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1

Personalized medicine from the perspective of oncologist

100%

Wysocki P. J., Handshuh P., Mackiewicz A.

Biotechnologia

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2009

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issue 5

18-26

EN

Personalized medicine is becoming very important in oncology. New achievements in genomics, molecular biology, toxicology or immunology lead to optimization and personalization of systemic therapy in cancer patients. Breast cancer is an excellent example for which personalized medicine is a real breakthrough in oncology. Targeted molecular therapies have significantly increased cancer patients' benefits and reduced adverse effects of the treatment. A large number of new promising anti-cancer agents and genomic tests are currently being tested in clinical trials. Results of the early clinical trails (Phase I and II) are very promising and provide a real hope for the fast progress of personalized oncology development.

2

Is p53 intronic variant G13964C associated with predisposition to cancer?

100%

Fiszer-Maliszewska L., Kazanowska B., Kusnierczyk P., Manczak M., Niepieklo W., Pochron-Zeman B., Nowakowska B.

Journal of Applied Genetics

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2003

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vol. 44

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issue 4

547-552

EN

Germline mutations of the p53 gene confer a high risk of diverse malignancies. The highest frequency of inherited p53 defects was noted in Li-Fraumeni syndrome (LFS), but almost half of the mutations were found in families with incomplete Li-Fraumeni-like syndrome (LFL), including familial breast cancer cases. Recently, a germline intronic G13964C base change of the p53 was reported as a high-risk mutation associated with familial breast cancer (Lehman et al. 2000). We genotyped Polish cancer patients and healthy control individuals for the G13964C variant. Patients were chosen from cancer families with phenotypes typical for germline mutations of p53 (LFS, LFL), BRCA1 [hereditary breast (ovarian) cancer, HB(O)C] or a complex consistent with both LFL and HB(O)C. Children with leukemia were included in the study as another high risk group (Felix et al. 1992). The G13964C variant was detected in six of 87 (6.9%) cancer patients (including two ALL children), but also in eight of 96 (8.3%) control individuals (p > 0.4). Thus we found no evidence of the variant?s association with a high risk of cancer.

3

Quantification of the CD8+ T cell response against a mucin epitope in patients with breast cancer

100%

Kokowski K., Harnack U., Dorn D. C., Pecher G.

Archivum Immunologiae et Therapiae Experimentalis

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2008

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vol. 56

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issue 2

141-145

EN

Mucin 1, encoded by the MUC1 gene, is a tumor-associated antigen expressed on the surface of breast cancer cells. It would be of interest to see whether there is a naturally existing T cell immune response against mucin epitopes in cancer patients. Materials and Methods: Using tetramer and interferon gamma assays, the immune response to one MUC1 peptide epitope in the peripheral blood of breast cancer patients was quantified. The data were compared with the clinical course of the patients. Results: CD8+ T cells capable of recognizing the HLA-A*0201-restricted STAPPVHNV epitope were detected in 9 of 19 patients with a frequency ranging 0.01?0.082%. No significant difference was found between the occurrence of epitope-specific CD8+ T cells of patients with progressive disease and disease-free patients. However, all patients with stable disease showed a specific immune response, including both patients with the highest frequency. Conclusions: The results of this study provide further evidence that a natural specific cellular immune response against this mucin epitope exists in breast cancer patients.

4

Immune reaction to breast cancer: for better or for worse?

88%

Ogmundsdotti H. M.

Archivum Immunologiae et Therapiae Experimentalis

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2001

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vol. 49

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issue 2 suppl.

75-82

EN

The infiltration of breast carcinomas with lymphoid cells has often been interpreted as an indication of an active immune response against the tumor and thus a favorable prognostic sign. Several studies have, however, cast doubt on this assumption. In situ breast carcinomas are more common than invasive cancers and it may be speculated that immune surveillance plays a role in preventing some localized cancers from becoming invasive. A secondary type of immune surveillance might be implicated in the long persistence of dormant breast carcinoma cells in the bone marrow. Breast cancer cells can carry tumor-associated antigens, particularly MUC1. These may elicit specific antibody responses but there is less evidence for a CTL response. There are indications that professional antigen presenting cells may be present and active at the edge breast tumours. Breast cancer cells may also interact directly with macrophages and NK cells. In terms of immune effector mechanisms in breast cancer, the communication with potential effector cells is likely to be often faulty because of altered expression of HLA class I molecules. Pleiotrophic cytokines are frequently present and could have a variety of effects ranging from growth inhibition to stimulated proliferation, loss of cell adhesion and activation of matrix degrading enzymes. Fas ligand is unlikely to play a role in the immune evasion of breast cancer. There is thus evidence for a variety of immune reactions to breast cancer. It is possible that they mediate some form surveillance, but growing, invasive tumors have escape routes and may even use cytokines to their advantage.

5

TNF-alpha, IL-6 and their soluble receptor serum levels and secretion by neutrophils from cancer patients

88%

Jablonska E., Kiluk M., Markiewicz W., Piotrowski L., Grabowska Z., Jablonski J.

Archivum Immunologiae et Therapiae Experimentalis

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2001

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vol. 49

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issue 1

63-70

EN

Simultaneous evaluation of cytokines and their soluble receptor production and serum levels can be helpful in understanding the local and systemic immune response of a tumor-bearing host. In the present study we examined the serum levels of TNF-, IL-6 and their soluble receptors sTNFRp55, sTNFRp75 and sIL-6R compareded with their production by the polymorphonuclear neutrophils (PMN) from cancer patients. Examinations were carried out in patients with adenocarcinoma breast cancer and squamous cell carcinoma of the oral cavity and related to the clinical course and to different phases of therapy. Secretion of IL-6, sTNFRp55 and sTNFRp75 by PMN appeared to be dependent on tumor type, clinical progression of disease as well as on therapy, suggesting a significant role of these cells at different phases of the immune response to cancer associated with these mediators. Changes in values of TNF-alpha, IL-6 and their soluble receptors in sera of both cancer groups, dependent on tumor type, clinical progression and cancer therapy, could have a diagnostic and prognostic role in cancer disease.

6

Association between single-nucleotide polymorphisms of selected genes involved in the response to DNA damage and risk of colon, head and neck, and breast cancers in a Polish population

75%

Jelonek K., Gdowicz-Klosok A., Pietrowska M., Borkowska M., Korfanty J., Rzeszowska-Wolny J., Widlak P.

Journal of Applied Genetics

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2010

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vol. 51

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issue 3

343-352

EN

Single-nucleotide polymorphisms in genes involved in DNA-damage-induced responses are reported frequently to be a risk factor in various cancer types. Here we analysed polymorphisms in 5 genes involved in DNA repair (XPD Asp312Asn and Lys751Gln, XRCC1 Arg399Gln, APE1 Asp148Glu, NBS1 Glu185Gln, and XPA G-4A) and in a gene involved in regulation of the cell-cycle (CCND1 A870G). We compared their frequencies in groups of colon, head and neck, and breast cancer patients, and 2 healthy control groups: (1) matched healthy Polish individuals and (2) a NCBI database control group. Highly significant differences in the distribution of genotypes of the APE1, XRCC1 and CCND1 genes were found between colon cancer patients and healthy individuals. The 148Asp APE1 allele and the 399Gln XRCC1 allele apparently increased the risk of colon cancer (OR = 1.9-2.3 and OR = 1.5-2.1, respectively). Additionally, frequencies of XPD genotypes differed between healthy controls and patients with colon or head and neck cancer. Importantly, no differences in the distribution of these polymorphisms were found between healthy controls and breast cancer patients. The data clearly indicate that the risk of colon cancer is associated with single-nucleotide polymorphism in genes involved in base-excision repair and DNA-damage-induced responses.

Refine search results

Personalized medicine from the perspective of oncologist

Is p53 intronic variant G13964C associated with predisposition to cancer?

Quantification of the CD8+ T cell response against a mucin epitope in patients with breast cancer

Immune reaction to breast cancer: for better or for worse?

TNF-alpha, IL-6 and their soluble receptor serum levels and secretion by neutrophils from cancer patients

Association between single-nucleotide polymorphisms of selected genes involved in the response to DNA damage and risk of colon, head and neck, and breast cancers in a Polish population