Expression of Connexins 26 and 43 in Canine Hyperplastic and Neoplastic Mammary Glands

2005 ◽  
Vol 42 (5) ◽  
pp. 633-641 ◽  
Author(s):  
L. N. Torres ◽  
J. M. Matera ◽  
C. H. Vasconcellos ◽  
J. L. Avanzo ◽  
F. J. Hernandez-Blazquez ◽  
...  

Gap junctions are the only communicating junctions found in animal tissues and are composed of proteins known as connexins. Alterations in connexin expression have been associated with oncogenesis; reported studies in rodent and human mammary glands, which normally express connexins 26 and 43, confirm these alterations in malignancies. Mammary neoplasms represent the second most frequent neoplasm in dogs, and since there are no reports on the study of connexins in canine mammary glands, the present study investigated the expression of connexins 26 and 43 in normal, hyperplastic, and neoplastic mammary glands of this species, to verify if altered patterns of connexin staining are related to higher cell proliferation and malignant phenotypes. A total of 4 normal, 8 hyperplastic mammary glands, 9 benign, and 51 malignant mammary gland neoplasms were submitted for the immunostaining of connexins 26 and 43, E-cadherin, and proliferating cell nuclear antigen (PCNA). Normal, hyperplastic, and benign neoplastic mammary glands showed a punctate pattern for connexin 26 and 43 staining and an intercellular E-cadherin staining. Malignant neoplasms, especially the most aggressive cases with high cell proliferation rates, presented either fewer gap junction spots on the cell membranes or increased cytoplasmic immunostaining. Malignant tumors also expressed a less intense immunostaining of E-cadherin; the expression of this adhesion molecule is important for the transportation of connexins to cell membranes and in forming communicating gap junctions. Deficient expression of E-cadherin could be related to the aberrant connexin localization and may contribute to the malignant phenotype. In conclusion, the expression and distribution of connexins and E-cadherin are inversely correlated to cell proliferation in malignant mammary neoplasms of dogs and may well be related to their more aggressive histologic type and biologic behavior.

2017 ◽  
Vol 45 (1) ◽  
pp. 8
Author(s):  
Mariana Batista Andrade ◽  
Ednaldo Carvalho Guimarães ◽  
Arlinda Flores Coleto ◽  
Nicolle Pereira Soares ◽  
Alessandra Aparecida Medeiros-Ronchi

Background: Mammary tumors are a type of neoplasia that are most commonly found in female dogs and are mostly malignant. The aim of this study, performed in the Laboratory of Veterinary Pathology of the Federal University of Uberlândia (LVP-FUU) from 2004 to 2014, was to determine the prevalence of mammary tumors in bitches and to verify the relationship between the epidemiological factors (age and breed) and clinicopathological aspects (ulceration, tumor size, and malignancy) in the occurrence of tumors.Materials, Methods & Results: A retrospective study was carried out using histopathological information retrieved from the LPV-UFU database. We collected the information on age and breed of female dogs, as well as about the location, macroscopic aspects, and histological diagnosis of mammary lesions. Only female dogs were considered for this study; a total of 911 histopathological protocols (with only one diagnosis) were analyzed along with 36 protocols that presented more than one diagnosis of mammary tumor. The age of animals ranged from one to 20 years, and the mean age was 9.99 years. The most affected breeds of dogs were: Cross breed (39.56% - 288/728) and Poodle (20.19% - 147/728). The inguinal glands were most affected by the malignant tumors (P < 0.05). A prevalence of tumors bigger than 5 cm in diameter (T3) was observed in the elderly animals (P = 0.0154) and in the inguinal mammary glands (P = 0.044). Simple carcinoma was the most frequent histological type.Discussion: Research shows that more than 40% of the tumors in bitches are located in the mammary glands, emphasizing the importance of this type of neoplasia in female dogs. Mammary tumors develop more frequently in the middle-aged and elderly bitches, with the highest occurrence being in the age range of 8 and 10 years, corroborating our observation in the present study that the mean age of bitches was 9.99 years. In this survey, a higher incidence was observed in mongrel bitches compared to that in the Poodle breed. Some authors affirm that there is no racial predisposition for the occurrence of this pathology; however, a compilation of data suggests a predisposition of at least 10 breeds, with the involvement of an as yet unidentified genetic component. Of these, six breeds (Poodle, Cocker Spaniel, Pointer, Maltese, Yorkshire Terrier, and Dachshund) were found to be predisposed to mammary tumors in this study. The percentage (49.23%) of malignant tumors found in the inguinal glands is consistent with the findings reported in literature, and might be associated with a greater amount of parenchyma, abundance of hormone receptors in these glands, and vascularization provided by the caudal superficial epigastric artery and vulvar branches of external pudendal artery. Tumor size is considered to be a prognostic factor and tumors  ≤ 3 cm in diameter  (T1) have a better prognosis. Consequently, the prevalence of tumors  ≥ 5 cm in diameter  (T3) in elderly animals is probably related to malignancy of the lesions, because tumors usually progress to a worse histological grade with time. The higher occurrence of T3 in inguinal glands might be related to the abundance of parenchyma and/or hormonal receptors in them. As in the present study, data from literature refer to the superiority of malignant histological types, with prevalence varying between 68 and 91%. When prolonged, the time between the onset of tumor and clinical evaluation may be a determinant in the progression from benign to malignant tumors. Among the malignant neoplasms, simple carcinoma was observed to be prevalent, followed by mixed tumors with carcinoma, in agreement with the results of several studies. It is concluded that mammary tumors are more prevalent in older mongrel dogs and Poodle. Attention should be paid to inguinal mammary tumors, because these are mainly malignant.


1993 ◽  
Vol 3 (6) ◽  
pp. 391-394 ◽  
Author(s):  
N. Wilkinson ◽  
C. H. Buckley ◽  
H. Fox ◽  
R. J. Hale ◽  
L. Chawner ◽  
...  

Sixty-two serous and mucinous ovarian tumors, an admixture of benign, borderline and malignant neoplasms, were immunostained for proliferating cell nuclear antigen (PCNA), with the monoclonal antibody PC10. The PC10 index, the proportion of cells showing nuclear positive staining, was calculated in each case. All the tumors showed positive immunoreactivity for PCNA. There was no overlap of PC10 counts between benign, borderline and malignant serous tumors but within the mucinous group of neoplasms there was considerable overlap between the counts for borderline and malignant tumors. There was no relationship between the PC10 index and the surgical stage of the malignant neoplasms and the index could not be correlated with patient death. Staining for PCNA does not, therefore, appear to be of any prognostic value in ovarian adenocarcinomas.


2021 ◽  
Vol 41 ◽  
Author(s):  
Claudia Russo ◽  
Sandra Maria Simonelli ◽  
Marcela B. Luz ◽  
Alefe C. Carrera ◽  
Isabela F. Moreno ◽  
...  

ABSTRACT: The result of the reaction of free radicals with biomolecules is the formation of substances with the potential of inducing oxidative damage, a condition known as oxidative stress. There are voluminous literature data reporting the association, both as a cause and as a consequence, between different diseases and oxidative stress. In this study, 144 female dogs with mammary neoplasia were analyzed. The animals were submitted to clinical evaluation for disease staging, hematological evaluation, serum biochemistry (renal and hepatic function tests), and dosage of the oxidative damage biomarker, malondialdehyde (MDA), at the time of its approach and 30 days after treatment. A control group of 100 healthy animals was also submitted to determination of serum MDA levels. The mean age of the animals affected by mammary neoplasms was 9.88±2.95 (4 to 14) years, while in healthy animals it was 2.31±1.90 years (1 to 6). Of the 144 animals, 113 (78.9%) had malignant neoplasms, and 15, 21, 46, 17 and 14 animals were in clinical stage I, II, III, IV and V respectively and the carcinoma in a mixed tumor was the most frequent histological pattern in this group (26%). Thirty-one animals were diagnosed with benign neoplasms and mammary adenoma was the most frequent histological pattern in 15 animals (51.61%). Hematological changes in the preoperative period were observed in 44 (38.9%) and 12 (38.7%) animals with malignant and benign neoplasias, respectively, and there was a positive correlation between anemia and higher levels of MDA (P=0.0008) for animals with malignant tumors. Regarding serum biochemical parameters, the most frequent alterations in animals with malignant neoplasms were elevated ALT levels in 12 animals (10.6%), creatinine in 10 animals (8.84%) and urea in eight animals (7.07%). Females with benign neoplasms presented less occurrence of changes in these parameters. In the group of healthy animals (control), the mean serum MDA values were 12.08±4.18, whereas in the pre-treatment group, mean MDA was 24.80±5.74 for bitches with benign neoplasms and 32.27±10.24 for bitches with malignant tumors. A significant increase (P<0.001) in MDA levels was observed in animals with malignant mammary neoplasms when compared to healthy animals and with benign tumors. In addition, a significant reduction (P<0.001) was observed 30 days after treatment in MDA levels (27.37±7.86) in animals with malignant tumors. In conclusion, our results indicate an association between MDA seric levels and mammary neoplasms in dogs. The results suggest that this factor can be used as a biomarker of oxidative stress with a potential impact in the prognostic of mammary tumors, since significantly higher levels of MDA were detected especially in dogs carrying malignant tumors and presenting anemia.


Author(s):  
Islam Mohamed ◽  
Ahmed Moahmed ◽  
Mennatallah Abdelkader ◽  
Alaaeldin Saleh ◽  
Ala-Eddin Al-Moustafa

Introduction: Elaeagnus angustifolia (EA) is a medicinal plant that has been used for centuries in treating many human diseases, in the Middle East, including fever, amoebic dysentery, gastrointestinal problems. However, the effect of EA plant extract on human cancer progression especially oral malignancy has not been investigated yet. Thus, first we examined the effect of EA flower extract on angiogenesis in ovo, and on selected parameters in human oral cancer cells. Materials and methods: Chorioallantoic membranes (CAMs) of chicken embryos at 3-7 days of incubation were used to assess the effect EAflower plant extract on angiogenesis. Meanwhile, cell proliferation, soft agar, cell cycle, cell invasion and cell wounding assays were performed to explore the outcome of EA plant extract on FaDu and SCC25 oral cancer cell lines. On the other hand, western blot analysis was carried out to evaluate E-cadherin and Erk1/Erk2 expression and activation, respectively, in FaDu and SCC25 under the effect of EA extract. Results: Our data show that EA extract inhibits cell proliferation and colony formation, in addition to the initiation of Scell cycle arrest and reductionof G1/G2 phases. In parallel, EA extract provokes differentiation to an epithelial phenotype “mesenchymal-epithelial transition: MET” which is the opposite of “epithelial-mesenchymal transition, EMT”: an important event in cell invasion and metastasis. Thus, EA extract causes a dramatic decrease in cell motility and invasion abilities of FaDu and SCC25 cancer cells in comparison with their controls. These changes are accompanied by an up-regulation of E-cadherin expression. The molecular pathway analysis of the EA flower extract reveals that it can inhibit the phosphorylation of Erk1/Erk2, which could be behind the inhibition of angiogenesis, the initiation of MET event and the overexpression of E-cadherin. Conclusions: Our findings indicate that EA plant extract can downgrade human oral cancer progression by the inhibition of angiogenesis and cell invasion via Erk1/Erk2 signaling pathways.


2020 ◽  
pp. 85-87
Author(s):  
O. S. Plotnikova ◽  
V. I. Apanasevich ◽  
M. A. Medkov ◽  
A. A. Polezhaev ◽  
V. I. Nevozhai ◽  
...  

Objective: The creation of the medicine for a local radiomodification of tumors.Methods: The level of the secondary radiation on the surface of the phosphate glass powder with the inclusion of tantalum oxide processed by 6 MeV deceleration emission was studied. Medical linear accelerator TrueBeam (Varian, USA), and Semiconductor diode detector PDI 2.0 (Sun Nuclear Corp., USA) having the system of moving in vertical plane and the system of position video recording were used.Results: The presence of the phosphate glass (containing 20% Та2О5) on the surface gave a 63.7% increase to the secondary radiation. It’s around two thirds of the overall level.Conclusion: An opportunity to create a medicine on the basis of phosphate glass, containing tantalum oxide, for local radiomodification of malignant tumors. 


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Philip J. Landrigan ◽  
Kurt Straif

Abstract Background Aspartame is one of the world’s most widely used artificial sweeteners and is an ingredient in more than 5000 food products globally. A particularly important use is in low-calorie beverages consumed by children and pregnant women. The Ramazzini Institute (RI) reported in 2006 and 2007 that aspartame causes dose-related increases in malignant tumors in multiple organs in rats and mice. Increased cancer risk was seen even at low exposure levels approaching the Acceptable Daily Intake (ADI). Prenatal exposures caused increased malignancies in rodent offspring at lower doses than in adults. These findings generated intense controversy focused on the accuracy of RI’s diagnoses of hematopoietic and lymphoid tissue tumors (HLTs). Critics made the claim that pulmonary lesions observed in aspartame-exposed animals were inflammatory lesions caused by Mycoplasma infection rather than malignant neoplasms. Methods To address this question, RI subjected all HLTs from aspartame-exposed animals to immunohistochemical analysis using a battery of markers and to morphological reassessment using the most recent Internationally Harmonized Nomenclature and Diagnostic (INHAND) criteria. Findings This immunohistochemical and morphological re-evaluation confirmed the original diagnoses of malignancy in 92.3% of cases. Six lesions originally diagnosed as lymphoma (8% of all HLTs) were reclassified: 3 to lymphoid hyperplasia, and 3 to chronic inflammation with fibrosis. There was no evidence of Mycoplasma infection. Interpretation These new findings confirm that aspartame is a chemical carcinogen in rodents. They confirm the very worrisome finding that prenatal exposure to aspartame increases cancer risk in rodent offspring. They validate the conclusions of the original RI studies. These findings are of great importance for public health. In light of them, we encourage all national and international public health agencies to urgently reexamine their assessments of aspartame’s health risks - especially the risks of prenatal and early postnatal exposures. We call upon food agencies to reassess Acceptable Daily Intake (ADI) levels for aspartame. We note that an Advisory Group to the International Agency for Research on Cancer has recommended high-priority reevaluation of aspartame’s carcinogenicity to humans.


Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 795-804
Author(s):  
Junjie Hang ◽  
Feifei Wei ◽  
Zhiying Yan ◽  
Xianming Zhang ◽  
Kequn Xu ◽  
...  

Abstract Purpose Colon cancer is one of the malignant tumors that threatens human health. miR-510 was demonstrated to play roles in the progression of various cancers; its dysregulation was speculated to be associated with the development of colon cancer. Methods One hundred and thirteen colon cancer patients participated in this research. With the help of RT-qPCR, the expression of miR-510 in collected tissues and cultured cells was analyzed. The association between miR-510 expression level and clinical features and prognosis of patients was evaluated. Moreover, the effects of miR-510 on cell proliferation, migration, and invasion of colon cancer were assessed by CCK8 and Transwell assay. Results miR-510 significantly upregulated in colon cancer tissues and cell lines relative to the adjacent normal tissues and colonic cells. The expression of miR-510 was significantly associated with the TNM stage and poor prognosis of patients, indicating miR-510 was involved in the disease progression and clinical prognosis of colon cancer. Additionally, the upregulation of miR-510 significantly promoted cell proliferation, migration, and invasion of colon cancer, while its knockdown significantly inhibited these cellular processes. SRCIN 1 was the direct target of miR-510 during its promoted effect on the development of colon cancer. Conclusion The upregulation of miR-510 acts as an independent prognostic indicator and a tumor promoter by targeting SRCIN 1 in colon cancer, which provides novel therapeutic strategies for colon cancer.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mingwu Deng ◽  
Xiangsheng Wang ◽  
Ziyou Yu ◽  
Yizuo Cai ◽  
Wei Liu ◽  
...  

Abstract Background Tissue expansion techniques play an important role in plastic surgery. How to improve the quality of the expanded skin and shorten the expansion period are still worth investigating. Our previous studies found that a cell-free fat extract (CEFFE) possessed pro-angiogenic and pro-proliferative activities. However, the role of CEFFE on tissue expansion has remained unclear. The purpose of this study was to evaluate the effect of CEFFE on tissue expansion. Methods A rat tissue expansion model was used. Animals were treated with CEFFE by subcutaneous injection. After 4 weeks of tissue expansion, the skin necrosis and retraction rates were evaluated, the thicknesses of the epidermis and dermis were determined by histological analyses, blood vessel density was measured by anti-CD31 staining, cell proliferation was assessed by proliferating cell nuclear antigen staining, and the expression of specific proteins was evaluated by western blot analyses. In addition, the effects of CEFFE on the proliferation and cell cycle of cultured HaCaT cells were evaluated in vitro. Results CEFFE treatment significantly decreased the necrosis rate and retraction of the expanded skin. The thickness of the epidermal and dermal layers was higher in CEFFE-treated compared to untreated skin. The density of blood vessels and cell proliferation in the epidermis of the expanded skin was improved by CEFFE treatment. In addition, CEFFE treatment significantly increased the expression of the vascular endothelial growth factor receptor, epidermal growth factor receptor, collagen type 1, and collagen type 3. CEFFE also increased the proliferation of HaCaT cells in culture. Conclusions CEFFE improves the quality of the expanded skin by promoting angiogenesis and cell proliferation. It could be potentially used clinically for augmenting tissue expansion.


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