Search PubMed⌕ Search

Biomedical subjects

A T Porter

Publications and source records attributed to A T Porter.

At least 73 records · Page 4Linked to original sources
PubMed1994

12(S)-HETE enhancement of prostate tumor cell invasion: selective role of PKC alpha.

BACKGROUND: Prostate carcinoma has become the second most fatal cancer in American men. In Dunning R3327 rat prostate adenocarcinoma cells, elevated invasiveness positively correlates with metastatic potential. However, the mechanism(s) responsible for regulation of tumor cell motility and invasion is poorly understood. We have reported that a lipoxygenase metabolite of arachidonic acid, 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], augments tumor cell metastatic potential through activation of protein kinase C (PKC). PURPOSE: We proposed to determine the effect of 12(S)-HETE on the motility and invasion of low-metastatic rat prostate AT2.1 tumor cells and the effect of 12(S)-HETE activation of specific PKC isoform(s) in these processes. METHODS: The motility of AT2.1 cells was determined by the colloidal gold phagokinetic track assay and the invasiveness measured as their ability to invade through basement membrane Matrigel-coated filters. Expression of PKC isoforms was determined by Western blotting of the whole cell lysate with isoform-specific anti-PKC antibodies. Cytosol and membrane fractions were prepared and the subcellular distribution of PKC was analyzed by Western blotting and activity assay. The effect of 12(S)-HETE on cell proliferation was examined. Data were analyzed for significance of difference with the two-sampled, two-sided Student's t test. RESULTS: 12(S)-HETE increased the motility and invasion of AT2.1 cells, and this 12(S)-HETE-increased motility and invasion were inhibited by a selective PKC inhibitor, calphostin C, as well as a Ca2 chelator, bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/tetra(acetoxy-methyl)ester. AT2.1 cells expressed the PKC isoforms alpha and delta, and 12(S)-HETE increased the membrane association of PKC alpha but not delta. Further, the motility and invasion of AT2.1 cells were increased by thymelea toxin, a selective activator of PKC alpha over PKC delta. CONCLUSION: 12(S)-HETE augments the invasiveness of AT2.1 cells via selective activation of PKC alpha. IMPLICATIONS: 12(S)-HETE modulation of PKC alpha invasiveness may be an important mechanism of action for the regulation of the invasive potential of rat prostate carcinoma cells, and the 12-lipoxygenase enzyme and/or PKC alpha may serve as key targets for the development of anti-invasive agents useful for combating the spread of prostate cancer.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1994

Prostate inhibin peptide (PIP) in prostate cancer: a comparative immunohistochemical study with prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP).

Prostate inhibin peptide (PIP) is a polypeptide synthesized by the prostate gland that is involved in prostatic growth and differentiation. The objective of this study was to evaluate PIP as an immunocytochemical marker for prostatic adenocarcinoma (PCA) by comparing it with PSA and PAP. A total of 71 cases of primary PCA and 5 cases of metastatic PCA were studied. Primary tumors were specially selected to include a disproportionate number of high-grade tumors. The distribution of cases by Gleason score was 2-5, 14 cases; 6-7, 24 cases; and 8-10, 33 cases. Four metastases were to bone (decalcified tissue) and one to soft tissue. All 71 cases of primary PCA stained positively for the three antibodies tested, with none demonstrating obvious superiority, although individual case variability was seen. In one bone metastasis, staining for PSA was negative, with both PAP and PIP giving positive results. All non-prostatic carcinomas tested were negative. These results indicate that PIP is as sensitive and specific an immunohistochemical marker as PSA and PAP in untreated prostate adenocarcinomas. Further, the androgen-independent nature of PIP may give it an advantage over PSA/PAP in tumors exposed to androgen ablating agents.

Acid Phosphatase↗
PubMed1994

Systemic administration of new therapeutic radioisotopes, including phosphorus, strontium, samarium, and rhenium.

New advances in systemic radionuclide therapy have increased the number of treatment options available for patients with painful osseous metastases. This form of therapy has three major appeals: 1) it addresses all sites of involvement; 2) selective absorption into bone limits irradiation of normal tissues; and 3) as a result, toxicity may be reduced and the therapeutic ratio improved. The clinical experience with radioactive phosphorus, strontium, samarium, and rhenium are reviewed. To date, the best studied and the only Food and Drug Administration approved agent is strontium-89. About 60% to 90% of patients treated with strontium-89 respond with complete or partial relief of pain for a median duration of 6 months. Large, prospectively randomized clinical trials have established the efficacy of strontium-89 as a first-line therapy and as an adjuvant to external-beam radiotherapy. Particularly advantageous is its usefulness in situations in which external-beam radiotherapy options have been exhausted and normal tissue tolerance has been reached. Newer radiopharmaceuticals are still under investigation.

Bone Neoplasms↗
PubMed1994

A retrospective analysis of the cost effectiveness of treatment with Metastron (89Sr-chloride) in patients with prostate cancer metastatic to bone.

The objectives of the study were to estimate the cost of medical care for patients recruited into the Trans Canada trial of Metastron (89Sr-chloride) as adjunct therapy in patients with prostate cancer metastatic to bone and to compare the costs of those receiving Metastron with those receiving placebo. Data from case report forms, hospital records and, where necessary, telephone follow-up were used. Twenty-nine patients, recruited into the trial at the Cross Cancer Institute, were followed from time of entry into the trial over the balance of their lifetime. Data were costed by reference to fee schedule, pharmacy and government and hospital defined costs as indirect (investigations, outpatient visits and total and tertiary hospital inpatient days) and direct (analgesics, hormones, radiotherapy and transfusions). Meaningful differences in analgesic, hormone and radiotherapy costs were seen between the two groups, with the group receiving Metastron showing a lifetime reduction of Can $1720 per person when compared with placebo. A reduction of Can $5696 per patient in the Metastron group was shown based upon requirements for admission for tertiary care; however, if total hospital stay costs are calculated there is no difference between the two groups. This retrospective study suggests that treatment with Metastron can bring about meaningful reductions in lifetime management costs in patients with advanced prostate cancer. These findings should be correlated with the significant improvement in quality of life reported in the Trans Canada study and appear to offer financial support to the clinical rationale for the use of Metastron in the palliative treatment of these patients.

Aged↗
PubMed1994

Measurement of augmentation of 252Cf implant by 10B and 157Gd neutron capture.

252Cf has been used as a brachytherapy source since the early 1970s. The dominant mechanism of interactions of 252Cf neutrons with tissue is elastic scattering. The scattered neutrons lose part of their energy, which is released as kinetic energy of the recoiling nuclei. By multiple scattering, neutrons lose their energy and eventually become thermalized (in energetic equilibrium with tissue atoms with an average energy of 0.025 eV) and do not play any role in radiotherapy. These thermal neutrons may interact with hydrogen nuclei or with nitrogen, but the cell killing effects by these reaction products are negligibly small compared to the elastic scattering by fast neutrons or by photons emitted by californium. Nonetheless, these thermal neutrons are still potentially usable for neutron capture therapy and can be used to enhance californium brachytherapy effects. Neutron capture therapy is a two-part therapy relying on the selective loading of tumor cells with compounds containing 10B or 157Gd and subsequent irradiation with thermal neutrons. To calculate neutron capture doses one has to know thermal neutron flux. This paper presents results of an experimental study of thermal neutron flux and calculations of boron neutron capture and gadolinium neutron capture doses in the vicinity of 252Cf sources.

Boron Neutron Capture Therapy↗
PubMed1994

Strontium-89 (Metastron) in the treatment of prostate cancer metastatic to bone.

Bone metastases that develop in patients with advanced prostate cancer often cause deep, unremitting pain. Palliative options for the control of this pain include analgesic support, cytotoxic chemotherapy and external-beam radiotherapy. In addition to external irradiation, interest in intravenously injected radioisotopes that are preferentially localized to bone has been mounting. Metastron (an isotope of strontium) imitates the biodistribution of calcium in vivo and is avidly taken up into bony metastases where it has a biological half-life of just over 50 days. The biological half-life in undiseased bone is far shorter, approximately 14 days. Various studies have been conducted to evaluate the role of Metastron in metastatic prostate cancer. An optimum dose has yet to be finalized, but it is clear that the change of haematological toxicity becomes more significant at much larger doses. In the large, randomized Trans Canada study in which Metastron or placebo was given to patients as an adjunct to local field irradiation, those patients treated with Metastron had a significantly reduced intake of analgesics. Furthermore, progression of pain, as measured either by sites of new pain or by the requirement for further palliative radiotherapy, demonstrated statistically significant differences in favour of Metastron. There is thus increasing evidence of a useful role for Metastron in the treatment of prostate cancer metastatic to bone.

Antineoplastic Agents↗
PubMed1994

A retrospective analysis of the cost effectiveness of treatment with Metastron in patients with prostate cancer metastatic to bone.

A retrospective study was performed on the cost-effectiveness of treatment for advanced prostate cancer metastatic to bone. Patients (n = 29) recruited into the trans Canada trial at the Cross Cancer Institute, Edmonton and randomized to treatment with Metastron (strontium-89 chloride) (n = 14) or placebo (n = 15) after local field irradiation therapy for pain palliation were studied over their entire survival time. Estimates were made of the direct costs of treatment, i.e. drugs (analgesics and hormonal agents) and external radiotherapy, and the indirect costs (investigations, outpatient visits and inpatient days, either total or for tertiary care) based on records from the referring hospital, the cancer clinic and any hospitals to which the patients may subsequently have been referred. Meaningful differences were apparent between the two groups in direct costs with the group receiving Metastron showing a reduction over the entire survival time of Can$ 1,720/person compared with placebo; it should be noted that in this analysis neither the costs of the Metastron, nor of the initial radiotherapy, have been included. The Metastron group also showed a reduction in costs of hospitalization for tertiary care of Can$ 5,696/person, though the total cost of hospitalization was similar in the two groups. These results suggest that treatment with Metastron can bring about reductions in management costs for patients with advanced prostate cancer and, coupled with the findings of the Trans Canada trial on the improvement in quality of life for patients given Metastron, they add financial support to the clinical rationale for the use of Metastron for the palliative treatment of patients with bone metastases resulting from prostate cancer.

Aged↗
PubMed1994

Does hyperbaric oxygen have a cancer-causing or -promoting effect? A review of the pertinent literature.

We reviewed all known published reports or studies related to a possible cancer-causing or growth-enhancing effect by hyperbaric oxygen. Published articles were retrieved using Medline searches for the period 1960-1993. Additional references were obtained from bibliographies included in those articles discovered in the computer search. Also, hyperbaric medicine text books and the published proceedings of international hyperbaric conferences were visually searched. Studies and reports discovered in this fashion and related to the topic were included in the review. Twenty-four references were found: 12 were clinical reports, 11 were animal studies, and 1 reported both an animal study and a clinical report. Three clinical reports suggested a positive cancer growth enhancement, whereas 10 clinical reports showed no cancer growth enhancement. Two animal studies suggested a positive cancer-enhancing effect, and 10 animal studies showed no such effect. (The report that included both animals and humans is counted in both groups). The vast majority of published reports show no cancer growth enhancement by HBO exposure. Those studies that do show growth enhancement are refuted by larger subsequent studies, are mixed studies, or are highly anecdotal. A review of published information fails to support a cancer-causing or growth-enhancing effect by HBO.

Animals↗
PubMed1994

High frequency of mutator phenotype in human prostatic adenocarcinoma.

Mutator phenotype of nucleotide repeats has been implicated to be involved in human cancer and other diseases. This type of instability may be the direct result of DNA replication and/or repair errors. To examine mutator phenotype during the development of human prostate cancer, we undertook this study to screen 57 patients with prostatic adenocarcinoma for possible mutator phenotype at 18 microsatellite marker loci on 12 chromosomes (3p, 5q, 6p, 7p, 8p, 10q, 11p, 13q, 16q, 17p, 18q and Xq). Overall, in 37 of 57 patients, we have found positive mutator phenotype in at least one of the loci analysed. A significantly greater number of cases were found to be positive for this phenotype among the poorly differentiated than the moderately- and well-differentiated prostatic adenocarcinomas. Our data suggest that mutator phenotype may play an important role in the development and progression of human prostate cancer.

Adenocarcinoma↗
PubMed1994

Systemic radionuclide therapy of bone metastases with strontium-89.

Bone metastases can have a devastating effect on a patient's quality of life due to pain and pathologic fractures. Local external beam radiotherapy is very effective for patients with only a few involved areas. Systemic therapy consisting of chemotherapy and hormonal therapy is extremely useful until the patient becomes refractory to treatment. Systemic radionuclide therapy using Strontium-89 has been shown to be very valuable, specifically in patients with bone metastases from hormonally-resistant prostate cancer. Studies have shown a significant improvement in analgesic requirement, time to further radiotherapy, and a reduction in tumor markers with this treatment. The use of Strontium-89 in the treatment of other bone neoplasms and the use of other radionuclides, such as Rhenium-186 HEDP and Samarium-153 EDT-MP, are still investigational.

Bone Neoplasms↗
PubMed1994

New understanding from Cf brachytherapy trials and considerations for neutron therapy of bulky gyn carcinoma for future.

PURPOSE: This study reviews the radiobiology of neutrons and the results and methods that have evolved in the Cf-252 neutron brachytherapy trials to postulate methods to explore for their potential applicability to fast neutron beam therapy. METHODS AND MATERIALS: The results of radiobiological experimental studies are reviewed for RBE for different fraction number and dose per fraction. RBE was always higher for fractionated neutrons based on comparison with isoeffective doses of photons. This is inherent in the basic radiobiological properties of photons. RBE was highest for low dose rate (LDR) Cf brachytherapy. RESULTS: Brachytherapy methods deliver radiation dose which is localized and conformal to the tumor. These methods have been used for Cf therapy and led to good tissue tolerance and local tumor control. The use of large dose/session (or fraction), small fraction number, short treatment times, followed by photon beam therapy has been the practice in Cf brachytherapy. It has been found that bulky or localized advanced tumors responded better if neutron treatment preceded the photon beam therapy. Therapeutic efficacy is dependent on the fraction size of neutrons and not the time duration of application. CONCLUSIONS: Available radiobiological data on neutron RBE with fraction number and size of dose and the favorable experience from Cf brachytherapy with up-front neutron applications suggest new avenues to explore for the neutron beam trials. The high efficacy noted for small volume dose, 10 to 20 Gy-eqs of dose per session, localized dose, conformal methods, small number of sessions, short treatment times and an up-front or early schedule in combining neutron and photon therapy suggests that similar schedules and methodology may also be effective for neutron beam therapy. Further clinical trials are indicated and bulky GYN tumors represents suitable tumors for study.

Animals↗
PubMed1993

A comparative study on expression of prostatic inhibin peptide, prostate acid phosphatase and prostate specific antigen in androgen independent human and rat prostate carcinoma cell lines.

Prostatic inhibin peptide (PIP), consisting of 94 amino-acid residues is synthesized and secreted by the prostate gland. Previous studies on immunohistochemical localization of PIP in primary prostatic tumor and their metastasis, have documented the value of this peptide as a tumor marker for diagnosis of prostate cancer (PCa). The present study was undertaken to compare the expression of PIP with that of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in androgen independent human PCa cell lines (PC-3, DU-145 and TSU-Prl) by immunoperoxidase technique. The results of the study indicated that the staining for PIP was more intense than that of PSA and PAP. The PSA staining was either weakly positive (PC-3) or totally absent (TSU-Prl and DU-145) while PAP staining was intense in PC-3 and moderate in the other two human cell lines. The intense staining observed for PIP in all of the androgen independent cell lines suggests that the synthesis and secretion of PIP is not primarily dependent on androgens. Furthermore, expression of these markers in Dunning rat cultured adenocarcinoma cell lines and tumors were studied. Positive staining for all three human tumor associated antigens (PIP, PSA and PAP) cross-reacting with the Dunning rat PCa cell lines and the tumors, suggest the suitability of this model for preclinical screening of various therapeutic agents.

Acid Phosphatase↗
PubMed1993

Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer.

PURPOSE: A large proportion of the practice of radiotherapy in the management of metastatic adenocarcinoma of the prostate is associated with palliation of pain from osseous metastases and improving quality of life. Radiation therapy is well known to be effective in treating painful sites and may also be effective in reducing the propensity for adjuvantly treated disease to become symptomatic. Strontium-89 is a systemic radionuclide that has clinical efficacy in the palliation of pain from bony metastases. METHODS AND MATERIALS: The study was a Phase-III randomized placebo control trial performed in eight Canadian Cancer Centers to evaluate the effectiveness of strontium-89 as an adjunct to local field radiotherapy. Patients with endocrine refractory metastatic prostate cancer received local field radiotherapy and either strontium-89 as a single injection of 10.8 mCi or placebo. RESULTS: One hundred twenty-six patients were recruited. No significant differences in survival or in relief of pain at the index site where noted. Intake of analgesics over time demonstrated a significant reduction in the arm treated with strontium-89. Progression of pain as measured by sites of new pain or the requirement for radiotherapy showed statistically significant differences between the arms in favor of strontium-89. Tumor makers including prostate specific antigen, acid phosphatase, and alkaline phosphatase were also reduced in patients receiving strontium-89. A Quality-of-Life analysis was performed as a multivariate data set and demonstrated an overall superiority of strontium-89 with alleviation of pain and improvement in physical activity being statistically significant. Toxicity was evaluated and demonstrated increased hematological toxicity in the group receiving strontium-89. CONCLUSIONS: It is concluded that the addition of strontium-89 is an effective adjuvant therapy to local field radiotherapy reducing progression of disease as evidenced by new sites of pain and the requirement of further radiotherapy and improving quality-of-life and need for analgesic support in this group of patients.

Aged↗
PubMed1993

The relative biological effectiveness of ytterbium-169 for low dose rate irradiation of cultured mammalian cells.

PURPOSE: An important step in the development of 169Yb as a new brachytherapy source is to determine its biological effectiveness relative to other commonly used radioisotopes. The purpose of this paper is to determine the relative biological effectiveness of 169Yb, with respect to 60Co, for a range of low dose rates. METHOD AND MATERIALS: The relative biological effectiveness of photon radiation from encapsulated 169Yb was determined by exposing Chinese hamster ovary cells, in exponential growth, to graded doses of radiation from either 169Yb or 60Co. Clonogenic cell survival was determined for continuous low dose rates ranging from 6.5 cGy/hr to 52 cGy/hr. RESULTS: The relative biological effectiveness of 169Yb, with respect to 60Co, was determined to be 1.2 +/- 0.3 and did not vary significantly over the dose-rate range from 13 cGy/hr to 50 cGy/hr. An inverse dose-rate effect was observed, but only for 60Co irradiation at 8.9 cGy/hr. Therefore, relative biological effectiveness values could not be determined reliably for dose rates less than 13 cGy/hr. CONCLUSIONS: We have established that 169Yb is approximately 20% more effective than 60Co in vitro. It is hoped that this study will guide the introduction of 169Yb into clinical brachytherapy practice.

Animals↗
PubMed1993

Prostate brachytherapy. An overview.

BACKGROUND: Prostate brachytherapy represents one of the oldest techniques of using radiation therapy to treat prostate cancer. Over the past 10 years, there have been major changes in the types of prostate brachytherapy that can be performed with the introduction of new radioactive isotopes, new afterloading techniques, and an improved understanding of the radiobiology associated with differing dose rates. METHODS: Prostate brachytherapy can be divided into temporary implantation using high activity sources such as iridium-192, or permanent brachytherapy using the interstitial implantation of iodine-125 or palladium-103 sources. There are various techniques that can be used to actually insert the radioactive material into the prostate. This can be done as an open or closed procedure and can be performed via a suprapubic or a perineal retropubic approach. The use of remote afterloading has substantially reduced the radiation protection problems associated with manually loaded radioactive sources. RESULTS: Results using brachytherapeutic isotopes in the treatment of prostate cancer have been variable, but it appears that using the higher dose rate sources and delivering a high relative integral dose to the prostate can result in improved histologic control of prostate cancer. In patients with aggressive prostate cancer, the use of iodine-125 permanent implantation has not been successful. CONCLUSIONS: The role of brachytherapy in the treatment of prostate cancer remains an exciting alternative in the management of prostate cancer. Its role is becoming more defined in the treatment of large, bulky prostatic neoplasms as a way of improving the dose distribution achieved between normal and tumor tissue.

Brachytherapy↗
PubMed1993

Effect of prostatic inhibin peptide (PIP) on prostate cancer cell growth in vitro and in vivo.

Prostatic inhibin peptide (PIP), is a 94 amino acid protein which is secreted by the prostate gland in an androgen-independent manner. Previously, it has been demonstrated that PIP appears to inhibit follicle-stimulating-hormone (FSH) secretion by the pituitary and prostate glands. In vitro, the Dunning R3327 rat prostate cancer cell line MAT-LyLu (MLL) cells and the human prostate cancer cell line PC-3, are stimulated to grow in response to exogenous FSH and these effects are blocked by PIP. In vivo, PIP inhibits the growth of the highly metastatic MLL prostate cancer cell line. A comparison of hormone levels in control and PIP-treated rats demonstrates a significant inhibition of FSH in treated animals. It appears that, in vivo, PIP may inhibit prostate cancer growth by inhibiting FSH. PIP may represent a novel hormonal treatment for prostate cancer.

Adenocarcinoma↗