ABSTRACT
A new class of 3-substituted isocoumarin/3-alkylidenephthalide based novel small molecules derived from rosuvastatin were designed and synthesized via the ultrasound assisted Cu-mediated coupling-cyclization in a single pot with remarkable regioselectivity. The phthalides were generally obtained at lower temperature whereas the use of elevated temperature afforded isocoumarins. Two compounds e.g. 3n and 4d showed promising cytotoxic effects when tested against HCT 116, HepG2 and PA-1 cell lines at 10 μM. Indeed, 4d was found to be a potent cytotoxic agent (IC50 ∼ 0.76-4.51 μM). Both 3n and 4d were tested for their effects on PANC-1 cells. Considerable decrease in p-Akt substrates shown by 4d and 3n at 50 μM (western blot analysis) indicated their ability to inhibit p-Akt signal transduction pathway and arresting growth of PANC-1 cells in vitro. This was further supported by the cytotoxic effect of 4d on PANC-1 cells (MTT assay) that was better than rosuvastatin. While none of 3n and 4d showed any significant effect on non-cancerous HEK cell line (indicating their potential selectivity towards cancer cells) these compounds were further evaluated for their toxicities in Zebrafish embryo. The NOAEL (No Observed Adverse Effect Level) for teratogenicity, hepatotoxicity and cardiotoxicity was found to be 100 μM for both compound. Thus, 4d as a novel and potent but safer cytotoxic agent with potential to treat colorectal/ovarian and pancreatic cancer is of further medicinal interest.
PMID:32599323 | DOI:10.1016/j.ejmech.2020.112335
07:22
PubMed articles on: Cancer & VTE/PE
Clinical effect of bronchial arterial infusion chemotherapy and CalliSpheres drug-eluting beads in patients with stage II-IV lung cancer: A prospective cohort study
Shang B, et al. Thorac Cancer 2020.
ABSTRACT
BACKGROUND: CalliSpheres are drug-eluting beads used for tumor artery embolization, with clinical benefits in a number of cancer types. The aim of the study was to examine the clinical benefits and complications of patients with stage II-IV lung cancer treated with CalliSpheres drug-eluting beads for embolization versus conventional vascular interventional treatment.
METHODS: This was a prospective cohort study conducted from August 2018 to May 2019. The patients were grouped according to traditional bronchial arterial infusion chemotherapy (infusion group) or bronchial arterial chemoembolization with CalliSpheres drug-eluting beads loaded with adriamycin (CallisSphere group). Short-term effects, serum tumor markers, and adverse reactions during follow-up were compared between the two groups.
RESULTS: There were 60 participants enrolled into the study with 30 in each group including 54 men and six women, 42-78 years of age. In the CalliSphere group, compared with the infusion group, the disease control rate was 93.3% versus 73.3% (P = 0.080) and the objective remission rate (ORR) was 86.7% versus 60.0% (P = 0.039); the three- and six-month progression-free survival (PFS) and six-month overall survival (OS) were better in the CalliSphere group (three-month PFS: 96.7% vs. 73.3%, P = 0.026; six-month PFS: 87.5% vs. 57.1%, P = 0.045; six-month OS: 87.5% vs. 52.7%, P = 0.024); after treatment, the tumor markers in the CalliSphere group were lower (CEA: P < 0.001; CYFRA21-1: P = 0.014). There were no differences in adverse reactions between the two groups.
CONCLUSIONS: The clinical effect of bronchial arterial chemoembolization with drug-eluting beads on lung cancer is probably significant and could improve the short-term response, PFS, and OS in patients with stage IIIV lung cancer, without increasing severe adverse reactions.
KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: The clinical effect of bronchial arterial chemoembolization with drug-eluting beads on lung cancer is probably significant and could improve the short-term response, PFS, and OS in patients with stage II-IV lung cancer, without increasing severe adverse reactions.
WHAT THIS STUDY ADDS: The ORR, PFS, OS was better in the CalliSphere group than that of infusion group; CEA and CYFRA21-1 were significant lower in CalliSphere group.
PMID:32603550 | DOI:10.1111/1759-7714.13522
07:22
In reply to this message
the management of surgery or invasive procedures in patients taking anti-vitamin K oral anticoagulants Body Weight (kg)Enoxaparin dose every 12 hours (IU)<50200050-69400070-89600090-110800011010000 The treatment with Enoxaparin will be initiated soon after randomization (maximum allowed starting time 12h after randomization). The treatment will be administered every 12 hours in the intervention group and every 24 hours in the control group. Treatments will be administered in the two arms until hospital discharge or the primary outcomes detailed below occur.
MAIN OUTCOMES: Primary Efficacy Endpoint: Clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first: 1.Death2.Acute Myocardial Infarction [AMI]3.Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]4.Need of either: a.Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orb.IMV in patients who at randomisation were in standard oxygen therapy by delivery interfaces5.Need for IMV, in patients who at randomisation were in Cpap or NIV Time to the occurrence of each of these events will be recorded. Clinical worsening will be analysed as a binary outcome as well as a time-to-event one. Secondary Efficacy Endpoints: Any of the following events occurring within the hospital stay 1.Death2.Acute Myocardial Infarction [AMI]3.Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]4.Need of either: a.Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orb.IMV in patients who at randomisation were in standard oxygen therapy by delivery interfaces5.Need for IMV in patients who at randomisation were in Cpap or NIV6.Improvement of laboratory parameters of disease severity, including: o D-dimer levelo Plasma fibrinogen levelso Mean Platelet Volumeo Lymphocyte/Neutrophil ratioo IL-6 plasma levels MORTALITY AT 30 DAYS: Information about patients' status will be sought in those who are discharged before 30 days on Day 30 from randomisation. Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Primary safety endpoint: Major bleeding, defined as an acute clinically overt bleeding associated with one or more of the following: Decrease in haemoglobin of 2 g/dl or more;Transfusion of 2 or more units of packed red blood cells;Bleeding that occurs in at least one of the following critical sites [intracranial, intraspinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal];Bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death);Bleeding that necessitates surgical intervention Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Secondary safety endpoint: Clinically Relevant non-major bleeding, defined as an acute clinically overt bleeding that does not meet the criteria for major and consists of: 1.Any bleeding compromising hemodynamic2.Spontaneous hematoma larger than 25 cm2, or 100 cm2 if there was a traumatic cause3.Intramuscular hematoma documented by ultrasonography4.Epistaxis or gingival bleeding requiring tamponade or other medical intervention5.Bleeding from venipuncture for >5 minutes6.Haematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures7.Haemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention8.Any other bleeding requiring temporary cessation of a study drug. Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one.
RANDOMISATION: Randomisation (wit[...]
07:22
In reply to this message
h a 1:1 randomisation ratio) will be centrally performed by using a secure, web-based system, which will be developed by the Methodological and Statistical Unit at the Azienda Ospedaliero-Universitaria of Modena. Randomisation stratified by 4 factors: 1) Gender (M/F); 2) Age (<75<302) with random variable block sizes will be generated by STATA software. The web-based system will guarantee the allocation concealment. Blinding (masking) The study is conceived as open-label: patients and all health-care personnel involved in the study will be aware of the assigned group.
NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size is based on the hypothesis that LMWH administered at high doses versus low doses will significantly reduce the risk of clinical worsening. The overall sample size in this study is expected to be 300 with 150 in the Low-Dose LMWH control group and 150 in the High-Dose LMWH intervention group, recruited over 10-11 months. Assuming an alpha of 5% (two tailed) and a percentage of patients who experience clinical worsening in the control group being between 25% and 30%, the study will have 80% power to detect at least 50% relative reduction in the risk of death between low and high doses of heparin.
TRIAL STATUS: Protocol version 1.2 of 11/05/2020. Recruitment start (expected): 08/06/2020 Recruitment finish (expected): 30/04/2021 Trial registration EudraCT 2020-001972-13, registered on April 17th, 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
PMID:32586394 | PMC:PMC7316577 | DOI:10.1186/s13063-020-04475-z
07:22
PubMed articles on: Cardio-Oncology
Involvement of ROS/NLRP3 Inflammasome Signaling Pathway in Doxorubicin-Induced Cardiotoxicity
Wei S, et al. Cardiovasc Toxicol 2020.
ABSTRACT
Doxorubicin (Dox) is widely used in cancer therapy, but the clinical application is limited by its cardiotoxicity. The underlying mechanism of Dox-induced cardiotoxicity remains unclear. Present study aimed to evaluate the role of NLRP3 inflammasome in Dox-induced cardiotoxicity. The NLRP3 inflammasome was activated in the myocardium of Dox-treating (5 mg/kg, once every other day, cumulative dosage to 15 mg/kg and sacrificed after 2 days of last Dox injection) C57BL/6 mice as shown by the up-regulation of NLRP3 and Caspase-1 p20. Dox (1 μM for 48 h) induced the apoptosis of H9c2 cells and primary cardiomyocytes concomitantly with up-regulation of NLRP3, ASC and Caspase-1 p20 expressions, as well as the increased IL-1β secretion, suggesting the activation of NLRP3 inflammasome. These effects of Dox on H9c2 cells and primary cardiomyocytes can be reversed by MCC950, a specific inhibitor of NLRP3. In view of the key role of ROS on the Dox-induced cardiotoxicity, the relationship between ROS and NLRP3 was further investigated. The ROS level was increased in myocardium, H9c2 cells and primary cardiomyocytes after treating with Dox. Decreasing ROS level by NAC can inhibit the NLRP3 inflammasome activation, secretion of IL-1β and apoptosis in Dox-treating H9c2 cells and primary cardiomyocytes. Collectively, this study reveals a crucial role of ROS/NLRP3-associated inflammasome activation in Dox-induced cardiotoxicity, and NLRP3 inflammasome may represent a new therapeutic target for Dox-induced cardiotoxicity.
PMID:32607760 | DOI:10.1007/s12012-020-09576-4
07:22
PubMed articles on: Cardio-Oncology
Exploring Social Ecological Determinants of Physical Activity Among Adult Survivors of Childhood Cancer
Dugan KF, et al. J Adolesc Young Adult Oncol 2020.
ABSTRACT
Purpose:Adult survivors of childhood cancer (ASCCs) are at high risk for cardiovascular disease from chemotherapy- and radiation therapy-related cardiotoxicity. Physical activity (PA) can reduce this risk, but the majority of ASCCs do not engage in sufficient PA. The purpose of this study was to identify barriers, facilitators, and resources for PA among ASCCs using the ecological model of physical activity (EMPA) as a theoretical framework. Methods:A concept elicitation survey was distributed independently to ASCCs (diagnosed with cancer before the age of 18, and currently 18-39 years old) and parents/legal guardians of an ASCC. The survey consisted of open-ended questions asking about barriers, facilitators, and resources for PA. Content analysis of open-ended questions categorized responses into levels of the EMPA and identified key themes. Results:Seventeen ASCCs and eight parents of ASCCs completed the survey. The majority of barriers, facilitators, and resources reported were at the individual and microsystem level of the EMPA. Six themes emerged, suggesting that ASCC's PA was related to proximity/access, social support, equipment, time/schedule, finances, and health-related barriers. Conclusion:This is the first study to examine barriers, facilitators, and resources of PA among ASCCs using the EMPA. Findings from this study provide a multilevel perspective on the influences of PA among ASCCs, and can be used for future, in-depth qualitative studies and quantitative survey development, and as a foundational step toward supportive efforts in increasing PA among ASCCs.
PMID:32598196 | DOI:10.1089/jayao.2019.0169
07:22
PubMed articles on: Cardio-Oncology
Cardioprotective Strategies to Prevent Cancer Treatment-Related Cardiovascular Toxicity: a Review
Upshaw JN. Curr Oncol Rep 2020 - Review.
ABSTRACT
PURPOSE OF REVIEW: Patients with cancer have an elevated risk of cardiovascular disease. This review describes the cardiovascular risks of different cancer therapies and the evidence for cardioprotective strategies.
RECENT FINDINGS: Recent studies have provided additional support for the safety and efficacy of dexrazoxane and liposomal anthracycline formulations in certain high-risk patients receiving anthracyclines and for neurohormonal antagonist therapy in patients with breast cancer receiving sequential anthracyclines and trastuzumab. Ongoing studies are exploring the benefit of: (1) statins for anthracycline cardioprotection; (2) strict blood pressure control during vascular endothelial growth factor inhibitor treatment and; (3) dexrazoxane on long-term cardiac outcomes in pediatric populations. To date, there are no evidence-based cardioprotective strategies specifically for radiation-related heart and vascular disease, immunotherapy myocarditis, fluoropyrimidine cardiotoxicity, vascular endothelial growth factor inhibitor-related hypertension, BCR-Abl multikinase inhibitor vascular disease, and other established and emerging cancer therapeutics with cardiovascular effects. Current evidence supports specific cardioprotective strategies for high risk patients receiving anthracyclines or sequential anthracycline-trastuzumab therapy; however, major evidence gaps exist.
PMID:32564220 | DOI:10.1007/s11912-020-00923-w
07:22
PubMed articles on: Cancer & VTE/PE
Safety and Efficacy of Apixaban vs Enoxaparin for Preventing Postoperative Venous Thromboembolism in Women Undergoing Surgery for Gynecologic Malignant Neoplasm: A Randomized Clinical Trial
07:22
PubMed articles on: Cancer & VTE/PE
Urosepsis Increases the Risk of Pulmonary Embolism in Patients Affected by SARS-CoV-2
Cai T, et al. J Urol 2020.
NO ABSTRACT
PMID:32609571 | DOI:10.1097/JU.0000000000001228
07:22
Video file
Not included, change data exporting settings to download.
00:00, 4.3 KB
07:23
PubMed articles on: Cancer & VTE/PE
Single-Drug Approach with Edoxaban is Effective for Resolving Non-Acute Cancer-Associated Venous Thrombosis: A Single-Arm Retrospective Analysis
Toshima H, et al. Cancers (Basel) 2020.
ABSTRACT
Recently, cancer-related venous thromboembolism (VTE) has been termed "cancer-associated thrombosis (CAT)" and is the focus of current research. We retrospectively investigated the efficacy of a single-drug approach with edoxaban for the treatment of non-acute CAT. Thirty-two non-acute CAT patients who received edoxaban were analyzed. The primary endpoint of this analysis was the thrombus disappearance rate at the first evaluation. Secondary endpoints included progression/recurrence of VTE, major bleeding, and D-dimer levels. The thrombus disappearance rate was 62.5%. Therefore, the null hypothesis for the primary endpoint (thrombus disappearance rate of ≤32.0%) was rejected (p = 0.00038) based on the rate of the previous study as the historical control. Recurrent VTE and major bleeding occurred in two patients each. After the start of treatment with edoxaban, a significant difference in D-dimer levels was observed (p = 0.00655). We demonstrated that a single-drug approach with edoxaban is a potential treatment option for non-acute CAT.
PMID:32605234 | DOI:10.3390/cancers12071711
07:23
PubMed articles on: Cardio-Oncology
Cardio-toxicity among patients with sarcoma: a cardio-oncology registry
Shamai S, et al. BMC Cancer 2020.
Comments
Post a Comment
اكتب تعليق حول الموضوع