Intravenous Infusion Of Bromodeoxyuridine Research Articles

Cellular dynamics of macrophages and microglial cells in reaction to stab wounds in rat cerebral cortex.

To examine the cellular dynamics of macrophages and microglial cells in response to cerebral injury, we studied the brain adjacent to cortical stab wounds in young adult rats. Brains were obtained 30 min after intravenous infusion of bromodeoxyuridine (BrdU) on one day (day 1) to 28 days (day 28) after wounding. Brain sections were double-labelled immunohistochemically for monocyte/macrophage antigen ED1 and for BrdU. ED1-positive (ED1+) cells were classified morphologically into two groups, ED1+L and ED1+S cells, representing macrophages and microglial cells, respectively. ED1+L cells appeared on day 1 after wounding and rapidly increased in number to reach a maximum on day 3, but quickly disappeared by day 5. ED1+S cells also appeared on day 1, but the increase in number was slower, reaching a maximum only on day 7. ED1+L cells were all negative for BrdU, but some ED1+S cells were stained for BrdU, evidence of proliferation. The present investigation demonstrated different cellular dynamics for macrophages and microglial cells responding to a stab wound, and also indicated differing sources for the two cell type. It may be possible to prevent the accumulation of these cells which are harmful to the brain in reducing the damage suffered.

Radiation therapy and bromodeoxyuridine chemotherapy followed by procarbazine, lomustine, and vincristine for the treatment of anaplastic gliomas

Purpose : To conduct a Phase II study to evaluate the long-term efficacy and safety of radiotherapy combined with intravenous bromodeoxyuridine for patients with anaplastic glioma tumors. Methods and Materials : Between 1983 and 1987, study patients received 1.7–1.8 Gy radiation once a day, Monday through Friday, to a toatl dose of 60 Gy. On the Thursday prior to beginning radiotherapy and for the next 5 weeks (6 weeks total), patients received a continuous 96 h intravenous infusion of bromodeoxyuridine at 0.8 g/m 2/24 h; following radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until tumor progressed. Results : One-hundred thirty eight patients (median age, 43 years) were evaluated for analysis. Estimated 4-year survival for the anaplastic astrocytoma (AA) stratum ( n = 116) is 46%. For the astrocytoma (ASTRO) stratum ( n = 22), the 6-year survival is estimated at 79%. Estimated 4-year progression-free survival for AAs is 42%, and for ASTROs, 68%. Whole brain irradiation was used in 23% and limited-field irradiation in 77%; patients receiving limited-field irradiation had a better survival rate ( p = 0.07). Total tumor resection was performed in 15%, partial resection in 53%, and biopsy only in 32%. For the 81 patients with tumor recurrence, 34 (42%) are known to have received additional treatment(s). For AA, fits of the Cox proportional hazards regression model showed that covariates individually predictive of survival were younger age ( p < 0.001), Karnofsky performance score ( p = 0.04), and extent of surgery ( p = 0.04); limited-field irradiation was not significant ( p = 0.10). Major toxicities were rash during Weeks 1 through 6 requiring dose modification in 14%, Garde ≥III leukopenia in 18%, and Grad ≥III thrombocytopeni in 9%. Conclusion : The study suggests that the bromodeoxyuridine-radiotherapy-PCV, compared with other published therapies, can improve progression-free survival, and aggressive treatment of ASTRO patients can lead to substantial increases in survival compared to published survival data.

Bromodeoxyuridine in vivo labeling による膀胱腫瘍のS期細胞の検討

At the time of operation, 10 patients with bladder tumors were given an intravenous infusion of bromodeoxyuridine (BrdU, 250 mg) to label the cells in the DNA synthesis phase (S-phase). The removed tumor specimens were stained immunohistologically using anti-BrdU monoclonal antibody. The percentage of BrdU-labeled cells (S-phase cells) were calculated for each specimen, and expressed as Labeling Index (LI). The average LI of G1, G2 and G3 tumors were 0.9%, 2.3% and 11.9%, respectively. LI was almost parallel to pathological grade. In cases of G2 tumor, LI was varied from 0.2 to 6.2%. The higher LI, the more invasive was the tumor. The patient with the highest LI (12.2%) showed lung metastasis postoperatively and died 6 months after operation. S-phase cells were scattered along the basal layer in G1 papillary tumors, and were observed also near the superficial layer in G2 tumors. In cases of non-papillary tumors, S-phase cells were observed irregularly in various layers. This method will give us useful information on evaluation for malignancy and cell kinetics of bladder tumor.

Variability in the proliferative potential of human gliomas

One hundred forty-three patients with gliomas of astrocytic origin (61 with glioblastomas multiforme (GM) and 82 with astrocytomas) received an intravenous infusion of bromodeoxyuridine (BUdR), 150-200 mg/m2 at the time of surgery, to label tumor cells undergoing DNA synthesis. BUdR-labeled cells were identified by the indirect immunoperoxidase method using anti-BUdR monoclonal antibodies. The percentage of BUdR-labeled cells, or BUdR labeling index (LI), was calculated by microscopic examination of selected viable areas of the tissue sections. The GMs had a median LI of 7.5%, and three quarters of these tumors had LIs greater than 5%. Highly anaplastic astrocytomas (HAAs) and moderately anaplastic astrocytomas (MoAAs) had median LIs of 2.3% and less than 1%, respectively. Among the HAAs, the LI was 1% to 5% in 56% of tumors, greater than 5% in 26%, and less than 1% in 18%. More than 60% of MoAAs had LIs less than 1%, which agrees with the slow clinical progression of this type of tumor, and the remainder had LIs of 1.4% to 9.3%. These results show that histopathologically similar tumors may have different proliferative potentials. Measuring the proliferative potential of individual gliomas is therefore crucial for predicting the prognosis more accurately and for devising more tumor-specific treatment regimens for individual patients.

In vivo determinations of labelling index of metastatic colorectal carcinoma and normal colonic mucosa using intravenous infusions of bromodeoxyuridine.

In vivo determination of the labelling index of metastatic colon carcinoma was performed in 14 patients following intravenous infusion of bromodeoxyuridine (BrdU), at doses of 100 and 50 mg/M2. No toxicity was seen. Labelled cells were detected by an immunohistochemical technique using a monoclonal antibody to BrdU. Labelling was uniform and highly specific with good preservation of morphology. Labelling index values ranged from 15.0-40.6% for metastatic lesions and 3.6%-20% for normal colonic mucosa, with mean values of 24% and 11%, respectively. This represents a useful new method for in vivo labelling index determination in solid tumors.

Proliferative potential of brain metastases

Thirteen patients with metastatic brain tumors received an intravenous infusion of bromodeoxyuridine (BUdR) 200 mg/m2 at craniotomy) to label S-phase tumor cells. Excised tumors were stained immunohistochemically for BUdR. The percentage of BUdR-positive cells was calculated to determine the BUdR labeling index (LI) (or fraction of S-phase cells), which provides an estimate of the proliferative potential. Histologically, 11 patients had adenocarcinoma (four well-differentiated, three moderately differentiated, and four poorly differentiated), one had a large cell carcinoma, and one had a small cell carcinoma. All tumors had a BUdR LI greater than 5% (mean, 13.3 +/- 7% standard deviation). Moderately and poorly differentiated adenocarcinomas had a higher LI than well-differentiated adenocarcinomas (median, 15.3% versus 8.2%). These LI values are considerably higher than those reported for primary tumors with comparable histologic features. Thus, metastatic tumors in the brain may grow faster than the primary tumors from which they originate.

S Phase Fraction of Human Bladder Tumor Measured in Situ with Bromodeoxyuridine Labeling

A total of 18 patients with transitional cell bladder cancer was given a 0.5-hour intravenous infusion of bromodeoxyuridine at the time of endoscopic biopsy or transurethral resection to label tumor cells in the deoxyribonucleic acid synthesis phase (S phase). The tumor specimens were fixed with 70per cent ethanol, embedded in paraffin, sectioned and stained by an indirect immunoperoxidase method with anti-bromodeoxyuridine monoclonal antibody as the first antibody. The bromodeoxyuridine labeling index, S phase fraction, was determined by counting the number of bromodeoxyuridine-labeled cells in the tissue sections. All grade 1 tumors had an S phase fraction of lower than 10per cent. The average S phase fractions for noninvasive (11 cases) and invasive (7) tumors were 9.8 and 20.0per cent, respectively. Two distant metastatic bladder tumors showed an average S phase fraction of 25.3 and 30.0per cent. Thus, transitional cell bladder cancers with an S phase fraction of greater than 10per cent appears to grow faster and be more invasive more often than those with an S phase fraction of less than 10per cent. The higher S phase fraction may indicate greater biological malignancy. Our preliminary results suggest that measurement of the bromodeoxyuridine labeling index in bladder tumors may be a new objective and quantitative assay of biological potential of individual tumors.

Differences in cell cycle characteristics among patients with acute nonlymphocytic leukemia

The proliferative characteristics of myeloid leukemias were defined in vivo after intravenous infusions of bromodeoxyuridine (BrdU) in 40 patients. The percentage of S-phase cells obtained from the biopsies (mean, 20%) were significantly higher (P = .00003) than those determined from the bone marrow (BM) aspirates (mean, 9%). The post- BrdU infusion BM aspirates from 40 patients were incubated with tritiated thymidine in vitro. These double-labeled slides were utilized to determine the duration of S-phase (Ts) in myeloblasts and their total cell cycle time (Tc). The Ts varied from four to 49 hours (mean, 19 hours; median, 17 hours). Similarly, there were wide variations in Tc of individual patients ranging from 16 to 292 hours (mean, 93 hours; median, 76 hours). There was no relationship between Tc and the percentage of S-phase cells, but there was a good correlation between Tc and Ts (r = .8). Patients with relapsed acute nonlymphocytic leukemia (ANLL) appeared to have a longer Ts and Tc than those studied at initial diagnosis. A subgroup of patients at either extreme of Tc were identified who demonstrated clinically documented resistance in response to multiple courses of chemotherapy. We conclude that Ts and Tc provide additional biologic information that may be valuable in understanding the variations observed in the natural history of ANLL.

Differences in Cell Cycle Characteristics Among Patients With Acute Nonlymphocytic Leukemia

The proliferative characteristics of myeloid leukemias were defined in vivo after intravenous infusions of bromodeoxyuridine (BrdU) in 40 patients. The percentage of S-phase cells obtained from the biopsies (mean, 20%) were significantly higher (P = .00003) than those determined from the bone marrow (BM) aspirates (mean, 9%). The post-BrdU infusion BM aspirates from 40 patients were incubated with tritiated thymidine in vitro. These double-labeled slides were utilized to determine the duration of S-phase (Ts) in myeloblasts and their total cell cycle time (Tc). The Ts varied from four to 49 hours (mean, 19 hours; median, 17 hours). Similarly, there were wide variations in Tc of individual patients ranging from 16 to 292 hours (mean, 93 hours; median, 76 hours). There was no relationship between Tc and the percentage of S-phase cells, but there was a good correlation between Tc and Ts (r = .8). Patients with relapsed acute nonlymphocytic leukemia (ANLL) appeared to have a longer Ts and Tc than those studied at initial diagnosis. A subgroup of patients at either extreme of Tc were identified who demonstrated clinically documented resistance in response to multiple courses of chemotherapy. We conclude that Ts and Tc provide additional biologic information that may be valuable in understanding the variations observed in the natural history of ANLL.

The use of prolonged constant intravenous infusions of bromodeoxyuridine (BUdR) as a radiosensitizer

The use of prolonged constant intravenous infusions of bromodeoxyuridine (BUdR) as a radiosensitizer