Comparative effectiveness of two metronomic chemotherapy schedules-our experience in the preclinical field.

Metronomic chemotherapy refers to the chronic, equally spaced, delivery of low doses of chemotherapeutic drugs, without extended interruptions. Previously, we developed two combined metronomic schemes for the treatment of murine mammary tumors. The aim of this study was to compare their effects on tumor and metastasis growth, survival, and toxicity. Metronomic chemotherapy with Cyclophosphamide + Celecoxib (Cy + Cel) showed higher antimetastatic power than Cyclophosphamide + Doxorubicin (Cy + Dox), while being similar in other aspects. That difference, plus the advantage that represents its oral administration, suggests that the Cy + Cel combination is more suitable than Cy + Dox for metronomic chemotherapy of mammary tumors and could be proposed to the translation to the clinic.

Therapeutic efficacy of metronomic chemotherapy with cyclophosphamide and doxorubicin on murine mammary adenocarcinomas.

BACKGROUND: Metronomic chemotherapy (MCT) refers to the chronic and equally spaced administration of low doses of different chemotherapy drugs, without extended rest periods. Herein, we investigated the therapeutic efficacy of metronomic cyclophosphamide (Cy) combined with doxorubicin (Dox) in two mouse mammary adenocarcinoma models. MATERIALS AND METHODS: Mice were s.c. challenged with M-234p or M-406 mammary tumors, and when the tumors reached ∼150 mm(3), they were treated with: (I) no treatment (controls); (II) Cy in the drinking water (30 mg/kg body weight/day); (III) Dox (0.5 mg/kg body weight i.p. three times/week); (IV) treated as (II) + (III). Mice challenged i.v. with M-234p or M-406 tumor cells received, on day 3, the same treatments. RESULTS: We found that MCT with Cy plus Dox inhibited tumor growth, decreased lung metastases, and increased the median survival time, while having low toxic effect. Combined MCT was more effective than each monotherapy causing decrease in VEGF serum concentration and tumor proliferation rate plus increase in tumor apoptosis. CONCLUSION(S): The therapeutic benefits of combined MCT with Cy and Dox on mammary adenocarcinomas together with its low toxic effect profile suggest the possibility of future translation into the clinic.

Metronomic chemotherapy: changing the paradigm that more is better.

The introduction of the "maximum tolerated dose" in usual treatment protocols (and its concomitant overt toxicity) made necessary the imposition of rest periods between cycles of therapy-a practice that not only involves re-growth of tumour cells, but also growth of selected clones resistant to the therapy. To avoid the problems caused by traditional chemotherapeutic regimens, a new modality of drug administration called "metronomic chemotherapy" has been proposed. This name makes reference to the chronic, equally spaced administration of (generally) low doses of various chemotherapeutic drugs without extended rest periods. The novelty of this treatment modality lies not only in its antitumour efficacy with very low toxicity, but also in a cell target switch, now aiming at tumour endothelial cells. The knowledge acquired in the experimental field of metronomic chemotherapy, plus the increasing experience that is being obtained in the clinical setting, will help to lead a change in the design of therapeutic protocols against cancer.

[Strategic plan for reduction of hospital stay in renal transplantation]. / Plan estratégico para la reducción de la estancia hospitalaria en trasplante renal.

Since January 2015 we have carried out a multiple-intervention strategic plan to reduce hospital stay in renal transplant recipients. The main objective of this study is to compare results of renal transplantation before and after putting into effect this plan in terms of graft and patient survival, readmissions and incidence of acute rejection during the first year post transplantation. In this retrospective analysis we included all patients 18 years of age or older who were transplanted at our institution. The strategic plan resulted in a significant reduction of hospital stay of renal recipients from 13.5 days in the pre-plan group (n=97) to 4.6 days in the post-plan group (n=62; p≤0.0001). The incidence of acute rejection during the first year was similar (pre-plan group=14.4% vs. post-plan group=16% [p=0.77]) as it was graft survival (88% vs. 90% [p=0.71]) and patient survival (95% vs. 98% [p=0.37]), respectively. The multiple-intervention strategic plan has significantly reduced the hospital stay of patients after renal transplantation without affecting graft or patient survival, which are comparable to those internationally published, and without jeopardizing patient's safety.

A tracking system for laboratory mice to support medical researchers in behavioral analysis.

The behavioral analysis of laboratory mice plays a key role in several medical and scientific research areas, such as biology, toxicology, pharmacology, and so on. Important information on mice behavior and their reaction to a particular stimulus is deduced from a careful analysis of their movements. Moreover, behavioral analysis of genetically modified mice allows obtaining important information about particular genes, phenotypes or drug effects. The techniques commonly adopted to support such analysis have many limitations, which make the related systems particularly ineffective. Currently, the engineering community is working to explore innovative identification and sensing technologies to develop new tracking systems able to guarantee benefits to animals' behavior analysis. This work presents a tracking solution based on passive Radio Frequency Identification Technology (RFID) in Ultra High Frequency (UHF) band. Much emphasis is given to the software component of the system, based on a Web-oriented solution, able to process the raw tracking data coming from a hardware system, and offer 2D and 3D tracking information as well as reports and dashboards about mice behavior. The system has been widely tested using laboratory mice and compared with an automated video-tracking software (i.e., EthoVision). The obtained results have demonstrated the effectiveness and reliability of the proposed solution, which is able to correctly detect the events occurring in the animals' cage, and to offer a complete and user-friendly tool to support researchers in behavioral analysis of laboratory mice.

Regulatory T cells but not NKT I cells are modulated by a single low-dose cyclophosphamide in a B cell lymphoma tumor-model.

AIM: Experimental and clinical studies showed that the administration of cyclophosphamide (Cy) in low doses leads to an enhancement of the antitumor immune response. Our objective was to study the modulation, if any, by low dose Cy, of T regulatory (Treg) and natural killer T (NKT) I cells, two cell populations of the innate immune response with opposing effects on the tumors, in a rat B cell lymphoma model. METHODS: Inbred e rats were challenged s.c. with L-TACB lymphoma and on day 14 animals were distributed in two groups. Treated: injected i.p. with cyclophosphamide (10mg/kg of body weight) and CONTROL: injected i.p. with saline. Blood samples were taken from days 0 to 21 and the percentage of T regulatory and natural killer T I cells were determined by flow cytometry. RESULTS: We found that the increase of natural and inducible T regulatory cells of peripheral blood achieved during tumor growth was significantly downregulated by cyclophosphamide. On the contrary, natural killer T I cells were not modulated by the treatment. CONCLUSION: The antimetastatic effect of a single low dose of Cy would be due, at least in part, to downregulation of natural and inducible T regulatory cells.