Prediction of breast cancer size by ultrasound, mammography and core biopsy.

Neoadjuvant chemotherapy and non-surgical tumor ablation rely upon imaging studies to determine tumor size. In this study the accuracy of ultrasound (US) mammography and core biopsy in determining tumor size was examined in 202 patients with Stages I and II breast cancer. The most accurate single modality for determining tumor size was mammography with a correlation coefficient of 0.66, followed by US (r = 0.48) and core biopsy (r = 0.28). Size measurements were less accurate in lobular than ductal cancers. The combination of the three modalities understaged 25% of the tumors > 1cm in size, and overstaged 10% of those < 1cm. The inability to accurately determine tumor size has important implications for the use of non-surgical ablation.

Endogenous c-N-Ras provides a steady-state anti-apoptotic signal.

We report that c-N-Ras possesses an isoform-specific, functional role in cell survival under steady-state conditions. This function includes protection from programmed cell death by serum deprivation or upon treatment with apoptosis-inducing agents. The data demonstrate that c-N-Ras may play a functional role in the regulation of steady-state phosphorylated Akt and serine 136-phosphorylated Bad (Ser(136)-pBad). Immortalized N-Ras knockout fibroblasts possess nearly undetectable levels of steady-state Ser(136)-pBad. In contrast, wild-type control cells and the N-Ras knockout cells ectopically expressing c-N-Ras at control levels maintained easily detectable levels of Ser(136)-pBad both at steady-state and following treatment with tumor necrosis factor alpha. Similar results were seen with Ser(112)-pBad. These differences did not arise from differences in total Bad protein levels. These data correlate with the observation that the N-Ras knockout cells exhibit a heightened susceptibility to the induction of apoptosis. Ectopic expression of c-N-Ras in the N-Ras knockout cells at endogenous levels, compared with control cells, significantly rescues the apoptotically sensitive phenotype. Elevated expression of either c-Kirsten A-Ras or c-Kirsten B-Ras did not reverse the apoptotic sensitivity of the N-Ras knockout cells or result in increased levels of either phospho-Akt or phospho-Bad. Our results indicate that, at steady state, c-N-Ras possesses an isoform-specific, functional role in cell survival.

Alterations in the phosphorylation and activity of DNA polymerase alpha correlate with the change in replicative DNA synthesis as quiescent cells re-enter the cell cycle.

The regulation of DNA polymerase alpha was examined in quiescent, human fibroblast cells stimulated to re-enter the cell cycle by subculturing in fresh serum-containing medium. The level of DNA polymerase alpha activity was measured in cell lysates and after specific immunoprecipitation. DNA polymerase alpha activity increased approximately 10-fold during the period of measurement. The activity increase was coincident with an approximately 60-fold increase in thymidine incorporation in the whole cells representing the first S phase. The large increase in polymerase alpha activity was not predominantly the result of synthesis of new polymerase, since the abundance of the enzyme changed less than 2-fold over the measured period. The quantity of [32P]phosphate incorporated into two subunits (180 and 68 kilodaltons) of DNA polymerase alpha increased approximately 10-fold in parallel with the increase in polymerase activity. The specific activity of the cellular ATP pool remained nearly constant over the period of measurement, indicating that the increase in labeling reflects a true increase in incorporation of phosphate. Results from other laboratories indicate that phosphorylation of DNA polymerase alpha increases its catalytic activity. Our results then suggest that the activity increase observed in DNA polymerase alpha when quiescent, human fibroblasts are stimulated to proliferate is largely caused by a phosphorylation-dependent regulatory process.

Interspecies Lewis lung carcinoma x Chinese hamster ovary hybrids as protective agents against Lewis lung carcinoma tumor growth.

Interspecies somatic cell hybrids formed between a clone of Lewis lung carcinoma (LLC/9) and Chinese hamster ovary cells were assessed for tumorigenicity in C57BL/6 mice and capacity to protect mice against a challenge with LLC/9 cells. LLC/9 cells were fused with ouabain-resistant-Chinese hamster ovary cells deficient in hypoxanthine guanine phosphoribosyl transferase. Hybrids were selected in medium supplemented with hypoxanthine: aminopterin: thymidine and 5 mM ouabain. Hybrids were shown to contain chromosomes and surface antigens of both parents. At doses up to 10(7) cells, uncloned hybrids and hybrid clones obtained by limiting dilution were nontumorigenic in C57BL/6 mice, while 10(4) LLC/9 cells were tumorigenic in 80% of mice. In protection experiments, hybrid cells were injected i.p., followed by foot pad challenge with 10(6) LLC/9 cells. Three injections of live uncloned hybrids produced complete protection, while one or two injections gave partial protection. Individual live hybrid clones conferred no or partial but never complete protection. Administration of hybrids or LLC cells killed by freezing and thawing or arrested in division by treatment with mitomycin C failed to confer protection against subsequent challenge with LLC/9 cells. These LLC/9 X CHO hybrid cells will be useful for studying therapy of primary LLC tumors and their pulmonary metastases.

Studies on a radioassay for intrinsic factor antibody: comparison of methods and false positive results due to elevated serum B12 levels.

Availability of a kit method (Corning Immo Phase IFAB) for intrinsic factor antibody (IFAB) has made it possible for a routine radioimmunoassay (RIA) laboratory to test for the antibody, thereby providing another aid in diagnosing pernicious anemia. Comparison of data from a charcoal method with the kit method was favorable, each method detecting 35 (74%) positives and 12 (26%) negatives of 47 pernicious anemia patients. Compared with a charcoal method study the kit method had fewer false positives due to elevated serum B12. False positive results occurred for only 24 hours after a 1-mg injection of B12, and results remained negative the following seven days. The authors' studies supported the manufacturer's statement that results are unreliable when the serum B12 level exceeds 3,500 pg/ml. Clinical experience with the Corning Immo Phase IFAB test and false positive results is summarized.