The effects of soy-isoflavones, which are phytoestrogens derived from plants with a flavonoid structure, on cyclooxygenase -2 (COX-2) expression, PGE2 production, and mapkinases expression, were investigated in experimentally-induced atherogenic rats by feeding a high fat-high cholesterol diet. Female Sprague-Dawley rats were bilaterally ovariectomized; sham-operated animals were used as controls. Three weeks later, the animals were randomized to the following treatments for an eight-week experimental period: 17$\beta$-estradiol (200$\mu$ g/kg diet), low concentration of isoflavones (0.8g/kg diet), and high concentration of isoflavones (4.0g/kg diet). In the group supplemented with a high dose of isoflavones, COX-2 expression was down-regulated. This down-regulation was accompanied by a reduced expression of pERK1/2. In the second experiment using 48-week old female Sprague-Dawly rats, the effects of isoflavones and estrogen were compared in the basal estrogen-supplementation at the level of 600$\mu$ g/kg diet. Isoflavones induced the marked down-regulation of COX-2 protein and the decrease in $PGE_2$ production in estrogen supplemented states and this was followed by the down-regulation of p38 among mapkinases. The two different mapkinases are involved in the down-regulation of COX-2 depending on estrogen-deficient and estrogen supplemented states. This kind of COX-2 down-regulation by isoflavones was not observed in the different tissue, mammary glands. Further investigations on the relationship between COX-2 and biological activities such as vasodilation by isoflavonesin the absence or the presence of estrogen ave required in vivo system of female rats.
Apocrine carcinoma of the breast is a very rare subtype. Although it has no clinical differences from usual ductal carcinoma of the breast, it should be categorized as a subtype of breast carcinoma because the cells of apocrine carcinoma reveal characteristic abundant eosinophillic cytoplasms with intraductal apical snouting as well as round or oval nuclei and central macronucleoli. On fine needle aspiration cytology, the cells of apocrine carcinoma have a lot of similarity to benign or reactive apocrine cells of the breast. Therefore, it is difficult to make a differential diagnosis of apocrine carcinoma from mammary neoplasms with similar cytologic findings unless the subtle cytologic differences are recognized. We report the cytologic and histologic findings of a case of apocrine carcinoma in the breast of a 40-year-old female patient. After the fine needle aspiration cytology, she received the lumpectomy and lymph node dissection. The cellularity was moderate to high. The cytoplasmic borders of tumor cells of three-dimensional clusters were relatively distinctive, and the cytoplasm was abundant, eosinophilic, and granular. Although the nuclear/cytoplasmic ratio was low, the nuclei of the cells were variable in size and shape with prominent macronucleoli. Histologically, it was a typical invasive apocrine carcinoma, showing numerous cytoplasmic lysosomes and mitochondriae on electron microscopy.
Bandala, Cindy;Floriano-Sanchez, E.;Cardenas-Rodriguez, N.;Lopez-Cruz, J.;Lara-Padilla, E.
Asian Pacific Journal of Cancer Prevention
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v.13
no.6
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pp.2647-2653
/
2012
Involvement of cytochrome P450 genes (CYPs) in breast cancer (BCa) may differ between populations, with expression patterns affected by tumorigenesis. This may have an important role in the metabolism of anticancer drugs and in the progression of cancer. The aim of this study was to determine the mRNA expression patterns of four cytochrome P450 genes (CYP2W1, 3A5, 4F11 and 8A1) in Mexican women with breast cancer. Real-time PCR analyses were conducted on 32 sets of human breast tumors and adjacent non-tumor tissues, as well as 20 normal breast tissues. Expression levels were tested for association with clinical and pathological data of patients. We found higher gene expression of CYP2W1, CYP3A5, CYP4F11 in BCa than in adjacent tissues and only low in normal mammary glands in our Mexican population while CYP8A1 was only expressed in BCa and adjacent tissues. We found that Ki67 protein expression was associated with clinicopathological features as well as with CYP2W1, CYP4F11 and CYP8A1 but not with CYP3A5. The results indicated that breast cancer tissues may be better able to metabolize carcinogens and other xenobiotics to active species than normal or adjacent non-tumor tissues.
Background Flap volume is an important factor for obtaining satisfactory symmetry in breast reconstruction with a transverse rectus abdominis myocutaneous (TRAM) free flap. We aimed to develop an easy and simple method to estimate flap volume. Methods We performed a preoperative estimation of the TRAM flap volume in five patients with breast cancer who underwent 2-stage breast reconstruction following an immediate tissue expander operation after a simple mastectomy. We measured the height and width of each flap zone using a ruler and measured the tissue thickness by ultrasound. The volume of each zone, approximated as a triangular or square prism, was then calculated. The zone volumes were summed to obtain the total calculated volume of the TRAM flap. We then determined the width of zone II, so that the calculated flap volume was equal to the required flap volume ($1.2{\times}1.05{\times}$the weight of the resected mastectomy tissue). The TRAM flap was transferred vertically so that zone III was located on the upper side, and zone II was trimmed in the sitting position after vascular anastomosis. We compared the estimated flap width of zone II (=X) with the actual flap width of zone II. Results X was similar to the actual measured width. Accurate volume replacement with the TRAM flap resulted in good symmetry in all cases. Conclusions The volume of a free TRAM flap can be straightforwardly estimated preoperatively using the method presented here, with ultrasound, ruler, and simple calculations, and this technique may help reduced the time required for precise flap tailoring.
Objective: The dynamics of morbidity, disability and death rates due to malignant neoplasms in the population in Uralsk city of the Republic of Kazakhstan were studied for 2011-2015, with a focus on age and sex, as well as tumor location. Methods: Statistics for total morbidity, primary disability and mortality from cancer in the adult population of the city of Uralsk for 2011-2015 were calculated per 100 thousand. Estimation of morbidity was based on data from form - $N{\underline{o}}12$${\ll}$Report on the number of diseases registered in patients living in the area of health care organizations and patient population under medical observation". Evaluation of primary disability was based on form $N{\underline{o}}7$${\ll}$The distribution of newly recognized disabled by disease class, age, sex and disability groups" for 2011-2015 in Ural city and analysis of cancer was carried out using annual form 7 "Report on the sick, and diseases of malignant neoplasms". Result: The most common localizations of cancer were the trachea, bronchi, lungs, stomach and mammary glands. High death rates were noted for patients with cancer of the trachea, bronchi, lung, as compared to stomach and esophagus. Conclusion: The results of our investigation and data in the literature indicate that regional characteristics influence the impact of risk factors associated with cancer. An unfavorable environmental background contributes to ill health of urban populations, contributing to development of cancer. Moreover behavioral risk factors are very important, such as smoking, alcohol drinking, and an unhealthy diet. All these factors require urgent adoption of a package of measures for prevention, early detection and timely treatment. Detailed study of cancer is necessary to develop national programs and activities for prevention and control.
Chang, Mira;Lee, Jeong-Woong;Koo, Deog-Bon;Shin, Sang Tae;Han, Yong-Mahn
Asian-Australasian Journal of Animal Sciences
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v.23
no.6
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pp.806-813
/
2010
Animal bioreactors have been regarded as alternative tools for the production of limited human therapeutic proteins. The mammary glands of cattle are optimal tissues to produce therapeutic proteins that cannot be produced in large amounts in traditional systems based on microorganisms and eukaryotic cells. In this study, two knock-in vectors, pBCTPOKI-6 and pBCTPOKI-10, which target the hTPO gene on the bovine beta-casein locus, were designed to develop cloned transgenic cattle. The pBCTPOKI-6 and pBCTPOKI-10 vectors expressed hTPO protein in culture medium at a concentration of 774 pg/ml and 1,867 pg/ml, respectively. Successfully, two targeted cell clones were obtained from the bovine fibroblasts transfected with the pBCTPOKI-6 vector. Cloned embryos reconstructed with the targeted nuclei showed a lower in vitro developmental competence than those with the wild-type nuclei. After transfer of the cloned embryos into recipients, 7 pregnancies were detected at 40 to 60 days of gestation, but failed to develop to term. The results are the first trial for targeting of a human gene on the bovine milk protein gene locus, providing the potential for a large-scale production of therapeutic proteins in the animal bioreactor system.
In order to generate transgenic goats expressing human growth hormone (hGH) in their mammary glands, goat ${\beta}-Casein/hGH$ hybrid gene was introduced into goat zygotes by pronuclear microinjection. DNA-injected embryos were transferred to the oviduct of recipients at 2-cell stage or to the uterus at morula/blastocyst stage after cultivation in glutathione-supplemented mSOF medium in vitro. Pregnancy and survival rate were not significantly different between 2-cell embryos and morula/blastocysts transferred to oviduct and uterus, respectively. One transgenic female goat was generated from 153 embryos survived from DNA injection. Southern blot analysis revealed that the transgenic goat harbored single-copy transgene with a partial deletion in its sequences. Despite of the partial sequence deletion, the transgene was successfully expressed hGH at the level of $72.1{\pm}15.1{\mu}g/ml$ in milk throughout lactation period, suggesting that the sequence deletion had occurred in non-essential part of the transgene for the transgene expression. Unfortunately, however, the transgene was not transmitted to her offspring during three successive breeding seasons. These results demonstrated that goat ${\beta}-casein/hGH$ gene was integrated into the transgenic goat genome in a mosaic fashion with a partial sequence deletion, which could result in a low level expression of hGH and a failure of transgene transmission.
To investigate additive effects of endocrine disruptors, we have histopathologically studied the exchanges of the reproductive organ to ovariectomized ICR mice. Female ICR mice were ovariectomized and then treated with endocrine disruptors after two weeks. Macroscopic exchanges, which were body weight, feed and water intake, of all groups were not seen during experiment period. Histopathological changes of uterine epithelial cells, vaginal epithelial cells, mammary glands and the diameter in uterine tubles were observed. In the results, the histopathological sensitivity to endocrine disruptors effect was more seen to the vaginal epithelial cell height than others. The additive estrogenic effects of endocrine disruptors, which were combinations of DEHP, DBP and BPA, were seen with E2 and BPA treatments. These results offers a sysmatic and mechanistically informative approach to assessing estrogenicity. It provides a useful profile of activity using a reasonable amount of resources and is compatible with the study of individual chemicals as well as the investigation of interactions among combinations of chemicals.
Background: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) on the surface of Streptococcus dysgalactiae, coded with gapC, is a glycolytic enzyme that was reported to be a moonlighting protein and virulence factor. Objective: This study assessed GAPDH as a potential immunization candidate protein to prevent streptococcus infections. Methods: Mice were vaccinated subcutaneously with recombinant GAPDH and challenged with S. dysgalactiae in vivo. They were then evaluated using histological methods. rGAPDH of mouse bone marrow-derived dendritic cells (BMDCs) was evaluated using immunoblotting, reverse transcription quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay methods. Results: Vaccination with rGAPDH improved the survival rates and decreased the bacterial burdens in the mammary glands compared to the control group. The mechanism by which rGAPDH vaccination protects against S. dysgalactiae was investigated. In vitro experiments showed that rGAPDH boosted the generation of interleukin-10 and tumor necrosis factor-α. Treatment of BMDCs with TAK-242, a toll-like receptor 4 inhibitor, or C29, a toll-like receptor 2 inhibitor, reduced cytokines substantially, suggesting that rGAPDH may be a potential ligand for both TLR2 and TLR4. Subsequent investigations showed that rGAPDH may activate the phosphorylation of MAPKs and nuclear factor-κB. Conclusions: GAPDH is a promising immunization candidate protein for targeting virulence and enhancing immune-mediated protection. Further investigations are warranted to understand the mechanisms underlying the activation of BMDCs by rGAPDH in a TLR2- and TLR4-dependent manner and the regulation of inflammatory cytokines contributing to mastitis pathogenesis.
Purpose: Supernumerary nipple or polythelia is one of the developmental anomalies occurring at the embryonic stage and this anomaly usually arises from the milk line. While this atypical feature is determined during early developmental stage, it may not come out obviously or become troublesome until puberty or lactation. Moreover, sometimes it is confused with a pigmented nevus. Methods: Case 1, a 18-year-old woman with intramammary supernumerary breast consisted of another nipple with middle sized areola on the right lower breast was admitted for a $2.8{\times}3.1\;cm$-sized mass on the right breast which was starting appeared 1 year earlier. The preliminary cytological examination of the material obtained by needle aspiration biopsy from the mass was revealed by fibroadenoma with no malignant change. The patient had the surgical excision of the mass and accessory breast. Case 2, a 16 year-old woman admitted for intra-areolar polythelia of the left breast, even she doesn't have any family history of polythelia. Since she wanted surgical correction of her atypical nipple for aesthetic and psychological reasons, we reconstructed the areola using transposition flaps in an S-plasty design. Results: Case 1, the excised supernumerary nipple showed following histological features. In the superficial layer, an acanthotic and hyperpigmented epithelium with elongated rete ridges was found. In the dermis, there were follicles with hairs surrounded by hypertrophic sebaceous glands. In the deepest portion, abundant secretory glomerules and excretory ducts of apocrine gland type were observed. Case 2, follow-up visits 3 months after the procedure showed a satisfactory result with good shape and projection of the nipple. Conclusion: We report two cases of aberrant mammary tissue who underwent surgical correction, including complete breast (with nipple, areola, and glandular tissue) and intra-areolar polythelia according to the Kajava's classification, and the results were satisfactory.
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