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Chris Christophi

Publications and source records attributed to Chris Christophi.

7 recordsLinked to original sources
PubMed2006

The effect of hyperbaric oxygen therapy on tumour growth in a mouse model of colorectal cancer liver metastases.

BACKGROUND AND AIMS: Hyperbaric oxygen (HBO) therapy involves the administration of 100% oxygen at high pressure. It has been used to treat a variety of conditions including non-healing wounds, carbon monoxide poisoning, and as an adjuvant to radiotherapy or chemotherapy. The effect of HBO alone on the growth of malignancy remains controversial. This study investigates the impact of HBO on tumour growth, kinetics and microcirculation of colorectal cancer liver metastases in an experimental model. METHODS: Male CBA mice were induced with colorectal liver metastases via an intrasplenic injection of a murine derived colorectal cell line. Tumours were examined using quantitative stereological analysis, histology and scanning electron microscopy of microvascular resin casts. The effect of HBO on tumour proliferation and apoptosis was quantified using immunohistochemistry. RESULTS: Daily exposure to HBO at 2.4 atm for 90 min had no effect on the volume of liver metastases. At day 13, HBO caused a significant reduction in tumour necrosis and proliferation compared to the non-HBO group (p=0.002 and p=0.008, respectively). By day 25 however, no differences were observed (p>0.05). No differences in apoptosis or microvascular architecture were observed. CONCLUSION: HBO did not have a tumour stimulatory effect on colorectal liver metastases and may potentially be used safely in conjunction with other therapeutic treatment modalities.

Animals↗
PubMed2006

Hyperbaric oxygen therapy for malignancy: a review.

One unique feature of tumors is the presence of hypoxic regions, which occur predominantly at the tumor center. Hypoxia has a major impact on various aspects of tumor cell function and proliferation. Hypoxic tumor cells are relatively insensitive to conventional therapy owing to cellular adaptations effected by the hypoxic microenvironment. Recent efforts have aimed to alter the hypoxic state and to reverse these adaptations to improve treatment outcome. One way to increase tumor oxygen tensions is by hyperbaric oxygen (HBO) therapy. HBO therapy can influence the tumor microenvironment at several levels. It can alter tumor hypoxia, a potent stimulus that drives angiogenesis. Hyperoxia as a result of HBO also produces reactive oxygen species, which can damage tumors by inducing excessive oxidative stress. This review outlines the importance of oxygen to tumors and the mechanisms by which tumors survive under hypoxic conditions. It also presents data from both experimental and clinical studies for the effect of HBO on malignancy.

Apoptosis↗
PubMed2005

Effect of thalidomide on colorectal cancer liver metastases in CBA mice.

BACKGROUND AND AIMS: Thalidomide has undergone resurgence in the treatment of specific malignancies. One of the possible actions of thalidomide may be an antiangiogenic effect. This study investigates the effects of thalidomide on tumor growth and long-term survival in a murine model of colorectal liver metastases. METHODS: Liver metastases were produced in male CBA mice by intrasplenic injection of a dimethyl hydrazine induced MoCR colon cancer murine cell line. Thalidomide was administered daily at doses ranging from 50 to 300 mg/kg by intraperitoneal injection. Tumor growth was assessed using quantitative stereological analysis. The effect on long-term survival was determined at the maximum tolerated dose using Kaplan-Meier analysis. The microvascular effects of thalidomide were assessed by laser Doppler flowmetry (LDF) and microvascular resin casting. Immunohistochemistry was used to determine vascular endothelial growth factor (VGEF) and basic fibroblast growth factor (bFGF) expression. RESULTS: Thalidomide, (50-300 mg/kg) caused no significant reduction in tumor growth by day 21 following induction of liver metastases and caused systemic toxicity at a dose of 300 mg/kg. At a dose of 200 mg/kg given beyond 35 days, thalidomide significantly reduced tumor growth compared to control, (P = 0.029). No significant impact on survival was however observed (P = 0.93). LDF and microvascular resin casting showed no differences in blood flow or tumor microvascular architecture. VGEF and FGF were expressed in tumors, but remained unaltered by thalidomide administration compared to matched controls. CONCLUSIONS: Thalidomide caused a significant reduction in the volume of colorectal liver metastases during the late phase of tumor growth. There was however no improvement in survival. Tumor growth reduction in this model did not appear to be due to microvascular changes or altered expression of VGEF or basic FGF. Further investigation into potential mechanisms of action of thalidomide and its synergistic use with other therapies is required.

Analysis of Variance↗
PubMed2002

Effect of blood flow occlusion on laser hyperthermia for liver metastases.

BACKGROUND: Interstitial laser hyperthermia (ILH) is an in situ ablative technique for the treatment of colorectal liver metastases. A significant factor limiting tumor destruction is hepatic blood flow. Modulation of hepatic blood flow may increase the size of tumor necrosis achieved. Our aim was to investigate the effect of blood flow occlusion on ILH-induced necrosis in both tumor and normal liver tissue. MATERIALS AND METHODS: A model of colorectal liver metastases in male inbred CBA mice was used. ILH was applied to normal liver and tumor tissue using a bare optical quartz fiber from an SYL500 Nd:YAG surgical laser generator, with and without hepatic blood flow occlusion, and the extent of necrosis was studied. Tumor blood flow was assessed by laser Doppler flowmetry and scanning electron microscopy. RESULTS: Hepatic blood flow occlusion resulted in a significant reduction in blood flow in normal liver tissue (37.9% +/- 5.8, P < 0.001) and in the periphery of the tumor (17.5% +/- 7.8, P < 0.001). It did not affect the blood flow in the center of the tumor (13.4% +/- 4.3, P = 0.07). ILH of normal liver tissue, at low power (2 W), with hepatic blood flow occlusion, resulted in a significant increase in the diameter of necrosis. This effect was not seen when higher power (5 W) was used in normal liver. No significant effect was noted within tumor tissue at either power setting. CONCLUSION: The overall effect of hepatic blood flow occlusion in ILH-induced tissue necrosis appears to be negligible in tumor tissue. Its main applicability appears to be at the tumor-host interface, where a decrease in blood flow may lead to higher temperatures and therefore to a greater degree of tumor cell destruction.

Animals↗
PubMed2002

Autoimmune pancreatitis.

The recommended treatment for a focal mass in the head of the pancreas is pancreaticoduodenectomy. Preoperative biopsy is not advised in patients who are candidates for resection because of the documented risk of tumour dissemination along the needle tract and significant false negative results.1 Autoimmune pancreatitis is a relatively uncommon condition that can present as a pancreatic mass and mimic malignancy. It may respond to glucocorticoid therapy, and further assessment of such treatment is indicated.2 Such experience will only accumulate if wider knowledge of this condition leads to clinical suspicion.

Adult↗
PubMed2002

Interstitial laser hyperthermia for colorectal liver metastases: the effect of thermal sensitization and the use of a cylindrical diffuser tip on tumor necrosis.

OBJECTIVE: Our aim in this study was to investigate the characteristics of a diffuser-tipped optical fiber in producing tumor necrosis, compared to a standard bare-tipped fiber. The potential synergistic effect between thermal sensitization by metronidazole and interstitial laser hyperthermia (ILH)-induced tumor necrosis is also evaluated. BACKGROUND DATA: ILH is a minimally invasive technique for the treatment of colorectal liver metastases. One of the major limitations is the size of tissue necrosis achieved by a single optical fiber. Use of cylindrical diffuser-tipped fibers and thermal sensitization of tumor cells by metronidazole may increase the size of tumor necrosis achieved by a single optical fiber. MATERIALS AND METHODS: A model of colorectal cancer liver metastases in male inbred CBA mice was used. Laser hyperthermia was applied to tumor tissue using either a bare optical quartz fiber or a cylindrical diffuser-tipped fiber from a Medilas fibertom 4100 Nd:YAG surgical laser generator. Six hundred joules of energy was applied at two power settings, 5 and 10 watts, using bare- and diffuser-tipped fibers, respectively. The extent of necrosis was assessed by histological techniques. A similar study with three experimental groups was treated with 300 J of applied energy. Extent of immediate tumor necrosis was compared to that seen 24 h after ILH treatment. The third group, which had been treated with intraperitoneal metronidazole prior to ILH, was also assessed for tumor necrosis after 24 h and results compared with both the previous groups. RESULTS: ILH delivered using a cylindrical diffuser-tipped fiber resulted in a significantly larger diameter of tumor necrosis when compared to a bare-tipped fiber, for a given amount of applied energy. The differences were more significant at higher power settings. Six hundred joules of energy applied by ILH using a bare-tipped fiber at 5 and 10 watts produced 6.7 +/- 1.1 mm and 5.9 +/- 0.6 mm diameter of tumor necrosis, respectively. At equivalent settings, the diffuser-tipped fiber produced 7.7 +/- 1.0 mm and 8.1 +/- 0.6 mm diameter of tumor necrosis (p = 0.02 and p < 0.001). Using a diffuser-tipped fiber and an applied energy of 300 J delivered at 5 watts power, mean diameter of tumor necrosis immediately after treatment was 6.7 +/- 1.1 mm and after 24 h 7.9 +/- 1.3 mm (p = 0.006). Mean diameter of tumor necrosis 24 h after ILH in animals treated with metronidazole was 8.3 +/- 1.9 mm (p = 0.11). CONCLUSION: Diffuser-tipped optical fiber appears to significantly increase the diameter of ILH-induced tumor necrosis compared to the bare fiber. In contrast to the bare fiber, it enables the application of laser energy using higher power settings without compromising the diameter of tumor necrosis achieved. In animals treated with metronidazole, a trend towards increased tumor destruction at the tumor-host interface was seen on histolopathology. In addition, a trend towards increased diameter of tumor necrosis was also seen; however, statistical significance was not achieved.

Animals↗