Re: "Cancer risks associated with occupational exposure to magnetic fields among electric utility workers in Ontario and Quebec, Canada, and France: 1970-1989".
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Brain Neoplasms↗
Biomedical subjects
F K Storm
Publications and source records attributed to F K Storm.
Distribution of Hsp-27 and HER-2/neu in in situ and invasive ductal breast carcinomas.
BACKGROUND: The overexpression of heat shock protein 27 (hsp-27) in early-stage breast cancer is associated with histopathologic features of poor prognosis and clinically with an increased probability of disease recurrence. Hsp-27 is overexpressed in 25% of invasive ductal carcinomas (IDC); however, its distribution in ductal carcinoma in situ (DCIS) and DCIS associated with IDC has not been investigated. We postulated that hsp-27 might be detected and variably expressed in DCIS and, like HER-2/neu oncoprotein expression, might be a tumor-specific marker worthy of future clinical investigation. METHODS: To test these hypotheses, the distribution of hsp-27 in noncomedo and comedo DCIS, and DCIS associated with IDC, was evaluated by immunohistochemistry and compared with HER-2/neu expression within the same cancers. RESULTS: Hsp-27 was overexpressed in 28 of 47 (approximately 60%) cases of DCIS; expression in pure DCIS was 16 of 24 (67%), and 12 of 23 (approximately 50%) in DCIS associated with IDC. Hsp-27 expression by in situ and invasive components of the same neoplasm were concordant in 22 of 23 (approximately 95%) cases tested. Comedo variants appeared to have somewhat higher hsp-27 expression than noncomedo DCIS, whether or not there was an associated IDC. These results are reminiscent of HER-2/neu oncoprotein expression in DCIS and DCIS associated with IDC observed by others. However, although 4 of 22 (18%) cancers containing DCIS + IDC expressed HER-2/neu, no relationship with hsp-27 expression in the same cancers was observed. CONCLUSIONS: We found a high incidence of hsp-27 overexpression in DCIS and in DCIS associated with IDC. This rate is twice that previously observed in IDC alone. Hsp-27 expression is independent of HER-2/neu expression.
Adult↗
Retroperitoneal masses, adenopathy, and adrenal glands.
The diagnosis of primary retroperitoneal masses is approached best by CT scan-guided transretroperitoneal core biopsy or by open biopsy. Excisional or wedge biopsy is the preferred method for undiagnosed lymphadenopathy. Resection without biopsy is indicated for large or enlarging nonfunctional primary adrenal masses.
Adrenal Gland Neoplasms↗
Technical details of intraoperative lymphatic mapping for early stage melanoma.
The initial route of metastases in most patients with melanoma is via the lymphatics to the regional nodes. However, routine lymphadenectomy for patients with clinical stage I melanoma remains controversial because most of these patients do not have nodal metastases, are unlikely to benefit from the operation, and may suffer troublesome postoperative edema of the limbs. A new procedure was developed using vital dyes that permits intraoperative identification of the sentinel lymph node, the lymph node nearest the site of the primary melanoma, on the direct drainage pathway. The most likely site of early metastases, the sentinel node can be removed for immediate intraoperative study to identify clinically occult melanoma cells. We successfully identified the sentinel node(s) in 194 of 237 lymphatic basins and detected metastases in 40 specimens (21%) on examination of routine hematoxylin-eosin-stained slides (12%) or exclusively in immunohistochemically stained preparations (9%). Metastases were present in 47 (18%) of 259 sentinel nodes, while nonsentinel nodes were the sole site of metastasis in only two of 3079 nodes from 194 lymphadenectomy specimens that had an identifiable sentinel node, a false-negative rate of less than 1%. Thus, this technique identifies, with a high degree of accuracy, patients with early stage melanoma who have nodal metastases and are likely to benefit from radical lymphadenectomy.
Adolescent↗
Cellular effects of piezoelectric versus electrohydraulic high energy shock waves.
High energy shock waves produced by a piezoelectric lithotripter, (EDAP LT.01) and an electrohydraulic lithotripter, (Dornier HM3) were examined for their effects on Chinese hamster ovary cells in suspension. The EDAP caused acute lactate dehydrogenase release, consistent with severe membrane disruption in a proportion of cells, with the remaining proportion of cells replicating normally as measured by clonogenic assay. Similarly, the Dornier also caused lactate dehydrogenase release. However, a significant proportion of cells which remained "viable" after Dornier treatment, (intact to lactate dehydrogenase), did not replicate by clonogenic assay. The Dornier HM3 lithotripter has been reported to produce free radicals in aqueous solution. In the current investigation, we could not detect significant free radical formation from the EDAP LT.01. Chinese hamster ovary cell killing by the Dornier HM3 was significantly augmented by radiosensitizers, 5-iodo-2-deoxyuridine or buthionine sulfoximine, while radioprotectors cysteamine and WR-1065 had no protective effect. EDAP cell killing was not influenced by either radioprotectors or radiosensitizers. The mechanism of in vitro cytotoxicity differs between piezoelectric and electrohydraulic high energy shock wave delivery.
Animals↗
Diagnosis and management of retroperitoneal soft-tissue sarcoma.
Retroperitoneal soft-tissue sarcomas are locally invasive tumors that remain occult for long periods and grow quite large due to the abdominal cavity's remarkable ability to accommodate these slowly expanding masses with a paucity of attendant symptoms. An open biopsy is required to establish diagnosis definitively. Despite improved imaging techniques and preoperative and intraoperative patient management, resectability has not changed significantly in the past 20 years. Even with an aggressive operative approach, only one half the tumors can be resected completely, and of those, more than 90% recur locally and result in the death of the patient. The addition of adjuvant radiotherapy or chemotherapy has not altered this pattern of local failure, in contrast to promising results with extremity soft-tissue sarcoma. Because of the rarity of these tumors, there is an urgent need to establish a national retroperitoneal sarcoma registry and to form cooperative intergroup studies to evaluate, treat, and apply innovative multimodality combination therapies to these otherwise lethal tumors.
Antineoplastic Agents↗
Pulmonary and systemic fluid filtration after continuous versus bolus interleukin-2 infusion.
Interleukin-2 has been widely investigated as adjuvant therapy for advanced cancer and is administered by either bolus or continuous infusion. We compared the effects of bolus and continuous interleukin-2 infusion on pulmonary (QL) and systemic microvascular fluid filtration in 11 adult sheep prepared with chronic lung and soft-tissue lymph fistulas. Interleukin-2 was administered as a bolus infusion (100,000 units/kg) every 8 hours for 3 days or as a continuous infusion at the same dose for 3 days. No significant changes in pulmonary hydrostatic pressures or pulmonary vascular resistance were noted after either bolus or continuous interleukin-2 infusion. However, significantly decreased (p less than or equal to 0.05) systemic vascular resistances were observed in both groups. QL increased steadily throughout the infusion period in both groups, peaking at three times baseline on the third infusion day. The plasma/interstitial protein clearance (QL X lymph/plasma protein ratio) rose similarly in both groups, indicating increased barrier permeability. Increased lymphocyte clearance into lung lymph occurred by day 3 but was not associated with lymphocytic sequestration in the lung interstitium. We conclude that pulmonary and systemic microvascular fluid and protein flux exhibit similar changes after bolus or continuous interleukin-2 infusion. These changes are associated with increased clearance of lymphocytes into lung lymph that are not sequestered in the pulmonary interstitium after infusions of shorter duration.
Animals↗
cDNA sequence of a human heat shock protein HSP27.
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Amino Acid Sequence↗
In vitro and in vivo cytotoxicity of rhodamine 123 combined with hyperthermia.
Because both Rhodamine 123 (R123) and hyperthermia have been shown to be cytotoxic, we examined their effect, independently and in combination, on five different human malignant cell lines in vitro and on cultured melanoma cells grown intradermally in nude mice. The cell lines examined include two human melanomas, UCLA-SO-M14 and UCLA-SO-M21, the colon cancer cell line HT29, the human lung cancer cell line P3, and the human breast cancer cell line B231. R123 and hyperthermia, when used in combination, were found to be cytotoxic for these five different human malignant cell lines in vitro. The two agents together appear to enhance the cytotoxic effect of each alone, as documented by synergistic ratios ranging from 2.31 to 45 for the different cell lines. In the "nude" mouse model, animals were treated with a combination of R123 and hyperthermia (43 degrees C for 90 min). A statistically significant (P = 0.04) decrease in tumor growth rate was observed when compared with the rate of tumor growth in untreated animals. The results suggest a potential role for R123 in combination with hyperthermia in the treatment of malignant cells.
Animals↗
An unusual presentation of metastatic squamous cell carcinoma of the vulva.
Recurrent squamous cell cancer of the vulva metastasized via regional lymphatics. Hematogenous spread is late and unusual. A patient with metastatic disease presented with soft tissue mass in her thigh musculature. We believe this to be the first reported case of noncontiguous skeletal metastasis for this tumor.
Aged↗
Clinical hyperthermia and chemotherapy.
Hyperthermia may act additively or synergistically with a majority of clinically useful chemotherapeutic agents in vitro. In some cases enhanced responses are essentially linear at temperatures from 39 to 43 degrees C (thiotepa, the nitrosoureas, cisplatin), while other drugs become more effective only at 42 to 43 degrees (doxorubicin, bleomycin, amphotericin B). Synergism has been observed in vivo with methotrexate, cyclophosphamide, the nitrosoureas, doxorubicin, bleomycin, and cisplatin. Optimum enhancement occurs when heat and drug are given simultaneously. Clinical studies employing WBH at 41 to 41.8 degrees C have shown evidence of potential usefulness, but have been limited by high toxicity and a low benefit-to-risk ratio. Regional perfusion of metastatic melanoma of the extremity treated with L-phenylalanine mustard at 40 to 41 degrees C was significantly better than when treated with the drug alone, but some investigations suggest that heat alone may be just as effective. Localized hyperthermia combined with nearly all the standard types and doses of single and combination agents has shown objective responses in about one third of patients treated, without evidence of increased drug toxicity by either the IV or IA route. Responses appear to be thermal-dose related. Maximum enhancement appears at about 40 to 43 degrees C and prior drug resistance does not appear to confer heat resistance. The lack of enhanced drug toxicity with loco-regional hyperthermia with potential improvement in response of advanced disease suggests that thermochemotherapy is a viable and important option to drug treatment alone. Further in vitro, in vivo, and clinical studies are needed to increase our understanding of drug-heat interactions for the optimization of therapy.
Animals↗
Effects of interleukin-2 on pulmonary and systemic transvascular fluid filtration.
Interleukin-2 (IL-2) therapy for patients with advanced cancer may be compromised by dose-limiting and life-threatening pulmonary and systemic edema. We studied the effects of bolus IL-2 infusion on lung and soft-tissue transvascular fluid and protein filtration in six sheep with chronic lung and soft-tissue lymphatic cannulation. Changes in lung (QL) and soft-tissue (QS) lymph flow were used as indicators of transvascular fluid filtration. A dose of 100,000 U/kg IL-2 was administered every 8 hours for 3 days. A significant increase (p less than or equal to 0.05) in both QL and QS was observed after each IL-2 infusion, with maximal flow occurring 2 to 3 hours after infusion. After 72 hours of IL-2 infusion, a fourfold maximal increase in QL occurred, which recovered to near-baseline values within 24 hours. Elevations in QL and QS were not associated with increases in pulmonary arterial or pulmonary arterial wedge pressures, but these elevations were associated with significant (p less than or equal to 0.05) increases in cardiac output (7.7 +/- 0.5 to 11.4 +/- 0.4 L/min) and a consistent decrease in systemic vascular resistance. A significant increase in lung lymph/plasma protein ratio (0.49 +/- 0.06 to 0.93 +/- 0.04 for albumin) revealed a marked increase in pulmonary microvascular porosity. This change, however, was not observed in the systemic microcirculation. Serum concentrations of tumor necrosis factor did not increase with the observed changes in pulmonary microvascular porosity. We conclude that IL-2 increases both pulmonary and systemic microvascular fluid flux. In addition, there is a marked increase in pulmonary, but not systemic, protein permeability that is not a consequence of changes mediated by tumor necrosis factor.
Animals↗
Thermal resistance of human malignant melanoma modulated by prostaglandin E2.
The inhibition of DNA synthesis in a human malignant melanoma cell line as measured by tritiated thymidine (3H-TdR) incorporation was both time- and temperature dependent. Two components of cell damage were identified: a cytostatic, temporary component from which cells recovered within 2-6 days, and a cytotoxic, permanent component from which no recovery was observed. Thermotolerance was induced in M14 cells by sublethal heat treatment at 41 degrees C for 1 hr. However, induction of thermotolerance was blocked by indomethacin, a prostaglandin synthetase inhibitor. Exogenous PGE2 at concentrations up to 10 micrograms/ml also protected cells from heat damage. These data suggest that prostaglandin synthesis increases during heat stress and may play a role in protecting cells from thermal damage.
Dinoprostone↗
Thermal dose-response of magnetic-induction thermoradiotherapy.
Sixty-three patients with advanced cancer underwent greater than or equal to 5,000 cGy combined with Concentric Coil magnetic-induction localized hyperthermia. Tumor regression (CR + PR) was compared to thermal dose received, incorporating the premise that hyperthermia response is a function of time as well as temperature. A computer program was developed (after Sapareto and Dewey [2]) which stored minimum tumor temperatures recorded spatially and temporally during treatment and correlated response with T43 (equivalent minutes at 43 degrees C during the first treatment) and CT43 (cumulative T43, computed by multiplying T43 by the actual number of identical subsequent treatments received during the course of therapy). Those who responded--N = 46 (73%)--had significantly higher median thermal doses than those who did not respond. Comparison of T43 and CT43 thermal dose values between responders and nonresponders was significantly different at p values of 0.05 and 0.04, respectively. The data indicate that magnetic-induction hyperthermia and high-dose XRT was an effective treatment combination in advanced disease and that tumor response improved as thermal dose increased.
Combined Modality Therapy↗
Histologic features relating to prognosis in synovial sarcoma.
Although the American Joint Commission has classified all synovial sarcomas as "high grade," histologic subtypes can be identified. By histologically subclassifying synovial sarcoma tumors according to percent glandularity and mitotic rates, the authors were able to define high-risk and low-risk patients. Charts and original pathologic slides were reviewed on 45 synovial sarcoma patients. With a 41-month median follow-up, the low-risk patients showed 100% survival, whereas the high-risk patients showed 37% survival.
Actuarial Analysis↗
Tumor stabilization after hyperthermia: an important criterion of response to thermal therapy.
Several investigators have indicated that changes in tumor size may not occur after hyperthermia therapy even with substantial tumor cell kill, because of early edema and subsequent fibrosis of background stroma, suggesting that "tumor stabilization" might be an important benefit of thermal therapy. Recently, 9 institutions completed a national cooperative study of localized hyperthermia for patients with advanced, recurrent, or metastatic solid cancer that evaluated the potential significance of this response variable in a standardized clinical trial. Of 960 evaluable patients who completed at least one course of hyperthermia, thermoradiotherapy, or thermochemotherapy, 85 (9%) had complete responses for 1-34 months, 173 (18%) had partial responses for 1-39 months, 95 (10%) had minimal responses for 1-15 months, and 313 (33%) had disease stabilization for 1-32 months. Of 313 patients who had no change (i.e., +/- 25%) in the size of their tumors after hyperthermia, the response lasted only 1-3 months in 170 (54%) patients, a finding of questionable clinical significance. However, disease stabilization was observed for more than 3 months in 143 (46%), for more than 6 months in 67 (21%), more than 9 months in 33 (10%), and more than 12 months in 16 (5%). Disease stabilization was also associated with improved activity for 1-22 months in 79 (25%) of these patients, and improved pain for 1-22 months in 100 (32%). Disease stabilization appeared to be independent of tumor histology, location, or depth within the body, size, or minimum treatment temperature, but was somewhat more frequent after hyperthermia combination therapy. There is sufficient accumulative data to suggest that tumor stabilization after hyperthermia should not be dismissed as a placebo effect. This response variable well may be a unique and potentially important criterion of response to localized hyperthermia therapy.
Adult↗
Localized deep hyperthermia increases the traffic of lymphocytes through peripheral lymph nodes of sheep in vivo.
The production of localized deep hyperthermia by the radio frequency wave magnetic-loop induction method has been utilized to study the effects of deep hyperthermia on lymphocyte traffic in sheep in vivo. Deep hyperthermia has been applied both to primary peripheral lymph node drainage areas alone (popliteal and prefemoral) and directly over the study lymph node (popliteal). Deep tissue core temperatures were monitored in all studies and the findings were correlated with alterations in the levels of lymphocyte outputs into study node efferent lymph and the volume of efferent lymph flow. In all of 32 studies, there was a prompt and sharp increase in the output of lymphocytes into efferent lymph at 40-43 degrees C. Efferent lymph flow also was increased promptly but to a lesser degree than the output of lymphocytes. The two were not closely correlated. High deep temperature in the nodal area (45 degrees C) appeared to cause delayed nodal malfunction, which depressed lymphocyte output but did not affect lymph flow. Localized deep hyperthermia is an effective and noninvasive means for the local increase of lymphocyte traffic and lymph flow and may prove to be a useful means for the evaluation of the immunological consequences of altering both deep tissue temperature and lymphocyte traffic.
Animals↗
Natural history of surgically treated mucosal melanoma.
Thirty-three patients with melanoma arising in a mucosal site were reviewed. Sixteen patients were treated either with abdominoperineal resection or radical vulvectomy and superficial inguinal lymphadenectomy. Three patients were treated palliatively. Fourteen patients were treated conservatively with local excision, wide local excision, and radiation therapy. One patient received systemic chemotherapy and radiation therapy. Local recurrence developed in seven patients. The overall survival rate was poor. Neither local control nor survival appeared to be influenced by the initial surgical approach.
Adult↗