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Biomedical subjects

C M Rose

Publications and source records attributed to C M Rose.

At least 37 records · Page 2Linked to original sources
PubMed1988

Effect of various oxygenation conditions and fluosol-DA on cancer chemotherapeutic agents.

Adding Fluosol-DA and carbogen breathing to treatment with various anticancer drugs can result in a significant enhancement of tumor growth delay compared to the drug and air breathing. The optimal conditions for tumor response depend upon the drug, oxygenation level and duration, and perfluorochemical emulsion dosage. In this study, representative chemotherapeutic agents from several classes were tested in a tumor growth delay assay in combination with various doses of Fluosol-DA under conditions of normal aeration, carbogen breathing either for 1-2 hours or 6 hours, or with hyperbaric 100% oxygen (3 atmospheres) breathing for 1 hour to determine whether the antitumor activity of these drugs would be improved.

Animals↗
PubMed1987

Comparison of sustained-release with standard tiaprofenic acid in the treatment of rheumatic diseases in general practice.

An open, parallel-group study was carried out to compare the efficacy and tolerance of a sustained-release capsule formulation of tiaprofenic acid at a dosage of 600 mg once daily with standard 300 mg tiaprofenic acid tablets given twice daily. Four hundred and eighty-five general practice patients with rheumatic disease requiring long-term non-steroidal anti-inflammatory drug therapy were included in the analysis. Patients were randomly allocated to receive, in a ratio of 3:1, either 2 X 300 mg sustained-release capsules at night or standard 300 mg tablets twice daily for a treatment period of 3 months. Pain, impairment of function and duration of morning stiffness were assessed at Week 0 (after a 3-day washout period) and at the end of Weeks 4, 8 and 12. Side-effects and compliance were also recorded at the end of Weeks 4, 8 and 12. Eighty-one (16.7%) patients withdrew from the study, with no significant difference in the withdrawal rates for the two treatment groups. Both treatment groups showed significant improvements clinically during tiaprofenic acid treatment; there were no significant differences between the two groups at Weeks 4, 8 or 12, nor were there any significant differences between the two treatment groups in the number of patients reporting side-effects at any of the assessments. In total, 36% of patients reported side-effects during the trial. The results indicate that both formulations are effective, well-tolerated treatments for rheumatic disease in general practice.

Adult↗
PubMed1986

Effect of Fluosol-DA/O2 on tumor-cell and bone-marrow cytotoxicity of nitrosoureas in mice bearing FSA-II fibrosarcoma.

The perfluorochemical emulsion, Fluosol-DA, combined with carbogen breathing, potentiates the effects of radiation and a number of chemotherapeutic agents in several rodent tumors. The interaction of Fluosol-DA with drugs may be quite complex. In addition to increasing the oxygen supply in the tumor, Fluosol-DA may alter the pharmacokinetics of the drug and function as a drug delivery system. A series of 4 nitrosoureas of varying lipophilicity were administered as single doses intravenously (i.v.) to C3H/Be/FeJ mice bearing subcutaneous FSa-IIC fibrosarcomas. Doses of 40 mg/kg of CCNU, 15 mg/kg of BCNU, 20 mg/kg of MeCCNU and 15 mg/kg of chlorozoticin followed by 2 hr of breathing 95% oxygen produced tumor growth delays of 7.5, 4.0, 3.8 and 2.7 days, respectively. When the drug injection was followed immediately by 0.3 ml of Fluosol-DA and 2 hr of breathing 95% oxygen, the tumor growth delay produced by CCNU, BCNU, MeCCNU and chlorozoticin increased 2-fold, 10-fold, 4.5-fold and 3.5-fold, respectively. Administration of the drugs in Fluosol-DA followed by 2 hr of 95% oxygen breathing resulted in a 3.5-fold increase in tumor growth delay with CCNU, a 17-fold increase with BCNU, a 12.5-fold increase with MeCCNU and a 6-fold increase with chlorozoticin compared to drug and 95% oxygen breathing. These results are quantified in terms of cell survival by the tumor excision assay. Effects on the bone marrow from each treatment were measured using the granulocyte-monocyte colony-forming units (CFU-GM) assay. There was no correlation between the lipophilicity of the nitrosoureas tested and the tumor growth delay produced by each treatment.

Animals↗
PubMed1986

Effect of Fluosol-DA/O2 on the antitumor activity and pulmonary toxicity of bleomycin.

The effect of an oxygen-carrying perfluorochemical emulsion on bleomycin antitumor activity and pulmonary toxicity was examined. Fluosol-DA (0.3 ml/mouse, i.v.), combined with bleomycin (10 or 15 mg/kg, i.p.) and a 2 h exposure to 95% oxygen (BFO) increased by five- to six-fold the tumor growth delay of FSaIIC fibrosarcoma compared to bleomycin alone (B). Only a slight increase in tumor growth delay was noted with the incomplete combinations of bleomycin and O2 (BO) and bleomycin and Fluosol-DA (BF). When bleomycin (10 mg/kg) was co-administered with 0.3 ml Fluosol-DA and 95% O2, cell survival was reduced ten-fold compared to that seen with bleomycin alone. In contrast, the surviving fraction of cells obtained from FSaIIC tumors treated in vivo indicated that 0.3 ml Fluosol-DA per mouse or a 2 h exposure to 95% O2 did not markedly alter the effects of bleomycin alone. The pulmonary effects of the BFO combination were assessed during the course of the therapy by bronchoalveolar lavage (BAL) analysis and pulmonary hydroxyproline (OH-Pro) content. Mice treated with this combination had a 20-fold increase in total numbers of cells obtained in the BAL compared to control animals. An increased cellularity in the lungs was also seen morphologically. The composition of the cells in the lavage fluid was altered after BFO but not BO treatment and reflected a neutrophilic influx. Furthermore, total protein recovered in the BAL fluid was increased 5-fold in the BFO treatment group compared to that in the control mice. Pulmonary OH-Pro, an index of collagen and fibrosis, was unaffected acutely after three treatments of either BFO or BO compared to control mice. Thus, Fluosol-DA and O2 can enhance the antitumor activity of bleomycin. The increased pulmonary cellularity suggests that this combination may also have adverse effects on lung tissue.

Animals↗
PubMed1986

Effects of dose and scheduling on growth delay of the Lewis lung carcinoma produced by the perfluorochemical emulsion, Fluosol-DA.

The perfluorochemical emulsion, Fluosol-DA, combined with breathing a 95% oxygen/5% carbon dioxide atmosphere enhances the response of several rodent tumors. B6D2F1/J mice bearing Lewis lung tumors, measuring 50-100 mm3 were treated with 4, 8 and 12 ml/kg of Fluosol-DA intravenously each morning. Three Gy fractions twice per day were employed and carbogen breathing was maintained 1 hr prior to and during each X ray treatment. The dose modifying factors were 1.42 +/- 0.16 at 4 ml/kg, 1.85 +/- 0.23 at 8 ml/kg, and 2.17 +/- 0.34 at 12 ml/kg. In a second experiment, a single dose of Fluosol-DA (12 ml/kg) was administered on day 1 to B6D2F1/J male mice, bearing established subcutaneous Lewis lung tumors, as described above. X rays were delivered in 2, 3, or 4 Gy fractions once per day for five days. The dose modifying effect was 2.60 +/- 0.54. The effect of this treatment program was the same as that seen with single dose radiation. These experiments demonstrate that Fluosol-DA need not be administered with every fraction to produce an improved treatment outcome with fractionated X rays.

Animals↗
PubMed1985

Differential enhancement of melphalan cytotoxicity in tumor and normal tissue by Fluosol-DA and oxygen breathing.

The addition of Fluosol-DA carbogen breathing to melphalan treatment of the FSa-IIC fibrosarcoma was assessed by tumor growth delay and cell survival assays. Melphalan (10 mg/kg) administered intraperitoneally (i.p.) was preceded by Fluosol-DA (0.3 ml) administered intravenously (i.v.) and followed by 1 hr of carbogen breathing; this resulted in a tumor growth delay of 9.5 +/- 1.4 days or an approximately 3-fold increase compared to melphalan alone. Melphalan produced about 1.7 logs of cell killing; neither carbogen breathing nor Fluosol-DA pretreatment altered the cell killing observed. There was a 10-fold increase in tumor-cell killing when Fluosol-DA was administered immediately prior to melphalan administration followed by carbogen breathing for 1 hr. Density gradient separation identified a population of denser FSa-IIC cells which showed increased sensitivity to melphalan after Fluosol-DA administration. There was no additional toxicity to bone marrow as measured by CFU-GM with the combination of melphalan/Fluosol-DA/O2 compared to melphalan alone.

Animals↗
PubMed1985

Effect of oxygen on the cytotoxicity and antitumor activity of etoposide.

The selective cytotoxicity of the epipodophyllotoxin etoposide toward normally oxygenated and hypoxic EMT6 mouse mammary tumor cells in culture was examined. Etoposide was much more toxic to normally oxygenated cells. The ratio (hypoxic to oxygenated) of drug concentrations producing 1 log of cell kill was approximately 30:1. Established FSa-11C fibrosarcomas of C3HeB/FeJ mice were treated with 10, 15, or 20 mg etoposide/kg body weight in a 6-day protocol. Fluosol-DA with or without breathing of carbogen (i.e., 95% O2-5% CO2) was added to the treatment program on days 1, 3, and 5. The combination of etoposide-Fluosol-DA-carbogen markedly enhanced tumor growth delay compared to the result with etoposide alone. The dose-modifying effect observed was 1.9 +/- 0.3. With the use of both single-dose and multiple-dose protocols for etoposide and Fluosol-DA with air or carbogen breathing, the survival of bone marrow cells was measured by colony formation in vitro (granulocyte-monocyte colony-forming units). Fluosol-DA and carbogen breathing did not increase the toxicity of etoposide to the bone marrow. Thus the enhancement in antitumor activity produced by the addition of Fluosol-DA and carbogen breathing to etoposide treatment was not accompanied by a concomitant increase in normal tissue toxicity and represents an increase in the therapeutic efficacy of etoposide.

Animals↗
PubMed1984

Perfluorochemical emulsions can increase tumor radiosensitivity.

An oxygen-carrying perfluorochemical emulsion enhanced the effectiveness of radiation therapy in two transplantable solid tumors in mice. The perfluorochemical emulsion had no effect on tumor growth after x-irradiation, but delayed tumor growth significantly when administered to oxygen-breathing mice before or during irradiation.

Animals↗
PubMed1984

Oxygen-carrying perfluorochemical emulsion as an adjuvant to radiation therapy in mice.

The potential of an oxygen-carrying perfluorochemical emulsion (PFCE) to enhance radiation damage in Lewis lung tumor growing in C57BL/6J X DBA/2J F1 mice was examined. PFCE and 95% O2:5% CO2 (carbogen) breathing caused a significant enhancement of single-fraction radiation damage measured by the growth delay assay. The dose-response effect of PFCE was very broad; doses as small as 0.5 ml/mouse were effective, and doses of 0.3 to 0.4 ml/mouse gave maximal enhancement. The peak dose-modifying factor was 2.8 +/- 0.6 (S.E.). The addition of 0.3 ml of perfluorochemical-free annex solution with carbogen breathing produced a smaller enhancement in tumor growth delay; the dose-modifying factor was 1.5 +/- 0.2. When the perfluorochemical treatment was added to a fractionated course of radiation therapy, a dose-modifying effect of 1.8 +/- 0.3 was obtained. Oxygen-carrying PFCE may provide a nontoxic, clinically useful method of increasing the effectiveness of radiation therapy and of certain chemotherapeutic agents.

Animals↗
PubMed1983

Radiobiologic research for head and neck cancer therapy. Therapeutic implications.

Hypoxic cell sensitizers, particle therapy, hyperthermia, and combinations of chemotherapy and radiotherapy have potential to increase the therapeutic ratio in future clinical radiotherapy treatment regimens. The biologic bases of these investigations are beginning to appear as avenues of clinical investigation.

Head and Neck Neoplasms↗
PubMed1983

Axillary sampling in the definitive treatment of breast cancer by radiation therapy and lumpectomy.

Between January, 1967 and July, 1980, 176 women who were referred to the Joint Center for Radiation Therapy (JCRT) for definitive breast irradiation underwent low axillary dissection. A typical operative technique is described. The dissection stops short of the axillary vein although the vein is usually visualized. One hundred thirty-two axillae were thought to be N0 or N1a. Forty-six axillae were felt to be N1b. Seventeen percent of the T1 N0 patients had pathologically positive nodes. Twenty-seven percent of the T2 N0 patients had positive nodes. When 5 or less nodes were removed at axillary sampling the incidence of nodal involvement was very low. There were no differences in nodal positivity when comparing upper quadrant to lower or central lesions. Lateral lesions appeared to have higher positivity rates compared with either medial or central lesions. Ninety-four percent of axillae with N1b lesions were pathologically confirmed. The complication rate for this procedure was low. There were 5 transient non-surgical complications and 1 cellulitis resulting in a frozen shoulder, which required corrective surgery. There were no cases of moderate or severe arm edema. Axillary sampling is compared to axillary dissection as a diagnostic procedure. Axillary sampling may underestimate the true pathologic positive rate, but diagnostic accuracy appears excellent if level 1 and 2 nodes are sampled.

Axilla↗
PubMed1982

The role of postoperative local or regional irradiation in the treatment of stage I ovarian cancer.

Histological grade and cell type were major prognostic factors in a retrospective study of 63 patients with Stage I epithelial carcinoma of the ovary. Grading by architectural pattern seemed to predict relapse better than cytological grading. With serous, mucinous, and endometrioid cystadenocarcinomas, relapses increased with higher grades. Relapse occurred in none of 18 tumors of borderline malignancy, 2 of 27 (7%) with Grade I or II tumor, and 4 of 6 (67%) with Grade III. The upper abdomen and pelvis were both at risk. Because most recurrences were limited to the peritoneal surface in Grade III serous, mucinous, and endometrioid carcinoma, local and regional radiation therapy are justified; postoperative therapy is not recommended for borderline or Grade I tumors unless ascites or cytological evidence of peritoneal disease is present. Clear-cell carcinoma was uncommon and unfavorable; of 12 cases, 5 involved relapse, with 3 recurrences developing outside the abdomen.

Adult↗
PubMed1981

Enhanced cell killing in lewis lung carcinoma and a human pancreatic-carcinoma xenograft by the combination of cytotoxic drugs and misonidazole.

The "chemosensitizing" properties of the radiosensitizer misonidazole (MISO) were examined in 2 tumour systems, murine Lewis lung carcinoma and human pancreatic adenocarcinoma xenografted into immune-suppressed mice, using a soft-agar colony assay to measure tumour-cell survival. In mice bearing Lewis lung tumour, the administration of MISO simultaneously with melphalan, cyclophosphamide. CCNU, FU or vincristine gave substantial enhancement of cytotoxicity (DEFs from 1.5 to 3.5). However, no enhancement was seen with bleomycin, VP 16-213 or cis-Pt. The same level of enhancement of cyclophosphamide effect (DEF = 2.0) was seen with both cell survival and growth delay end-points effect (DEF = 2.0) was seen with both cell survival and growth delay end-points of tumour response. Enhancement was also seen in the human tumour xenograft with melphalan, cyclophosphamide and MeCCNU, using a cell survival assay, but cis-Pt was again not enhanced.

Adenocarcinoma↗