Showing papers by "Larry W. Oberley published in 1995"

Phenotypic changes induced in human breast cancer cells by overexpression of manganese-containing superoxide dismutase.

Abstract: Human manganese containing superoxide dismutase (MnSOD) cDNA was transfected into a human breast cancer cell line (MCF-7) in order to examine the effect of increased functional MnSOD on the cellular phenotype. A MnSOD-overexpressing clone was compared to control vector-transfected cells and to wild type MCF-7 cells. Southern blotting indicated incorporation of MnSOD cDNA into genomic DNA in the MnSOD overexpressing cell line. The MnSOD overexpressing cell line showed a 5.7-fold increase in MnSOD activity compared to wild type MCF-7 cells. Similar increases in MnSOD immunoreactive protein and mRNA levels were observed by Western and Northern blotting as well as using RT-PCR. The plating efficiency of cells grown in different concentrations of serum (1 to 20%) was decreased in the MnSOD overexpressing cell line. The clonogenic fraction in soft agar culture was also decreased after MnSOD cDNA transfection. When inoculated in nude mice, tumor growth was markedly inhibited in MnSOD overexpressing cells compared to wild type MCF-7 cells or plasmid control cells. These results support the hypothesis that increased MnSOD expression suppresses the malignant phenotype of human breast cancer cells and suggests that the MnSOD gene is a tumor suppressor gene in human breast cancer.

Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer : A new noninvasive predictive assay

Abstract: Purpose: This study investigated sequential changes in tumor blood supply using magnetic resonance (MR) perfusion imaging and assessed their significance in the prediction of outcome of patients with advanced cervical cancer The purpose of this project was to devise a simple, noninvasive method to predict early signs of treatment failure in advanced cervical cancer treated with conventional radiation therapy Methods and Materials: Sixty-eight MR perfusion studies were performed prospectively in 17 patients with squamous carcinomas (14) and adenocarcinomas (3) of the cervix, Stages bulky IB (1), IIB (5), IIIA (1), IIIB (8), and IVA (1), and recurrent (1) Four sequential studies were obtained in each patient: immediately before radiation therapy (pretherapy), after a dose of 20–22 Gy/∼2 weeks (early therapy), after a dose of 40–45 Gy/∼4–5 weeks (midtherapy), and 4–6 weeks after completion of therapy (follow-up) Perfusion imaging of the tumor was obtained at 3-s intervals in the sagittal plane A bolus of 01 mmol/kg of MR contrast material (gadoteridol) was injected intravenously 30 s after beginning image acquisition at a rate of 9 ml/s using a power injector Time/signal-intensity curves to reflect the onset, slope, and relative signal intensity (rSI) of contrast enhancement in the tumor region were generated Median follow-up was 8 months (range 3–18 months) Results: Tumors with a higher tissue perfusion (rSI ≥ 28) in the pretherapy and early therapy (20–22 Gy) studies had a lower incidence of local recurrence than those with a rSI of p = 005) An increase in tumor perfusion early during therapy (20–22 Gy), particularly to an rSI of ≥ 28, was the strongest predictor of local recurrence (0% vs 78%; p = 0002) However, pelvic examination during early therapy (20–22 Gy) commonly showed no appreciable tumor regression The slope of the time/signal-intensity curve obtained before and during radiation therapy also correlated with local recurrence Follow-up perfusion studies did not provide information to predict recurrence Conclusion: These preliminary results suggest that two simple MR perfusion studies before and early in therapy can offer important information on treatment outcome within the first 2 weeks of radiation therapy before response is evident by clinical examination Highg tumor perfusion before therapy and increasing or persistent high perfusion early during the course of therapy appear to be favorable signs High perfusion suggests a high blood and oxygen supply to the tumor The increase in tumor perfusion seen in some patients early during radiation therapy suggests improved oxygenation of previously hypoxic cells following early cell kill Radiation tehrapy is more effective in eradicating these tumors, resulting in improved local control Our technique may be helpful in identifying early —while more aggressive therapy can still be implemented—those patients who respond poorly to conventional radiation therapy

Immunohistochemical localization of antioxidant enzymes during hamster kidney development

Abstract: Immunolocalization studies of hamster kidney development were performed using polyclonal antibodies to antioxidant enzymes, including antibodies to copper, zinc and manganese superoxide dismutases, catalase, glutathione peroxidase and glutathioneS-transferases and their subunits. Antibodies to extracellular matrix proteins were also studied to determine the temporal sequence between expression of immunoreactive protein for basement membrane proteins, which serve as markers of embryonic induction of nephron development, and antioxidant enzyme expression in kidney development. Immunoreactive proteins for antioxidant enzymes were not detectable in the developing kidney until after extracellular matrix proteins had been deposited. However, immunoreactive proteins for the antioxidant enzymes copper, zinc and manganese superoxide dismutases, catalase, and α class glutathioneS-transferase Ya subunit were detected in renal tubules before birth. μ class glutathioneS-transferase subunits Yb1 and Yb2 stained transitional epithelium at high levels before birth. Our results indicate: (1) each type of kidney cell has a unique antioxidant enzyme profile, (2) antioxidant enzymes are expressed in different types of cell at different times during development, but antioxidant enzyme immunoreactive protein was not present until after immunoreactive proteins for extracellular matrix molecules were detected, and (3) certain antioxidant enzymes are present before birth, indicating that high oxygen tension present at birth is not crucial for induction of immunoreactive protein.