ABSTRACT
The purpose of the present work is to establish an ultra-minimal invasive percutaneous puncture inoculation method for a VX2 orthotopic lung cancer rabbit model with fewer technical difficulties, lower mortality of rabbits, a higher success rate and a shorter operation time, to evaluate the growth, metastasis and apoptosis of tumor by CT scans, necropsy, histological examination, flow cytometry and immunohistochemistry. The average inoculation time was 10–15 min per rabbit. The tumor-bearing rate was 100%. More than 90% of the tumor-bearing rabbits showed local solitary tumor with 2–10 mm diameters after two weeks post-inoculation, and the rate of chest seeding was only 8.3% (2/24). The tumors diameters increased to 4–16 mm, and irregularly short thorns were observed 3 weeks after inoculation. Five weeks post-inoculation, the liquefaction necrosis and a cavity developed, and the size of tumor grew further. Before natural death, the CT images showed that the tumors spread to the chest. The flow cytometry and immunohistochemistry indicated that there was less apoptosis in VX2 orthotopic lung cancer rabbit model compared to chemotherapy drug treatment group. Minimal invasive percutaneous puncture inoculation is an easy, fast and accurate method to establish the VX2 orthotopic lung cancer rabbit model, an ideal in situ tumor model similar to human malignant tumor growth.
Subject(s)
Humans , Rabbits , Apoptosis , Drug Therapy , Flow Cytometry , Immunohistochemistry , Lung Neoplasms , Lung , Methods , Mortality , Necrosis , Neoplasm Metastasis , Punctures , Thorax , Tomography, X-Ray ComputedABSTRACT
Our study aims to determine the metabolism and excretion of novel pulmonary-targeting docetaxel liposome (DTX-LP) using the in vitro and in vivo animal experimental models. The metabolism and excretion of DTX-LP and intravenous DTX (DTX-IN) in New Zealand rabbits were determined with ultraperformance liquid chromatography tandem mass spectrometry. We found DTX-LP and DTX-IN were similarly degraded in vitro by liver homogenates and microsomes, but not metabolized by lung homogenates. Ultra-performance liquid chromatography tandem mass spectrometry identified two shared DTX metabolites. The unconfirmed metabolite M(un) differed structurally from all DTX metabolites identified to date. DTX-LP likewise had a similar in vivo metabolism to DTX-IN. Conversely, DTX-LP showed significantly diminished excretion in rabbit feces or urine, approximately halving the cumulative excretion rates compared to DTX-IN. Liposomal delivery of DTX did not alter the in vitro or in vivo drug metabolism. Delayed excretion of pulmonary-targeting DTX-LP may greatly enhance the therapeutic efficacy and reduce the systemic toxicity in the chemotherapy of non-small cell lung cancer. The identification of M(un) may further suggest an alternative species-specific metabolic pathway.
Subject(s)
Rabbits , Animal Experimentation , Carcinoma, Non-Small-Cell Lung , Chromatography, Liquid , Drug Therapy , Feces , In Vitro Techniques , Liposomes , Liver , Lung , Lung Neoplasms , Mass Spectrometry , Metabolic Networks and Pathways , Metabolism , Microsomes , Models, Animal , Tandem Mass SpectrometryABSTRACT
Objective To compare the difference between modified peroral endoscopic myotomy (Liu?POEM) and conventional POEM for achalasia. Methods Thirty achalasia patients treated with Liu?POEM and 30 with conventional POEM were enrolled. A retrospective study was performed to compare the conventional POEM and Liu?POEM procedures by evaluating total operation time, postoperative complications and symptoms( Eckardt score) . Results The average total operation time of Liu?POEM was 27?13 ±11?42 min and the average myotomy time was 13?20±5?09 min. There was no pneumomediastinum, subcutaneous emphysema or fever. The average total operation time of conventional POEM was 51?22 ± 25?63 min. The average myotomy time was 11?18±7?61 min. There were three cases(10%) of subcutaneous emphysema but recovered after two days without any special treatment. One patient who underwent conventional POEM had fever( the highest temperature was 37?6℃) and his temperature subsided to normal after physical cooling in one day. Postoperative Eckardt scores of patients were all less than 3. After postoperative follow?up of 3 to 12 months, no complications occurred in any patient. Conclusion Liu?POEM is a modified approach to treat achalasia, advantageous over conventional POEM in more simplified operation procedure, shorter operation time and less invasiveness.