In vivo Recombinant Adenovirus-mediated p53 Gene Therapy in a Syngeneic Rat Model for Colorectal Cancer

The p53 gene has a significant role in controlling genomic stability of cancer. The purpose of this study was to evaluate the tumor response of allograft colorectal tumor treated with Ad5CMV-p53 in a syngeneic rat model. Two weeks after the inoculation of WB-2054-M5 tumor cells in the flank of rats, rats were randomly assigned by tumor size to one of three groups (n=18 in each): phosphate buffered saline (PBS), Ad5CMV, and Ad5CMV-p53. Recombinant adenovirus or PBS was administered through intratumoral injection at three divided doses every other day for 4 weeks. Apoptosis of the tumors was evaluated using TUNEL assay. After 2 and 4 weeks of treatment, the volume (cm3) of tumors in PBS, Ad5CMV, and Ad5CMV-p53 was as follows: 2 week: 1.66±0.43, 1.40±0.47, 0.75±0.26 (p<0.001), 4 week: 4.41±0.88, 3.93±1.86, 2.33±0.51 (p<0.001). Tumor growth showed no statistically significant difference between the PBS and Ad5CMV groups (6-week vol. p=0.32). The TUNEL assay results revealed more apparent apoptotic cells in Ad5CMV-p53-treated tumors than in other groups. Growth of allograft colorectal cancer in the syngeneic rat model was significantly suppressed by intratumoral Ad5CMV-p53 gene therapy. These results demonstrate that gene replacement therapy with p53 may provide a novel modality of treatment in conjunction with other present treatments for metastatic colorectal cancer

Expert Opinion on Laparoscopic Surgery for Colorectal Cancer Parallels Evidence from a Cumulative Meta-Analysis of Randomized Controlled Trials

PMID: 22532846 [PubMed - indexed for MEDLINE] PMCID: PMC3332109 Free PMC ArticlePeer reviewedPublisher PD

Single-Incision Laparoscopic Surgeries for Colorectal Diseases: Early Experiences of a Novel Surgical Method

Objectives. This paper aims to analyze the feasibility and safety of single-incision laparoscopic colectomy (SILC) and its potential benefits. Methods. Systematic review was performed for the years 1983–August 2011 to retrieve all relevant literature. A total of 21 studies with 477 patients undergoing SILC were selected. Results. Range of operative times and estimated blood losses were 75–229 min and 0–100 mL, respectively. Overall conversion rate was 5.9% (28/477) and an additional laparoscopic port was used in 4.9% (16/329) cases. Range of lymph node number for malignant cases was 12–24.6 and surgical margins were all negative. Overall mortality and morbidity rate was 0.4% (2/477) and 11.7% (43/368), respectively. The length of hospital stay (LOS) varied across reports (2.7–9.2 days). Among 6 case-matched studies, one showed less blood loss in SILC as compared to LAC and 2 showed shorter LOS after SILC versus HALC or LAC/HALC groups. In addition, one study reported maximum pain score on postoperative days 1 and 2 was lower in SILS compared to LAC and HALC. Conclusions. SILC procedure is feasible and safe when performed by surgeons highly skilled in laparoscopy. In spite of technical difficulties, there may be potential benefits associated with SILC over LAC/HALC

Evolution of muscle phenotype for extreme high altitude flight in the bar-headed goose

Bar-headed geese migrate over the Himalayas at up to 9000 m elevation, but it is unclear how they sustain the high metabolic rates needed for flight in the severe hypoxia at these altitudes. To better understand the basis for this physiological feat, we compared the flight muscle phenotype of bar-headed geese with that of low altitude birds (barnacle geese, pink-footed geese, greylag geese and mallard ducks). Bar-headed goose muscle had a higher proportion of oxidative fibres. This increased muscle aerobic capacity, because the mitochondrial volume densities of each fibre type were similar between species. However, bar-headed geese had more capillaries per muscle fibre than expected from this increase in aerobic capacity, as well as higher capillary densities and more homogeneous capillary spacing. Their mitochondria were also redistributed towards the subsarcolemma (cell membrane) and adjacent to capillaries. These alterations should improve O2 diffusion capacity from the blood and reduce intracellular O2 diffusion distances, respectively. The unique differences in bar-headed geese were much greater than the minor variation between low altitude species and existed without prior exercise or hypoxia exposure, and the correlation of these traits to flight altitude was independent of phylogeny. In contrast, isolated mitochondria had similar respiratory capacities, O2 kinetics and phosphorylation efficiencies across species. Bar-headed geese have therefore evolved for exercise in hypoxia by enhancing the O2 supply to flight muscle