Leuk Lymphoma. 2019 01;60(1):60-68
Authors: Schramm F, Zimmermann M, Jorch N, Pekrun A, Borkhardt A, Imschweiler T, Christiansen H, Faber J, Feuchtinger T, Schmid I, Beron G, Horstmann MA, Escherich G
Abstract
Anthracyclines are integral components of antileukemic treatment. Apart from cardiotoxicity, myelosuppression and infectious complications have been described for doxorubicin (DOX) and daunorubicin (DNR) as predominant side effects, but little is known about their differential toxicities. To address the question whether DNR is associated with a lower rate of infectious complications compared with DOX, 307 children with newly diagnosed acute lymphoblastic leukemia, enrolled in trial CoALL 08-09, were randomized to receive either DOX 30 mg/m2 (n = 153) or DNR 36 mg/m2 (n = 154) in delayed intensification. Hematologic toxicities and stomatitis were less frequent in the DNR group resulting in a significantly lower rate of infections in the DNR arm (27% vs. 59%, p < .0001).
PMID: 29966458 [PubMed - indexed for MEDLINE]
3 January 2020
12:54
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Lymphoma: Diagnosis and Treatment.
Lymphoma: Diagnosis and Treatment.
Am Fam Physician. 2020 Jan 01;101(1):34-41
Authors: Lewis WD, Lilly S, Jones KL
Abstract
Lymphoma is a group of malignant neoplasms of lymphocytes with more than 90 subtypes. It is traditionally classified broadly as non-Hodgkin or Hodgkin lymphoma. Approximately 82,000 new U.S. patients are diagnosed with lymphoma annually. Any tobacco use and obesity are major modifiable risk factors, with genetic, infectious, and inflammatory etiologies also contributing. Lymphoma typically presents as painless adenopathy, with systemic symptoms of fever, unexplained weight loss, and night sweats occurring in more advanced stages of the disease. An open lymph node biopsy is preferred for diagnosis. The Lugano classification system incorporates symptoms and the extent of the disease as shown on positron emission tomography/computed tomography to stage lymphoma, which is then used to determine treatment. Chemotherapy treatment plans differ between the main subtypes of lymphoma. Non-Hodgkin lymphoma is treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without rituximab (R-CHOP), bendamustine, and lenalidomide. Hodgkin lymphoma is treated with combined chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), Stanford V (a chemotherapy regimen consisting of mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone), or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) with radiotherapy. Subsequent chemotherapy toxicities include neuropathy, cardiotoxicity, and secondary cancers such as lung and breast, and should be considered in the shared decision-making process to select a treatment regimen. Once remission is achieved, patients need routine surveillance to monitor for complications and relapse, in addition to age-appropriate screenings recommended by the U.S. Preventive Services Task Force. Patients should receive a 13-valent pneumococcal conjugate vaccine followed by a 23-valent pneumococcal polysaccharide vaccine at least eight weeks later with additional age-appropriate vaccinations because lymphoma is an immunosuppressive condition. Household contacts should also be current with their immunizations.
PMID: 31894937 [PubMed - in process]
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R-(-)-carvone Attenuated Doxorubicin Induced Cardiotoxicity In Vivo and Potentiated Its Anticancer Toxicity In Vitro
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R-(-)-carvone Attenuated Doxorubicin Induced Cardiotoxicity In Vivo and Potentiated Its Anticancer Toxicity In Vitro
Balkan Med J. 2020 Jan 02;:
Authors: Abbas MM, Kandil YI, Abbas MA
Abstract
Background: Doxorubicin (DOX) is one of the most potent broad-spectrum antitumor and chemotherapeutic agents. However, it produces cardiotoxicity.
Aim: To investigate whether (R)-(-)-carvone exerts cardioprotective effect against DOX toxicity in vivo and in vitro.
Study design: Tissue culture and animal study.
Methods: The synergistic effect of (R)-(-)-carvone with DOX was evaluated in MCF7 cancer cell line while its protective effect against doxorubicin (DOX) toxicity was evaluated in normal heart cell line (H9C2) and in vivo. Furthermore, the mechanism of its cardioprotective effect was studied.
Results: (R)-(-)-carvone exerted cytotoxic action on MCF7 cancer cell line with IC50 value of 14.22 μM and potentiated the cytotoxic action of DOX while it decreased the toxicity of DOX on normal heart cell line (H9C2). In BALB/c mice, (R)-(-)-carvone protected the heart from the toxic action of DOX as was evident by biochemical and histological studies. The protective effect of (R)-(-)-carvone on H9C2 heart cell line and on heart in vivo was due to an increase in catalase activity.
Conclusion: (R)-(-)-carvone has synergistic anticancer action with DOX on MCF7 cell line while decreasing its cardiotoxicity.
PMID: 31893584 [PubMed - as supplied by publisher]
4 January 2020
13:26
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A case of left ventricular assist device application for chemotherapy-related cardiomyopathy caused by trastuzumab and anthracycline.
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A case of left ventricular assist device application for chemotherapy-related cardiomyopathy caused by trastuzumab and anthracycline.
J Artif Organs. 2020 Jan 02;:
Authors: Inui T, Kohno H, Matsuura K, Ueda H, Tamura Y, Watanabe M, Inage Y, Yakita Y, Matsumiya G
Abstract
Left ventricular assist device (LVAD) is an established therapy for patients with severe heart failure. Because the incidence of cardiotoxicity owing to anticancer agents is low, it is difficult to predict the recovery prospects when the cause of heart failure is due to anticancer agents. In this context, cancer patients who present with severe symptoms of heart failure and who fail medical therapy for heart failure may pose a dilemma, especially in countries such as Japan where implantable LVADs are not approved for purposes other than bridging to transplant. Recently, we encountered a 32-year-old woman with chemotherapy-related cardiomyopathy that developed after anticancer treatment using trastuzumab and anthracycline. LVAD therapy was the only option to save the young woman. The patient received an extracorporeal LVAD, her cardiac function gradually recovered while on support, and the device was successfully removed.
PMID: 31897739 [PubMed - as supplied by publisher]
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5 January 2020
13:55
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Effects of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use on cancer therapy-related cardiac dysfunction: a meta-analysis of randomized controlled trials.
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Effects of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use on cancer therapy-related cardiac dysfunction: a meta-analysis of randomized controlled trials.
Heart Fail Rev. 2020 Jan 03;:
Authors: Fang K, Zhang Y, Liu W, He C
Abstract
Angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) may attenuate cancer therapy-related cardiac dysfunction (CTRCD). However, results of the previous studies were not consistent. We performed a meta-analysis to evaluate the influence of ACEI/ARB on CTRCD. Randomized controlled trials (RCTs) were obtained by searching of PubMed, Embase, and Cochrane's Library databases. A random-effect model was used to pool the results. Nine RCTs with 1095 cancer patients that underwent chemotherapy with anthracycline and/or trastuzumab were included. Using of ACEI/ARB significantly preserved left ventricular ejection fraction (LVEF, weighed mean difference = 4.24%, p = 0.002) compared with controls. Subgroup analyses showed that the benefits of ACEI/ARB on LVEF following chemotherapy were consistent and independent of study characteristics including study design, sample size, cancer type, chemotherapy protocols, preventative medications of ACEI or ARB, methods for LVEF measurement, and follow-up durations. The benefits on LVEF following chemotherapy were more remarkable in studies using ACEI and followed ≤ 12 months (p for subgroup difference = 0.04 and 0.02). Use of ACEI/ARB did not significantly reduce the risk of cardiotoxicity events (risk ratio [RR] = 0.63, p = 0.22) but increased the risk of hypotension in these patients (RR = 3.94, p = 0.008). These results indicated that using of ACEI/ARB may moderately attenuate CTRCD following chemotherapy with anthracycline and/or trastuzumab. Large-scale RCTs are needed to evaluate whether the benefits of ACEI/ARB on LVEF are clinically relevant.
PMID: 31900787 [PubMed - as supplied by publisher]
7 January 2020
13:22
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Mononuclear phagocyte system blockade improves therapeutic exosome delivery to the myocardium.
Mononuclear phagocyte system blockade improves therapeutic exosome delivery to the myocardium.
Theranostics. 2020;10(1):218-230
Authors: Wan Z, Zhao L, Lu F, Gao X, Dong Y, Zhao Y, Wei M, Yang G, Xing C, Liu L
Abstract
Rationale: Exosomes are emerging as a promising drug delivery carrier. However, rapid uptake of exosomes by the mononuclear phagocyte system (MPS) remains an obstacle for drug delivery into other targeted organs, including the heart. We hypothesized that prior blocking of uptake of exosomes by the MPS would improve their delivery to the targeted organs. Methods: Exosomes were isolated from the cell culture medium. Fluorescence-labeled exosomes were tracked in vitro and in vivo by fluorescence imaging. The expression of clathrin heavy chain (Cltc), cavolin1, Pak1 and Rhoa, known genes for endocytosis, were profiled in various cell lines and organs by qPCR. The knockdown efficiency of siRNA against Cltc was analyzed by Western blotting. Exosomecontrol and exosomeblocking were constructed by encapsulating isolated exosomes with siControl or siClathrin via electroporation, while exosometherapeutic was constructed by encapsulating isolated exosomes with miR-21a. Doxorubicin-induced cardiotoxicity model was used to verify the therapeutic efficiency of the exosome-based miR-21a delivery by echocardiography. Results: Exosomes were preferentially accumulated in the liver and spleen, mainly due to the presence of abundant macrophages. Besides the well-known phagocytic effect, efficient endocytosis also contributes to the uptake of exosomes by macrophages. Cltc was found to be highly expressed in the macrophages compared with other endocytosis-associated genes. Accordingly, knockdown of Cltc significantly decreased the uptake of exosomes by macrophages in vitro and in vivo. Moreover, prior injection of exosomeblocking strikingly improved the delivery efficiency of exosomes to organs other than spleen and liver. Consistently, compared with the direct injection of exosometherapeutic, prior injection of exosomeblocking produced a much better therapeutic effect on cardiac function in the doxorubicin-induced cardiotoxicity mouse model. Conclusions: Prior blocking of endocytosis of exosomes by macrophages with exosomeblocking successfully and efficiently improves the distribution of following exosometherapeutic in targeted organs, like the heart. The established two-step exosome delivery strategy (blocking the uptake of exosomes first followed by delivery of therapeutic exosomes) would be a promising method for gene therapy.
PMID: 31903116 [PubMed - in process]
13:22
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Persistent Impairment in Cardiopulmonary Fitness after Breast Cancer Chemotherapy.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--tools.ovid.com-images-wklogo.jpg Related Articles
Persistent Impairment in Cardiopulmonary Fitness after Breast Cancer Chemotherapy.
Med Sci Sports Exerc. 2019 08;51(8):1573-1581
Authors: Foulkes SJ, Howden EJ, Bigaran A, Janssens K, Antill Y, Loi S, Claus P, Haykowsky MJ, Daly RM, Fraser SF, LA Gerche A
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