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Biomedical subjects

F K Storm

Publications and source records attributed to F K Storm.

At least 55 records · Page 3Linked to original sources

The pharmacologic manipulation of blood flow in hyperthermia therapy.

Many human tumors treated by hyperthermia do not reach therapeutic temperatures (42 degrees C). The explanation for this difference may be that some tumors react to thermal stress in a manner similar to normal tissues; ie, they increase blood flow during hyperthermia in order to dissipate the heat. Higher temperatures might be achieved in these heat-resistant tumors by administering vasoconstrictive agents in an effort to reduce blood flow. In this preliminary study, we determined the extent to which pharmacologic inhibition of local blood flow might allow higher temperatures to develop in normal muscles exposed to localized radiofrequency hyperthermia. We found that the local muscle temperature rise could be increased by at least 90% in two dogs and six rabbits with the use of a local vasoconstrictive drug.

Animals↗

Natural thermal resistance of human tumor cells and the role of prostaglandin.

We found that human malignant melanoma cells had varying thermal sensitivity and that some exhibited natural thermal resistance, a heretofore unrecognized phenomenon. Samples of 73 melanoma cell suspensions were heated at 42 degrees C for 1 hour before plating in the soft agar clonogenic assay or the thymidine assay for proliferating cells. We observed greater than 75% cell kill after hyperthermia in 39 (53%) tumors. Native thermal resistance was apparent in 17 (23%) tumors and growth enhancement in 17 (23%) at this temperature and exposure time. We postulated that prostaglandin, known to protect stomach mucosa against thermal injury, has a role in stabilizing the tumor cell membrane exposed to heat. Three melanoma cell lines known to be thermosensitive were heated to 42 degrees C without and with exogenous prostaglandin E2 (PGE2). The survival of colony-forming cells was increased in all three lines in the presence of 30 microM PGE2. A naturally thermoresistant cell line was exposed to 1 microgram/ml indomethacin for 24 hours before hyperthermic treatment. The survival of colony-forming cells was significantly decreased compared to cells not treated with indomethacin. The addition of 30 microM of exogenous PGE2 to indomethacin-treated cells reestablished thermal resistance. These preliminary data suggest that some tumor cells synthesize prostaglandins to render the cell thermoresistant. Treatment with indomethacin blocks prostaglandin synthesis and induces thermosensitivity. These discoveries may have important clinical applications for hyperthermia treatment of human cancers.

Cell Line↗

Thermochemotherapy for melanoma metastases in liver.

Metastatic melanoma in the liver has carried an extremely poor prognosis regardless of therapy. Because transient responses (1/6 disease regressions and 2/6 disease stabilizations for four months) in selected patients treated with intraarterial (IA) DTIC infusion were encouraging and because localized hyperthermia may be both tumoricidal and synergistic with chemotherapy, these modalities were combined for treatment of patients with advanced liver metastases. Of 10 patients treated with IA-DTIC plus heat, three (30%) had disease-regression and five (50%) had disease stabilization for 3-14 months (median 6.5 months) and survived 3.5-18 months (median 8.5 months). During treatment, 4/5 patients had pain relief and 7/10 retained or acquired normal activities. Myelosuppression was minimal and no hyperthermia toxicity occurred. A retrospective review of 10 patients with similar disease levels who were treated with conventional intravenous (IV)-DTIC indicated no responses, and no responses were seen in five patients treated with IV-DTIC plus heat. However, this latter group may have been selected patients due to the inability to place a percutaneous hepatic artery infusion catheter. This pilot study suggests that combination IA-DTIC and hyperthermia has a high response rate, is safe, and can provide quality survival for many patients.

Adult↗

Thermal distribution of magnetic-loop induction hyperthermia in phantoms and animals: effect of the living state and velocity of heating.

Hyperthermia has shown promise for the treatment of cancer. The magnetrode radio-frequency magnetic-loop induction applicator was recently introduced and is being evaluated at many centers with encouraging initial results. This investigation was undertaken to delineate the thermal distribution patterns of magnetrode hyperthermia in both normal tissue phantoms and healthy dogs. Temperatures on homogeneous and heterogeneous tissue equivalents and animal tissue phantoms, a dead animal extremity, a dead dog and a live dog subjected to rapid high-dose heating showed preferential and potentially injurious peripheral heating with a central "cold spot." However, sequential moderate-dose heating in live dogs showed virtually uniform (less than 1 degree C) and potentially tumoricidal temperatures greater than or equal to 42 degrees C in both peripheral and central internal organs without injury to surface tissues. These data indicate that magnetic-loop induction can produce potentially safe and effective deep central heat in living, normal animals, but that safety and effectiveness are significantly influenced by the velocity of heat deposition. Furthermore, normal tissue phantom models and dead animals are unreliable predictors of magnetrode heat patterns in living systems.

Animals↗

Clinical radiofrequency hyperthermia: a review.

Localized radiofrequency (RF) hyperthermia is being investigated for potential use in cancer therapy, both as a single agent and in combination with radiation therapy and chemotherapy. Standard capacitive and inductive heating techniques and new technology, including magnetrode magnetic-loop induction, are being compared for safety and efficacy. Clinical trials suggest that effective localized RF hyperthermia may be administered safely to both superficial and deep visceral tumors with proper equipment. Temperatures of 42 degrees C or greater appear to be tumoricidal, though higher temperatures and longer and multiple treatments seem most beneficial. Effective heating of tumors has been independent of histology but could be related to size and blood flow. Combined with radiation therapy and chemotherapy, hyperthermia appears to have a synergistic or additive effect. These trials indicate that localized RF hyperthermia may soon provide a significant contribution to our armamentarium against cancer.

Adenocarcinoma↗

Retroperitoneal sarcomas: a reappraisal of treatment.

Retroperitoneal sarcoma, regardless of the histopathologic grade of malignancy, has a high incidence of local recurrence that is usually fatal. Surgical resection is mandatory and resectability may be improved by a midline transabdominal approach. However, even with total tumor excision, recurrence is high. A preliminary study, combining resection and preoperative adriamycin, found to be effective for established disease, suggests potentially improved prognosis. Further clinical trials employing combined with adjuvant chemotherapy are warranted.

Adolescent↗

Radio frequency hyperthermia of advanced human sarcomas.

Hyperthermia greater than or equal to 42 degrees C is tumoricidal in vitro and in many animal models, although such temperatures have only recently been achieved experimentally in some human cancers. A recently developed radio frequency device that provides safe hyperthermia to any depth without surface tissue injury now permits evaluation of the effects of hyperthermia on advanced human sarcomas. Twelve patients with large sarcomas located intraabdominally [7], in the chest wall [2], proximal extremity [2], and the neck [1], were evaluated in this study. Tumor types include liposarcoma [3], rhabdomyosarcoma [2], leiomyosarcoma [2], neurofibrosarcoma [2], and one each malignant mesothelioma, undifferentiated sarcoma, and osteosarcoma. Intratumor temperatures greater than or equal to 42 degrees C were observed in all tumors, with virtually no normal tissue injury. Selective tumor heating greater than or equal to 45 degrees C occurred in 9/12 (75%) and greater than or equal to 50 degrees C in 6/12 (50%). One to five weekly treatments greater than or equal to 50 degrees C and ten daily treatments greater than or equal to 45 degrees C resulted in significant tumor necrosis and pain relief in some patients. Hyperthermia of advanced sarcomas is possible with little host toxicity and may be of potential therapeutic benefit.

Adult↗

Hyperthermia.

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Animals↗