Issues
Authors: S.B. Detmar, N.K. Aaronson, L.D. V. Wever, M. Muller, J.H. Schornagel
Journal: Journal of Clinical Oncology (2000)

PURPOSE: This study investigated (1) the attitudes of cancer patients toward discussing health-related quality-of-life (HRQL) issues; (2) the association between such attitudes and patients’ characteristics; and (3) oncologists’ attitudes and self-reported behavior regarding these same issues. PATIENTS AND METHODS: Two hundred seventy-three patients receiving palliative chemotherapy and ten physicians were asked to complete a series of questionnaires. RESULTS: Almost all patients wanted to discuss their physical symptoms and physical functioning and were also willing to address their emotional functioning and daily activities. However, 25% of the patients were only willing to discuss these latter two issues at the initiative of their physician. Patients varied most in their willingness to discuss their family and social life, with 20% reporting no interest in discussing these issues at all. Female patients were more reluctant to discuss various HRQL issues than male patients. Older and less well-educated patients were more likely to prefer that their physician initiate discussion of HRQL issues. All physicians considered it to be primarily their task to discuss the physical aspects of their patients’ health, whereas four physicians indicated that discussion of psychosocial issues was a task to be shared with other health care providers. All physicians indicated that they generally defer to their patients in initiating discussion of psychosocial issues. CONCLUSION: Although both patients and oncologists seem willing to discuss a wide range of HRQL issues, communication regarding psychosocial issues may be hampered by competing expectations as to who should take the lead in initiating such discussions.
Abstract 14457: LDL Particle Number (LDL-P) Distribution in Patients with Angiographic Coronary Artery Disease on Lipid-Lowering Medication
Authors: Hector A Malave, Manuel Castro, Nancy Seigle, Deborah A Winegar, Ray Pourfarzib
Journal: Circulation (2012)

Background:  Measures of LDL particle concentration (LDL-P) have been shown to better predict the risk of future cardiovascular events than LDL cholesterol (LDL-C). Many patients with coronary artery disease are treated with lipid-lowering drugs to reduce LDL-C to treatment goals below 80 mg/dL. However despite successful LDL-C lowering, many patients continue to experience cardiovascular events (i.e. residual cardiovascular risk). Drugs that effectively reduce LDL-C to target goals (e.g., statins) often do not reduce LDL-P to the same extent. Thus, more aggressive treatment regimes may be required to achieve LDL-P goals.   Objective:  To assess variations in lipoprotein particle concentrations in patients with coronary artery disease diagnosed by angiography who are receiving lipid-lowering therapy, in order to determine residual cardiovascular risk.   Methods:  Data were derived from a single laboratory database (Cardiology of Atlanta, PC). Cases were patients diagnosed with coronary artery disease by angiography who were on lipid-lowering therapy and whose serum was analyzed for lipoprotein concentrations using NMR between June 2010 and March 2012. Total cholesterol, triglycerides and HDL cholesterol were measured using standard automated methods and LDL-C was calculated using the Friedewald equation. The NMR lipoprotein profile was determined using a 400-MHz proton NMR analyzer.   Results:  Among the 83 patients meeting inclusion criteria, 78% were men and the mean age was 64 years old. Mean LDL-C was 85 + 30 mg/dL, mean HDL-C was 47 + 14 mg/dL and mean LDL-P was 1364 + 510 nmol/L. Most patients had LDL-C levels within the target goal for high risk patients: 64% had LDL-C levels  th  MESA percentile) while 52% had LDL-C levels  th  MESA percentile). However, LDL-P levels for most patients were higher than goals: Only 18% had LDL-P levels  th  MESA percentile) and 6% had LDL-P levels  th  MESA percentile).   Conclusion:  The majority of patients in this high risk cohort with angiographic coronary artery disease on lipid-lowering therapy met LDL-C target goals, but failed to achieve LDL-P goals suggesting that they harbor residual risk for cardiovascular events.
Co-targeting of Cyclooxygenase-2 and FoxM1 is a viable strategy in inducing anticancer effects in colorectal cancer cells
Authors: Maqbool Ahmed, Azhar R Hussain, Abdul K. Siraj, Shahab Uddin, Nasser Al-Sanea, Fouad Al-Dayel, Mohammed Al-Assiri, Shaham Beg, Khawla S. Al-Kuraya
Journal: Molecular Cancer (2015)

Cross-talk between deregulated signaling pathways in cancer cells causes uncontrolled growth and proliferation. These cancers cells become more aggressive and quickly develop resistance to therapy. Therefore targeting of these deregulated pathways simultaneously can result in efficient cell death of cancer cells. In this study we investigated co-expression of Cox-2 and FoxM1 in a cohort of colorectal carcinoma (CRC) samples and also examined whether inhibition of Cox-2 and FoxM1 simultaneously can lead to inhibition of cell viability and induction of apoptosis in colorectal cancer cell lines and in vivo xenografts. Protein expression of Cox-2 and FoxM1 was determined in a large cohort of 770 clinical CRC samples in a tissue micro-array format by immunohistochemistry. Cell death was measured using live dead assay. Apoptosis was measured by annexin V/PI dual staining. Immunoblotting was performed to examine the expression of proteins. Calcusyn software was utilized to estimate the synergistic doses using chou and Talalay method. Co-expression of Cox-2 and FoxM1 was detected in 33.3 % (232/697) of CRC's and associated with an aggressive phenotype characterized by younger age (p = 0.0191), high proliferative index marker; Ki-67 (p = 0.004) and MMP-9 (p = 0.0116) as well as activation of AKT (p = 0.0214). In vitro, inhibition of FoxM1 and Cox-2 with pharmacological inhibitors; Thiostrepton and NS398 resulted in efficient down-regulation of FoxM1 and Cox-2 expression along with in-activation of AKT and inhibition of colony formation, invasion and migratory capability of CRC cells. In addition, there was also inhibition of cell viability and induction of apoptosis via the mitochondrial apoptotic pathway in CRC cell lines. Finally, treatment of CRC xenograft tumors in nude mice with combination of Cox-2 and FoxM1 inhibitors inhibited tumor growth significantly via down-regulation of Cox-2 and FoxM1 expression. These findings demonstrate that co-expression of Cox-2 and FoxM1 might play a critical role in the pathogenesis of CRC. Therefore, targeting of these pathways simultaneously with sub toxic doses of pharmacological inhibitors can be a potential therapeutic approach for the treatment of this subset of CRC.
Subcutaneous Ustekinumab Provides Clinical Benefit for Two-Thirds of Patients With Crohn’s Disease Refractory to Anti–Tumor Necrosis Factor Agents
Authors: Pauline Wils, Yoram Bouhnik, Pierre Michetti, Bernard Flourie, Hedia Brixi, Anne Bourrier, Matthieu Allez, Bernard Duclos, Jean-Charles Grimaud, Anthony Buisson, Aurélien Amiot, Mathurin Fumery, Xavier Roblin, Laurent Peyrin-Biroulet, Jérôme Filippi, Guillaume Bouguen, Vered Abitbol, Benoit Coffin, Marion Simon, David Laharie, Benjamin Pariente
Journal: Clinical Gastroenterology and Hepatology (2015)
Pitfalls of RNA isolation from sputum in COPD
Authors: Csilla Páska, Imre Barta, Krisztina Kelemen, Balázs Antus
Journal: European Respiratory Journal (2014)

Aims:  Sputum could be a valuable source for molecular analysis of respiratory diseases; however, various methodological problems have to be overcome. We attempted to maximize the quality and the quantity of RNA by optimizing sputum processing, RNA isolation and transcription methods.   Methods:  Sputum samples (n=20) were obtained from COPD patients at our Institute, and processed using dithiothreitol (DTT), n-acetyl cysteine or RNAlater solutions. Three different RNA isolation methods were tested. DNA contamination was tested by reverse transcription negative controls with GAPDH and universal bacterial primers. RNA quality was assessed by real-time PCR yielding GAPDH amplicons of different length. Data are presented as mean±SD.   Results : Sputum cell counts varied between 0.95-7´10 6  cells/g sputum. Isolated RNA content was 332.9±322.2 ng/g sputum. All three processing methods yielded similar amount of RNA, with a slight advantage for DTT (p=NS). Cell integrity was only preserved in DTT. DNase treatment diminished the yield by 30-50%. Surprisingly, in most samples several rounds of DNase treatment was needed to clean the samples from the contaminating DNA. The choice of RNA isolation kit, the speed and the temperature of centrifugation significantly influenced the amount of RNA. The choice of reverse transcriptase had a lesser effect on the PCR products.   Conclusion:  The quality and the quantity of sputum RNA depends on several factors during the isolation. However, the biggest challenge is the elimination of bacterial DNA, which is of high importance, since contaminating bacterial background might mask the human RNA in gene expression studies.
Characterising asthma therapy in Scotland: Are the guidelines confusing?
Authors: Jordan Covvey, Blair Johnston, Anne Boyter
Journal: European Respiratory Journal (2012)

Background:  Current British Thoracic Society (BTS)/Scottish Intercollegiate Guidelines Network (SIGN) guidelines recommend a five-step escalation of treatment in chronic asthma; combination therapy with a long-acting beta agonist (LABA) and an inhaled corticosteroid (ICS) is recommended as first line therapy at step 3.   Aim:  To stratify therapy prescribed to patients with asthma in NHS Forth Valley according to the BTS/SIGN guidelines.   Methods:  Data were obtained from 46 practices in NHS Forth Valley via an electronic interface with practice clinical software. Patients diagnosed with asthma (adults & children ≥ 5 years) with prescriptions issued in 2008 were classified into 5 steps according to guideline definitions. Patients meeting criteria for two steps were classified as the higher step.   Results:  12409 adults and 1401 children were included. In the primary adult analysis with a step 2 definition of ICS dose ≤ 800mcg/day of beclometasone dipropionate (BDP) equivalent, the distribution was 15.8%, 31.4%, 15.3%, 32.6% and 1.2% for steps 1 – 5. The secondary analysis (step 2 definition of ICS dose ≤ 400mcg/day), resulted in an allocation of 15.8%, 22.2%, 24.6%, 32.6% and 1.2%. A breakdown of step 3 showed similar prescribing of an increase in ICS dose (37.6%) versus LABA as an add-on (32.2%). In the primary analysis (ICS ≤ 400mcg/day) for children, prescribing tended towards step 2 (59.0%). In the secondary analysis, step 3 therapy showed higher prescribing of increased ICS dose (61.1%) versus LABA as an add-on (27.0%).   Conclusion:  The BTS/SIGN asthma guidelines are subject to variable interpretation. Step 3 asthma therapy in NHS Forth Valley deviates from the recommended preference for combination therapy.
On Chlorofluorocarbon Bans and Inhaled Albuterol Prices
Authors: Joseph S. Ross, Rita F. Redberg
Journal: JAMA Internal Medicine (2015)

Thecompetingconcernsand interestsofboth individuals and society must be considered when establishing regulatory policy. In 2008, the US Food and Drug Administration (FDA) banned albuterol inhalers containing chlorofluorocarbons.Thisdecisionwasquestionedat the timebecause the chlorofluorocarbons emitted from inhalershavean insignificant effect onozoneandbecause of the anticipated costs of transitioning tohydrofluoroalkane inhalers for patientswith respiratorydisease.1With the ban, generically manufactured chlorofluorocarbon inhalers were discontinued, leaving only branded hydrofluoroalkane inhalers available for use, even though the main pharmacological ingredient inboth typesof inhalers (albuterol)hadbeen available invarious generic formulations since the 1990s. Jena and colleagues examine the consequences of the ban on privately insuredpatientswithasthma, finding that themeanoutof-pocket prescription costs for albuterol increased by 50%, with a small decline in inhaler use but reassuringly no increased risk for emergency department visits or hospital admission.2 Left unanswered is how uninsured individuals with asthma are faring. Whether banning chlorofluorocarbon inhalers will lead to any improvement in the environment is unclear. It is clear that the ban has increased health care costs and improved the bottom line of pharmaceutical companies that are making hydrofluoroalkane-based inhalers. Although albuterol inhalers have been in use for more than 30 years, pharmaceutical companies have used the chlorofluorocarbon ban as an opportunity to raise the price on inhalers from approximately $13 for a generic formulation to more than $50 today. When the FDA banned albuterol inhalers containing chlorofluorocarbons, it was “encouraged that the manufacturers of [these] products [were] implementing programs to help assure access ... for patients for whom price could be a significant barrier to access to this important medicine.”3 However, in this unique situation, it would have made more sense to not ban chlorofluorocarbon inhalers until hydrofluoroalkane inhalers were available in generic formulations. This would have balanced the best interests of society and the best interests of individuals with respiratory disease, allowing the FDA to protect the environment without making inhalers that had been on the market for many years expensive and unaffordable for many.
Abstract 2355: A Randomized Comparison of Triple Antiplatelet Therapy with Dual Antiplatelet Therapy after Drug-Eluting Stent Implantation: <i>D</i> rug- <i>E</i> luting Stenting Followed by <i>C</i> ilostazol treatment reduces <i>LA</i> te <i>RE</i> stenosis in Patients with <i>DIABETES</i> mellitus: DECLARE - DIABETES Trial
Authors: Seong-Wook Park, Seung-Whan Lee, Young-Hak Kim, Sung-Cheol Yun, Duk-Woo Park, Cheol Whan Lee, Myeong-Ki Hong, Hyun-Sook Kim, Jae-Ki Ko, Jae-Hyeong Park, Jae-Hwan Lee, Si Wan Choi, In-Whan Seong, Yoon Haeng Cho, Nae-Hee Lee, June Hong Kim, Kook-Jin Chun, Seung-Jung Park
Journal: Circulation (2007)

Objectives: To determine whether cilostazol improves the efficacy of drug-eluting stent (DES) in patients with diabetes mellitus (DM). Background: Cilostazol has been reported to reduce neointimal hyperplasia and restenosis after bare-metal stent (BMS) implantation. But it is not known that its effect is extrapolated to drug eluting stent (DES) in patients with DM. Methods: This randomized, multicenter, prospective study compared triple antiplatelet therapy (aspirin, clopidogrel and cilostazol, triple group, n=200) and dual antiplatelet therapy (aspirin and clopidogrel, standard group, n=200) for 6 months in patients with DM receiving DES. The primary end point was in-stent late loss at 6-month angiography according to the intention-to-treat principle. Results: The both groups had similar baseline clinical and angiographic characteristics. The in-stent (0.25±0.53 mm vs. 0.38±0.54 mm, p=0.025) and in-segment (0.42±0.48 mm vs. 0.53±0.49 mm, p=0.031) late loss were significantly lower in the triple versus standard group. Six-month in-segment restenosis (8.0% vs. 15.6%, p=0.033) and 9-month target lesion revascularization (TLR) (2.5% vs. 7.0%, p=0.034) was significantly lower in triple group versus standard group. At 9 months, major adverse cardiac events (MACE) including death, myocardial infarction, and TLR had a lower tendency in triple group versus standard group (3.0% vs. 7.0%, p=0.066). Subgroup analysis showed that triple plus SES patients had significantly lower in-segment restenosis (0%, 0/88) than standard plus SES (8%, 7/88, p=0.014), triple plus PES (17.3% 13/75, p&lt;0.001), and standard plus PES (24.1%, 19/79, p&lt;0.001) patients. On the multivariate analysis, SES and the use cilostazol were strong predictors of restenosis and TLR. Conclusions: In patients with DM, compared with dual antiplatelet therapy, triple antiplatelet therapy after DES implantation is associated with a decrease in angiographic restenosis as well as the extent of late luminal loss, resulting in reduced risk of 9-monthTLR.
Combined Irinotecan and Oxaliplatin Plus Granulocyte Colony-Stimulating Factor in Patients With Advanced Fluoropyrimidine/Leucovorin-Pretreated Colorectal Cancer
Authors: Werner Scheithauer, Gabriela V. Kornek, Markus Raderer, Julia Valencak, Georg Weinländer, Michael Hejna, Karin Haider, Werner Kwasny, Dieter Depisch
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To evaluate the efficacy and tolerance of combined irinotecan and oxaliplatin in patients with advanced colorectal cancer pretreated with leucovorin-modulated fluoropyrimidines. PATIENTS AND METHODS: Thirty-six patients with metastatic colorectal cancer, who progressed while receiving or within 6 months after discontinuing palliative chemotherapy with fluoropyrimidines/leucovorin, were enrolled onto this study. Treatment consisted of oxaliplatin 85 mg/m 2 on days 1 + 15 and irinotecan 80 mg/m 2 on days 1 + 8 + 15 every 4 weeks. Depending on the absolute neutrophil counts (ANC) on the day of scheduled chemotherapeutic drug administration, a 5-day course of granulocyte colony-stimulating factor (G-CSF) 5 μg/kg/d was given. RESULTS: The overall response rate was 42% for all 36 assessable patients (95% confidence interval, 26% to 59%), including two complete remissions (6%). Thirteen additional patients (36%) had stable disease, and only eight (22%) progressed. The median time to treatment failure was 7.5 months (range, 1 to 13.5+ months). After a median follow-up time of 14 months, 19 patients (53%) are still alive. Hematologic toxicity was commonly observed, although according to the ANC-adapted use of G-CSF (in 31 patients during 81 of 174 courses), it was generally mild: grade 3 and 4 granulocytopenia occurred in only five and two cases, respectively. The most frequent nonhematologic adverse reactions were nausea/emesis and diarrhea, which were rated severe in 17% and 19%, respectively. CONCLUSION: Our data suggest that the combination of irinotecan and oxaliplatin with or without G-CSF has substantial antitumor activity in patients with progressive fluoropyrimidine/leucovorin-pretreated colorectal cancer. Overall toxicity was modest, with gastrointestinal symptoms constituting the dose-limiting side effects. Further evaluation of this regimen seems warranted.
A randomized trial of carboplatin versus iproplatin in untreated advanced ovarian cancer.
Authors: C Trask, A Silverstone, C M Ash, H Earl, C Irwin, A Bakker, J S Tobias, R L Souhami
Journal: Journal of Clinical Oncology (1991)

Between August 1984 and October 1987, 120 patients with stage IC to IV epithelial ovarian cancer were randomly assigned to receive carboplatin (400 mg/m2) or iproplatin (300 mg/m2) every 4 weeks as initial treatment. Stratification was made according to International Federation of Gynecology and Obstetrics (FIGO) stage and according to size of residual disease after surgery. Response was evaluated after six courses when patients were restaged, with laparoscopy or laparotomy in clinical complete responders or those with no assessable disease. Treatment was then stopped in surgically proven complete responders. Patients with partial (PR) or minor response (MR) received a further six courses of their original drug at a reduced dose (carboplatin 300 mg/m2, iproplatin 225 mg/m2). Patients with stable (SD), progressive (PD), or recurrent disease were treated with cyclophosphamide (1 g/m2). The response rates were 63% (95% confidence interval [CI], 50% to 74%) for carboplatin and 38% (95% CI, 26% to 51%) for iproplatin. Fifteen patients were not assessable for response. The median survival was 114 weeks (95% CI, 82 to 233 weeks) for carboplatin patients and 68 weeks (95% CI, 48 to 82 weeks) for iproplatin patients (P = .008). The amount of residual disease after initial laparotomy was a prognostic factor for survival. Myelosuppression was the main toxicity and was greater with iproplatin. This study shows carboplatin to be more active than iproplatin in the treatment of ovarian cancer and less toxic. Few responses to cyclophosphamide occurred following either drug, implying resistance to the alkylating agent.