Effects of hyperthermia and/or hyperglycemia on pH and p02 in well oxygenated xenotransplanted human sarcoma

Roszinski, S.; Wiedemann, G. J.; Jiang, Shuai; Baretton, Gustavo; Wagner, Th.; Weiss, Christoph

doi:10.1016/0360-3016(91)90238-y

Cited by 39 publications

(14 citation statements)

References 16 publications

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“…The benefits of hyperthermia in the clinical setting (other than its cytotoxic and radiosensitizing effects) may result from improvements in oxygenation, as shown earlier in a series of human sarcoma patients (19,20). Results from several studies in rodent tumors and human tumor xenografts support the notion that an overall improvement in tumor oxygenation can result from lower thermal doses, whereas at higher thermal doses tumor oxygenation decreases (21)(22)(23)(24). These results are reviewed by Song et al (25).…”

Section: Discussionmentioning

confidence: 82%

Thermochemoradiotherapy Improves Oxygenation in Locally Advanced Breast Cancer

Jones

Prosnitz

Dewhirst

et al. 2004

Clinical Cancer Research

130

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Purpose: The purpose of this research was to evaluate toxicity, response, and changes in oxygenation (pO 2 ) in patients with locally advanced breast cancer (LABC) treated with concurrent taxol, hyperthermia (HT), and radiation therapy (RT) followed by mastectomy.Experimental Design: Eighteen patients with LABC were enrolled from October 1995 through February 1999. Treatment consisted of taxol (175 mg/m 2 ) given every 3 weeks for three cycles. Radiation therapy included the breast and regional nodes with a dose of 50 Gy, followed by a boost to 60 -65 Gy for those not undergoing surgery. Mastectomy was performed for patients deemed resectable after this neoadjuvant program. HT was administered twice per week. Oxygenation was measured before the first HT treatment and 24 h after the first HT treatment.Results: Fifteen of 18 patients responded, 6 with a clinical complete response, 9 with a partial clinical response, and 3 nonresponders. Thirteen underwent mastectomy with 3 pathological complete responses. Tumor hypoxia was present in 8 of 13 patients (pO 2 ‫؍‬ 4.7 ؎ 1.2 mmHg). Five patients had well-oxygenated tumors (pO 2 ‫؍‬ 27.6 ؎ 7.8 mmHg). Patients with well-oxygenated tumors before treatment as well as those with significant reoxygenation had a favorable clinical response. Tumor reoxygenation appeared to be temperature dependent and associated with the lower thermal doses.Conclusions: This novel therapeutic program resulted in a high response rate in patients with LABC. Hyperthermia may offer a strategy for improving tumor reoxygenation with consequent treatment response. However, the effect of hyperthermia on tumor reoxygenation appears to depend on thermal dose and requires additional investigation.

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Section: Discussionmentioning

confidence: 82%

Thermochemoradiotherapy Improves Oxygenation in Locally Advanced Breast Cancer

Jones

Prosnitz

Dewhirst

et al. 2004

Clinical Cancer Research

130

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“…Heating at high temperatures (44 -46 ºC) causes vascular damage and reduces the blood flow, while mild-temperature HT, 40-43 ºC, increases the blood flow in the tumor with little vascular damage [19]. In vivo investigations demonstrated that the mild HT with 42.5-43 ºC intensifies the blood flow and tumor tissue oxygenation [19][20][21][22]. This raises the effectiveness of the radiation and supports the transport of cytostatics in the tumor.…”

Section: Discussionmentioning

confidence: 99%

Posttreatment Histology and Microcirculation Status of Osteogenic Sarcoma after a Neoadjuvant Chemo- and Radiotherapy in Combination with Local Electromagnetic Hyperthermia

BogoviC

Douwes²,

Muravjov³

et al. 2001

Oncol Res Treat

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Background: Many biological attributes of tumors (including regional blood flow and microcirculation) can deteriorate the homogeneity of heat distribution and temperature elevation during hyperthermia. We analyzed the connection between the microcirculation status of osteogenic sarcomas and the posttreatment histology after neoadjuvant chemotherapy, irradiation and local hyperthermia. Patients and Methods: 62 patients with histologically verified osteosarcoma (35 men, 27 women, age 9–53, average 21 years) were enrolled in the retrospective pathohistological study. 61 patients were evaluable. In 72.6% of cases the tumor was localized in bones forming knee joints. All patients received neoadjuvant treatment [6 hyperthermias (60 min, 42–45 °C), daunorubicin 30–50 mg/m² , 6 infusions, adriamycin or cisplatin 30 mg/m² for 3 days or once 90 mg/m² monochemotherapy before the hyperthermic procedure; subsequently γ-therapy, 20–36 Gy] followed by surgery. From archives, a control group was formed of 20 therapy-naive tumors. Resected tumors were histologically examined for assessment of spontaneous and therapeutically induced alterations. For analysis of the functionality status of microcirculation on histological cuts, 40 tumors (without selection) were investigated: 10 controls and 10 cases each with minimal, subtotal and total posttreatment alterations. Results: Chemotherapy and radiotherapy in combination with local hyperthermia induced a distinct damage to osteosarcoma. In 39.3 and 35.7% of cases there was subtotal and total devitalization of tumor parenchyma, respectively. Thrombosis of magistral and middle vessels, stasis in the microcirculation tree (collapse), damage to intimal vessels and endothelial cells, and necrotic alterations of the vessel walls appeared predominantly in central areas of tumors. Tumors with minimal devitalization of the parenchyma had a share of nonfunctional vessels ranging from 10.6 to 61.7%, mean 29.7%. In tumors with subtotal necrosis, between 34.5 and 72.0% (mean 49.46%) of vessels were nonfunctional (stasis, thrombosis). In 10 cases with 100% necrosis of the osteosarcoma parenchyma, a mean of 56.05% of nonfunctional vessels was registered (12.3–83.0%). In the control group, between 2.85 and 73.4% (mean 21.69%) of vessels showed damage to the microcirculation. Conclusion: There is a direct correlation between deterioration of the microcirculation in osteosarcoma and thermo-radiochemotherapy- induced tissue alteration; the devitalization grade is directly proportional to the number of nonfunctional vessels in the tumor.

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“…These changes are most pronounced during S-phase and mitosis [1]. The perfusion of human tumors is increased by HT, leading to better oxygenation [2]. However,…”

mentioning

confidence: 99%

“…An increase in blood flow and tumor oxygenation [2] as well as an enhancement of the cytotoxic effect of multiple antineoplastic drugs [7][8][9][10][11][12][13] has been demonstrated. Data concerning the impact of WBH on stimulation of the immune system are now starting to emerge and results seem to indicate that WBH indeed activates the immune system, at least to some extent.…”

Section: Ht and The Immune Systemmentioning

confidence: 99%

Hyperthermia as an Adjunct to the Standard Treatment of Neoplastic Diseases: Few Cures but some Advances

Feyerabend¹,

Wiedemann²,

Richter³

et al. 1999

Oncol Res Treat

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Laboratory and clinical data confirm that hyperthermia may enhance the therapeutic index of ionizing radiation and specific cytotoxic drugs. As for whole-body hyperthermia (WBH), several generations of trials have been performed. Especially in refractory sarcomas, the combination of WBH and chemotherapy with ifosfamide, carboplatin, and etoposide led to a striking increase of response rates compared to chemotherapy alone. Toxicity of WBH procedures can be limited by using a radiant heat device. To evaluate the role of WBH in different tumor entities, several trials are under way. Hyperthermia, especially WBH, seems to stimulate the immune system, e. g. natural killer cell activity and number of cytotoxic T cells. Furthermore, the expression of the intracellular adhesion molecule 1 in tumors is enhanced by WBH, leading to an increased response of lymphokine-activated killer cells. As for locoregional hyperthermia, local control rates can be increased in combination with radiotherapy, e. g. in recurrent breast cancer and melanoma. Triple modality therapy (radiochemo-thermotherapy) seems to be useful especially in large lesions with poor prognosis.

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Effects of hyperthermia and/or hyperglycemia on pH and p02 in well oxygenated xenotransplanted human sarcoma

Cited by 39 publications

References 16 publications

Thermochemoradiotherapy Improves Oxygenation in Locally Advanced Breast Cancer

Thermochemoradiotherapy Improves Oxygenation in Locally Advanced Breast Cancer

Posttreatment Histology and Microcirculation Status of Osteogenic Sarcoma after a Neoadjuvant Chemo- and Radiotherapy in Combination with Local Electromagnetic Hyperthermia

Hyperthermia as an Adjunct to the Standard Treatment of Neoplastic Diseases: Few Cures but some Advances

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