Dataset Information

In Vivo Delivery and Therapeutic Effects of a MicroRNA on Colorectal Liver Metastases.

ABSTRACT: Multiple therapeutic agents are typically used in concert to effectively control metastatic tumors. Recently, we described microRNAs that are associated with the oligometastatic state, in which a limited number of metastatic tumors progress to more favorable outcomes. Here, we report the effective delivery of an oligometastatic microRNA (miR-655-3p) to colorectal liver metastases using nanoscale coordination polymers (NCPs). The NCPs demonstrated a targeted and prolonged distribution of microRNAs to metastatic liver tumors. Tumor-targeted microRNA miR-655-3p suppressed tumor growth when co-delivered with oxaliplatin, suggesting additive or synergistic interactions between microRNAs and platinum drugs. This is the first known example of systemically administered nanoparticles delivering an oligometastatic microRNA to advanced metastatic liver tumors and demonstrating tumor-suppressive effects. Our results suggest a potential therapeutic strategy for metastatic liver disease by the co-delivery of microRNAs and conventional cytotoxic agents using tumor-specific NCPs.

SUBMITTER: Oshima G

PROVIDER: S-EPMC5498809 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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In Vivo Delivery and Therapeutic Effects of a MicroRNA on Colorectal Liver Metastases.

Oshima Go G Guo Nining N He Chunbai C Stack Melinda E ME Poon Christopher C Uppal Abhineet A Wightman Sean C SC Parekh Akash A Skowron Kinga B KB Posner Mitchell C MC Lin Wenbin W Khodarev Nikolai N NN Weichselbaum Ralph R RR

Molecular therapy : the journal of the American Society of Gene Therapy 20170428 7

Multiple therapeutic agents are typically used in concert to effectively control metastatic tumors. Recently, we described microRNAs that are associated with the oligometastatic state, in which a limited number of metastatic tumors progress to more favorable outcomes. Here, we report the effective delivery of an oligometastatic microRNA (miR-655-3p) to colorectal liver metastases using nanoscale coordination polymers (NCPs). The NCPs demonstrated a targeted and prolonged distribution of microRNA ...[more]

PMID: 28457664

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Project description:Electrochemotherapy (ECT) is a combined treatment in which high voltage electroporation (EP) pulses are used to facilitate the uptake of a chemotherapeutic drug into tumor cells, thus increasing antitumor effectiveness of the drug. The effect of ECT of deep-seated tumors located close to the heart on functioning of the heart has not been previously investigated. In this study, we investigate the effects of intra-abdominal ECT of colorectal liver metastases on functioning of the heart during the early post-operative care period.For ECT high voltage EP pulses with amplitudes of up to 3000 V and 30 A were delivered in synchronization with electrical activity of the heart. Holter electrocardiographic (ECG) signals were obtained from 10 patients with colorectal liver metastases treated with ECT. ECG was recorded during the periods of 24 hours before and after the surgical procedure involving ECT. Four-hour long night-time ECG segments from both periods exhibiting the highest level of signal stationarity were analyzed and compared. Changes in several ECG and heart rate variability (HRV) parameters were evaluated.No major heart rhythm changes (i.e., induction of extrasystoles, ventricular tachycardia or fibrillation) or pathological morphological changes (i.e., ST segment changes) indicating myocardial ischemia were found. However, we found several minor statistically significant but clinically irrelevant changes in HRV parameters after ECT procedures: a decrease in median values of the mean NN interval, a decrease in the low-frequency and in the normalized low-frequency component, and an increase in the normalized high-frequency component.Only minor effects of intra-abdominal ECT treatment on functioning of the heart were found. They were expressed as statistically significant but clinically irrelevant changes in heart rate and long-term HRV parameters and were as such not life-threatening to the patients. The nature of these changes is such that they can be attributed to the known effects of the drugs given to the patients in the post-operative care. Further investigation is still warranted to unambiguously resolve whether ECT with high voltage EP pulses applied in immediate vicinity of the heart is responsible for the observed effects.

Project description:ImportanceSurgery represents the mainstay treatment of colorectal liver metastases. Indications for the laparoscopic approach in this setting have been widened and there is a need to confirm the benefits of minimally invasive liver surgery (MILS) in patients with complex disease states.ObjectiveTo compare outcomes of laparoscopic surgery with those of open surgery for liver metastases from colorectal cancer, focusing on the characteristics of modern MILS and therefore overcoming possible selection bias related to different policies for patients' eligibility for MILS over time.Design, setting, and participantsA cohort study of 885 resections performed for liver metastases from colorectal cancer between January 1, 2004, and June 30, 2017, at the Hepatobiliary Surgery Unit of San Raffaele Hospital, Milano, Italy, comprising 187 laparoscopic and 698 open resections. Procedures performed using the MILS approach with a ratio of MILS to total resections per year of more than 30% were considered and were matched by propensity scores (ratio of 1:4) to procedures performed using the open approach with a ratio of MILS to total resections per year of less than 30%.Main outcomes and measuresThe primary end point was short-term outcomes, including morbidity, mortality, functional recovery, and interval between surgery and adjuvant treatments; the secondary end point was long-term outcomes.ResultsAmong this cohort (104 patients in the MILS group; 46 women and 58 men; median age, 62 years [range, 35-81 years]; and 412 patients in the open group; 181 women and 231 men; median age, 60 years [range, 37-80 years]), primary end-point data showed a significantly higher incidence of postoperative morbidity in patients who underwent open resections compared with those who underwent MILS (94 [22.8%] vs 21 [20.2%]; P?=?.04). Patients in the MILS group had fewer major complications (Dindo-Clavien grades III-V) compared with patients in the open group (Dindo-Clavien grades III-V; 7 [6.7%] vs 35 [8.5%]; P?=?.03) as well as shorter lengths of stay (median [range] duration, 3 [2-35] vs 5 [4-37] days; P?=?.02). Oncologic results were not compromised by the laparoscopic approach.Conclusions and relevanceIn this study, the results of the propensity score matching analysis between modern laparoscopic surgery and previous open surgery appear to confer more comparable cohorts for complexity, further supporting the advantages of laparoscopy in the surgical treatment of liver metastases from colorectal cancer. The increase in use that laparoscopy has experienced appears to be based on increased feasibility, widening of eligibility criteria for patients, enhanced clinical effectiveness, and oncologic outcomes. All these elements together suggest that up to 70% of patients appear to be candidates for this minimally invasive surgical approach in high-volume centers.

Dataset Information

In Vivo Delivery and Therapeutic Effects of a MicroRNA on Colorectal Liver Metastases.

Publications

In Vivo Delivery and Therapeutic Effects of a MicroRNA on Colorectal Liver Metastases.

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