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Biomedical subjects

T Patrice

Publications and source records attributed to T Patrice.

At least 55 records · Page 3Linked to original sources

Endothelial cell growth regulation by PGE1 analog misoprostol and indomethacin.

The role of prostaglandins on growth regulation of different cell types was investigated. We studied the effect of exogenous misoprostol in the presence or absence of indomethacin on the cell growth kinetics. Our results clearly show that misoprostol strongly inhibited the growth of several cancer cells but only slightly affected that of endothelial cells. Moreover, indomethacin alone (which decreases PG synthesis) had little effect on DNA synthesis in endothelial cells or C6 cells but inhibited colonic cancer cells. Conversely, misoprostol stimulated DNA synthesis in endothelial or C6 cells preincubated with indomethacin. This phenomenon was not observed with colonic cancer cells. The role of NSAIDs in the field of cytoprotection is discussed.

Alprostadil↗

Influence of hematoporphyrin derivative concentration, incubation time, temperature during incubation and laser dose fractionation on photosensitivity of normal hemopoietic progenitors or leukemic cells.

Photodynamic therapy represents a new approach for the local control of cancers. It has recently been claimed that photodynamic therapy mediated by hematoporphyrin derivative (HPD) is selectively more efficient for killing leukemic cells than normal progenitors. To improve this effect, we studied the influence of hematoporphyrin dose, temperature during incubation and/or treatment, hematoporphyrin derivative incubation time, and fractionation of the argon laser light (488-514 nm) used for hematoporphyrin stimulation. Plating efficiency calculated after a 7-day period of growth on collagen gel medium showed a dose-dependent phototoxicity of HPD reaching 0.01% for normal hemopoietic progenitors and 0.001% for leukemic cells (dose = 12.5 micrograms/ml). The 10:1 ratio of normal hemopoietic progenitors to leukemic cells was also found to be the same or increased when temperature was 37 degrees C during incubation and 4 degrees C during laser irradiation. Similar results were also found when incubation time was varied from 75-120 min, or when laser irradiation dose was fractionated into 2 or 3 periods. The ratio of normal progenitors to leukemic cells reached 100:1 when 75 J/cm2 were fractionated into 3 periods after an incubation time of 120 min with 10 micrograms/ml HPD. Selectivity in photodynamic treatment seems to occur between normal hemopoietic progenitors and leukemic cells. The mechanism of this selectivity remains unclear, but experiments with the fractionated irradiation dose suggest that as in radiotherapy, better potentially lethal damage repair in normal cells could be a factor for selectivity in photodynamic therapy. Our results obtained with leukemic cells are fully in agreement with data in the literature concerning similar experimental models.

Animals↗

[Palliative treatment by photochemotherapy of 54 digestive cancers: phase I clinical trial].

Photochemotherapy (PDT) is based on the interaction of a phototoxic drug (HPD) retained by cancer tissues and excited with a specific laser light. We present here a phase I clinical trial including 54 patients selected on the grounds of non-operability and T1 NO MO staging (UICC) and divided into 3 groups: I) 24 squamous cell carcinoma (SCC), II) 14 adenocarcinomas (ADN) of the upper GI tract, III) 16 ADN of the rectosigmoid colon. All received an HPD infusion of 2.5 to 5 mg/kg I.V. 72 hours before being laser irradiated endoscopically (632 nm, 150 to 220 j/cm2). Results documented on histology obtained after grip biopsies and on resected specimens (6 cases), were classified as complete response (ST), partial response (PR) or no change (NC). Eleven patients of group I, 5 of group II, and 8 of group III (24/54 patients) were classified ST with a mean follow-up of 15.2 months. Analysis of resected specimens showed a complete disappearance of tumor tissue and prominent fibrosis all around the treated area. Adverse effects were noted in 22% of patients, PDT of rectosigmoid ADN gave a survival (life table analysis) at least equal to SCC. These results should allow clinical indications for PDT to be broadened in combined protocols.

Adenocarcinoma↗

Photochemotherapy mediated by hematoporphyrin derivative in gastroenterology.

While results concerning photodynamic treatments of cancers in pneumology or dermatology have been published regularly, few works have been devoted to gastroenterology. Twenty-seven non-operable patients bearing various G.I. tumors of less than 40 mm dia. have been treated by PDT for palliative purpose to appreciate the local efficacy of a single treatment. Before July, 1985, the parameters of treatment were 2.5 mg/kg of HPD injected intravenously for theoretical power of delivered laser light (630 mm) 300 mW. After July, 1985, HPD was injected at the dose of 5 mg/kg and the laser dose was 400 mW. A normalization of grip biopsies was observed on 12 patients (6 squamous cell carcinomas, 6 adenocarcinomas), transient in 3 cases. Our main finding is that PDT seems able to destroy significant volumes of tumor by itself although subsequent biopsies proved negative in very few cases. This method remains to be compared to others less sophisticated than the YAG laser.

Aged↗

Experimental aspects of in vitro and in vivo photochemotherapy.

The selectivity of in vitro photodynamic reactions and the in vivo effects induced by PRT, whether the irradiation is applied interstitially or externally, still remains unclear. In vitro studies were performed using leukemic cell lines and syngeneic normal hemopoietic progenitors. For these, cells incubated with hematoporphyrin derivative (HPD) and non-incubated cells were irradiated with an argon laser. Data were obtained as the count of cell colonies found after a 7-day incubation period on semi-solid collagen gel medium. In vivo studies employed the HT 29 tumor model grafted into nude mice. Both animals injected with HPD and non-infected controls were irradiated with a dye laser pumped by an argon laser (Coherent) using a 400 micron optic fiber located either at a distance of 65 mm from the skin or inserted into the tumor. The temperature increase occurring during PRT was measured using non-absorbing thermocouples. In vitro, after HPD treatment and argon irradiation leukemic cells showed a greater phototoxicity (greater than 2 log10) than did the normal cells (0.25 log10). In vivo, when the heat rise is very similar (less than 4 degrees C) in both the tissues irradiated externally and those irradiated interstitially after HPD injection, histological examination of these did not reveal any quantitative differences (90% of tumor mass). These results are discussed.

Animals↗

The benefit of chilling in argon-laser treatment of port-wine stains.

The authors compare results obtained in argon laser treatment of port-wine stains with and without preliminary chilling, noting that the success rate is considerably greater with the former procedure (68.6 percent) than with the latter (37.5 percent) (X2 = 4.37 p less than 0.05). The effect of chilling has been studied with special reference to the vitropressure test. Different hypotheses are presented to account for the difference and possible complications of the treatment are considered.

Adolescent↗

Thermography as a predictive tool for laser treatment of port-wine stains.

The argon laser, which has been proven both useful and safe for port-wine stain therapy, interacts with the hemoglobin of the vessels. In a percentage of cases, this treatment is still inefficient, and there is a lack of correlation between these bad results and clinical or histologic criteria. Thermography, which explores the vascularization of the port-wine stain, leads us to consider port-wine stains from a physical point of view. This very simple test shows no correlation with the clinical parameters of port-wine stain but is closely related to the results obtained with laser therapy. It seems to be a good criterion to estimate the argon laser treatment prognosis.

Adolescent↗

[The laser in dermatology. Critical study of 63 cases].

With reference to their personal experience in sixty-three patients, the authors try to specify the indications of laser treatment in dermatology: evenly-colored flat angiomas, especially those of the face, which should not be treated before the age of fourteen. Vasoconstriction induced by the application of ice prior to treatment seems helpful. Widespread anal or vaginal venereal warts are another good indication. In common warts laser treatment is indicated only in some specific cases. The authors do not advocate laser treatment in malignant tumors. Results in tattoos are often unsatisfactory.

Hemangioma↗

Neodymium-yttrium aluminium garnet laser destruction of nonsensitized and hematoporphyrin derivative-sensitized tumors.

The injection of hematoporphyrin derivative (5 mg/kg i.v.) followed 24 hr later by a neodymium-yttrium aluminium garnet laser irradiation shows the destruction of CX1 tumors grafted on nude mice. This acidophilic necrosis occurred with a significantly increased frequency in tumors treated by hematoporphyrin derivative injection and irradiated with the neodymium-yttrium aluminium garnet laser as compared with noninjected but irradiated tumors or with injected tumors irradiated with sunlight. On the basis of our data, it seems difficult to maintain the hypothesis of singlet oxygen production as the only mechanism of the phenomenon. Further studies will be necessary to explain the necrosis that we observed.

Adenocarcinoma↗

Tetra-p-aminophenylporphyrin conjugated with Gd-DTPA: tumor-specific contrast agent for MR imaging.

Tetra-p-aminophenylporphyrin (TPP) was conjugated with gadolinium diethylenetriaminepentaacetic acid (DTPA) and used as a contrast agent in magnetic resonance (MR) imaging to achieve tumor selectivity in nude mice. A substantial decrease in T1 was measured in excised tissues (kidneys, tumor, and liver) from mice that received the porphyrin derivative Gd2(DTPA)4 TPP. Toxicity and phototoxicity were less than those obtained with hematoporphyrin derivative in both L1210 lymphoblastic leukemia cells and HT 29 human colonic cancer cells, as determined with in vitro assays. MR images showed an enhancement of contrast between the tumor and adjacent tissue after injection of this agent. The results indicate that Gd2(DTPA)4TPP could be a useful prototype paramagnetic porphyrin MR imaging contrast agent with an affinity for tumors.

Adenocarcinoma↗

Effects of photodynamic therapy on adhesion molecules and metastasis.

Photodynamic therapy (PDT) induces among numerous cell targets membrane damage and alteration in cancer cell adhesiveness, an important parameter in cancer metastasis. We have previously shown that hematoporphyrin derivative (HPD)-PDT decreases cancer cell adhesiveness to endothelial cells in vitro and that it reduces the metastatic potential of cells injected into rats. The present study analyzes the influence of PDT in vivo on the metastatic potential of cancers cells and in vitro on the expression of molecules involved in adhesion and in the metastatic process. Photofrin and benzoporphyrin derivative monoacid ring A (BPD) have been evaluated on two colon cancer cell lines obtained from the same cancer [progressive (PROb) and regressive (REGb)] with different metastatic properties. Studies of BPD and Photofrin toxicity and phototoxicity are performed by colorimetric MTT assay on PROb and REGb cells to determine the PDT doses inducing around 25% cell death. Flow cytometry is then used to determine adhesion-molecule expression at the cell surface. ICAM-I, MHC-I, CD44V6 and its lectins (àHt1.3, PNA, SNA and UEA) are studied using cells treated either with BPD (50 ng/ml, 457 nm light, 10 J/cm2) or Photofrin (0.5 microgram/ml, 514 nm light, 25 J/cm2). Changes of metastatic patterns of PROb cells have been assessed by the subcutaneous injection of non-lethally treated BPD or Photofrin cells and counting lung metastases. First, we confirm the metastatic potential reduction induced by PDT with respectively a 71 or 96% decrease of the mean number of metastases (as compared with controls) for PROb cells treated with 50 ng/ml BPD and 10 or 20 J/cm2 irradiation. Concerning Photofrin-PDT-treated cells, we find respectively a 90 or 97% decrease (as compared with controls) of the mean number of metastases for PROb cells treated with 0.5 microgram/ml Photofrin and 25 or 50 J/cm2 irradiation. Then, we observe that CD44V6, its lectins (àHt1.3, PNA, SNA) and MHC-I are significantly decreased (compared with the other molecules tested) in PROb and REGb cells after both BPD and Photofrin PDT treatment. These modifications in adhesion-molecule expression, particularly of CD44V6, can thus account only for part of the decrease in the metastatic potential of PDT-treated cancer cells. Changes in adhesion-molecule expression induced by PDT are only transient, implying that the rate of metastatic reduction is probably not linked simply to these changes.

Animals↗

[The role of the argon laser in the treatment of condylomata acuminata of the anal margin and canal].

Condyloma acuminata of the anal margin or anal canal raise therapeutic problems as soon as they become important. In this study, we report the results obtained by 24 patients after Argon-ion laser therapy. This laser, the beam of which is mainly absorbed by haemoglobin allowed us to cure 91,7 percent of our patients. This results was obtained in one (14 patients) or two sessions (10 patients) with at least 3 months as follow-up. Furthermore we can notice the excellent quality of cicatrization and the complete lack of incidents during or after the treatment. So argon laser could be a new kind of treatment used preferentially in extensive genital warts.

Adolescent↗