Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

Klopfleisch, Robert; Lenze, Dido; Hummel, Michael; Gruber, Achim D.

doi:10.1186/1471-2407-10-618

Cited by 90 publications

(123 citation statements)

References 50 publications

(53 reference statements)

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“…The percentage of GrB + cells was calculated by counting all lymphocytic cells per complete longitudinal section of cerebrum and cerebellum, and the number of all GrB + lymphocytic cells per complete longitudinal section of cerebrum and cerebellum. The presence of intravascular leukocytes, endothelial activation, and vessel wall hyalinization was evaluated in sagittal H&E-stained sections of the cerebrum and cerebellum as described previously (39). The presence of intravascular leukocytes was evaluated positive (score 1) if the majority of intracerebral and intracerebellar vessels contained more than one nucleated cells or were otherwise scored as 0.…”

Section: Brain Histologymentioning

confidence: 99%

The C-Type Lectin Receptor DCIR Is Crucial for the Development of Experimental Cerebral Malaria

Maglinao

Klopfleisch

Seeberger

et al. 2013

The Journal of Immunology

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Cerebral malaria (CM) is the most severe complication of malaria. The murine Plasmodium berghei ANKA (PbA) infection model has helped to identify crucial players in the pathogenesis of CM. However, the role of pattern recognition receptors in innate immunity to CM induction is still poorly understood. C-type lectin receptors (CLRs) represent a family of pattern recognition receptors that recognize carbohydrate structures on pathogens and self-Ags often in a Ca2+-dependent manner. In this study, we investigated the role of the CLR dendritic cell immunoreceptor (DCIR) in the genesis of CM. Using the murine PbA infection, we show in this article that DCIR is essential for the development of CM. Although PbA infection led to 80% CM in wild-type C57BL/6 mice, DCIR-deficient mice were highly protected with only 15% CM development. In accordance with the reduced CM incidence in DCIR−/− mice, CD8+ T cell sequestration was markedly reduced in brains of PbA-infected DCIR−/− mice, which was accompanied by reduced brain inflammation. Reduced T cell sequestration in the brain was caused by decreased TNF-α levels in sera, as well as a modulated activation of CD4+ and CD8+ T cells in spleen of PbA-infected DCIR−/− mice. This study indicates that DCIR is critically involved in CM induction, thus highlighting the importance of this CLR in innate immunity during malaria infection.

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Section: Brain Histologymentioning

confidence: 99%

The C-Type Lectin Receptor DCIR Is Crucial for the Development of Experimental Cerebral Malaria

Maglinao

Klopfleisch

Seeberger

et al. 2013

The Journal of Immunology

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“…On the contrary in the present study Bax expression was higher only in tumours in T5 stage (P<0.05). Although there is no sufficient data about the pathogenetic meaning of overexpression of Bax in metastatic tumours, it was reported that proapoptotic and anti-apoptotic gene transcription increases significantly in metastatic tumours [33] . This finding can be explanatory for both Bax and Bcl-2 results obtained.…”

Section: Discussionmentioning

confidence: 99%

Köpek Meme Tümörlerinde Bcl-2, Bcl-XL ve Bax Sunulumu İle Apoptotik İndeksin Değerlendirilmesi

Yıldırım¹,

Sönmez²,

Özyoğurtçu³

et al. 2014

Kafkas Univ Vet Fak Derg

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SummaryMammary tumours are the most common neoplasms in intact female dogs. Dysregulation of programmed cell death mechanisms plays an important role in the pathogenesis and progression of mammary gland tumours. The aim of this study was to investigate the relationship between some anti-apoptotic proteins (Bcl-2, Bcl-X L and Bax), apoptotic index (AI) and histopathological diagnosis, tumour grading, tumour staging and survival time of canine mammary tumours (CMT). Twenty seven tissue samples were collected from twenty seven animals with mammary tumours. The samples were evaluated and graded histopathologically. All cases were staged according to the TNM system. The expression of Bcl-2, Bcl-X L and Bax proteins was investigated using indirect immunoperoxidase test and apoptosis was evaluated using terminal deoxynucleotidyltransferase (TdT)-mediated nick end-labelling (TUNEL) technique. Follow-up examination and survival estimation analysis were performed. While there was a significant statistical relation between Bcl-2 expression and histopathological diagnosis (P<0.005), there was no considerable association between histopathological diagnosis and Bax, Bcl-X L and AI (P>0.05). The differences between T1 and T5, T2 and T5 stages were statistically significant in terms of Bax expression (P<0.05), and Bax expressions were higher in T5 when compared with T1 or T2. No association between survival time and Bcl-2, Bax, Bcl-X L and AI was determined (P>0.05). Bcl-2 was overexpressed in highly malignant tumours such as solid and tubulopapillary adenocarcinomas and Bax had high expression levels in metastatic tumours. As a result, it is concluded that Bcl-2 and Bax expression can be accessory parameters for anticipating the biologic behaviour and prognosis of CMT but these markers alone are not sufficient for the determination of survival time. Keywords ÖzetMeme tümörleri intakt dişi köpeklerin en sık karşılaşılan tümörleridir. Programlı hücre ölüm mekanizmalarında meydana gelen düzensizlikler meme bezi tümörlerinin patogenezis ve progresyonunda önemli bir rol oynamaktadır. Bu çalışmanın amacı köpek meme tümörlerinde (KMT) bazı anti-apoptotik proteinler (Bcl-2, Bcl-X L and Bax) ve apoptotik indeksin (AI), histopatolojik tanı, tümör derecelendirmesi, tümör evreleri ve kalan yaşam süreleri ile ilişkisini ortaya koymaktır. Meme tümörü olan yirmi yedi hayvandan yirmi yedi biyopsi örneği toplandı. Örnekler histopatolojik olarak incelendi ve derecelendirildi. Bütün olgular TNM sistemine göre evrelendi. Bcl-2, Bcl-X L ve Bax proteinlerinin sunulumu indirect immunoperoksidaz testi ile ve apoptozis ise terminal deoksinükleotidiltransferaz (TdT)-aracılı nick end-labelling (TUNEL) tekniği ile incelendi. Hasta takibi ve hayatta kalma süresi tahmini analizleri gerçekleştirildi. Bcl-2 sunulumu ve histopatolojik tanı arasında önemli bir istatistiksel ilişki belirlenirken (P<0.005), histopatolojik tanı ile Bax, Bcl-X L ve AI arasında dikkate değer bir ilişki saptanmadı (P>0.05). Bax sunulumu açısından T1 ve T5 ile T2 ve T5 evreleri aras...

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“…A similar decreased receptor expression with increasing malignancy has been described in several canine tumors before, including the serotonin receptor on canine MCT and several growth factor receptors on metastatic canine mammary carcinomas. 8,[20][21][22] This down-regulation of mostly proliferative but also inhibitory receptors therefore seems to be a common mechanism in canine tumors and reflects the increasing independency of malignant tumors from external proliferation stimuli when compared with benign tumor variants or nonneoplastic cells.…”

Section: Discussionmentioning

confidence: 99%

CD25 Is Expressed by Canine Cutaneous Mast Cell Tumors but not by Cutaneous Connective Tissue Mast Cells

2012

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Canine cutaneous mast cell tumors (MCT) of different histological grades have distinct biological behaviors. However, little is known about underlying molecular mechanisms that lead to tumor development and increasing malignancy with higher tumor grade. Recent studies have identified the interleukin-2 receptor (IL-2R) subunits CD25 and CD2 as markers that distinguish nonneoplastic from neoplastic mast cells in human systemic mastocytosis. In this study, their potential as a marker for canine MCT and their possible impact on MCT carcinogenesis were evaluated. mRNA expression levels of both genes were compared between grade 1 ( n = 12) and grade 3 ( n = 8) MCT, and protein expression levels of CD25 were compared in 90 MCT of different tumor grades. mRNA expression levels of both CD25 and CD2 were upregulated in grade 3 MCT. In contrast, CD25 protein was expressed by fewer tumor cells and at decreased levels in grade 3 tumors, while most grade 1 MCT had strong CD25 protein expression. Moreover, CD25 was not expressed by nonneoplastic, resting cutaneous mast cells, while few presumably activated mast cells in tissue samples from dogs with allergic dermatitis had weak CD25 expression. Taken together, these findings suggest that CD25 may play a critical role in early MCT development and may be a stimulatory factor in grade 1 MCT, while grade 3 MCT seem to be less dependent on CD25. Because of the low number of CD25-positive tumor cells in high-grade tumors, the usefulness of CD25 as a tumor marker is, however, questionable.

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Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

Cited by 90 publications

References 50 publications

The C-Type Lectin Receptor DCIR Is Crucial for the Development of Experimental Cerebral Malaria

The C-Type Lectin Receptor DCIR Is Crucial for the Development of Experimental Cerebral Malaria

Köpek Meme Tümörlerinde Bcl-2, Bcl-XL ve Bax Sunulumu İle Apoptotik İndeksin Değerlendirilmesi

CD25 Is Expressed by Canine Cutaneous Mast Cell Tumors but not by Cutaneous Connective Tissue Mast Cells

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