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D J Castro

Publications and source records attributed to D J Castro.

69 records · Page 4Linked to original sources

Rhodamine 123 as a chemosensitizing agent for argon laser therapy. A new technique for treatment of superficial malignancies.

Rhodamine 123 (Rh 123), a mitochondrial-specific dye with an absorption maxima at 511 nm, was tested as a new chemosensitizing agent for argon laser treatment of P3 human squamous carcinoma cells. After exposure of P3 cells in vitro to Rh 123 at doses of 1, 3, 6, and 10 micrograms/mL for one hour, we observed significant inhibition of DNA synthesis, except at the lowest dose. Rhodamine 123 at 1 microgram/mL was selected to sensitize P3 tumor cells for treatment with the monochromatic argon laser at 514.5 nm. Exposure of P3 cells to laser energy levels of 700 to 950 J/cm2 (36 degrees C to 40 degrees C) after sensitization with Rh 123 completely inhibited tumor development of the P3 cells transplanted subcutaneously into nude mice. Control P3 cells treated with the laser alone at 36 degrees C to 40 degrees C or only with Rh 123 formed visible tumors by one week and continued to grow for the entire-week observation period. These results show that Rh 123 is a highly sensitive new fluorochrome for argon laser phototherapy of human squamous carcinoma cells.

Animals↗

Rhodamine-123 as a new photochemosensitizing agent with the argon laser: "nonthermal" and thermal effects on human squamous carcinoma cells in vitro.

A human squamous carcinoma cell line (P3) was first exposed to a nontoxic dose of Rhodamine-123 (1 microgram/ml for 1 hour), then subjected to treatment with a single mode argon laser at 514.5 nm. The temperature and energy levels delivered to the target cells were determined by a reproducible method of dosimetry. Cell viability was assessed by the trypan blue exclusion test. Cell duplication and DNA synthesis were measured by the incorporation of 3H-thymidine at 6 and 24 hours post-treatment. The results indicate that Rhodamine-123 at nontoxic doses of 1 microgram/ml enhanced the tumoricidal effects of the argon laser at reduced temperatures as low as 40 degrees C. Furthermore, at physiological temperature ranges as low as 28 to 39 degrees C, an immediate and/or delayed inhibition of cell duplication was demonstrated, while cell viability was not affected. These observations, suggest that Rhodamine-123 can be used effectively as a chemosensitizing agent in the treatment of human tumor cells with the argon laser at 514.5 nm. This new technique of tumor cell targeting by Rhodamine sensitization and specific laser treatment may offer real advantages without the extreme photosensitivity associated with hematoporphyrin derivatives.

Antineoplastic Agents↗

Biostimulative effects of Nd:YAG Q-switch dye on normal human fibroblast cultures: study of a new chemosensitizing agent for the Nd:YAG laser.

Kodak Q-switch II is a new chemical with an absorption maxima at 1,051 nm, designed to be used as an Nd:YAG dye laser. The potential for this dye as a new chemosensitizing agent in the treatment of connective tissue diseases and wound healing with low energy Nd:YAG laser was examined. Two normal fibroblast cell lines were tested for sensitivity to various levels of this dye in vitro. These cells were exposed to Q-switch II dye at concentrations of 0.01, 0.1, 1, 10, 50, and 100 micrograms/ml for 1 and 24 hours. Cell viability was assessed by the trypan blue exclusion test. Cell duplication and DNA synthesis were measured by the incorporation of [3H]-thymidine at 6 and 24 hours postexposure to Q-switch II dye. At concentrations up to 10 micrograms/ml, both cell lines tested showed no changes in cell viability. However, at concentrations equal or higher than 50 micrograms/ml, more than 40% of the fibroblasts incorporated trypan blue after 24 hours of exposure to this dye, indicating significant cell destruction. The results indicate that Q-switch II dye is nontoxic to normal human fibroblast cultures and showed significant biostimulative effects on cell duplication at concentrations equal to or lower than 10 micrograms/ml. Further studies will be required to determine the usefulness of Q-switch II dye as a new photochemosensitizing agent for potential biostimulation of wound healing and/or treatment of connective tissue diseases with the Nd:YAG laser (near infrared, 1,060 nm) at "nonthermal" levels of energies.

Benzopyrans↗

Multicentric fibromatosis of familial inheritance.

This is an unusual case presentation of a young woman with a clinical history and course simulating juvenile hyaline fibromatosis, but without hyalinization in the stroma. Because of the age of onset, the apparent familial inheritance, the nonaggressive and nonregressive tumor traits, the disease cannot be classified as multicentric fibromatosis. Therefore, we are referring to this case as multicentric fibromatosis with familial inheritance, a previously unreported entity to our knowledge.

Adult↗

Cervical mycobacterial lymphadenitis. Medical vs surgical management.

After years in its decrease, cervical mycobacterial adenitis is once again an increasing problem in Los Angeles County. We reviewed 54 cases of cervical lymphadenopathies treated over ten years. Twenty-five (46%) of these patients were found to have mycobacterial cervical lymphadenitis. Medical approaches often failed to conclusively diagnose this disease. In our series, none of the patients with cervical adenopathies (36%) treated only medically regressed, even after an average time of 18 months of antituberculosis drug treatment. The treatment of choice seems to be surgical excision and long-term antituberculosis drugs. Surgery provides a rapid tissue diagnosis and confirms the bacterial type, including atypical mycobacterium. This approach is simple, shortens hospitalization, is cost-effective, and carries a low morbidity.

Adolescent↗

Treatment of condyloma acuminata with carbon dioxide laser: a prospective study.

The common wart has been a ubiquitous problem throughout recorded history. In recent times, the genital wart has assumed more and more importance. These viral growths cause itching and burning as well as more severe problems. Treatment traditionally has included a large variety of preparations from nature. Subsequently, man-made chemicals were used along with freezing, burning, and surgical excision. Because of the pain, bleeding, scarring, and high recurrence rate with these treatments, a study was instituted in 1978 to evaluate the advantages of the CO2 laser for treatment of this condition. Results have been excellent, far exceeding what we expected. Recurrence rate has been under 2%. The control group had the usual high rate of persistence and recurrence. Recent work pointing to a strong association between human papilloma virus (HPV) and cancer of the female genitals suggests an increasing need for early, vigorous, and more effective treatment of these lesions.

Adult↗

Wound healing: biological effects of Nd:YAG laser on collagen metabolism in pig skin in comparison to thermal burn.

Pig skin was treated with the Nd:YAG laser at 1,060 nm or electrocautery, at energy densities of 649 +/- 20 J/cm2 and 612 J/cm2, respectively. Biopsies of treated areas and of normal skin were performed at 7, 14, and 60 days after treatment and processed for histology, electron microscopy and biochemical assays. Wound healing, as shown histologically, was similar in both treated groups. Depth of injury appeared to reach reticular dermis at day 7 in each treated group. However, thermal burn was more destructive of regular collagen, whereas the laser appeared to damage deep dermal blood vessels without destroying surrounding connective tissue. Biochemical assays revealed increased collagen production and increased collagenolytic activity 7 days after laser injury. However, by day 60, there was a reduction in total collagen content in laser treated skin below that of normal skin, which correlated with decreased collagen synthesis and unchanged collagenolytic activity. In burn specimens there was an initial decrease in total collagen content which reverted to normal by day 60. Active collagen degradation occurred at all 3 time points, but a marked increase in synthetic activity occurred as the burn scar was laid down. Laser treatment resulted in reduction of the amount of collagen below that in burn scarred or normal skin, suggesting that classical scar formation may be inhibited. These results indicate that the Nd:YAG laser may be useful for the treatment of keloids and hypertrophic scars.

Animals↗

Effects of the Nd:YAG laser on DNA synthesis and collagen production in human skin fibroblast cultures.

Human skin fibroblasts were subjected to treatment with a Neodymium:YAG laser at 1060 nm with varying levels of energy determined by a reproducible method of dosimetry. DNA synthesis in the cells was measured by the incorporation of [3H]thymidine, and collagen production was monitored by the synthesis of nondialyzable [3H]hydroxyproline after incubation of cells with [3H]proline. Using energy levels equal to 1.7 X 10(3) J/cm2, a significant reduction in DNA synthesis was noted, while the cells remained viable as tested by the trypan blue exclusion test. With energy levels higher or equal to 2.3 X 10(3) J/cm2, the suppression of DNA synthesis was accompanied by cell nonviability. The collagen production, when measured immediately following the treatment with 1.7 X 10(3) J/cm2, was markedly reduced, and similar effects were observed with higher energy levels. However, when the cells were tested for collagen production at 20 hours following laser treatment, there was a significant decrease in collagen production at energy levels as low as 1.1 X 10(3) J/cm2, a dose that did not affect DNA synthesis or cell viability. Thus, the results indicate that the Nd:YAG laser can selectively suppress collagen production without affecting cell proliferation. These observations suggest that laser treatment could potentially be used to reduce collagen deposition in conditions such as keloids and hypertrophic scars.

Cells, Cultured↗

MR imaging-guided interstitial Nd:YAG laser phototherapy: dosimetry study of acute tissue damage in an in vivo model.

A dosimetry study of acute tissue damage induced by interstitial application of the neodymium-yttrium-aluminum-garnet (Nd:YAG) laser was performed with magnetic resonance (MR) imaging. The MR appearance of the lesion was correlated with gross and histopathologic findings. Seventy-six lesions were induced in rabbit muscle with laser power outputs of 5-20 W and exposure times of 20-600 seconds. MR imaging was performed immediately after laser exposure. T2-weighted spin-echo images clearly showed the acute thermal injuries caused by laser energy deposition and correlated best with histopathologic findings. These images showed three distinct layers, corresponding to central ablation, coagulative necrosis, and interstitial edema, respectively, in the pathologic findings. Lesion diameters measured on MR images showed a linear correlation with those in gross sections. Lesion volume increased not only with increasing total energy delivered but with increasing power output for a fixed total energy delivered. MR imaging is an accurate modality for dosimetry studies of laser-induced acute lesions.

Animals↗

MR imaging-histopathologic correlation of thermal injuries induced with interstitial Nd:YAG laser irradiation in the chronic model.

Magnetic resonance (MR) imaging-histopathologic correlation of thermal injuries induced with interstitial laser irradiation was performed in a chronic model up to 12 weeks after laser exposure. T2-weighted MR images showed irreversible coagulative necrosis as a low-signal-intensity area. A higher-intensity surrounding area, corresponding to edema, was also present in acute lesions on T2-weighted images. Serial studies of the chronic model showed that a substantial portion of the interstitial edema zone progressed to coagulative necrosis up to 7 days after laser irradiation. This necrotic zone decreased in size beyond 2 weeks, presumably through biologic healing. MR imaging and pathologic findings correlated well in the chronic model. MR imaging has the potential to depict acute, irreversible thermal damage even before morphologic change is seen at the standard pathologic examination. Recognizing the dynamics of tissue response to interstitial laser irradiation on MR images is valuable for estimation of true lesion volume.

Animals↗

Interstitial photoablative laser therapy guided by magnetic resonance imaging for the treatment of deep tumors.

The failure rate of cancer treatment remains unacceptably high, still being a leading cause of mortality in adults and children despite major advances over the past 50 years in the fields of surgery, radiation therapy, and, more recently, chemo and immunotherapy. In the United States, the 5-year survival rate for all cancers in the population has increased by only approximately 10% since 1960. Surgical access to some deep tumors of the head and neck and other areas often require extensive dissections with residual functional and cosmetic deformities. Repeated treatment is not possible after maximum dose radiotherapy and chemotherapy is still limited by its systemic toxicity. An attractive solution to these problems would be the development of a new adjunctive method combining the best features of interstitial laser phototherapy for selective tumor destruction via minimally invasive techniques for access and 3D-magnetic resonance imaging (MRI) as a monitoring system for laser-tissue interactions. Our experience with this new technique is reviewed.

Animals↗

Laser photochemotherapy: a less invasive approach for treatment of cancer.

The effectiveness of combining surgery with chemo- and radiation therapy in treatment of human cancer provides a useful model for further development of new multimodality approaches including laser photochemotherapy. Laser endoscopy often is a useful treatment for obstructive tumors in airways, but interstitial laser fiberoptics is becoming a more precise, minimally invasive alternative for ablation of unresectable or recurrent neoplasms. Combining intratumor chemotherapy with laser energy delivery via interstitial fiberoptics should be most effective using drugs activated by photothermal energy. A number of investigators have shown that anthracyclines and cis-platinum are likely candidates for light or heat activation in cancer cells. An advantage of anthracyclines is their dual role as antitumor drugs and as photosensitizers. Because they are effective chemotherapy agents without photoactivation, two approaches are possible to increase tumor responses. Maximum tolerated dose followed by photoillumination via laser fiberoptics can be used to obtain better tumor palliation. Improved treatment response to lower intratumor drug levels after laser activation also should reduce systemic toxicity. Preclinical studies and recent case reports from several groups suggest photochemotherapy with currently approved drugs and lasers may soon become an attractive alternative for treatment of recurrent tumors in cancer patients.

Anthracyclines↗

Tumors of diverse histology are sensitive to rhodamine 123 laser phototherapy in vitro.

Rhodamine 123 has been shown to be an efficient photosensitizer for the argon laser treatment of a human squamous carcinoma and a melanoma cell line in vitro. Rhodamine 123 laser phototherapy also eradicates these human squamous cell carcinomas when grown as subcutaneous tumor transplants in athymic mice. This study extends these observations by testing a panel of 19 human tumor cell lines of various histologic origins for in vitro sensitivity to rhodamine 123 and the argon laser. Rhodamine 123 with an absorption maxima of 502 nm in water was found to undergo a redshift to 516 nm after uptake by the mitochondria of human tumor cells. Rhodamine 123-sensitized brain tumor cells were inhibited by over 80% after 15 seconds and by 98% after 60 seconds of laser exposure (514.5 nm, 4 W, Tmax = 39 degrees C), as measured by reduced [3H]thymidine incorporation into cellular DNA. Laser or rhodamine 123 alone did not significantly inhibit (greater than 20%) tumor cell [3H]thymidine uptake. Sensitization with 20 micrograms rhodamine 123 for 1 hour before 45 seconds of laser illumination decreased cell [3H]thymidine uptake by 40% to 99% in four melanoma lines, five carcinomas, five leukemias, and four of five other human tumor lines. Two melanomas, two leukemias, and a lymphoma cell line also exhibited a 70% to 80% reduction in [3H]thymidine uptake after sensitization in vitro with 1 microgram/mL rhodamine 123 and laser illumination. Rhodamine 123-sensitized tumor cells were inhibited even more strongly by fractional dose laser irradiation at nonthermal temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Line↗

The effects of argon lasers on human melanoma cells sensitized with rhodamine-123 in vitro.

A human melanoma cell line, M14, was first exposed to a nontoxic dose of Rhodamine-123 (1 microgram/ml) for one hour, then subjected to a treatment with a single mode argon laser at 514.5 nm. The temperature and energy levels delivered to the target cells were determined by a reproducible method of dosimetry. Cell viability was assessed by the Trypan Blue exclusion test. Cell duplication and DNA synthesis were measured by the incorporation of 3H-thymidine at 6 and 24 hours post-treatment. At energy levels and temperatures higher or equal to 950 J/cm2 (40 degrees C), an immediate suppression of DNA synthesis was accompanied by nonviability of the M14 carcinoma cells. At energy levels between 130-900J/cm2 corresponding to temperatures between 28 to 39 degrees C, both an immediate and delayed inhibition of DNA synthesis was noted but the cells remained viable. The results indicate that Rhodamine-123 at nontoxic doses of 1 microgram/ml enhances the tumoricidal effects of the argon laser at reduced temperatures as low as 40 degrees C. Furthermore, at physiological temperature ranges as low as 28 to 30 degrees C, an immediate inhibition of cell duplication was demonstrated while cell viability was not affected. These observations suggest that Rhodamine-123 can be used effectively as a chemosensitizing agent in the treatment of human tumor cells with the argon laser at 514.5 nm.

Animals↗