Design and implementation of a community-based exercise program for breast cancer patients.

Research has indicated that exercise is critical in the recovery process for breast cancer patients, and yet this evidence has infrequently been translated into sustainable community programming. The present article describes the processes and operations of beauty (the Breast Cancer Patients Engaging in Activity and Undergoing Treatment program). This evidence-based 12-week exercise program, with an optional 12-week maintenance component, is supported by the Wings of Hope Foundation, allowing the program to be delivered at no cost to participants. The program was designed to restore and improve the physical well-being of women living with breast cancer as they undergo chemotherapy or radiation treatments. Evaluations measure safety and adherence to the program and the effects of the program on physiologic and psychological outcomes and quality of life. The beauty program addresses the gap between the level of evidence for the benefits of exercise after a cancer diagnosis and translation of that evidence into community programming by providing an accessible, individualized, and safe physical activity program for women during treatment for breast cancer.

Risk factors for benign breast biopsies: a nested case-control study in the Alberta breast screening program.

A nested case-control study was conducted to identify risk factors for benign breast biopsies in 382 cases (women with a benign biopsy result) and 399 controls (women who had not undergone a biopsy) who were sampled from the Alberta breast cancer screening program. The breast biopsy specimens of the cases were reviewed by a panel of pathologists, and percent fibroglandular tissue density was assessed. The multivariable odds ratios for the risk of open benign breast biopsy associated with current cigarette smoking was 2.04 (95% CI 1.32-3.13), for ever regular smoking was 1.61 (1.20-2.16), and for passive smoking was 1.41 (0.99-2.02). A risk reduction was found for ever alcohol consumption (0.61 [0.44-0.85]). Some risk reductions were found when the highest and the lowest quintiles of total aerobic recreational activity were compared (0.71 [0.42-1.20]), stair climbing (0.61 [0.37-1.01]) and walking pace (0.13 [0.02-0.741). Lifestyle risk factors may be implicated in the continuum between detection of an abnormality on a screening mammogram and a breast biopsy specimen. By considering these risk factors, breast screening programs may be better able to identify those women who require a breast biopsy and reduce the number of benign breast biopsies.

Survey of gene expression in winter rye during changes in growth temperature, irradiance or excitation pressure.

Previous comparisons of winter rye plants (Secale cereale L. cv. Musketeer) grown in a combination of specific temperature (degrees C)/irradiance (micromol m(-2) s(-1)) regimes (20/50; 20/250; 20/800; 5/50; 5/250) revealed (1) that photosynthetic acclimation to low temperature mimics photosynthetic acclimation to high light because both conditions result in comparable reduction states of photosystem II (PSII), that is, comparable PSII excitation pressure; (2) that the relative redox state of PSII also appears to regulate a specific cold acclimation gene, Wcs19. In order to identify additional genes regulated differentially by either low temperature, irradiance or excitation pressure, we initiated a detailed analysis of gene expression. We identified and characterized 42 differentially expressed genes from wheat and rye. Based on their patterns of regulation under the five growth conditions employed, 37 of the cDNAs could be classified into four groups: genes regulated by PSII excitation pressure, low temperature, growth irradiance and interaction between growth temperature and irradiance. Partial sequence analyses revealed that several of these genes encode known chloroplastic proteins such as ELIPs, transketolase, carbonic anhydrase and Mg-chelatase. However, five of the genes could not be classified unambiguously into any one of these four categories. The implications of these results and the limitations of the experimental design are discussed in terms of larger-scale genomic studies designed to understand the interactions of multiple abiotic stresses to which a plant may be exposed when examining regulation of gene expression.

Chitinase genes responsive to cold encode antifreeze proteins in winter cereals.

Antifreeze proteins similar to two different chitinases accumulate during cold acclimation in winter rye (Secale cereale). To determine whether these cold-responsive chitinases require post-translational modification to bind to ice, cDNAs coding for two different full-length chitinases were isolated from a cDNA library produced from cold-acclimated winter rye leaves. CHT9 is a 1,193-bp clone that encodes a 31.7-kD class I chitinase and CHT46 is a 998-bp clone that codes for a 24.8-kD class II chitinase. Chitinase-antifreeze proteins purified from the plant were similar in mass to the predicted mature products of CHT9 and CHT46, thus indicating that there was little chemical modification of the amino acid sequences in planta. To confirm these results, the mature sequences of CHT9 and CHT46 were expressed in Escherichia coli and the products of both cDNAs modified the growth of ice. Transcripts of both genes accumulated late in cold acclimation in winter rye. Southern analysis of winter rye genomic DNA indicated the presence of a small gene family homologous to CHT46. In hexaploid wheat, CHT46 homologs mapped to the homeologous group 1 chromosomes and were expressed in response to cold and drought. We conclude that two novel cold-responsive genes encoding chitinases with ice-binding activity may have arisen in winter rye and other cereals through gene duplication.

Risk factors for benign proliferative breast disease.

BACKGROUND: As part of a nested case-control study of benign proliferative breast disease (BPBD) conducted within the cohort of women participating in the Alberta breast screening programme, an analysis of all women who had a benign breast biopsy between 1990 and 1995 was undertaken to identify the epidemiological risk factors for BPBD. METHODS: The breast biopsies of all eligible women were re-reviewed by a panel of four pathologists using Page's classification for benign breast disease. Cases were 165 women whose biopsies, upon review, showed benign breast tissue changes ranging from sclerosing adenosis to atypical ductal hyperplasia. Controls were 217 women whose biopsies showed no evidence of any proliferative or neoplastic changes. In-person interviews were conducted with all study subjects. RESULTS: Women with >/=25% fibroglandular breast tissue density, as compared to women with <25% density, experienced nearly a doubling in risk of BPBD (OR = 1.91, 95% CI : 1.24-2.94). All other possible risk factors examined were not associated with BPBD. CONCLUSION: This study suggests that fibroglandular tissue density may be a risk factor, or marker, for increased risk of BPBD.

Two novel intrinsic annexins accumulate in wheat membranes in response to low temperature.

Four immunologically related proteins that belong to the annexin family were identified in cold acclimated wheat (Triticum aestivum). Two soluble forms with molecular masses of 34 and 36 kDa were found to bind phospholipid membranes in a calcium-dependent manner. These two forms are similar to the previously reported doublet in several plant species. The other two forms, with molecular masses of 39 and 22.5 kDa, were found associated with the microsomal fraction. Biochemical analysis showed that both forms are intrinsic membrane proteins and their association with the membrane is calcium independent. This is, to our knowledge, the first report of the presence of these annexin forms in plants. Membrane purification by two phase partitioning demonstrated that the p39 form is localized to the plasma membrane. Immunoblot analysis showed that the protein level of both p39 and p22.5 increases gradually reaching a maximum level after one day of low temperature exposure. The protein accumulation was similar in both hardy and less hardy cultivars, suggesting that the accumulation is not correlated with freezing tolerance. The results are discussed with respect to the possible role of these new intrinsic membrane annexins in low temperature signal transduction pathway.

Biotechnological applications of plant freezing associated proteins.

Plants use a wide array of proteins to protect themselves against low temperature and freezing conditions. The identification of these freezing tolerance associated proteins and the elucidation of their cryoprotective functions will have important applications in several fields. Genes encoding structural proteins, osmolyte producing enzymes, oxidative stress scavenging enzymes, lipid desaturases and gene regulators have been used to produce transgenic plants. These studies have revealed the potential capacity of different genes to protect against temperature related stresses. In some cases, transgenic plants with significant cold tolerance have been produced. Furthermore, the biochemical characterization of the cold induced antifreeze proteins and dehydrins reveals many applications in the food and the medical industries. These proteins are being considered as food additives to improve the quality and shelf-life of frozen foods, as cryoprotective agents for organ and cell cryopreservation, and as chemical adjuvant in cancer cryosurgery.

Accumulation of an acidic dehydrin in the vicinity of the plasma membrane during cold acclimation of wheat

Expression of the acidic dehydrin gene wcor410 was found to be associated with the development of freezing tolerance in several Gramineae species. This gene is part of a family of three homologous members, wcor410, wcor410b, and wcor410c, that have been mapped to the long arms of the homologous group 6 chromosomes of hexaploid wheat. To gain insight into the function of this gene family, antibodies were raised against the WCOR410 protein and affinity purified to eliminate cross-reactivity with the WCS120 dehydrin-like protein of wheat. Protein gel blot analyses showed that the accumulation of WCOR410 proteins correlates well with the capacity of each cultivar to cold acclimate and develop freezing tolerance. Immunoelectron microscope analyses revealed that these proteins accumulate in the vicinity of the plasma membrane of cells in the sensitive vascular transition area where freeze-induced dehydration is likely to be more severe. Biochemical fractionation experiments indicated that WCOR410 is a peripheral protein and not an integral membrane protein. These results provide direct evidence that a subtype of the dehydrin family accumulates near the plasma membrane. The properties, abundance, and localization of these proteins suggest that they are involved in the cryoprotection of the plasma membrane against freezing or dehydration stress. We propose that WCOR410 plays a role in preventing the destabilization of the plasma membrane that occurs during dehydrative conditions.

Chromosome mapping of low-temperature induced Wcs120 family genes and regulation of cold-tolerance expression in wheat.

Low-temperature (LT) induced genes of the Wcs120 family in wheat (Triticum aestivum) were mapped to specific chromosome arms using Western and Southern blot analysis on the ditelocentric series in the cultivar Chinese Spring (CS). Identified genes were located on the long arms of the homoeologous group 6 chromosomes of all 3 genomes (A, B, and D) of hexaploid wheat. Related species carrying either the A, D, or AB genomes were also examined using Southern and Western analysis with the Wcs120 probe and the WCS120 antibody. All closely related species carrying one or more of the genomes of hexaploid wheat produced a 50 kDa protein that was identified by the antibody, and a Wcs120 homoeologue was detected by Southern analysis in all species. In the absence of chromosome arm 6DL in hexaploid CS wheat no 50 kDa protein was produced and the high-intensity Wcs120 band was missing, indicating 6DL as the location of Wcs120 but suggesting silencing of the Wcs120 homoeologue in the A genome. Levels of proteins that cross-reacted with the Wcs120 antibody and degrees of cold tolerance were also investigated in the Chinese Spring/Cheyenne (CS/CNN) chromosome substitution series. CNN chromosome 5A increased the cold tolerance of CS wheat. Densitometry scanning of Western blots to determine protein levels showed that the group 5 chromosome 5A had a regulatory effect on the expression of the Wcs120 gene family located on the group 6 chromosomes of all three hexaploid wheat genomes.

Identification and characterization of a low temperature regulated gene encoding an actin-binding protein from wheat.

A cDNA corresponding to a putative actin-binding protein was cloned from a cold-acclimated wheat cDNA library. The cDNA, designated Wcor719, encodes a polypeptide of 142 amino acids with a calculated molecular mass of 15.8 kDa and a pI of 4.27. The protein has the two conserved domains identified as actin and phosphatidylinositol 4,5-biphosphate (PIP2) binding sites found in members of the cofilin family. Northern analyses revealed that Wcor719 transcript accumulation is rapid and strongly up-regulated by low temperature. This accumulation was greater in the tolerant winter wheat and rye species compared to the less tolerant ones. The rapidity of transcript induction and the significant homology with actin-binding proteins (ABP) from different organisms suggest that the product of this gene might be involved in the dynamic reorganization of the cytoskeleton during low temperature acclimation. It may also serve as a key factor in the signal transduction pathway during cold acclimation.

Differential expression of a gene encoding an acidic dehydrin in chilling sensitive and freezing tolerant gramineae species.

We have characterized a new wheat cold-regulated cDNA clone, Wcor410, that accumulates to equivalent levels in root, crown and leaf tissues during cold acclimation. The Wcor410 cDNA contains an ORF encoding a dehydrin-like glutamate-rich protein of 28 kDa with a pI of 5.1. However, the acidic nature, the absence of the glycine-rich repeat and of the conserved N-terminal region, DEYGNP, suggest that Wcor410 belongs to a different subgroup of the D11 protein family. Northern analysis showed that this gene is expressed only in freezing tolerant gramineae, whereas Southern analysis showed that the Wcor410 gene is present in all monocot species tested. The presence of freezing tolerance-associated genes in sensitive species such as rice and corn is interesting. Characterization of the regulatory factors controlling these genes may help to establish an appropriate strategy to improve freezing tolerance.

Her-2/neu expression in node-negative breast cancer: direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of recurrent disease.

The HER-2/neu proto-oncogene (also known as c-erb B-2) is homologous with, but distinct from, the epidermal growth factor receptor. Amplification of this gene in node-positive breast cancers has been shown to correlate with both earlier relapse and shorter overall survival. In node-negative breast cancer patients, the subgroup for which accurate prognostic data could make a significant contribution to treatment decisions, the prognostic utility of HER-2/neu amplification and/or overexpression has been controversial. The purpose of this report is to address the issues surrounding this controversy and to evaluate the prognostic utility of overexpression in a carefully followed group of patients using appropriately characterized reagents and methods. In this report we present data from a study of HER-2/neu expression designed specifically to test whether or not overexpression is associated with an increased risk of recurrence in node-negative breast cancers. From a cohort of 704 women with node-negative breast cancer who experienced recurrent disease (relapsed cases) 105 were matched with 105 women with no recurrence (disease-free controls) after the equivalent follow-up period. Immunohistochemistry was used to assess HER-2/neu expression in archival tissue blocks from both relapsed cases and their matched disease-free controls. Importantly, a series of molecularly characterized breast cancer specimens were used to confirm that the antibody used was of sufficient sensitivity and specificity to identify those cancers overexpressing the HER-2/neu protein in this formalin-fixed, paraffin-embedded tissue cohort. In addition, a quantitative approach was developed to more accurately assess the amount of HER-2/neu protein identified by immunostaining tumor tissue. This was done using a purified HER-2/neu protein synthesized in a bacterial expression vector and protein lysates derived from a series of cell lines, engineered to express a defined range of HER-2/neu oncoprotein levels. By using cells with defined expression levels as calibration material, computerized image analysis of immunohistochemical staining could be used to determine the amount of oncoprotein product in these cell lines as well as in human breast cancer specimens. Quantitation of the amount of HER-2/neu protein product determined by computerized image analysis of immunohistochemical assays correlated very closely with quantitative analysis of a series of molecularly characterized breast cancer cell lines and breast cancer tissue specimens.(ABSTRACT TRUNCATED AT 400 WORDS)

Cloning, characterization, and expression of a cDNA encoding a 50-kilodalton protein specifically induced by cold acclimation in wheat.

We have isolated, sequenced, and expressed a cold-specific cDNA clone, Wcs120, that specifically hybridizes to a major mRNA species of approximately 1650 nucleotides from cold-acclimated wheat (Triticum aestivum L.). The accumulation of this mRNA was induced in less than 24 hours of cold treatment, and remained at a high steady-state level during the entire period of cold acclimation in the two freezing-tolerant genotypes of wheat tested. The expression of Wcs120 was transient in a less-tolerant genotype even though the genomic organization of the Wcs120 and the relative copy number were the same in the three genotypes. The mRNA level decreased rapidly during deacclimation and was not induced by heat shock, drought, or abscisic acid. The Wcs120 cDNA contains a long open reading frame encoding a protein of 390 amino acids. The encoded protein is boiling stable, highly hydrophilic, and has a compositional bias for glycine (26.7%), threonine (16.7%), and histidine (10.8%), although cysteine, phenylalanine, and tryptophan were absent. The WCS120 protein contains two repeated domains. Domain A has the consensus amino acid sequence GEKKGVMENIKEKLPGGHGDHQQ, which is repeated 6 times, whereas domain B has the sequence TGGTYGQQGHTGTT, which is repeated 11 times. The two domains were also found in barley dehydrins and rice abscisic acid-induced protein families. The expression of this cDNA in Escherichia coli, using the T(7) RNA polymerase promoter, produced a protein of 50 kilodaltons with an isoelectric point of 7.3, and this product comigrated with a major protein synthesized in vivo and in vitro during cold acclimation.

Gene expression during cold and heat shock in wheat.

Translatable messenger RNAs expression was compared in cold- and heat-stressed winter wheat (Triticum aestivum L. 'Fredrick' and 'Norstar') and spring wheat (T. aestivum L. 'Glenlea'). Polyadenylated RNA isolated from the crown and leaf tissues was translated in a wheat germ cell free system and the acidic and basic in vitro products were resolved by two-dimensional SDS-PAGE and autoradiography. The results showed that low temperature stress rapidly induced two groups of mRNAs. The first group was transient in nature and consists of 18 mRNAs that reached their highest levels of induction after 24 h of low temperature exposure and then decreased to undetectable levels. The second group consists of 53 mRNAs that were also induced or increased rapidly, but maintained their levels of expression during the 4 weeks required to induce freezing tolerance. Among those, at least 34 were expressed at higher levels in the freezing tolerant winter wheat compared with the less tolerant spring wheat. This suggests a possible relation between the expression of these mRNAs and the capacity of each genotype to develop freezing tolerance. In the case of heat shock, 50 mRNAs were induced or increased after 3 h at 40 degrees C. Among these, the expression of only six mRNAs was altered in a similar manner in the three genotypes by both treatments. The remaining mRNAs code for typical heat shock proteins which are different from those induced by low temperature. None of these mRNAs has been associated with the development of freezing tolerance. These results suggest that heat and cold stress are controlled by different genetic systems.

Correlation between c-erbB-2 amplification and risk of recurrent disease in node-negative breast cancer.

Drawing upon the comprehensive population-based Northern Alberta Breast Cancer Registry containing 704 patients with histologically negative axillary lymph nodes who have been followed for 5-16 years, we have undertaken a retrospective case-control study to evaluate the utility of genomic amplification of specific protooncogenes [c-erbB-2 (nee HER-2/neu), c-erbA, c-myc, int-2, and hst-1] as predictive indicators of clinical outcome in node-negative disease. To this end, 115 women with node-negative breast cancer who had recurred at any time up to 16 years posttreatment (cases) were matched pairwise for appropriate clinicopathological variables (size of primary tumor, menopausal state, estrogen receptor status, anniversary year of treatment, and patient age) with a second group of 115 women (controls) selected from a cohort of 502 node-negative patients who had not relapsed during long-term follow-up. Tumor DNA extracted from archival formalin-fixed, paraffin-embedded tissue blocks were analyzed for protooncogene copy number by slot-blot hybridization. Taking a gene copy number of 3 as the cutoff, 27 of the 230 tumor samples examined contained from 3- to 22-fold elevation in c-erbB-2 genomic equivalents. Twenty-one of the 27 tumors amplified for c-erbB-2 were derived from cases and 6 from controls, signifying that 18% of the node-negative patients who had relapsed harbored excessive copies of the protooncogene in their malignant tissue compared to only 5% for the patients who had remained in remission. Accordingly, the occurrence of amplification of c-erbB-2 proved to be a statistically significant predictor of poor prognosis, especially disease-free interval (P = 0.006). Moreover, this genetic alteration appeared to be independent of and to have greater predictive power than most commonly used prognostic factors. Our findings also indicated that as a clinical test, measurement of c-erbB-2 amplification suffers from low sensitivity; however, when greater than 6 gene copies are present, the test has a positive predictive value for recurrence of 70%. Concurrent analysis of tumor DNA blots with probes for the other four protooncogenes examined revealed that their amplification, which others have reported to arise often, especially in node-positive disease, was seldom found even in our high-risk case group (2-3%). In short, our data strongly suggest that amplification of c-erbB-2 may contribute to the pathogenesis of some forms of node-negative breast cancer and thus may serve as a useful genetic marker to identify a subset of high-risk patients.

Multicentric gastric carcinoids complicating pernicious anemia. Origin from the metaplastic endocrine cell population.

We report three cases of multicentric carcinoid tumors of the stomach in patients with long-standing pernicious anemia and severe atrophic gastritis (type A). The tumor nodules arose in nonantral gastric mucosa showing marked intestinal metaplasia. Diffuse endocrine cell hyperplasia was present in both fundus and antrum. Antral G-cell hyperplasia was observed. A widely accepted pathogenesis of this syndrome suggests that the proliferating cell type is the argyrophilic, enterochromaffinlike cell native to the gastric body and fundus. Our findings conflict with this view, in that focal argentaffin staining was also present within tumor cells, as well as immunoreactivity for serotonin and substance P (more characteristic of small-intestinal enterochromaffin or Kulchitsky's cells and small-intestinal carcinoids). Findings in these cases at least suggest an alternative possibility: the tumors may derive from small-intestinal-type metaplastic endocrine cells within the atrophic mucosa, rather than the hypertrophic native endocrine cell population.

Malignant fibrous histiocytoma of prostate gland.

The English language medical literature does not contain any definitive reports of malignant fibrous histiocytoma (MFH) arising in the prostate gland. A case of prostatic MFH is described, characterized by rapid local tumor progression and pulmonary metastases. The histologic diagnosis was supported by immunohistochemical and electron microscopic studies.

Papillary cystic tumor of the pancreas.

We studied three cases of papillary cystic tumor of the pancreas and reviewed the literature concerning this uncommon neoplasm. This tumor almost always behaves in a benign fashion and occurs predominantly in young women. The histogenesis remains uncertain, but results of electron microscopic and immunocytochemical studies are consistent with an origin from a primitive cell capable of differentiating along both acinar and endocrine lines.