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Background: This study compared the findings of cervical cytology screening by ThinPrep Papanicolaou (Pap) tests (TP) with the findings of screening by conventional cervical smears (CS) in a screening population involving what to the authors' knowledge is the largest sample of ThinPrep Pap tests published to date., Method: Data from 191,581 CS that were screened in the period from March 1, 1998 to February 28, 2000 were compared with data from 190,667 TP performed from March 1, 2000 to February 28, 2002 and that were obtained from the same sources., Results: With TP, the unsatisfactory rate was reduced from 0.48% to 0.32%. Fewer cases were considered to be suboptimal (19.12% vs. 12.97%). The detection rates of squamous cell carcinomas, adenocarcinomas, and high-grade squamous intraepithelial lesions (HSIL) were essentially unchanged in the TP group (0.005%, 0.003%, and 0.25%, respectively) compared with the rates for the CS group (0.01%, 0.006%, and 0.25%, respectively). There was an increase in the detection of atypical squamous cells of undetermined significance (ASCUS; 3.74% vs. 3.19%) and low-grade SIL (LSIL; 1.67% vs. 1.01%) with a decrease in the ASCUS-to-LSIL ratio from 3.15 for CS to 2.33 for TP. The detection of atypical glandular cells of undetermined significance (AGUS) increased slightly from 0.07% to 0.09%. The proportion of cells reported to have reactive atypia dropped from 2.71% to 1.48%. Limited biopsy correlation (range, 73.2-76.2%) confirmed the increased sensitivity of TP. More actinomyces (1.07% vs. 0.52%) were detected in TP samples despite of a similar portion of intrauterine-device users. The average primary screening and rapid rescreening time of each slide were reduced from 8 minutes to 4 minutes and from 2 minutes to less than 1 minute, respectively., Conclusions: The preliminary experience of the authors of the current study appears to support the use of the ThinPrep Pap test to enhance the efficiency of cervical cytology screening., (Copyright 2003 American Cancer Society.)

Tamoxifen (NSC-180973), a synthetic antiestrogen, was studied for efficacy and toxicity in patients with metastatic breast adenocarcinoma. Two dose levels were used, 10 mg bid and 15 mg/m2 bid, in separate groups. In the 10-mg bid dosage group, 30 of the 31 patients were considered evaluable for efficacy. Five complete and 11 partial responses were recorded, for an overall response rate of 53%. In the 15-mg/m2 bid dosage group, 44 of the 45 patients were considered evaluable for efficacy. Three complete and 16 partial responses were recorded, for an overall response rate of 43%. All 76 patients were evaluated for toxicity. Side effects were generally mild, consisting mostly of hot flushes, transient leukopenia, transient thrombocytopenia, nausea, and fluid retention. A high degree of correlation between response and positive estrogen-receptor assay suggests the value of the test as a means to select patients for tamoxifen treatment. The conclusion from this study is that tamoxifen used as a single agent is an effective drug with minimal toxicity for treatment of metastatic breast adenocarcinoma.

Hormonal influences on dimethylbenz(a)anthracene-induced tumor growth were investigated in detail by endocrine ablation and replacement of hormones. The majority of tumors regressed following ablation and most of them were reactivated by subsequent administrations of estrogen (0.1 to 5 mug) or prolactin (2 mg). Increasing numbers of tumors, however, were not stimulated by prolactin when administration was delayed, and a basal level of estradiol (0.01 mug) in addition to prolactin was required for reactivation of tumors. Nafoxidine hydrochloride, a competitor of estrogen at the receptor sites, arrested growth of a large portion of dimethylbenz(a)anthracene-induced tumors in intact animals but failed to retard growth of prolactin-stimulated tumors. On withdrawal of prolactin-nafoxidine, rapid regression of tumor occurred and readministration of prolactin failed to activate most of the tumors for as long as 28 days. Our results give good supporting evidence that estrogen plays a primary role in tumor growth. The interactions of prolactin and estrogen at tumor sites are necessary for regulatory events related to tumor growth.

From 1977 to 1981, 39 cases of primary cervical carcinoma were assayed for the presence or absence of cytoplasmic estrogen (ERc) and progesterone (PRc) receptors by a saturation point dextran-coated charcoal assay. The levels of ERc and PRc were compared with clinical stage, histologic type, histologic grade, menstrual status, age, and survival. Carcinomas were divided into positive and negative receptor groups with the use of greater than 5 fmol/mg of cytosol protein for ERc and 10 fmol/mg of cytosol protein for PRc as discrimination points. Survival of the patients studied was computed by means of the product-limit analysis according to Kaplan-Meier. A statistically significant difference in survival in the PRc + group versus the PRc - group in the total group of patients was noted with the Mantel-Cox test (P = 0.049). When patients were stratified according to menopausal status, a statistically significant difference in survival was noted between the PRc + group versus the PRc - group in the premenopausal patients only.

Both serum and estrogen affect cell proliferation in CAMA-1 cells. Their effects on cell cycle kinetics are being investigated with partially synchronized cells following 48 hours of serum deprivation. By comparing the growth kinetics of synchronized (serum-deprived) cells with asynchronized (normal-fed) cells, we observed that there was a delay of cell proliferation for approximately 25 hr for synchronized cells and that estrogen only induced cell proliferation in serum-supplemented culture. A serum protein (RPF), precipitated by ammonium sulfate, dialyzed in 3,500 daltons cut off membrane and reconstituted in culture medium, was shown to stimulate cell proliferation in a dose-related manner. In the absence of RPF, estrogen had no effect on cell growth and S-phase formation in serum-free medium, but significantly induced cell growth in the presence of RPF. Experiments conducted with a synchronized cell population showed that estrogen increased the proportion of G1 phase cells to enter S phase, shortened the G1 phase duration, and ultimately increased the proportion of mitotic cells per cycle. Collectively, these results show that (a) estrogen effects of cell proliferation in vitro requires a serum component, a "G1/S-promoting factor" and (b) estrogen-induced tumor growth is a result of an accelerated rate of G1/S transition and an increased number of dividing cells per cycle. The knowledge of the interaction of estrogen with the G1/S promoting factor on cell growth is of both fundamental and therapeutic importance.

Phospholipids and their acyl group composition in mammary adenocarcinomas and mammary tissue of the same tumor-bearing animals were investigated. Breast adenocarcinoma induced by dimethybenz(a)anthracene exhibited a phospholipid pattern which was different from that of the mammary tissue. Tumor phospholipids had higher proportions of diacyl-GPI, diacyl-GPE, and alkenylacyl-GPE and a lower proportion of diacyl-GPC than the controls. The acyl groups of most phospholipids in tumors showed a marked increase in the proportion of 18:1 and a decrease in the proportion of 18:2. The fatty acid composition of plasmalogen and triglyceride, however, remained unchanged. In spite of the decrease in the proportion of 18:2, there was no apparent difference in the proportion of 20:4 in most of the phosphoglycerides; however, a significant decrease in this fatty acid was noted in diacyl-GPI. Results of this study demonstrated that the membrane phospholipids of mammary adenocarcinoma were altered in respect to acyl group composition. Changes in physical properties of the cell membrane, in turn, could lead to abnormal manifestation of membrane regulated events in tumor cells.