Breast carcinomas

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Cytoplasmic Skp2 expression is associated with p-Akt1 and predicts poor prognosis in human breast carcinomas.

Cytoplasmic Skp2 expression is associated with p-Akt1 and predicts poor prognosis in human breast carcinomas.

increased cytoplasmic Skp2 expression may be at least partly due to Akt1 activation in invasive breast carcinomas. Cytoplasmic relocalization of Skp2 expression is associated with rapid proliferation, aggressive cellular behavior, and potentially with poor prognosis for breast carcinoma patients. As expected, patients with cytoplasmic Skp2 expression showed significantly poorer survival for both DFS and OS in univariate and multivariate analyses. Lin et al. reported that cytosolic Skp2 mediates cell migration, suggesting that cytosolic Skp2 may play an important role in tumor invasion and metastasis [12]. Our results demon- strate that cytoplasmic Skp2 may facilitate not only progression, but also metastasis in breast carcinoma patients.
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Chromogenic in situ hybridization compared with other approaches to evaluate HER2/neu status in breast carcinomas

Chromogenic in situ hybridization compared with other approaches to evaluate HER2/neu status in breast carcinomas

The v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma-derived oncogene homo- log (avian), ERBB2/HER2 (other aliases: CD340, HER-2, HER-2/neu, MLN 19, NEU, NGL, TKR1) plays a role in the pathogenesis of a significant number of human cancers. This membrane receptor protein of the growth factor receptor gene family presents tyrosine kinase activity and is associated with cell growth, survival and differentiation. In human breast cancer, HER2 overexpression is reported in 20-30% of breast carcinomas (1-5), mostly due to HER2 gene gains or amplification. HER2 over- expression is associated with constitutive activation of different pathways, in particular the PI3K and ERK pathways, leading to a significant increase in cell proliferation (6).
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Expression of E-cadherin, Snail and Hakai in epithelial cells isolated from the primary tumor and from peritumoral tissue of invasive ductal breast carcinomas

Expression of E-cadherin, Snail and Hakai in epithelial cells isolated from the primary tumor and from peritumoral tissue of invasive ductal breast carcinomas

Epithelial intercellular cohesion, mainly mediated by E-cadherin (CDH1) expression and function, may be deregulated during cancer cell invasion of adjacent tissues and lymphatic and vascular channels. CDH1 expression is down-modulated in invasive lobular breast carcinomas but its regulation in invasive ductal carcinomas (IDC) is less clear. CDH1 expression is repressed by transcription factors such as Snail (SNAI1) and its product is degraded after Hakai ubiquitination. We compared CDH1, SNAI1 and HAKAI mRNA expression in IDC and paired adjacent normal breast tissue and evaluated its relation with node metastasis and circulating tumor cells. Matched tumor/peritumoral and blood samples were collected from 30 patients with early IDC. Epi- thelial cells from each compartment (tumor/peritumoral) were recovered by an immunomagnetic method and gene expression was determined by real-time RT-PCR. There were no differences in CDH1, SNAI1 and HAKAI mRNA expression between tumor and corresponding peritumoral samples and no differential tumoral gene expression according to nodal involvement. Another 30 patients with a long-term follow-up (at least 5 years) and a differential prognosis (good or poor, as defined by breast cancer death) had E-cadherin and Snail protein detected by immunohistochemistry in tumor samples. In this group, E-cadherin-positive expression, but not Snail, may be associated with a better prognosis. This is the first report simultaneously analyzing CDH1, SNAI1 and HAKAI mRNA expression in matched tumor and peritumoral samples from patients with IDC. However, no clear pattern of their expression could distinguish the invasive tumor compartment from its adjacent normal tissue.
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Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

In the present study, we investigated the Cdx2 polymorphism in the vdr gene in a large spec- trum of ER-positive (MCF7 and T-47D) and ER-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, we explored the association between Cdx2 polymorphism and VDR immu- nohistochemical expression in an ad hoc retrospective series of 80 human breast carcinomas taking into account breast cancer molecular classification (Luminal A, Luminal B, HER2-Sub- type (HS), and Triple Negative) and clinical-pathological parameters routinely detected in breast cancer management.
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Preclinical therapy of disseminated HER-2⁺ ovarian and breast carcinomas with a HER-2-retargeted oncolytic herpesvirus.

Preclinical therapy of disseminated HER-2⁺ ovarian and breast carcinomas with a HER-2-retargeted oncolytic herpesvirus.

Tumor dissemination is the main cause of cancer-related death. A major challenge in oncolytic virotherapy is whether viruses can reach metastatic tumors upon systemic (e.g. intravenous or intraperitoneal) administration. To address this issue, not previously investigated for any retargeted HSVs, we employed mouse models that mirror the intraperitoneal dissemination of the two main HER- 2+ cancers, ovarian and breast. This represents an aggressive, advanced form of cancer, associated with dismal prognosis. The HER-2-redirected HSV R-LM249 was administered i.p., to ensure that it readily reached the intraperitoneal metastatic masses. R- LM249 strongly inhibited the peritoneal growth of human HER-2+ trastuzumab-resistant ovarian and breast carcinomas, and its metastatic growth in the brain, but not in the lungs.
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Relationship between the inflammatory molecular profile of breast carcinomas and distant metastasis development.

Relationship between the inflammatory molecular profile of breast carcinomas and distant metastasis development.

The result of the present study was that tumors developing worse prognosis and identified by MMP-11 expression by intratumoral MICs, showed an up-regulation of inflammatory- related genes. The classification of these tumor groups in good or bad prognosis was based on the expression of MMP-11 by MICs, as described previously by our group [3]. Our study emphasizes the importance of IL-1, 25, 26 and 217, IFNb and NFkB in promoting disease metastasis and recurrence, as demonstrated by their high expression in tumors from patients with a higher rate of distant metastasis development (97.6%) [3]. Some of these molecules implicated in the cross-talk between the tumor and inflammatory microenvironment may emerge as attractive targets in breast cancer. Therefore, these data contribute to a better biological characterization of tumors and open up the possibility of undergoing new studies to determine which cell type specifically express those factors, and their biological signification.
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In situ identification of CD44+/CD24- cancer cells in primary human breast carcinomas.

In situ identification of CD44+/CD24- cancer cells in primary human breast carcinomas.

Fifty-six breast carcinoma cases were selected from the archives of the Department of Pathology at the Campus Bio-Medico Hospital. The primary selection criterion was the absence of residual disease; all patients were staged before surgery by clinical examination, CT scan of thorax, abdomen, and pelvis and, when indicated, intraoperative ultrasound of the liver. All patients were female, with a median age of 63 y (range, 37–88 y); no patient had received chemo, hormone or radiation therapy before surgery. All patients received conventional postoperative treatment according to their disease. Clinical follow-up was recorded for at least three years after surgery. Metastasis-free survival (MFS) was defined as the time elapsed between excision of the primary tumour and manifestation of metastasis. To evaluate the biological features of aggressive cancers, 16 patients were specifically selected on the basis of the development of distant metastasis during the first three years of follow-up. The pathological findings were obtained from the original pathology reports. In addition, tumour–node–metas- tasis status classification was reassessed according to AJCC [22]. The combined histological grade (1, 2, and 3) of infiltrating ductal carcinomas was obtained according to a modified Scarff-Bloom- Richardson histological grading system with guidelines as suggest- ed by Nottingham City Hospital pathologists [23]. The clinico- pathological features are summarised in Table 6. The study was approved by the Campus Bio-Medico University Ethics Commit- tee (project: ‘‘Tumourigenic cells in breast and pancreas cancer’’). Informed written consent was obtained from all patients.
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Cytogenetic evaluation of 20 primary breast carcinomas

Cytogenetic evaluation of 20 primary breast carcinomas

Breast cancer is the most common neoplasm and the leading cause of cancer related deaths among women in most countries (PARKIN et al. The natural history of breast cancer va[r]

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Induction of ErbB-3 expression by alpha6beta4 integrin contributes to tamoxifen resistance in ERbeta1-negative breast carcinomas.

Induction of ErbB-3 expression by alpha6beta4 integrin contributes to tamoxifen resistance in ERbeta1-negative breast carcinomas.

Methods and Findings: Using human breast cancer cell lines displaying different levels of a6b4 and ErbB-3 receptors and a series of 232 breast cancer biopsies from patients submitted to adjuvant Tamoxifen monotherapy for five years, we evaluated the functional interaction between both receptors in relationship to Tamoxifen responsiveness. In mammary carcinoma cells, we evidenced that the a6b4 integrin strongly influence Akt phosphorylation through ErbB-3 protein regulation. Moreover, the ErbB-3 inactivation inhibits Akt phosphorylation, induces apoptosis and inhibits in vitro invasion favouring Tamoxifen responsiveness. The analysis of human tumors revealed a significant relationship between a6b4 and ErbB-3 in P-Akt-positive and ERb1-negative breast cancers derived from patients with lower disease free survival. Conclusions: We provided evidence that a strong relationship occurs between a6b4 and ErbB-3 positivity in ERb1-negative breast cancers. We also found that the association between ErbB-3 and P-Akt positivity mainly occurs in ERb1-negative breast cancer derived from patients with lower DFS indicating that both receptors are clinically relevant in predicting the response to Tamoxifen.
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Levels of estrogen receptor B splice variant (ERBΔ5) mRNA correlates with progesterone receptor in breast carcinomas

Levels of estrogen receptor B splice variant (ERBΔ5) mRNA correlates with progesterone receptor in breast carcinomas

Furthermore, we analyzed the expression level of ERβΔ5 in cancer samples in comparison with healthy mammary tissue. The median ERβΔ5 mRNA expression in the samples of healthy mammary tissue was 35.3. We chose the arbitrary cut-off value of 20 to divide cancer samples into two groups. In 46% of the samples (31 out of 67) the ERβΔ5 mRNA relative levels were higher than 20 – BC group I (median 35.7); in 54% of the analyzed samples (36 out of 67) the ERβΔ5 mRNA expression was lower than 20 – group II (median 8.4). The levels of ERβΔ5 mRNAs in the group II breast cancers (less ERβΔ5 than in group I) significantly differs from the levels in healthy mammary tissue and group I (p < 0,05 Kruskal Wallis). In group I of breast cancer samples, the levels of ERβΔ5 mRNAs was in the range specific for healthy mammary tissue (Figure 2).
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Clinics  vol.65 número10

Clinics vol.65 número10

As a receptor tyrosine kinase that plays essential roles in both normal physiological conditions and cancerous condi- tions, EGFR can affect many important characteristics of a cancer’s phenotype, including evasion of apoptosis, prolif- eration, invasion, and metastasis. In a previous study, the frequency of EGFR-positive tumors among young patients was found to be higher than among older women (5.9% vs. 3.3%, respectively), although the difference was not statis- tically significant. 16 Based on the results of that study and the data presented in this report, EGFR expression appears to play an important role in the early onset of breast cancer, and we hypothesize that this role is related to intrinsic genetic differences that result in an adverse outcome that is associated with the aggressive breast carcinomas. Further- more, we propose that EGFR immunostaining and/or amplification should be further investigated as predictor of a patient’s response to targeted therapy.
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Standardization for Ki-67 assessment in moderately differentiated breast cancer. A retrospective analysis of the SAKK 28/12 study.

Standardization for Ki-67 assessment in moderately differentiated breast cancer. A retrospective analysis of the SAKK 28/12 study.

Clinical guidelines increasingly incorporate the potential or recommended use of Ki-67 LI in the clinical oncological decision algorithm, although caution is drawn to the still relevant re- producibility issues in midrange breast cancer in routine histopathological diagnostics [1, 2, 13]. Along with the recommendation of current German guidelines, very similar to our own observations from 2012, the degree of Ki-67 LI can be reliably assessed and reproduced in low- and high ranges, however, caution is needed in mid-range breast carcinomas when dealing with an adjuvant oncological situation [1, 3, 13]. The impact of Ki-67 LI in neoadjuvant setting, especially in triple negative breast cancer, nevertheless has level I evidence and is increasingly applied in core biopsies in the neoadjuvant setting [1, 13, 20].
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Morphological Aspects and Immunophenotypic Profiles of Mammary Carcinomas in Benign-Mixed Tumors of Female Dogs

Morphological Aspects and Immunophenotypic Profiles of Mammary Carcinomas in Benign-Mixed Tumors of Female Dogs

The molecular-based classification system adopted for breast cancer is a valuable tool for assessing prognosis and investigating similarities between the canine and human tumor types. According to this data, at least five different molecular subtypes of human breast carcinomas were identified, based on gene expression profiling: luminal A, luminal B, HER2, basal-like, and normal type carcinoma, all of which differ in their pathological and clinical profiles [9, 10]. However, there are few studies for the molecular characteristics of breast tumors in female dogs [11, 12].
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Molecular biology of human epidermal receptors, signaling pathways and targeted therapy against cancers : new evidences and old challenges

Molecular biology of human epidermal receptors, signaling pathways and targeted therapy against cancers : new evidences and old challenges

Two classes of drugs against HER receptors have reached clinical phases: monoclonal antibodies against the extracellular portion of the receptor and tyrosine kinase inhibitors (TKIs). Trastuzumab is a humanized monoclonal antibody (Figure 5) directed to the domain IV of HER2 extracellular juxtamembrane segment (Eccles, 2011). In addition to the direct action on HER2, trastuzumab promotes its internalization and degradation by the ubiquitin-proteasome pathway and causes antibody-depedent cell-mediated cytotoxicity by natural killer (NK) leukocytes (Shuptrine, Surana, Weiner, 2012). This drug was approved as part of the protocol to treat women with breast cancers that markedly overexpress HER2, which consists of a) doxorubicin, cyclophosphamide and paclitaxel or docetaxel; b) carboplatin, or docetaxel or c) anthracycline. In metastatic cancers, trastuzumab is combined with paclitaxel as first choice against tumors that overexpress HER2 or as single agent in cancers that overexpress HER2 in patients who have already received diferent treatment protocols. Pertuzumab is another humanized monoclonal antibody that recognizes the HER2 extracellular segment (domain II). It has been prescribed in clinical trials for patients who have not been treated with anti-HER2 and anti-metastatic chemotherapies in association with trastuzumab and docetaxel against metastatic breast carcinomas (Franklin et al., 2004). As both HER2 and
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Radiol Bras  vol.47 número2

Radiol Bras vol.47 número2

F-FDG PET/CT study performed under specific protocol for breast assessment has good sensitivity for the diagnosis of breast carcinomas, allowing for the identifica- tion of most aggressive tumors at histological analysis. The authors of the present study observed statistically significant association between maximum SUV values and relevant his- tological and immunohistochemical factors related to breast carcinomas aggressiveness and prognosis. The authors be- lieve that the method is potentially useful for a more effec- tive management of breast lesions, in the near future, with the improvement of spatial resolution of the PET appara- tuses and the introduction of new radiopharmaceuticals.
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Breast adenomyoepithelioma

Breast adenomyoepithelioma

Involvement of chromosome regions 8p and 16q have shown to be involved in breast tumors, frequently reported as acquired clonal abnormalities, and thus might represent genomic hot spots in the pathogenesis of such tumors. The evidence suggests a possible clustering of 8p breakpoints in breast carcinomas, but none of the studies have identified any possible candidate gene(s) within this region. The chromosomal translocation seen in Gatalica et al. (34) case report is distinct, as it appears at the cytogenetic level to be balanced with no

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Braz. J. Pharm. Sci.  vol.53 número2

Braz. J. Pharm. Sci. vol.53 número2

Two classes of drugs against HER receptors have reached clinical phases: monoclonal antibodies against the extracellular portion of the receptor and tyrosine kinase inhibitors (TKIs). Trastuzumab is a humanized monoclonal antibody (Figure 5) directed to the domain IV of HER2 extracellular juxtamembrane segment (Eccles, 2011). In addition to the direct action on HER2, trastuzumab promotes its internalization and degradation by the ubiquitin-proteasome pathway and causes antibody-depedent cell-mediated cytotoxicity by natural killer (NK) leukocytes (Shuptrine, Surana, Weiner, 2012). This drug was approved as part of the protocol to treat women with breast cancers that markedly overexpress HER2, which consists of a) doxorubicin, cyclophosphamide and paclitaxel or docetaxel; b) carboplatin, or docetaxel or c) anthracycline. In metastatic cancers, trastuzumab is combined with paclitaxel as first choice against tumors that overexpress HER2 or as single agent in cancers that overexpress HER2 in patients who have already received diferent treatment protocols. Pertuzumab is another humanized monoclonal antibody that recognizes the HER2 extracellular segment (domain II). It has been prescribed in clinical trials for patients who have not been treated with anti-HER2 and anti-metastatic chemotherapies in association with trastuzumab and docetaxel against metastatic breast carcinomas (Franklin et al., 2004). As both HER2 and
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Ductal carcinoma in situ in core needle biopsies and its association with extensive in situ component in the surgical specimen

Ductal carcinoma in situ in core needle biopsies and its association with extensive in situ component in the surgical specimen

EIC has been implicated as an independent predictor of recurrence in breast carcinomas treated with conser- vative surgery and radiotherapy. In patients with invasive carcinoma, the risk of metastatic disease is already present at diagnosis and many failures can occur without evidence of local recurrence, but in DCIS the risk of me- tastases at diagnosis is negligible. Therefore, an invasive local recurrence brings the possibility of death from breast cancer, especially when conservative surgery for treatment is used [28,29].

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Carcinoma medular do rim.

Carcinoma medular do rim.

No diagnóstico diferencial do carcinoma medular renal estão incluídos os carcinomas renais de ductos coletores e de células renais papilares, carcinomas uroteliais com ou sem diferenciação glandular, adenocarcinomas originados do urotélio da pelve renal e carcinomas metastáticos. Es- pecificamente perante o carcinoma de ductos coletores e o carcinoma urotelial, há uma superposição dos achados da histologia do carcinoma medular em relação ao primeiro (o que sugere que os dois tumores fazem parte de um es- pectro comum de neoplasias, sendo o carcinoma medular colocado num extremo mais agressivo) e dos achados da imuno-histoquímica em relação a ambos, o que torna essa
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Tradução, adaptação e validação da Breastfeeding SelfEfficacy Scale : aplicação em gestantes

Tradução, adaptação e validação da Breastfeeding SelfEfficacy Scale : aplicação em gestantes

Introduction: Several risk factors for breast cancer are well established, however the role of stress as one of these factors requires proof. Objective: Verify the association of life events which produce stress with the primary incidence of breast cancer among women. Method: Systematic review in the data bases MEDLINE/Pubmed, LILACS and Cochrane Library, in the period between 2006 and 2007, with no language restriction. The selection of studies was carried out by three researchers and included the following inclusion criteria: patients over 18 years old, primary observational studies, first occurrence of breast cancer, measurement of stress according to categories, intensity and frequency of events, results expressed as relative risk (RR) with interval of confidence (IC). The methodological quality was evaluated by Downs and Black’s criteria, while the level of evidence was evaluated by Melnyk and Fineout-Oveholt’s classification. For meta-analysis the studies were grouped in three analyses: two analyses owing to the categories widowhood and divorce, and one analysis considering the intensity self perceived and frequency of events. The meta-analysis was carried out by the program Data Analysis and Statistical Software-Stata, version 9.0. with application of the test Q to estimate heterogeneity and random effects model to calculate the combined effect. Analyses of sensibility and bias were not carried out due to the small number of studies. Result: Eight students were included in an initial sample of 621 articles. The meta- analysis consisted of six case-control studies and two of cohort. The scores of methodological quality varied between 14 and 20 (average=17), all of them with evidence level IV. No association was found for stressing events, widowhood and divorce. However, the result of the study suggests that there may be an association for stress degree/intensity. The RR regarding widowhood was 1,04 (0,75-1,44; p= 0,800); regarding divorce 1,03 (0,72-1,48; p=0,850), and regarding degree, intensity/frequency of stress 1,73 (0,98-3,05; p=0,059). Conclusion: There was no association of stressing life events with breast cancer. The small number of studies included, what reduced the statistical power, does not permit us to eliminate the possibility of association of stress degree/intensity and breast cancer
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