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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have used monoclonal antiestrophilin antibodies to develop an improved immunocytochemical method for localizing estrogen receptors in tissue sections with an indirect immunoperoxidase technique. Rat monoclonal antibodies were raised against human estrogen receptor (estrophilin) protein derived from the cytosol of MCF-7 human breast cancer cells. These monoclonal antibodies have been shown to have extensive cross-reactivity with estrogen receptors from various primate and nonprimate tissues. We have used frozen sections of human proliferative phase endometrium and an indirect immunoperoxidase technique to establish conditions for demonstrating estrogen receptor antigenic determinants in frozen tissue sections. The method involves (a) brief fixation with formaldehyde-containing fixatives either prior to freezing or immediately after cutting cryostat sections, (b) bleaching the tissue of endogenous peroxidase activity, (c) application of primary antibody or control immunoglobulin, (d) application of an adsorbed bridging antibody (goat antirat IgG), and (e) application of rat peroxidase-antiperoxidase followed by diaminobenzidine. Specific nuclear staining for estrogen receptor antigenic determinants was observed in the vast majority of epithelial and stromal cells. No specific cytoplasmic staining was identified in cryostat sections of any of the 17 cases studied for this report.
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PMID:An immunocytochemical method for demonstrating estrogen receptor in human uterus using monoclonal antibodies to human estrophilin. 636 73

Mortality records from 24 states, gathered from 1984 to 1989 and coded for occupation and industry, were used to develop leads to workplace exposures as possible breast cancer risk factors. A case-control approach was used, with separate analyses for blacks and whites. After excluding homemakers, 33,509 cases and 117,794 controls remained. A job exposure matrix was used to estimate the probability and level of 31 workplace exposures. After adjusting for socioeconomic status, suggestive associations for probability and level of exposure were found for styrene, several organic solvents (methylene chloride, carbon tetrachloride, formaldehyde), and several metals/metal oxides and acid mists. Because of the methodologic limitations of this study, its primary value is in suggesting hypotheses for further evaluation. The findings for styrene, selected solvents, and metals and metal-related exposures deserve additional study.
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PMID:Occupational exposures and female breast cancer mortality in the United States. 779 2

Cytospins of a human breast cancer cell line (MCF-7) were studied for the expression of PCNA, a cell cycle-related protein, using a variety of fixation and immunostaining procedures. The best fixative for PCNA was found to be buffered formaldehyde solution at 4 degrees C followed by methanol at 20 degrees C, whereas alcoholic fixatives decreased greatly the PCNA immunoreactivity. Air-drying procedures of cytospins prior to and after fixation greatly undermined the PCNA immunostaining. A modified immunoperoxidase method provided a stronger staining of the PCNA-reactive cells than the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. PCNA immunoreactivity could be maintained up to 2 mo, putting slides in methanol at -20 degrees C. In conclusion, our report indicates that PCNA is a labile antigen, which may critically be affected by temperature and air-drying procedures.
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PMID:Methodological aspects of the immunostaining of proliferating cell nuclear antigen (PCNA) in cytospin preparations of MCF-7 cell line. 791 57

The function of different growth factors in the development and progression of malignant tumors and the role of cytotoxic cytokines in the host response generated against neoplasms have been recently studied. Anti-TGF-alpha and anti-TNF-alpha monoclonal antibody families have been developed and characterized previously by our laboratory. Libraries of anti-TGF-alpha and anti-TNF-alpha monoclonal antibodies were selected for equal immunoreactivity both in native (frozen) and in formaldehyde fixed, paraffin embedded histological sections. No differences were found between native and fixed samples demonstrated in 10 cases in the present prospective study. Retrospective investigation was performed in 35 histopathological specimens of breast cancer patients detailed clinically and observed during 5 years after the surgical treatment. Correlation between TGF-alpha and/or TNF-alpha expression and clinical staging--TNM score, lymph node metastasis, tumor recurrence and survival time--was analyzed. According to our present study, the TGF-alpha positive patients had worse clinical prognosis than the TNF-alpha positive and double positive cases during long term observation.
Breast Cancer Res Treat 1994
PMID:Prognostic relevance of transforming growth factor alpha (TGF-alpha) and tumor necrosis factor alpha (TNF-alpha) detected in breast cancer tissues by immunohistochemistry. 804 57

Striking differences were found between different histological types of breast cancer when 263 invasive breast carcinomas were tested for nuclear p53 accumulation in formaldehyde-fixed paraffin sections. Nuclear p53 accumulation was found in > 10% of tumor cells in 61% of medullary carcinomas (22/36), 37% of grade 3 ductal not otherwise specified carcinomas (32/86), 4% of lobular carcinomas (2/47), and 0% (0/7) of mucinous carcinomas. Strong cytoplasmic p53 staining was noted in 32% of lobular carcinomas. High percentages of medullary and high-grade ductal breast carcinomas accumulate nuclear p53, but these tumors have favorable and poor prognoses, respectively. Thus, whereas nuclear p53 accumulation can be associated in these tumors with high morphological malignancy grades in general and with tumor cell proliferation in particular, p53 accumulation is not necessarily correlated with biological aggressiveness. Overall incidence of p53-positive tumors in a particular series of breast carcinomas (in our study 28%) will depend on the ratio of ductal not otherwise specified, medullary, and lobular carcinomas.
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PMID:Nuclear p53 protein accumulates preferentially in medullary and high-grade ductal but rarely in lobular breast carcinomas. 829 10

The extent of co-expression of estrogen receptors (ER) and progesterone receptors (PgR) in breast cancer cells was examined immunocytochemically. Eight surgical cases of infiltrating ductal carcinoma designated as ER-positive and PgR-positive (ER+/PgR+) by enzyme immunoassay (EIA) were used. They were fixed with 4% formaldehyde and cut into serial frozen semithin sections. Using sections stained with either anti-ER or anti-PgR antibody, we ascertained the co-localization of ER and PgR in a single cell and estimated the ratio of the number of cells co-expressing ER and PgR. Twenty-six to 95% of the cells were immunopositive for both ER and PgR, 2-25% of them, varying in cases, were positive for ER but not for PgR, and <3% of the cells were positive for PgR but not for ER. The remaining 5-60% cells were positive for neither ER nor PgR. A significant percentage of breast cancer cells in tissues designated as ER+/PgR+ by EIA showed the phenotype of ER-positive but PgR-negative. The co-expression ratio of ER and PgR in biochemically detected ER+/PgR+ breast cancer may reflect a particular clinical parameter, such as the heterogeneous responsiveness of ER+/PgR+ breast cancers to hormonal treatment. Immunostaining of serial semithin frozen sections for two or more different antigens is a useful method to assess the correlation of localization of antigens.
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PMID:Use of serial semithin frozen sections to evaluate the co-localization of estrogen receptors and progesterone receptors in cells of breast cancer tissues. 866 46

Proliferation variables such as mitotic activity and the percentage of S-phase cells have been shown to be of prognostic value in many tumors, especially in breast cancer. However, some studies reported a decrease in mitotic activity caused by delay in fixation of the tissue. In contrast, other studies showed that the identifiability of mitotic figures decreases after fixation delay, but the total number of mitotic figures and also the percentage of S-phase cells remain unchanged. Most studies have been done on small numbers of experimental tumors, thus introducing the risk of selection bias. The aim of this study was to reinvestigate the influence of fixation delay on mitotic activity and cell cycle variables assessed by flow cytometry in an adequate number of resected human tissues to reach firmer conclusions. Resection specimens of 19 and 21 cases, respectively, for the mitotic activity estimate and the flow cytometric percentage of S-phase calculation were collected directly from the operating theater using lung, breast, and intestinal cancers and normal intestinal mucosa. The tissues were cut in pieces, and from each specimen, pieces were fixed in 4% buffered formaldehyde (for mitosis counting) as well as snap frozen (for flow cytometry) immediately after excision, as well as after a fixation delay of 1, 2, 4, 6, 8, 18, and 24 hours. Moreover, during the fixation delay, one series from each specimen was kept in the refrigerator and the second at room temperature. Thus, a total of 304 (19 X 16) and 336 (21 X 16) specimens were investigated for the mitotic activity estimate and the percentage of S-phase cells calculation, respectively. With regard to the estimation of the mitotic activity, both clear and doubtful mitotic figures were registered separately, obtaining an "uncorrected" and "corrected" (for doubtful mitotic figures) mitotic activity estimate. The percentage of S-phase cells was obtained by cell cycle analysis of flow cytometric DNA-histograms. The results showed that the quality of the material decreased during the fixation delay, as reflected by poorer cellular morphology in the hematoxylin-and-eosin-stained slides, resulting in more difficult identification of mitotic figures and a more time-consuming procedure with regard to the mitosis counts, but not in a worse intraobserver and interobserver reproducibility, which was acceptable. The reduction in quality of the tissues also was shown by the flow cytometric measurements because the coefficient of variation and percentage of debris increased after 4 hours or more of fixation delay. However, the mean values of the "uncorrected" mitotic activity and the "corrected" mitotic activity showed no decreasing trend; neither did the average percentage of S-phase cells. In conclusion, within the time investigated, fixation delay has no clear influence on the proliferation features studied. Because of the decreasing quality of the histological sections, resulting in more difficult identification of mitoses and interpretation of DNA histograms, fixation delay should be kept as short as possible, keeping the tissue at 4 degrees C until fixation.
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PMID:The influence of fixation delay on mitotic activity and flow cytometric cell cycle variables. 901 39

The recent discovery that the clinically important antitumor drugs doxorubicin and daunorubicin alkylate DNA via catalytic production of formaldehyde prompted the synthesis of derivatives bearing formaldehyde. Reaction of the parent drugs with aqueous formaldehyde at pH 6 produced in 40-50% yield conjugates consisting of two molecules of the parent drug as oxazolidine derivatives bound together at their 3'-nitrogens by a methylene group. The structures were established as bis(3'-N-(3'-N,4'-O-methylenedoxorubicinyl)) methane (Doxoform) and bis(3'-N-(3'-N,4'-O-methylenedaunorubicinyl))methane (Daunoform) from spectroscopic data. Both derivatives are labile with respect to hydrolysis to the parent drugs. 3'-N,4'-O-Methylenedoxorubicin and 3'-N,4'-O-methylenedaunorubicin are intermediates in the hydrolysis. Daunoform reacts with the self-complementary deoxyoligonucleotide (GC)4 faster than the combination of daunorubicin and formaldehyde at an equivalent concentration to given drug-DNA adducts. In spite of hydrolytic instability, Doxoform is 150-fold more toxic to MCF-7 human breast cancer cells and 10000-fold more toxic to MCF-7/ADR resistant cells. Toxicity to resistant cancer cells is interpreted in terms of higher lipophilicity of the derivatives and circumvention of catalytic formaldehyde production.
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PMID:Doxoform and Daunoform: anthracycline-formaldehyde conjugates toxic to resistant tumor cells. 925 51

Formaldehyde, acetaldehyde and acetone expired from tumor-bearing transgenic mice and formaldehyde exhaled from breast cancer patients were analyzed using gas chromatography. The tumor-bearing mice expired significantly more formaldehyde per unit metabolic size (1.43-2.98 micromol) than did control mice (0.77-1.01 micromol). There was no detectable difference in the levels of expired acetaldehyde and acetone between the two groups of mice. The exhaled formaldehyde levels from three women with breast cancer and from three healthy women were satisfactorily determined using the method developed in this study. The results suggest that these carbonyl compounds may be used as a biomarker.
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PMID:Quantitative analysis by gas chromatography of volatile carbonyl compounds in expired air from mice and human. 944 73

The recent discovery that the formaldehyde conjugates of doxorubicin and daunorubicin, Doxoform and Daunoform, are cytotoxic to resistant human breast cancer cells prompted the search for hydrolytically more stable anthracycline-formaldehyde conjugates. Doxoform and Daunoform consist of two molecules of the parent drug bound together with three methylene groups, two forming oxazolidine rings and one binding the oxazolidines together at their 3'-amino nitrogens. The 4'-epimer of doxorubicin, epidoxorubicin, reacts with formaldehyde at its amino alcohol functionality to produce a conjugate, Epidoxoform, in 59% yield whose structure consists of two molecules of epidoxorubicin bound together with three methylene groups in a 1, 6-diaza-4,9-dioxabicyclo[4.4.1]undecane ring system. The structure was established from spectroscopic data and is consistent with products from reaction of simpler vicinal trans-amino alcohols with formaldehyde. Epidoxoform hydrolyzes at pH 7.3 to an equilibrium mixture with dimeric and monomeric epidoxorubicin-formaldehyde conjugates without release of formaldehyde or epidoxorubicin. The hydrolysis follows the rate law (A if B) if C + D where A (Epidoxoform) is in rapid equilibrium with B, and B is in slow equilibrium with C and D. The forward rate constant for A/B going to C+D gives a half-life of approximately 2 h at 37 degrees C. At equilibrium the mixture is stable for at least 2 days. At pH 6.0, hydrolysis proceeds with first-order kinetics to epidoxorubicin and formaldehyde with a half-life of 15 min at 37 degrees C. Epidoxoform and epidoxorubicin plus formaldehyde react with the self-complementary DNA octamer (GC)4 to yield five drug-DNA adducts which have structures analogous to the doxorubicin-DNA adducts from reaction of Doxoform with (GC)4. Epidoxoform is 3-fold more toxic to MCF-7 human breast cancer cells and greater than 120-fold more toxic to MCF-7/ADR resistant cells than epidoxorubicin. Epidoxoform in equilibrium with its hydrolysis products is greater than 25-fold more toxic to resistant cells with respect to epidoxorubicin.
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PMID:Epidoxoform: a hydrolytically more stable anthracycline-formaldehyde conjugate toxic to resistant tumor cells. 954 20


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