Search Results - (Author, Cooperation:H. Robins)

2014-11-28

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Adaptive Immunity/*immunology ; Aged ; Aged, 80 and over ; Biomarkers ; CD8-Positive T-Lymphocytes/cytology/*immunology ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; *Immunotherapy ; Male ; Melanoma/diagnosis/immunology/pathology/*therapy ; Middle Aged ; *Models, Biological ; Multivariate Analysis ; Programmed Cell Death 1 Receptor/antagonists & inhibitors/genetics/immunology ; Treatment Outcome

2013-05-10

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Adult ; CD8-Positive T-Lymphocytes/cytology/*immunology ; Clone Cells/cytology/immunology ; Herpes Genitalis/*immunology/virology ; Herpesvirus 2, Human/*immunology ; Humans ; Immunologic Memory/immunology ; *Immunologic Surveillance ; Receptors, Antigen, T-Cell, alpha-beta/immunology/metabolism ; Skin/*cytology/*immunology

2018-03-23

American Society of Hematology (ASH)

0006-4971

1528-0020

Biology

Medicine

Pediatric Hematology, Free Research Articles, Lymphoid Neoplasia, Clinical Trials and Observations

2018-07-24

The American Association of Immunologists (AAI)

0022-1767

1550-6606

Medicine

1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] Table 1 Lysis of autologous leukaemia cells by T cells sensitised to pooled allogeneic normal cells Responding %51Crrelease±s.d. T cells Stimulating cells from target cells Pi's splenic Pi's peripheral Pi's peripheral A's peripheral leukaemic cells leukaemic cells T ...

Electronic Resource

1432-1335

Key words Whole-body hyperthermia ; Nephrotoxicity ; Ifosfamide ; Carboplatin

Springer Online Journal Archives 1860-2000

Medicine

Abstract It was previously postulated on the basis of clinical data that the cardiovascular sequelae of extracorporeal whole-body hyperthermia (e-WBH), i.e., hypotension (which requires catecholamine support) results in unique nephrotoxicity in combination with select chemotherapeutic agents. In an attempt to explain this phenomenon, we mimicked e-WBH physiological conditions in a rat model. Animals were treated with and without ifosfamide (IFO) and/or carboplatin (CBDCA) at 37°C or 41.5–41.8°C, with blood pressure monitoring and catecholamine support comparable to the clinical setting. Ex vivo post-treatment data (24 h) from artificially perfused kidneys (i.e., histology, urine volume, perfusion rate, glomerular filtration rate, and the reabsorption of sodium, glucose, and water) demonstrated unique toxicity including proximal tubular necrosis for the combination of WBH and IFO, for WBH and CBDCA and for WBH and IFO plus CBDCA, but not for IFO and CBDCA without WBH. These data, considered together with results derived from a subsequent clinical trial and the laboratory work of others were consistent with the hypothesis.

Electronic Resource

1432-1335

Key words Whole-body hyperthermia ; Nephrotoxicity ; Ifosfamide ; Carboplatin ; Etoposide ; AbbreviationsICE ifosfamide, carboplatin, etoposide ; e-WBH extracorporeal whole-body hyperthemia ; r-WBH radiant-heat-induced whole-body hyperthermia

Springer Online Journal Archives 1860-2000

Medicine

Abstract Although whole-body hyperthermia combined with specific genotoxic chemotherapy can be shown to enhance neoplastic cell killing without a concomitant rise in bone marrow toxicity, nephrotoxicity can become treatment-limiting. This study compares the kidney toxicity to the kidney of ifosfamide, carboplatin and etoposide (ICE) chemotherapy alone, and ICE chemotherapy combined with either extracorporeal (e-WBH) or radiant-heat-induced hyperthermia (r-WBH) in 43 patients with refractory sarcoma. Within 3 days of ICE chemotherapy treatment there was a significant increase in urinary protein excretion and a reduction of the glomerular filtration rate. These effects were more pronounced if WBH was added. The use of immunoluminometric assays revealed a predominance of low-molecular-mass proteins. This increase in protein excretion persisted in the e-WBH-treated group, whereas it vanished within 3 weeks in both the group treated with ICE alone and that treated with r-WBH. Our findings suggest that ICE chemotherapy causes transient tubular and glomerular damage, which is enhanced by WBH. In terms of long-term nephrotoxicity e-WBH was more nephrotoxic than r-WBH. This finding is consistent with our clinical observations.

Electronic Resource

1432-0843

Key words Whole body hyperthermia  ;  Chemotherapy  ;   Ifosfamide

Springer Online Journal Archives 1860-2000

Medicine

Abstract Purpose: To study the effect of hyperthermia on the cytotoxicity of glucose isophosphoramide mustard (D-19575), a derivative of ifosfamide, which does not require activation and preclinically demonstrates less nephrotoxicity and myelosuppression than ifosfamide.Methods: In vitro studies (using a crystal violet cell survival assay) of the interaction of hyperthermia with D-19575, as well as the activated form of ifosfamide (4-hydroperoxy-ifosfamide, D-18851), were performed using L929 and OVCAR-3 cell lines held at various temperatures (i.e. 37 °C (control), 40.5 °C, 41.8 °C, 42.5 °C, and 43 °C) for 65 min.Results: The following thermal enhancement ratios (TER) were demonstrated: D-19575 in L929 1.2, 2.0 and 2.3 at 40.5, 41.8 and 42.5 °C, respectively; for D-18851 in L929 1.7 at 41.8 °C; for D-19575 in OVCAR-3 2.1, 3.2 and 3.3 at 40.5, 41.8 and 42.5 °C, respectively; for D-18851 in OVCAR-3 4.6 at 41.8 °C. Conclusion: The significant observed increase in cytotoxicity of D-19575 caused by hyperthermia taken together with its known preclinical toxicity profile, encourage its further preclinical and ultimately clinical testing, including its use with whole body and regional hyperthermia.

Electronic Resource

1432-0843

Key words Whole body hyperthermia ; Melphalan ; Tumor necrosis factor ; Melanoma

Springer Online Journal Archives 1860-2000

Medicine

Abstract Purpose: To evaluate the feasibility of sequencing (based on preclinical modeling) tumor necrosis factor-α (TNF) at two dose levels with melphalan (L-PAM) and 41.8 °C whole-body hyperthermia (WBH)  for 60 min. Patients and methods: Nine patients with refractory cancer were treated from October 1995 to June 1997. The study encompassed a total of 20 trimodality treatment courses. Three patients were treated at TNF dose level I (50 μg/m2) and six patients were treated at TNF dose level II (100 μg/m2). TNF was delivered as a 24-h intravenous infusion, 48 h prior to the combination of L-PAM and WBH; L-PAM was given over 10 min at target temperature at a dose of 17.5 mg/m2 based on a previous phase I WBH/L-PAM trial. WBH was administered with an Aquatherm radiant heat device. Results: Myelosuppression was the major toxicity associated with therapy, but there were no instances of bleeding or neutropenic fevers. Grade 3 thrombocytopenia was seen with 15% of treatments. Regarding absolute neutrophil count, 15% of treatments were associated with grade 3 toxicity, and 45% with grade 4 toxicity, and regarding white blood cell count, 50% of treatments were associated with grade 3 toxicity and 10% with grade 4 toxicity. The myelosuppression observed was equivalent to that seen in our earlier phase I study of WBH and L-PAM (without TNF). Only mild toxicities (grade 1 or 2) were associated with TNF; these were seen with ≤25% of treatments and included nausea, vomiting, diarrhea, fevers, and headache. There were no instances of hypotension. There was no relationship between toxicities observed and the two TNF dose levels. Mild WBH toxicities were seen with less than 15% of treatments; these included nausea, vomiting, and herpes simplex I. Responses included two complete remissions (malignant melanoma, TNF dose level I; breast cancer, TNF dose level II), and two disease stabilizations (both malignant melanoma, TNF dose level I). Conclusion: We conclude that the combination of TNF, L-PAM, and WBH is well tolerated at the dose levels studied. The clinical results justify further clinical investigation for this trimodality treatment approach.

Electronic Resource

1432-1238

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1573-0646

chemotherapy ; platinum (IV) analogues ; cisplatin resistance ; pharmacodynamics

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Abstract Ormaplatin (NSC 363812, tetraplatin) is a stable platinum (IV) analog which has exhibited activity against cisplatin-resistant cell lines. A phase I trial of ormaplatin administered as a 1-h infusion every 4 weeks was performed. Forty-one patients received 101 cycles of drug over the dose range 4–128 mg/m2. The dose-limiting toxicity was reversible thrombocytopenia and granulocytopenia. Minimal myelosuppression was observed at dose levels ≤ 78 mg/m2, while grade 3 or 4 myelosuppression (thrombocytopenia and/or granulocytopenia) was seen in 4/8 patients at 98 mg/m2 and 4/5 patients at 123 mg/m2. Nausea and vomiting was observed at all dose levels but was controlled with antiemetic premedication. Neurotoxicity was observed in 5/41 patients and the incidence appeared related to cumulative dose rather than to dose level or drug clearance. Platinum was measured by furnace atomic absorption spectrophotometry. Ormaplatin-derived plasma ultrafilterable platinum (UF-Pt) exhibited linear pharmacokinetics over the dose range studied. The mean total body clearance of UF-Pt was 135 ml/min/m2 and the mean elimination half-life (t1/2β) was 13.6 h. Ormaplatin exhibited a high degree of protein binding, with more than 70% of platinum protein bound by the end of the infusion. Urinary excretion of platinum accounted for 37% of the total dose of ormaplatin in 24 hours. A phase II dose of 98 mg/m2 is recommended for testing in a patient population with cisplatin-refractory disease.

Electronic Resource

1573-0646

diethyldithiocarbamate ; disulfiram ; cytotoxicity ; human ; cancer

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Summary Diethyldithiocarbamate (DDTC) and other dithiocarbamates are currently receiving attention as potential adjuncts to traditional chemotherapy. In vitro studies with rodent cancer cell lines have consistently shown that DDTC concentrations of 0.1–1.0μ g/ml are highly cytotoxic. Paradoxically, however, concentrations of 10–100 μg/ml have been significantly less toxic. In the present study, such a ‘biphasic’ pattern was reproduced when 3 rodent cell lines were exposed for 1 hour to 0.001 to 1000 μg DDTC/ml. In contrast, in 7 human cell lines survival decreased steadily with increasing DDTC concentration (in the same dose range) without evidence of a biphasic pattern. These data might have implications for studies in which rodent cell lines are used to model the effects of dithiocarbamates in human tissues.

Electronic Resource

1573-0646

lonidamine ; breast cancer

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Summary The Eastern Cooperative Oncology Group conducted a phase II study of lonidamine in patients with metastatic breast cancer. The drug was given orally to a maximum daily dose of 340 mg/m2. Forty-two patients were entered on study. One partial response was observed; there were no life-threatening toxicities. The results of this study are compared to two similar phase II trials.

Electronic Resource

1573-7373

glioblastoma multiforme ; anaplastic astrocytoma ; high grade glioma ; etoposide (VP-16) ; procarbazine ; vincristine

Springer Online Journal Archives 1860-2000

Medicine

Abstract This study is a combined modality Phase II therapeutic trial to determine the efficacy of the novel combination of VP-16, Vincristine and Procarbazine in addition to postoperative radiation therapy in patients with high grade intracranial gliomas. Thirty three patients (median age 51 years) were entered (27 with glioblastoma multiforme, 6 with anaplastic astrocytoma). Toxicity was manageable with no lethal toxicities. Five of seven life threatening toxicities were hematologic. Median overall survival was 14.2 months. These data suggest this regimen is effective treatment for patients with high grade gliomas.

Electronic Resource

1573-7373

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1573-7373

glioma ; hyperthermia ; carboplatin ; thymidine

Springer Online Journal Archives 1860-2000

Medicine

Summary Thymidine (a nucleoside metabolite) and 41.8° C hyperthermia were used to sensitize C6 glioma cells to carboplatin cytotoxicity in vitro. Clinically achievable thymidine concentrations (0, 200, 400, or 1000 µg/ml × 24 hours) significantly enhanced carboplatin killing. Clinically achievable hyperthermia exposures (40.5 or 41.8° C x 1 hour) also enhanced carboplatin killing; 41.8° C was more effective than was 40.5° C. Thymidine and 41.8°C hyperthermia together enhanced carboplatin killing significantly more than did the thymidine-carboplatin or hyperthermia-carboplatin combinations. These results illustrate the concept of ‘combination chemosensitization’ for simultaneously addressing the divergent drug resistance mechanisms of malignant gliomas.

Electronic Resource

1573-8752

Radiosurgery ; glioblastoma multiforme ; recurrence ; liver metastases

Springer Online Journal Archives 1860-2000

Medicine

Abstract A rare case of isolated liver metastases in a patient with recurrent glioblastoma multiforme (GBM) treated with surgery, chemotherapy, external beam irradiation, and salvage stereotactic radiosurgery is described. Our review of literature has revealed only 8 other cases of isolated liver metastases in patients with GBM in the last three decades. Recent data suggest that stereotactic radiosurgery may alter the prognosis of specific subsets of patients with GBM. The potential for combined modality therapy, including radiosurgery to impact on the survival of GBM patients, and, hence, the natural history of this disease, is discussed.

Electronic Resource