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Biomedical subjects

D J Castro

Publications and source records attributed to D J Castro.

At least 37 records · Page 2Linked to original sources
PubMed1995

Interstitial laser photochemotherapy with new anthrapyrazole drugs for the treatment of xenograft tumors.

Photodynamic therapy (PDT) with lasers and new dyes has gained popularity in recent years as a minimally invasive technique with high tumoricidal effects in vitro and in some cancer patients. However, because new laser dyes are not FDA approved at present, the clinical evaluation of PDT may be years away. During the past 6 years we have used laser alone for photothermal ablation in both preclinical studies and in a large number of patients with an observed 60% tumor response rate. The 40% treatment failure led us to explore the possibility of combined therapy with lasers and standard chemotherapeutic drugs. We have recently tested a promising preclinical alternative using implantation of a bare 600-microns KTP 532 laser fiberoptic in multiple tumor sites 30 min after intratumor injection of the anthrapyrazole DUP-941. As a control, this drug was injected in 3 sites of P3 human squamous cell tumor transplants in nude mice, which led to tumor stasis without regression. Similar 400-600 mm3 tumors exposed to laser illumination alone (0.8 W for 5 sec) at multiple sites resulted in tumor regrowth after 10 weeks in 80% of the animals. However, combining interstitial laser illumination with intratumor DUP-941 injections led to complete tumor regression in 85% of the mice. We propose that intratumor drug injection followed by interstitial laser fiberoptic treatment represents a potentially useful new method for tumor ablation in advanced cancer patients.

Animals↗
PubMed1995

A Fourier-transform infrared spectroscopic comparison of cultured human fibroblast and fibrosarcoma cells: a new method for detection of malignancies.

Infrared vibration spectroscopy appears to be a more powerful technique for tumor diagnosis than visible or UV spectroscopy. In the present work, Fourier-transform infrared (FTIR) spectroscopy was used to compare cultured normal fibroblast and fibrosarcoma cells. Significant differences were observed by comparing the spectra of the normal human cells with that of the cancer cells. The PO2 symmetric stretching mode at 1082 cm-1 is shifted to a higher frequency in the cancer cell and a broad band, whose center is located at 1064 cm-1 in the cancer cell is reduced in intensity. In addition, the decrease in intensity of the CH2 bending mode relative to that of CH3 mode is detectable only in the fibrosarcoma cell. This FTIR difference between fibroblast and fibrosarcoma cells suggests that either fatty acid chains or protein side chains of the cancer cells are partially degraded resulting in more terminal carbon (e.g., CH3). It is also possible that changes in the environment upon carcinogenesis induces a change in the relative absorption cross section for CH3 and CH2 bending vibrations. These results suggest that FTIR spectroscopy may become a promising and sensitive technique for tumor identification.

Cells, Cultured↗
PubMed1995

Dynamic MRI-guided interstitial laser therapy: a new technique for minimally invasive surgery.

Interstitial laser therapy (ILT) is a promising therapeutic technique in which laser energy is delivered percutaneously to various depths in tissue. In this study, the authors compared high-speed magnetic resonance imaging (MRI) of ILT in tissues during treatment with post-treatment histopathologic specimens. The use of 5-second MRI scans allowed detection of thermal damage by the 1064-nm neodymium:yttrium-aluminum-garnet laser in ex vivo liver and brain tissues. These tissues were treated by ILT with 20 W of laser output for 5 to 30 seconds via a 600-microns fiberoptic inserted 1 cm into the specimens at a power density of 7 kW/cm2 at the tip of the bare fiber. Sequential MRI measurements of lesion areas made during and after treatment were compared to measurements of laser-induced tissue damage in histopathologic sections. Fast MRI scans and tissue histology both demonstrated increased lesion size with time of ILT. Serial images obtained during ILT detected thermal changes as areas of low signal intensity that exceeded the size of the post-treatment lesions as measured on either final MRI or histology. The thermal effects detectable by these high-speed MRI sequences can be used to monitor laser-induced tissue changes during therapy, thereby providing a valuable noninvasive method for the intraoperative assessment of heat distribution during ILT.

Animals↗
PubMed1994

Minimally invasive palliative tumor therapy guided by imaging techniques: the UCLA experience.

Imaging-guided palliative therapy of recurrent and/or inaccessible head and neck tumors may soon become clinically practical since sensitive and noninvasive monitoring techniques of energy deposition in tissues are now available. Interstitial tumor therapy (ITT) is a technique whereby a source of energy (laser, radiofrequency, ultrasonic, cryoenergy, etc.) is directly applied into tumors at various depths. Recent studies have demonstrated the efficiency of ultrasound (UTZ) and magnetic resonance imaging (MRI) for real and/or "near" real time tumor and vessel identification as well as monitoring and quantifying energy-induced tissue damage. We now report our initial clinical experience with patients in which UTZ and/or MRI-guided ITT techniques were successfully applied for the treatment of recurrent, nonresectable, local, and/or metastatic head and neck carcinomas. Patients were treated on an outpatient basis either in the operating room or in an upgraded specially equipped SIGNA 1.5T MR suite. Most patients tolerated these procedures well and were successfully palliated for periods ranging from 3 months to 5 years posttreatment. The upgrades introduced in a standard MRI suite, the clinical experience, and future perspectives will be reviewed.

Aged↗
PubMed1994

Evaluation of four new carbocyanine dyes for photodynamic therapy with lasers.

The search for improved photosensitizers for laser phototherapy of malignancies has led to the examination of a new group of carbocyanine dyes as effective fluorochromes. In this study, four carbocyanine dyes with different absorption maxima of 483 nm [DiOC6(3)], 545.5 nm (DiIC5(3)], 556.6 nm [DiSC5(3)], and 651.0 nm [DiSC3(5)] were tested in vitro. The kinetics of uptake and toxicity of these four dyes were assessed for P3 human squamous cell carcinoma, HT29 colon carcinoma, M26 melanoma, and TE671 fibrosarcoma cell lines at 15, 30, 45, 60, and 180 minutes after exposure with each dye. After sensitization with DiOC6(3), the P3 and M26 cell lines were also tested for phototherapy by treatment with 488-nm light from an argon laser. The results showed that these four carbocyanine dyes had rapid and significant uptake by the carcinoma cell lines with no toxicity at concentrations < 0.1 micrograms/mL. Nontoxic DiOC6(3) levels in sensitized tumor cells after laser phototherapy resulted in approximately 85% inhibition of P3 and approximately 95% inhibition of M26 cell lines by MTT assays. The results suggest that these carbocyanine dyes can be used for tumor photosensitization and wavelength-matched laser photodynamic therapy. Further in vivo studies will be necessary to define the clinical potential of carbocyanine dyes as tumor-targeting agents for phototherapy of cancer.

Adenocarcinoma↗
PubMed1994

Dose response of human tumor cells to rhodamine 123 and laser phototherapy.

Previous studies have shown that Rhodamine 123 (Rh123) is an efficient tumor targeting agent for argon laser photodynamic therapy in vitro. Effectiveness of this approach for cancer treatment in vivo will depend on Rh123 tumor uptake kinetics and laser energy delivery via fiberoptics to the tumor site. In the present study, tumor and normal cells were exposed in vitro to 1 micrograms/mL Rh123 until 10%, 50%, and 100% of maximum uptake was achieved. Laser treatment response was monitored by trypan blue exclusion for tumor cell viability and by MTT tetrazolium assays to measure mitochondrial dehydrogenase activity. TE671 fibrosarcoma cells were highly sensitive to argon laser phototherapy (514 nm, 5 W, 1 minute, Tmax = 8 degrees C), with mitochondrial inhibition seen after Rh123 uptake of 12, 50, and 100 ng/million cells. P3 squamous cell carcinoma cells were inhibited 20% and 75% by the laser after Rh123 uptake of 13 or 30 ng/million cells, respectively. M26 melanoma cells were not sensitive to the laser after 15 ng/million cells Rh123 uptake but were inhibited 45% and 75% after Rh123 uptake of 80 and 160 ng/million cells. Micro2 fibroblast mitochondrial activity was reduced less than 25% by the laser after Rh123 uptake of 50 ng/million cells. Cell viability after maximum Rh123 uptake and laser treatment was decreased to 30%, 15%, and 2% for M26 melanoma, P3 squamous cell carcinoma, and TE671 fibrosarcoma cells, but remained over 80% for Micro2 fibroblasts. The results suggest that Rh123 laser treatment response depends on tumor type and drug uptake level, with normal cells being much less sensitive to phototherapy.

Antimetabolites, Antineoplastic↗
PubMed1994

Hypericin uptake in rabbits and nude mice transplanted with human squamous cell carcinomas: study of a new sensitizer for laser phototherapy.

Tissue uptake and biodistribution of hypericin was measured in rabbits and in nu/nu mice xenografted with P3 human squamous cell carcinoma to assess the value of this dye as an in vivo sensitizer for laser photoinactivation of solid tumors. Hypericin has absorption maxima at 545 and 590 nm with a fluorescence emission peak at 640 nm in ethanol. Dye uptake after intravenous injection was tested at 4 and 24 hours in rabbit tissues by ethanol extraction and quantitative fluorescence spectrophotometry. Maximum dye levels were seen at 4 hours in most vascular organs with lung having fivefold higher uptake than spleen followed by liver, blood, and kidney. Mice were examined after 2, 4, 6, 8, and 24 hours and after 3 and 7 days for dye uptake. The peak concentration of hypericin in murine organs was reached at 4 hours with uptake per gram of tissue as follows: lung > spleen > liver > blood > kidney > heart > gut > tumor > stomach > skin > muscle > brain. Elimination of hypericin was rapid in most murine organs with residual dye under 10% of maximum by 7 days compared to 25% to 30% retention for the squamous cell tumors and several normal tissues. These results suggest that hypericin may be a useful photosensitizer for KTP/532 laser interstitial therapy of human cancer.

Animals↗
PubMed1994

Clear cell sarcoma of the pre-parotid region: an initial case report.

An unusual case of clear cell sarcoma (CCS) found in the parotid region of a 75-year-old man with a long history of chronic lymphoid leukemia is reported. Treatment of the patient included a total parotidectomy with preservation of the facial nerve. The tumor was pathologically consistent with a clear cell sarcoma. Since CCS originates from the neural crest and is melanin producing, we suggest that this particular tumor originated from the superficial musculo-aponeurotic system (SMAS). To our knowledge, this is the first case of CCS that has been reported in the parotid region.

Aged↗
PubMed1993

Subglottic plasmacytoma: the use of jet ventilation and contact Nd:YAG laser for tissue diagnosis.

Extramedullary plasmacytomas (EMP) constitute only 1% of all head and neck malignancies, with the vast majority occurring in the upper respiratory tract. The diagnosis of laryngeal EMP can be difficult since the symptoms are non-specific and the tumor usually mucosally covered. This paper discusses the successful combination of jet Venturi ventilation technique with suspension microlaryngoscopy and contact Nd:YAG laser for tissue diagnosis in a patient presenting with a large subglottic mass. Previous attempts using standard endotracheal intubation and forceps technique for biopsy failed to reach the diagnosis and resulted in significant bleeding from the biopsy site. A review of the disease and technique is presented.

Biopsy↗
PubMed1993

The surgical management of facial syringomas using the superpulsed CO 2 laser.

Syringomas are benign tumors of eccrine origin that occur primarily in the lower eyelid region of females. Since they do not involute and are typically refractory to conventional forms of therapy, they may grow to become considerable, chronic cosmetic and functional deficits. The current study reports on a patient with familial syringomas, previously refractory to two different standard therapies, who was successfully treated with the superpulsed CO 2 laser. A simple, accurate, and reproducible method of dosimetry of laser energy was used to treat these lesions with the Sharplan 700 CO 2 laser connected to the operating microscope. Each lesion was irradiated separately with single pulses at a calculated energy density of 1 J/cm 2. Superficial scabbing was observed 1 week postoperatively, with no edema or pain. Mild erythema persisted for 1 month, with complete healing thereafter. No recurrences were noted after a 2 year follow-up. There was no evidence of scarring, ectropion, or changes in pigmentation. The disease and methods of treatment are reviewed.

Adenoma↗
PubMed1993

MRI and ultrasound guided interstitial Nd:YAG laser phototherapy for palliative treatment of advanced head and neck tumors: clinical experience.

Interstitial laser phototherapy (ILP) is a technique whereby laser energy is directly applied into tumors at variable depths. This technique is attractive, since it is minimally invasive and carries a low morbidity. It may allow treatment of deep and difficult to reach tumors in the head and neck and other areas when improved noninvasive monitoring techniques of laser-tissue interactions are developed. Recent studies demonstrate, respectively, the efficiency of ultrasound (UTZ) and magnetic resonance imaging (MRI) for real time interstitial needle placement in tumors, identification of vessels, monitoring and quantifying laser-induced tissue damages. We present a case in which a patient with recurrent, metastatic base of skull carcinoma has managed successfully with repeat ILP using MRI and UTZ guidance. Under heavy sedation, needles were placed in the tumor using MRI or UTZ guidance. Tumors were treated with a 600 mum flexible Nd:YAG laser fiberoptic passed through the needles. Laser-induced tissue photoablation was monitored using real time color flow Doppler UTZ or near real time fast spin-echo T2-weighted MRI. Posttreatment fine needle aspiration cytologic study demonstrated the presence of cellular debris and no viable cancer cells. Posttreatment follow-up MRI scans showed significant reduction of tumor size, and positron emission tomography (PET) revealed interval decrease in tumor metabolism. Treatments were accompanied by pain relief and improved functional abilities. ILP has now evolved into minimally invasive outpatient surgical procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Contraindications↗
PubMed1993

The synergistic effects of rhodamine-123 and merocyanine-540 laser dyes on human tumor cell lines: a new approach to laser phototherapy.

Many new photosensitizers and laser wavelengths are being tested to improve photodynamic therapy by enhancing specific tumor uptake and/or retention, lowering systemic toxicity, and increasing laser tissue penetration. In this study the potential synergistic effects of rhodamine-123 (Rh-123) and merocyanine-540 (MC-540) sensitization of human tumor cell lines after laser exposure were explored. In a first series of experiments, the kinetics of uptake of Rh-123 and M-540 were tested on three human leukemia cell lines (K562, RAJI, 729HF2), P3 squamous carcinoma, and M26 melanoma. Our results demonstrate a clear difference in the rate and amount of uptake of MC-540 (K562 > P3 > RAJI > 729HF2 > M26) and Rh-123 (P3 > RAJI > 729HF2 > K562 > M26) by these cell lines. In a second series of experiments, M26 tumor cells were sensitized with either Rh-123 (1 microgram/ml) or with MC-540 (20 micrograms/ml) alone or with a combination of the two dyes for 60 minutes, then exposed to the argon (514.5 nm) laser at nonthermal energy levels. Our results demonstrate a significant enhancement of the tumoricidal effects of the laser on M26 carcinoma cells after sensitization with both dyes together (MC-540 and Rh-123) when compared to each dye alone. As with combination antibiotherapy, the synergistic effects of two laser dyes that have different intracellular targeting sites appear to enhance tumoricidal effects significantly after exposure to a matching laser wavelength. The data provide evidence for effective laser phototherapy by dye synergy.

Antimetabolites, Antineoplastic↗
PubMed1992

Monoclonal antibody-coated magnetite particles as contrast agents for MR imaging and laser therapy of human tumors.

Attempts to improve human tumor detection by non-radioactive magnetic resonance techniques have led several investigators to develop antibody-linked paramagnetic contrast agents. Initial studies focused on gadolinium conjugated to monoclonal antibodies. However, very high levels of this contrast agent were needed to significantly reduce proton relaxation times and obtain improved MR images. The use of magnetite (Fe 3O 4) as an MR contrast agent provides a magnetic moment that is approximately one order of magnitude larger than gadolinium. In this study monoclonal antibodies 44 x 14 (specific for squamous cell carcinoma) and 436G10 (specific for melanoma) were obtained from ammonium sulfate precipitation of tumor ascitic fluid. Equal volumes of magnetite solution (1.87 mg Fe/ml) and antibody solution 44 x 14 (5.24 mg protein/ml) and 436G10 (0.64 mg protein/ml) were mixed and sonicated. The 44 x 14-magnetite and 436G10-magnetite solutions were then added to equal volumes of M20 and P3 squamous cell carcinoma cell lines. T1 and T2 values were obtained on a Praxis II NMR spectrometer equipped with a 10 mm probe and 0.25 Tesla permanent magnet. The T2 relaxation times of the magnetite-antibody-cell mixtures were 31 ms with an R = 0.985 for both experimental samples. Our results demonstrate a significant decrease in T2 by binding of the magnetite-coated antibodies to these melanoma and carcinoma cells in vitro. The possibility of detecting subclinical local and metastatic disease with magnetite linked to monoclonal antibodies followed by MRI guided laser tumor ablation therapy may render this technique clinically attractive for treatment of deep-seated tumors.

Antibodies, Monoclonal↗
PubMed1992

Laser and daunomycin chemophototherapy of human carcinoma cells.

Adriamycin and daunomycin anticancer drugs are detectable in leukemias and solid tumors by cell fluorescence. We observed initial cytoplasmic fluorescence followed by slow nuclear localization of adriamycin and daunomycin after incubation with cultured human squamous cell (P3, FADU) and adenocarcinoma (HT29, SW620) lines by digital video imaging microscopy. Tumor cells incubated with 10 mug/ml of these drugs exhibited increased uptake for more than 3 h with intracellular levels in the range 0.5-2.5 mug/10 6 cells measured by dimethyl sulfoxide (DMSO) extraction and fluorescence spectrophotometry. Daunomycin had 10- to 100-fold higher toxicity for these carcinoma cells than for normal human epithelial keratinocytes measured by in vitro MTT tetrazolium assays. The viability of daunomycin-sensitized carcinoma cells was decreased 2- to 10-fold further by argon laser illumination at 488 nm (5W, T max = 8 degrees C) for 2-3 minutes. The results suggest that adriamycin derivatives may be useful targeting agents for adjuvant treatment and chemophototherapy of human solid tumors by MR-guided laser fiberoptic endoscopy.

Adenocarcinoma↗
PubMed1992

Rhodamine-123 as a new chemosensitizing versus toxic agent on human squamous carcinoma cells and fibroblast cultures.

Rhodamine-123 is a specific dye with an absorption maxima at 511 nm which was tested as a potential chemosensitizing agent for laser treatment of tumor cells. Because Rhodamine, at high doses, has direct cytotoxic effects on human cells in the absence of laser exposure, we tested the human squamous P 3 carcinoma cell line and two normal fibroblast cell lines for sensitivity to various levels of this dye. These cells were exposed to Rhodamine-123 at concentrations of 1, 3, 6, and 10 mug/ml for 1, 8, and 24 hours. The results indicate that Rhodamine-123 is nontoxic to human P 3 carcinoma cells and normal fibroblast cultures at concentrations equal or lower than 1 mug/ml. However, at concentrations equal or higher than 3 mug/ml, a significant immediate and/or delayed inhibition of cell duplication was demonstrated. The results show that Rhodamine-123 at 1 mug/ml can be used to sensitize tumor cells for targeting by monochromatic 514.5 nm Argon lasers.

Carcinoma, Squamous Cell↗
PubMed1992

Metastatic head and neck malignancy treated using MRI guided interstitial laser phototherapy: an initial case report.

Interstitial laser phototherapy (ILP) guided by magnetic resonance imaging (MRI) may become an attractive adjunctive modality for the treatment of deep and surgically inaccessible tumors of the head and neck when accurate methods of laser dosimetry and "real-time" monitoring techniques with the MRI are introduced. We recently demonstrated in ex vivo and in vivo models, a linear relationship between levels of laser energies, thermal profiles, MR signal intensity changes, and histopathological tissue damage. Results of treatment in a patient with an unresectable large right jugulodigastric metastatic squamous carcinoma using new approach of MRI guided ILP are now reported. The patient complained of significant right-sided neck pain and headaches secondary to a rapidly growing metastatic lymphadenopathy which recurred after previous surgery, radiation, and chemotherapy. Two treatment sessions were used at an interval of 2 weeks. Each treatment was performed in the MRI suite under heavy sedation. Using a 600-microns bare fiber of the Nd:YAG laser implanted interstitially under MR guidance, the metastatic node was treated at three sites. T1- and T2-weighted images were performed prior to, immediately after, 24 and 48 hours, and 4, 5, 7, 9, 16, and 25 days post-treatment. Successful relief of pain and growth arrest of this node was observed after the second treatment and at the 3-month follow-up. These results demonstrate that this technique of ILP guided by MRI may be feasible in humans, and will become clinically practical when appropriate methods of dosimetry and instrumentation are developed.

Aluminum Silicates↗