The antitumor immune response in HER-2 positive, metastatic breast cancer patients

Juranić, Zorica D.; Nešković-Konstantinović, Z.; Stanojković, Tatjana; Zizak, Zeljko; Srdic, Tatjana; Stanojević-Bakić, N; Milosević, D; Jovanović, D.

doi:10.1186/1479-5876-3-13

Cited by 9 publications

(11 citation statements)

References 18 publications

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“…The presence of serum IgG antibodies that bind to the patient’s tumor antigens could be of real importance for the immune antitumor defense by activating antibody-dependent cellular cytotoxicity involving a subpopulation of peripheral blood mononuclear cells with RIII gamma receptors for Fcgamma chain, (CD16)-positive cells [32]. …”

Section: Discussionmentioning

confidence: 99%

Overexpression of Calreticulin in Malignant and Benign Breast Tumors: Relationship with Humoral Immunity

et al. 2012

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Objective: Calreticulin is a multicompartmental protein which regulates many important cellular responses. The aim of this study was to elucidate whether the intensity and location of calreticulin overexpression in tumor cells are related to the elevated humoral immunity to calreticulin in patients with benign or malignant breast disease. Methods: This study involved 27 patients with benign and 58 patients with malignant breast tumors before surgical resection and 38 healthy volunteers. Cytoplasmatic or membranous calreticulin overexpression in malignant or benign cells in paraffin-embedded tissues was determined using immunohistochemistry. Levels of the serum anti-calreticulin autoantibodies were detected by ELISA. Results: Statistically significant differences between serum levels of IgA of anti-calreticulin antibodies in controls and patients with breast tumors, and between controls and patients with nonmalignant breast diseases were found, but no statistically significant differences were found between levels of serum IgG anti-calreticulin antibodies. Humoral immunity to calreticulin developed against cytoplasmatic and co-localized membranous calreticulin was not correlated to the intensity of its overexpression and was present even in the absence of its membranous localization. Conclusions: The degree of calreticulin overexpression in lobular breast carcinoma is lower than in ductal breast carcinoma. Elevated concentrations of anti-calreticulin IgA antibodies were present more frequently in patients with metastasis in locoregional lymph nodes in comparison to anti-calreticulin IgG antibodies.

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Section: Discussionmentioning

confidence: 99%

Overexpression of Calreticulin in Malignant and Benign Breast Tumors: Relationship with Humoral Immunity

et al. 2012

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“…PBMC were obtained from heparinized blood, as it was reported before [17]. Briefly, 5,000 MRC-5 cells were seeded in a nutrient medium, or 150,000 PBMC (isolated from five healthy volunteers) were seeded into 96-well microtiter plates in nutrient medium only, or in a nutrient medium enriched with phytohaemagglutinin (5 μg/ml).…”

Section: Cytotoxic Action Of Metformin On Normal Cellsmentioning

confidence: 99%

“…Determination of cell survival was done by MTT test, as it was published earlier, 72 h after the continuous metformin action [17].…”

Section: Determination Of the Cytotoxic Metformin Action On Malignantmentioning

confidence: 99%

“…Cytotoxicity of peripheral blood mononuclear cells (PBMC) to malignant cells is one of the well known and very important mechanisms of the immune-mediated host anticancer action [14]. It is mainly occurring through the action of natural killer cells (NK) or, in persons with anticancer adaptive immune response through specific T cell tumor toxicity (CTL) and antibody-mediated cell cytotoxicity (ADCC) [15][16][17][18]. Furthermore, it is important to note that one external immunodrug Herceptin, synthetic monoclonal antibody to HER2, is very successful antitumor drug which is clinically used for therapy of patients bearing HER2+ tumors [19].…”

Section: Introductionmentioning

confidence: 99%

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Metformin Effects on Malignant Cells and Healthy PBMC; The Influence of Metformin on the Phenotype of Breast Cancer Cells

Damjanović

Matić

Đorđić

et al. 2014

Pathol. Oncol. Res.

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The aim of research was to determine the effects of maximally therapeutically achievable concentrations of metformin on malignant cells and healthy peripheral blood mononuclear cells (PBMC). Eight patients with T2D or hyperglycemia and nine healthy volunteers were included in the study. For determination of the influence of metformin on the phenotype of breast carcinoma, 1,410 patients with surgically removed tumors were included. From this group 37 breast cancer patients had DM type 2 or hyperglycemia and were pretreated with metformin alone or sometimes in combination with other antidiabetic drugs. Our results proved that metformin at low concentrations induced mild decrease in survival of malignant cells and PBMC stimulated for proliferation, but it didn't affect survival of resting PBMC. The effects of plasma of hyperglycemic patients who were under metformin therapy on autologous PBMC-induced decrease in survival of MDA-MB-361 cells, was noticeable in some patients. Metformin pretreatment for 24 h of HER2+ MDA-MB-361 cells, which were subsequently treated for 48 h with Herceptin, induced additional decline in cell survival. The analysis of influence of metformin on phenotype of breast cancer cells revealed significantly lower number of diabetic cancer patients treated with metformin with overexpressed HER2+ tumors (p < 0.013), while the number of patients with ER+PR+ tumors was not significantly changed (p < 0.832). In conclusion, therapeutically used concentrations of metformin exhibit mild cytotoxic action on malignant and dividing normal cells pointing to its preferred role in malignant and autoimmune diseases. The use of metformin was associated with pronounced decrease in HER2 overexpressing tumors.

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“…The marker possesses high clinical utility though at the present time the screening is conducted at phenotypical rather than at DNA level. There are preliminary results that show that Xray irradiation (which is a common therapeutic modality in cancer treatment), besides its cytotoxic effect on malignant cells, could lead to overexpression of HER-2 receptors on tumor cells, indicating change in biology of treated tumor cells (31). Further investigation in this direction may turn out to be helpful in order to fi ne-tune the selection of irradiated patients eligible for Herceptin therapy.…”

Section: Pharmacogenomics -The Elegant Way To Cure Diseasementioning

confidence: 99%

Genetic Bases for Predisposition to Common Multifactorial Disease in Man. Part II

Petkova

Chakarov

Ganev

2007

Biotechnology & Biotechnological Equipment

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The antitumor immune response in HER-2 positive, metastatic breast cancer patients

Cited by 9 publications

References 18 publications

Overexpression of Calreticulin in Malignant and Benign Breast Tumors: Relationship with Humoral Immunity

Overexpression of Calreticulin in Malignant and Benign Breast Tumors: Relationship with Humoral Immunity

Metformin Effects on Malignant Cells and Healthy PBMC; The Influence of Metformin on the Phenotype of Breast Cancer Cells

Genetic Bases for Predisposition to Common Multifactorial Disease in Man. Part II

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