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J V Moore

Publications and source records attributed to J V Moore.

At least 37 records · Page 2Linked to original sources
PubMed1999

An interstitial light assembly for photodynamic therapy in prostatic carcinoma.

OBJECTIVE: To develop an interstitial laser light delivery system using multiple optical fibres for photodynamic therapy (PDT) in the treatment of prostate cancer. PATIENTS AND METHODS: A laser beam was divided equally with a 1 x 4 fibre splitter to deliver PDT simultaneously through four 2-cm long, flexible cylindrical optical diffusers. Biplanar transrectal ultrasonography (TRUS) and a template were used to position the optical fibres percutaneously. In vivo measurements of light penetration depth (1/micro[eff] ) in prostate tissue were made in seven patients, using a sheathed isoprobe to measure light fluence rates at varying radial distances from the diffuser. The prostate was fixed with stabilization needles to minimize displacement during needle placement. RESULTS: The mean (sd, range) micro(eff) in the prostates of the seven patients was 0.35 (0.07, 0.22-0.44) mm-1, which produced closely parallel slopes of light attenuation. However, there was up to a 10-fold variation in absolute light levels at the same diffuser-detector separation distances amongst the seven patients, probably caused by blood pooling around the diffuser light source. A similar problem around the isoprobe detector was overcome by sheathing the probe in clear plastic tubing. By stabilizing the prostate, the optical fibre positioning was precise to within 2 mm. CONCLUSION: Although this light delivery and TRUS assembly were developed for clinical PDT in the prostate, the same instrumentation can be used reliably for in vivo light-penetration studies. Haemorrhage was unpredictable and highlighted one of the main problems which needs to be overcome.

Aged↗
PubMed1998

Insulin-like growth factor II and PAX3-FKHR cooperate in the oncogenesis of rhabdomyosarcoma.

The mouse myoblast C2C12 cell line transfected singly with cDNA for Pax-3, PAX3-FKHR, or insulin-like growth factor (IGF) II or cotransfected with IGF-II plus Pax-3 or with IGF-II plus PAX3-FKHR genes showed an altered morphology, a lack of differentiation, and higher proliferation rates in vitro. On s.c. injection into nude mice, tumors grew from transfected cell lines but not from cells transfected with the empty vector. Tumors derived from IGF-II/PAX3-FKHR- and IGF-II-transfected cells grew most rapidly. Cotransfection of IGF-II plus Pax-3 induced tumors comprised highly differentiated striated muscle cells; Pax-3, PAX3-FKHR, or IGF-II transfection produced tumors at varying stages of differentiation. Tumors derived from IGF-II plus PAX3-FKHR-cotransfected cells were composed of undifferentiated cells. This was the only tumor type to infiltrate the underlying muscle. The most angiogenesis and the least apoptosis were observed in the latter tumors. These results support the hypothesis that PAX3-FKHR interacts with IGF-II to play a critical role in the oncogenesis of rhabdomyosarcoma.

Animals↗
PubMed1998

Photodynamic therapy of ovarian tumours and normal cells using 5,10,15,20-tetra-(3-carboxymethoxyphenyl)-chlorin.

The photosensitizing ability of the second generation photosensitizer 5,10,15,20-tetra-(3-carboxymethoxyphenyl)-chlorin (m-TCMPC), a derivative of m-THPC, was tested on both three-dimensional multicellular spheroids of varying sizes and on monolayer cultures. These experiments were carried out on two spheroid-forming cell lines, A2780 (a human ovarian adenocarcinoma) and CHO (Chinese hamster ovarian cells). For both cell lines, photodynamic therapy (sensitizer plus visible light) treatments were carried out. The chlorin m-TCMPC was shown to have considerable promise as a photosensitizing agent. Cell kill was achieved for all situations tested, i.e. monolayer, 100, 500 and 750 microm spheroids. In addition no significant dark toxicity was observed.

Animals↗
PubMed1998

Feasibility of imaging photodynamic injury to tumours by high-resolution positron emission tomography.

One early effect of the treatment of tumours by the new modality photodynamic therapy (PDT) is a reduction in tumour glucose levels. We have employed the widely used positron-emitting glucose analogue flurorine-18 fluoro-2-deoxy-D-glucose ([18F]-FDG), to determine whether, in principle, PDT-induced injury might be delineated non-invasively and quantitatively by positron emission tomography (PET). The scanner was of the high-density avalanche-chamber (HIDAC) type with a resolution of 2.6 mm. Subcutaneous T50/80 mouse mammary tumours, sensitised by haematoporphyrin ester, were illuminated by graded doses of interstitial 630 nm light. Thirty hours later, any remaining viable tumour was detected (a) by region-of-interest analysis of the PET images and (b) by gamma counting the excised tumour. PET measurements of % uptake of [18F]-FDG into tumour correlated closely with ex vivo gamma counting (slope=0.976, r2=0. 995), validating the in situ method. Uptake into untreated, control tumours was 3.8%+/-1.1% of the injected activity. Uptake of [18F]-FDG into treated tumours decreased by 0.7% for every 100 mm3 reduction in remaining viable histological volume. Outcome was further compared with that measured by (a) T2-weighted proton imaging on a 4.7-T magnetic resonance imaging (MRI) system and (b) histological analysis of subsequently sectioned tumours. PET using [18F]-FDG described the absolute volume of surviving tumour histological mass to the same degree as high-resolution MRI. The conclusion of these initial studies is that PET with [18F]-FDG, although non-specific, quantitatively described at early times the extent of tumour destruction by PDT.

Animals↗
PubMed1997

Singlet oxygen and superoxide characteristics of a series of novel asymmetric photosensitizers.

The singlet oxygen quantum yields and superoxide quantum yields for a series of novel compounds based on an asymmetrical protoporphyrin molecule have been examined. Electron spin resonance was used to measure superoxide yield and time resolved luminescence for singlet oxygen. A comparison between these results and previously published cell survival data was carried out. A broad association was found between singlet oxygen quantum yield and clonogenic cell kill.

Cyclic N-Oxides↗
PubMed1997

A comet assay of DNA damage and repair in K562 cells after photodynamic therapy using haematoporphyrin derivative, methylene blue and meso-tetrahydroxyphenylchlorin.

Single-cell electrophoresis (comet assay) has been used to evaluate DNA damage and repair in the human myeloid leukaemia cell line K562 after low-dose (predominantly sub-lethal) treatments of hyperthermia and photodynamic therapy (PDT). Three different photosensitizers were examined: haematoporphyrin derivative (HpD), methylene blue (MB) and meso-tetrahydroxyphenylchlorin (mTHPC). None of the drugs in the absence of light, nor in light alone, resulted in detectable DNA damage. However, a significant amount of DNA damage was detected immediately after treatment with haematoporphyrin derivative or methylene blue PDT compared with drug-only or light-only treatments; no residual level of DNA damage was evident for either drug following a 4-h post-treatment incubation at 37 degrees C. No significant DNA damage was detected after meso-tetrahydroxyphenylchlorin PDT or hyperthermia either immediately or 4 h after treatment. We conclude that the alkaline comet assay can be applied as an effective screening assay for DNA damage induced by a range of laser therapies.

DNA Damage↗
PubMed1997

Expression of the collagen-related heat shock protein HSP47 in fibroblasts treated with hyperthermia or photodynamic therapy.

Heat shock protein (HSP) 47 is associated with collagen type I metabolism, both constitutively and after stress-inflicted injury. It has been claimed that, in contrast to hyperthermia (HT), photodynamic therapy (PDT) does not damage collagen, as measured at the level of tissue. We have studied HSP47 expression in normal murine skin fibroblasts (3T6) treated with hyperthermia or photodynamic therapy (PDT) mediated by three different photosensitizers: (1) haematoporphyrin ester (HpE), (2) meta tetra hydroxyphenyl chlorin (mTHPC) and (3) riboflavin (RB). Riboflavin is not an established photosensitizer for PDT and was chosen here because it is known to provoke collagen damage. The applied doses of the treatments were isoeffective in terms of 3T6 clonogenic cell survival. Analysis, at both transcriptional and translational levels, revealed HSP47 elevation after hyperthermia and after PDT with RB. PDT sensitized by HpE and mTHPC did not significantly alter HSP47 expression. These observations are consistent with our hypothesis that this collagen chaperone is up-regulated by laser-mediated modalities known to damage collagen (i.e. HT and RB PDT) but not by more conventional PDT treatments. Additionally, unexpected significant up-regulation of HSP47 was detected after illumination alone (no photosensitizer) of 3T6 cells at 653 nm laser light, but not at 630 nm.

Animals↗
PubMed1997

Interstitial photodynamic therapy in the canine prostate.

OBJECTIVE: To determine the depth of tissue destruction and the minimum light dose required for necrosis in interstitial photodynamic therapy (PDT), as a prerequisite for the investigational therapy of patients. MATERIALS AND METHODS: Seven adult beagle dogs were given 2 mg/kg of the photosensitizer Photofrin intravenously and two controls received none. After 24 h, 450 J/cm of 630 nm wavelength laser light was delivered interstitially to the prostate via a 2 cm long diffuser fibre. Seven single-fibre treatments were performed in five sensitized dogs and two single-fibre treatments in the controls. The two remaining sensitized dogs had two fibres placed 10 mm apart within the prostate to determine the coalescence of PDT lesions. The penetration depth of light was measured in all prostates, and after PDT the extent of necrosis was assessed histologically. RESULTS: The mean (standard deviation, SD) radius of PDT destruction around each diffuser was 5.3 (1.4) mm and PDT lesions overlapped in prostates treated with two fibres placed 10 mm apart. There was no observable tissue damage in the controls. The mean (SD) minimum light dose required for PDT necrosis was 84 (64) J/cm2. Differences among animals in the light penetration depth were small, with a mean of 2.14 (0.2) mm, and did not correlate with the depth of necrosis (P = 0.07). Bleeding around the optical diffuser fibre impeded light penetration. CONCLUSION: Interstitial PDT in the canine prostate using Photofrin produced modest volumes of tissue necrosis. The minimum light dose required to induce necrosis was variable because bleeding was unpredictable in relation to the optical fibre.

Animals↗
PubMed1997

The biology of photodynamic therapy.

The subcellular, cellular and tissue/tumour interactions with non-toxic photosensitizing chemicals plus non-thermal visible light (photodynamic therapy (PDT) are reviewed. The extent to which endothelium/vasculature is the primary target is discussed, and the biochemical opportunities for manipulating outcome highlighted. The nature of tumour destruction by PDT lends itself to imaging outcome by MRI and PET.

Animals↗
PubMed1996

Novel asymmetric photosensitizers: an in vitro study.

A series of compounds based on an asymmetrical protoporphyrin molecule have been examined. The paired groups of sensitizers differed in terms of the presence or absence of a permanent positive charge, in the alkyl side chain length and in having either a primary or secondary amine substituent. The effects of these variables on drug uptake, partition coefficient and photodynamic cell kill were tested. Drug uptake and partition coefficient were shown to be correlated. Differences in gross uptake were found within paired groups of sensitizers although cell-associated uptake alone did not correlate with clonogenic cell survival. Of the compounds tested it was the sensitizers with alkyl side chains, rather than the permanently positively charged compounds, which resulted in the greatest degree of clonogenic cell kill.

Cell Survival↗
PubMed1996

Comparison of photodynamic therapy with cryotherapy in the treatment of Bowen's disease.

The efficacy and suitability of photodynamic therapy (PDT) was compared with that of cryotherapy in the treatment of 40 lesions of Bowen's disease. Lesions were randomized to receive either cryotherapy with liquid nitrogen, or PDT using a portable desktop lamp incorporating a 300 W xenon short arc discharge source. A porphyrin precursor, 5-aminolaevulinic acid (5-ALA), was applied topically 4 h before irradiation in the PDT group. Each lesion received 125 J/cm2 at a fluence rate of 70 mW/cm2. All patients were reviewed at 2-monthly intervals and treatments repeated if required. Cryotherapy produced clearance in 10 of 20 lesions after one treatment, the remaining 10 lesions requiring two or three treatment applications. PDT resulted in clearance of 15 of 20 lesions after one treatment and of the remaining five lesions after a second treatment. The probability that a lesion cleared after one treatment was greater with PDT than cryotherapy (P < 0.01). Cryotherapy was associated with ulceration (five of 20), infection (two of 20) and recurrent disease (two of 20); no such complications occurred following PDT. PDT using a non-laser light source and topical 5-ALA appears to be at least as effective as cryotherapy in the treatment of Bowen's disease with fewer adverse effects.

Aged↗
PubMed1995

Pharmacokinetic and therapeutic outcome in melanoma cells, of the administration of symmetric and asymmetric cationic photosensitizers.

The response of melanoma cell lines to a range of novel cationic photosensitizers based on either a protoporphyrin or a mesotetra(4-carboxylphenyl)porphine molecule, has been examined. The drugs varied in terms of either their symmetry or their side chain configuration. The effect of these variables on drug uptake and photodynamic cell kill were tested. The absorption wavelengths for the drugs were measured and a shift to the red was seen in the presence of cells. Drug uptake was measured and the cationic sensitizers had a relatively high uptake when compared to anionic HpD. The efficiency of the drugs in causing cell kill was expressed in terms of clonogenic cell survival. The asymmetric photosensitizers were more efficient in destroying mouse and human melanoma cells than the clinically used anionic HpD, which was in turn more efficient than the symmetric sensitizers tested.

Animals↗
PubMed1995

Low-level direct electrical current therapy for hepatic metastases. I. Preclinical studies on normal liver.

Low-level direct electrical current has shown promise as a potential therapeutic modality (direct current therapy; DCT) in the treatment of malignant disease, including metastases, but to date much experimental work has been empirical and has added little to our knowledge of the mechanisms involved. As a prerequisite to a clinical trial for metastases in the liver, we have employed an in vivo liver model to examine the quantitative and qualitative relationships between electrode polarity, charge and tissue necrosis. Two distinct regions of necrosis were induced, distinguishable histologically and by magnetic resonance imaging: (i) a cylindrical region of primary necrosis centred on the electrode, its volume directly proportional to the charge passed, but greater at the anode than cathode; and (ii) a wedge-shaped infarct, apex at the electrode and base extending to the liver edge. The extent of this infarct was again greater at the anode than the cathode, but showed a sigmoidal relationship with charge. Results indicate pH changes at the electrodes as likely mediators of tissue injury, but show also that significant distant ischaemic injury can occur as a consequence of primary damage. These findings should be considered when selecting tumours for possible direct current therapy and when determining the sites of electrode placement.

Animals↗