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metronomic chemotherapy

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https://www.readbyqxmd.com/read/28088627/the-telomere-binding-protein-trf2-is-required-for-metronomic-therapeutic-effects-of-gemcitabine-and-capecitabine
#1
Wei-Ping Lee, Keng-Hsin Lan, Chung-Pin Li, Yee Chao, Ming-Chih Hou, Han-Chieh Lin, Shou-Dong Lee
Gemcitabine and capecitabine are two effective anticancer agents against solid tumors. The pharmacological mechanisms have been known as incorporation into DNA and thereby inhibition of DNA synthesis. When used as metronomic chemotherapy, they may inhibit angiogenesis and induce immunity. In our previous study, we showed that low-dose gemcitabine caused telomere shortening by stabilizing TRF2 that was required for XPF-dependent telomere loss. In this report, we established a SKOV3.ip1 ascites cell model. Tumor-bearing mice were treated with low-dose gemcitabine (GEM) or capecitabine (CAP)...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28056464/impact-of-ctla-4-blockade-in-conjunction-with-metronomic-chemotherapy-on-preclinical-breast-cancer-growth
#2
Karla Parra, Paloma Valenzuela, Natzidielly Lerma, Alejandra Gallegos, Luis C Reza, Georgialina Rodriguez, Urban Emmenegger, Teresa Di Desidero, Guido Bocci, Mitchell S Felder, Marian Manciu, Robert A Kirken, Giulio Francia
BACKGROUND: Although there are reports that metronomic cyclophosphamide (CTX) can be immune stimulating, the impact of its combination with anti-CTLA-4 immunotherapy for the treatment of cancer remains to be evaluated. METHODS: Murine EMT-6/P breast cancer, or its cisplatin or CTX-resistant variants, or CT-26 colon, were implanted into Balb/c mice. Established tumours were monitored for relative growth following treatment with anti-CTLA-4 antibody alone or in combination with; (a) metronomic CTX (ldCTX; 20 mg kg(-1) day(-1)), b) bolus (150 mg kg(-1)) plus ldCTX, or (c) sequential treatment with gemcitabine (160 mg kg(-1) every 3 days)...
January 5, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28050393/metronomic-chemotherapy-seems-prowess-to-battle-against-cancer-in-current-scenario
#3
Prema Muthusamy, Krishnan Vengadaragava Chary, G K Nalini
INTRODUCTION: Metronomic chemotherapy is an emerging method of chemotherapy. Metronomic 'lowdose' chemotherapy regimen induces tumour dormancy and reduces cancer resistance against anticancer drugs. It tends to improve overall success rate of cancer chemotherapy than conventional cyclical regimen. AIM: The aim of this systemic review was to provide comprehensive data of metronomic chemotherapy trials, regimens used and it's outcome in cancer therapeutics. MATERIALS AND METHODS: Fifty chemotherapy trial data were searched sequentially from web...
November 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28042155/evaluation-of-toxicity-of-a-chronic-alternate-day-metronomic-cyclophosphamide-chemotherapy-protocol-in-dogs-with-naturally-occurring-cancer
#4
Arata Matsuyama, J Paul Woods, Anthony J Mutsaers
Sterile hemorrhagic cystitis (SHC) is an important complication of cyclophosphamide chemotherapy in dogs as it is reported in up to 23% of cases with various protocols. The current study reports toxicities of a protocol of metronomic cyclophosphamide, and identifies risk factors for development of adverse effects. A retrospective cohort study of dogs treated with metronomic cyclophosphamide at an intended dose of 25 mg/m(2) every other day was conducted. Fifty dogs were included with a median length of treatment of 90 days (range: 1 to 1305 days)...
January 2017: Canadian Veterinary Journal. la Revue Vétérinaire Canadienne
https://www.readbyqxmd.com/read/28039473/nanometronomic-treatment-of-4t1-breast-cancer-with-nanocaged-doxorubicin-prevents-drug-resistance-and-circumvents-cardiotoxicity
#5
Serena Mazzucchelli, Michela Bellini, Luisa Fiandra, Marta Truffi, Maria A Rizzuto, Luca Sorrentino, Erika Longhi, Manuela Nebuloni, Davide Prosperi, Fabio Corsi
Chemotherapeutic treatment of breast cancer is based on maximum tolerated dose (MTD) approach. However, advanced stage tumors are not effectively eradicated by MTD owing to suboptimal drug targeting, onset of therapeutic resistance and neoangiogenesis. In contrast, "metronomic" chemotherapy is based on frequent drug administrations at lower doses, resulting in neovascularization inhibition and induction of tumor dormancy. Here we show the potential of H-ferritin (HFn)-mediated targeted nanodelivery of metronomic doxorubicin (DOX) in the setting of a highly aggressive and metastatic 4T1 breast cancer mouse model with DOX-inducible expression of chemoresistance...
December 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/28017894/metronomic-chemotherapy-for-advanced-breast-cancer-patients
#6
Marina Elena Cazzaniga, Maria Rita Dionisio, Francesca Riva
Metronomic chemotherapy refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen with no prolonged drug-free breaks that leads to antitumor activity. This schedule seems to have not only a direct cytotoxicity on cancer cells but also an effect on the tumor microenvironment by inhibiting tumor angiogenesis and modulating immune response. Metronomic chemotherapy was widely investigated in patients with breast cancer. The results of these studies showed that this strategy is not only effective but has a low toxicity profile too, proposing as a promising strategy for breast cancer patients...
December 23, 2016: Cancer Letters
https://www.readbyqxmd.com/read/28017892/metronomic-chemotherapy-a-potent-macerator-of-cancer-by-inducing-angiogenesis-suppression-and-antitumor-immune-activation
#7
Eirini Biziota, Leonidas Mavroeidis, Eleftheria Hatzimichael, Periklis Pappas
Metronomic chemotherapy is a low dosing treatment strategy that attracts growing scientific and clinical interest. It refers to dense and uninterrupted administration of low doses of chemotherapeutic agents (without prolonged drug free intervals) over extended periods of time. Cancer chemotherapy is conventionally given in cycles of maximum tolerated doses (MTD) with the aim of inducing maximum cancer cell apoptosis. In contrast, the primary target of metronomic chemotherapy is the tumor's neovasculature. This is relevant to the emerging concept that tumors exist in a complex microenvironment of cancer cells, stromal cells and supporting vessels...
December 23, 2016: Cancer Letters
https://www.readbyqxmd.com/read/28003122/metronomic-chemotherapy-a-relook-at-its-basis-and-rationale
#8
Tanujaa Rajasekaran, Quan-Sing Ng, Daniel Shao-Weng Tan, Wan-Teck Lim, Mei-Kim Ang, Chee-Keong Toh, Balram Chowbay, Ravindran Kanesvaran, Eng-Huat Tan
Metronomic administration of chemotherapy has long been recognized as having a different biological effect from maximal tolerated dose (MTD) administration. Preclinical studies have demonstrated these differences quite elegantly and many clinical trials have also demonstrated reproducible activity albeit small, in varied solid malignancies even in patients who were heavily pretreated. However, the concept of metronomic chemotherapy has been plagued by lack of a clear definition resulting in the published literature that is rather varied and confusing...
December 18, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27994645/next-generation-metronomic-chemotherapy-report-from-the-fifth-biennial-international-metronomic-and-anti-angiogenic-therapy-meeting-6-8-may-2016-mumbai
#9
Pan Pantziarka, Lisa Hutchinson, Nicolas André, Sébastien Benzekry, Francesco Bertolini, Atanu Bhattacharjee, Shubhada Chiplunkar, Dan G Duda, Vikram Gota, Sudeep Gupta, Amit Joshi, Sadhana Kannan, Robert Kerbel, Mark Kieran, Antonella Palazzo, Aparna Parikh, Eddy Pasquier, Vijay Patil, Kumar Prabhash, Yuval Shaked, Giselle Saulnier Sholler, Jaroslav Sterba, David J Waxman, Shripad Banavali
The 5(th) Biennial Metronomic and Anti-angiogenic Therapy Meeting was held on 6(th) - 8(th) May in the Indian city of Mumbai. The meeting brought together a wide range of clinicians and researchers interested in metronomic chemotherapy, anti-angiogenics, drug repurposing and combinations thereof. Clinical experiences, including many from India, were reported and discussed in three symposia covering breast cancer, head and neck cancers and paediatrics. On the pre-clinical side research into putative mechanisms of action, and the interactions between low dose metronomic chemotherapy and angiogenesis and immune responses, were discussed in a number of presentations...
2016: Ecancermedicalscience
https://www.readbyqxmd.com/read/27909934/current-achievements-and-future-perspectives-of-metronomic-chemotherapy
#10
REVIEW
Adriana Romiti, Rosa Falcone, Michela Roberto, Paolo Marchetti
In recent years, many anticancer drugs have been tested at metronomic dosages for a variety of tumours. Mechanisms of action attributed to metronomic chemotherapy (MCT) include antiangiogenesis, immunomodulation, direct inhibition of tumour growth, effect on tumour initiating cells and the modulation of clonal evolution. An active clinical research, aimed at testing MCT in several cancers, has been conducted over the past 15 years. However, because the majority of available results come from earlier phase II studies, mainly performed in the area of breast cancer (BC), it is clear that there are areas still to be investigated...
December 1, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27901449/incidence-of-sterile-hemorrhagic-cystitis-in-tumor-bearing-dogs-concurrently-treated-with-oral-metronomic-cyclophosphamide-chemotherapy-and-furosemide-55-cases-2009-2015
#11
Catherine M Chan, Angela E Frimberger, Antony S Moore
OBJECTIVE To determine the incidence of sterile hemorrhagic cystitis (SHC) in tumor-bearing dogs concurrently treated with oral metronomic cyclophosphamide chemotherapy and furosemide. DESIGN Retrospective case series. ANIMALS 55 dogs. PROCEDURES Record databases of 2 specialty practices were searched to identify dogs treated with oral metronomic cyclophosphamide chemotherapy in conjunction with furosemide for a minimum of 28 days between January 2009 and December 2015. Information extracted from the records included signalment, tumor diagnosis, cyclophosphamide and furosemide dosages, and concurrent medications...
December 15, 2016: Journal of the American Veterinary Medical Association
https://www.readbyqxmd.com/read/27881735/therapy-activated-stromal-cells-can-dictate-tumor-fate
#12
Robert S Kerbel, Yuval Shaked
In this issue of JEM, Chan et al. describe a novel way by which an investigational form of chemotherapy known as low-dose metronomic chemotherapy can inhibit tumor growth, which also has therapeutic implications for targeting tumor-initiating cells (TICs), the tumor stroma, and chemokine receptors, as well as invasion and metastasis.
December 12, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27881732/metronomic-chemotherapy-prevents-therapy-induced-stromal-activation-and-induction-of-tumor-initiating-cells
#13
Tze-Sian Chan, Chung-Chi Hsu, Vincent C Pai, Wen-Ying Liao, Shenq-Shyang Huang, Kok-Tong Tan, Chia-Jui Yen, Shu-Ching Hsu, Wei-Yu Chen, Yan-Shen Shan, Chi-Rong Li, Michael T Lee, Kuan-Ying Jiang, Jui-Mei Chu, Gi-Shih Lien, Valerie M Weaver, Kelvin K Tsai
Although traditional chemotherapy kills a fraction of tumor cells, it also activates the stroma and can promote the growth and survival of residual cancer cells to foster tumor recurrence and metastasis. Accordingly, overcoming the host response induced by chemotherapy could substantially improve therapeutic outcome and patient survival. In this study, resistance to treatment and metastasis has been attributed to expansion of stem-like tumor-initiating cells (TICs). Molecular analysis of the tumor stroma in neoadjuvant chemotherapy-treated human desmoplastic cancers and orthotopic tumor xenografts revealed that traditional maximum-tolerated dose chemotherapy, regardless of the agents used, induces persistent STAT-1 and NF-κB activity in carcinoma-associated fibroblasts...
December 12, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27879129/on-drug-resistance-and-metronomic-chemotherapy-a-mathematical-modeling-and-optimal-control-approach
#14
Urszula Ledzewicz, Shuo Wang, Heinz Schattler, Nicolas Andre, Marie Amelie Heng, Eddy Pasquier
Effects that tumor heterogeneity and drug resistance have on the structure of chemotherapy protocols are discussed from a mathematical modeling and optimal control point of view. In the case when two compartments consisting of sensitive and resistant cells are considered, optimal protocols consist of full dose chemotherapy as long as the relative proportion of sensitive cells is high. When resistant cells become more dominant, optimal controls switch to lower dose regimens defined by so-called singular controls...
February 1, 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/27879115/preface
#15
Avner Friedman, Mirosław Lachowicz, Urszula Ledzewicz, Monika Joanna Piotrowska, Zuzanna Szymanska
This volume was inspired by the topics presented at the international conference "Micro and Macro Systems in Life Sciences" which was held on Jun 8-12, 2015 in Będlewo, Poland. System biology is an approach which tries to understand how micro systems, at the molecular and cellular levels, affect macro systems such as organs, tissue and populations. Thus it is not surprising that a major theme of this volume evolves around cancer and its treatment. Articles on this topic include models for tumor induced angiogenesis, without and with delays, metastatic niche of the bone marrow, drug resistance and metronomic chemotherapy, and virotherapy of glioma...
February 1, 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/27876012/phase-i-study-of-low-dose-metronomic-temozolomide-for-recurrent-malignant-gliomas
#16
Eric T Wong, Joshua Timmons, Amy Callahan, Lauren O'Loughlin, Bridget Giarusso, David C Alsop
BACKGROUND: The treatment goal for recurrent malignant gliomas centers on disease stabilization while minimizing therapy-related side effects. Metronomic dosing of cytotoxic chemotherapy has emerged as a promising option to achieve this objective. METHODS: This phase I study was performed using metronomic temozolomide (mTMZ) at 25 or 50 mg/m(2)/day continuously in 42-day cycles. Correlative studies were incorporated using arterial spin labeling MRI to assess tumor blood flow, analysis of matrix metalloproteinase-2 (MMP-2) and MMP-9 activities in the cerebrospinal fluid (CSF) as surrogates for tumor angiogenesis and invasion, as well as determination of CSF soluble interleukin-2 receptor alpha (sIL-2Rα) levels as a marker of immune modulation...
November 22, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27832971/metronomic-chemotherapy-in-head-and-neck-cancer
#17
Francesca De Felice, Ilaria Benevento, Angela Musella, Daniela Musio, Vincenzo Tombolini
Head neck cancer (HNC) is generally treated with a multimodality approach. Loco-regional-distant control is often worst, due to the advantage stage disease at diagnosis and the optimal treatment option remains an unresolved issue. Metronomic chemotherapy (MCHT) is an emerging therapeutic option in clinical oncology and it may prove useful in HNC patients.
November 8, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27784377/-effect-of-cp-metronomic-chemotherapy-on-rpmi-8226-cell-proli-feration-and-notch1-nf-%C3%AE%C2%BAb-signaling-pathway-in-vitro
#18
Lie-Ping Guo, Fan Zhou, Hao-Tian Shi, Hai-Min Chen, Chen-Hui Lin, Xiao-Ling Chen, Jian Hou
OBJECTIVE: To investigate the effect of metronomic chemotherapy of low dose phosphoramide combined with prednisolone (CP metronomic chemotherapy) on proliferation and apoptosis of RPMI 8226 cells, and to explore its regulating effect on Notch1/NF-κB signaling pathways. METHODS: Experiment was divided into the DMSO control group, and the phosphoramide mustard (PM) group, the prednisolone group, the phosphoramide mustard plus prednisolone group (the CP group). RPMI 8226 cells were treated with different drugs, CCK-8 method was used to detect cell proliferation, flow cytometry was used to detect the cell cycle and apoptosis, reverse transcription PCR was used to detect Notch1 and NF-κB mRNA expression level...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27775375/limiting-the-development-of-anti-cancer-drug-resistance-in-a-spatial-model-of-micrometastases
#19
Ami B Shah, Katarzyna A Rejniak, Jana L Gevertz
While chemoresistance in primary tumors is well-studied, much less is known about the influence of systemic chemotherapy on the development of drug resistance at metastatic sites. In this work, we use a hybrid spatial model of tumor response to a DNA damaging drug to study how the development of chemoresistance in micrometastases depends on the drug dosing schedule. We separately consider cell populations that harbor pre-existing resistance to the drug, and those that acquire resistance during the course of treatment...
December 1, 2016: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/27767434/primary-nodal-hemangiosarcoma-in-four-dogs
#20
Catherine M Chan, Courtney H Zwahlen, Louis-Philippe de Lorimier, Stephen M Yeomans, Karon L Hoffmann, Antony S Moore
CASE DESCRIPTION 4 dogs with a slow-growing mass in the cervical region were evaluated. CLINICAL FINDINGS All dogs had no clinical signs at the time of the evaluation. There was no apparent evidence of visceral metastases or other primary tumor based on available CT or MRI data for any dog. TREATMENT AND OUTCOME For each dog, surgery to remove the mass was performed. Histologic examination of the excised tissue revealed a completely excised grade 1 or 2 lymph node hemangiosarcoma. All dogs received adjuvant chemotherapy; 2 dogs underwent curative intent chemotherapy, 1 dog underwent metronomic treatment with cyclophosphamide, and 1 dog underwent metronomic treatment with chlorambucil...
November 1, 2016: Journal of the American Veterinary Medical Association
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