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2.
J Surg Res ; 47(3): 276-81, 1989 Sep.
Article in English | MEDLINE | ID: mdl-2528031

ABSTRACT

Photodynamic therapy (PDT) using a dihematoporphyrin ether (DHE) sensitizes malignant cells to damage by 630-nm light. This study investigated in vitro PDT sensitivity of human lung cancer cells (A549) and those factors which influence cell survival as determined by the colony formation assay. After incubation for 2, 4, or 6 hr with [DHE] of 2.5, 25, or 50 micrograms/ml, A549 received red light at dose rates of 0.27 or 0.09 mW/cm2 and energies of 0-250 mJ/cm2. Neither 630-nm light alone nor DHE alone affected cell survival. A dose rate of 0.27 mW/cm2 required less energy than 0.09 mW/cm2 for 90% cytotoxicity (180 mJ/cm2 vs 250 mJ/cm2, P less than 0.05). The energy required for 90% cytotoxicity with 25 micrograms/ml [DHE] was dependent on DHE incubation time (2 hr, 90% cytotoxicity not reached; 4 hr, 116 mJ/cm2; 6 hr, 69 mJ/cm2; P less than 0.05). In contrast, cellular [DHE] as measured by fluorescence, plateaued after 2 hr of incubation. Fluorescence microscopy revealed a time-dependent redistribution of fluorescence from the cell membrane to perinuclear and intracytoplasmic organelles. A 99% cytotoxicity required significantly less energy as [DHE] was increased (2.5 micrograms/ml, no cytotoxicity; 25 micrograms/ml, 243 mJ/cm2; 50 micrograms/ml, 111 mJ/cm2; P less than 0.05). Intracellular [DHE] was directly dependent on the incubating media [DHE] (2.5 micrograms/ml, 0.09 +/- 0.01 micrograms/10(6) cells; 25 micrograms/ml, 0.80 +/- 0.07 micrograms/10(6) cells; 50 micrograms/ml, 1.31 +/- 0.11 micrograms/10(6) cells; P less than 0.05). PDT cytotoxicity was inversely proportional to concentration of serum in the DHE media. These data illustrate that lung cancer in vitro is sensitive to PDT and is influenced by dose rate, energy input, and DHE environmental manipulations. These factors may be important in increasing the efficiency of PDT of thoracic malignancies in vivo.


Subject(s)
Carcinoma/drug therapy , Lung Neoplasms/drug therapy , Photochemotherapy , Carcinoma/metabolism , Carcinoma/pathology , Dihematoporphyrin Ether , Dose-Response Relationship, Drug , Environmental Exposure , Hematoporphyrins/metabolism , Hematoporphyrins/therapeutic use , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Microscopy, Fluorescence , Osmolar Concentration , Proteins/pharmacology , Radiation-Sensitizing Agents/therapeutic use , Time Factors , Tumor Cells, Cultured
3.
J Surg Res ; 46(4): 386-90, 1989 Apr.
Article in English | MEDLINE | ID: mdl-2523009

ABSTRACT

Lung cancer cells are susceptible to photodynamic therapy (PDT) using 630 nm light and dihematoporphyrin ether (DHE). A light scattering media, intralipid (IL), was compared to balanced salt solution (PBS) for PDT of A549 human lung cancer cells. Differences in cellular DHE content after IL or PBS exposure were determined. Cells were incubated in 25 micrograms/ml DHE for 2 hr and then incubated in various concentrations of IL or PBS at room temperature for 2.5 to 10.0 min. Significant amounts of DHE were lost from IL-incubated cells compared to cells incubated in PBS. After 5 min in 1% IL, cellular DHE content was 0.32 +/- 0.04 microgram DHE/10(6) cells compared to 0.56 +/- 0.11 microgram DHE/10(6) cells in PBS-incubated cells (P less than 0.05). Despite this, superior PDT cytotoxicity was noted when cells were treated in IL with energy densities greater than or equal to 105 mJ/cm2. At an energy density of 210 mJ/cm2, the survival fraction (SF) of cells treated in 1% IL was 0.004 +/- 0.001 compared to 0.071 +/- 0.022 in PBS-treated cells (P less than 0.05). SF was dependent upon the IL concentration with the greatest cell killing noted with 1% IL. An apparent loss of cellular DHE ("DHE washout") was confirmed by demonstration of a higher SF of cells incubated in IL, rinsed, and subsequently PDT-treated in PBS with 157.5 mJ/cm2 (SF = 0.85 +/- 0.11) compared to cells incubated and treated in PBS (SF = 0.50 +/- 0.03, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Fat Emulsions, Intravenous/pharmacology , Hematoporphyrin Photoradiation/methods , Photochemotherapy/methods , Cell Survival/drug effects , Dihematoporphyrin Ether , Hematoporphyrins/metabolism , Humans , Light , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Scattering, Radiation , Tumor Cells, Cultured
4.
Surgery ; 103(4): 470-6, 1988 Apr.
Article in English | MEDLINE | ID: mdl-3353858

ABSTRACT

The heparin-induced thrombocytopenia and thrombosis (HITT) syndrome is associated with hemorrhage as well as development of systemic thrombosis. A case is presented in which a posthepatectomy patient had probable heparin-induced thrombocytopenia complicated by venous thrombosis and pulmonary emboli after receiving low doses of heparin as line flushes. HITT is reviewed and factors related to its successful management in this postoperative patient are analyzed in detail.


Subject(s)
Heparin/adverse effects , Postoperative Complications/chemically induced , Thrombocytopenia/chemically induced , Thromboembolism/chemically induced , Adenocarcinoma/surgery , Female , Heparin/administration & dosage , Hepatectomy , Humans , Iliac Vein , Liver Neoplasms/surgery , Middle Aged , Platelet Aggregation , Pulmonary Embolism/chemically induced , Renal Veins , Thrombocytopenia/blood , Thrombosis/chemically induced , Time Factors
5.
Arch Surg ; 121(11): 1248-52, 1986 Nov.
Article in English | MEDLINE | ID: mdl-3778195

ABSTRACT

Survival benefit and prognostic factors useful for patient selection have not been previously analyzed for patients with recurrent pulmonary metastases from soft-tissue sarcomas. Twenty-nine patients in our study had two or more resections of pulmonary metastases from 1976 to 1983. There were no operative deaths and three complications for 40 operations (7.5%). Factors predictive of increased survival following the second resection of pulmonary metastases were resectability and a disease-free interval of greater than six months from the first thoracotomy to the second recurrence in the lung. The tumor doubling time of the first recurrence and the presence of three or fewer nodules on full-lung tomography before the first thoracotomy, which were predictors of survival following initial resection, also predicted survival following subsequent resections. Overall median survival following the second resection was 14.5 months (22% overall three-year survival). The postresection actuarial survival curves for patients undergoing 1, 2, or 3 or more resections were not significantly different. Our findings demonstrate that patients undergoing repeated resections of pulmonary metastases from soft-tissue sarcomas can achieve prolonged survival.


Subject(s)
Lung Neoplasms/secondary , Neoplasm Recurrence, Local/surgery , Sarcoma/secondary , Soft Tissue Neoplasms , Actuarial Analysis , Adolescent , Adult , Child , Female , Humans , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Middle Aged , Prognosis , Sarcoma/pathology , Sarcoma/surgery
6.
Nutr Cancer ; 4(2): 140-5, 1982.
Article in English | MEDLINE | ID: mdl-7162995

ABSTRACT

In this study, the effect of tumor presence on the concentration of vitamin E in the liver, spleen, and kidney of BALB/c mice was measured, and the influence of the degree of fat saturation was assessed. In mice fed diets deficient in vitamin E, the presence of a transplanted sarcoma in the thigh significantly increased the concentration of the vitamin in all 3 organs. This was true whether the fat was saturated or unsaturated (hydrogenated coconut oil [HCO] or corn oil [CO], respectively). The tumor itself was generally lower in tocopherol than were other tissues of the tumor-bearing host. In mice fed diets containing vitamin E, the tumor increased the vitamin content in some organs but not others. Only in the kidney of tumor-bearing mice fed the HCO +/- E diet was there a significantly decreased content of the vitamin. A comparison of the spleen tocopherol content with mitogenesis by concanavalin A revealed a positive correlation, which explains why the spleens of tumor-bearing mice fed a diet deficient in vitamin E exhibited higher mitogenic activity than the spleens of normal mice fed the same diet (namely, the spleens from tumor-bearing mice had a higher content of tocopherol).


Subject(s)
Dietary Fats/pharmacology , Kidney/metabolism , Liver/metabolism , Sarcoma, Experimental/metabolism , Spleen/metabolism , Vitamin E/metabolism , Animals , Antibody Formation , Cell Transformation, Viral , Fats, Unsaturated/pharmacology , Kirsten murine sarcoma virus , Male , Mice , Mice, Inbred BALB C , Mitosis/drug effects , Vitamin E/administration & dosage
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