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The main role of tumour suppressor genes is the inhibition of cell proliferation. Somatic mutations in these genes are found frequently in sporadic tumors. Germ line mutations in tumour suppressor genes are responsible for hereditary cancer syndromes. In a carrier of such a germ line mutation, a somatic mutation or loss of the remaining functional copy of the gene is sufficient for the complete loss of function of the tumour suppressor. Therefore the carriers of germ line mutations have a high risk of developing malignancies. Many tumour suppressor genes have been cloned and characterized recently and many others are intensively searched for. Protein products of these genes serve different cellular functions and many of them directly participate in the cell cycle control. The characterization of tumour suppressor genes is important both for the understanding of processes of carcinogenesis and for practical use in the diagnostics, prognostics and therapy of tumours.
- MeSH
- lidé MeSH
- nádory genetika MeSH
- tumor supresorové geny * fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
Tumor regrowth and heterogeneity are important clinical parameters during radiotherapy, and the probability of treatment benefit critically depends on the tumor progression pattern in the interval between the fractional irradiation treatments. We propose an analytic, easy-to-use method to take into account clonal subpopulations with different specific growth rates and radiation resistances. The different strain regrowth effects, as described by Gompertz law, require a dose-boost to reproduce the survival probability of the corresponding homogeneous system and for uniform irradiation. However, the estimate of the survival fraction for a tumor with a hypoxic subpopulation is more reliable when there is a slow specific regrowth rate and when the dependence on the oxygen enhancement ratio of radiotherapy is consistently taken into account. The approach is discussed for non-linear two-population dynamics for breast cancer and can be easily generalized to a larger number of components and different tumor phenotypes.
- Klíčová slova
- dose-boost, radiotherapy, tumor instability,
- Publikační typ
- časopisecké články MeSH
- MeSH
- kojenec MeSH
- lidé MeSH
- nádory ledvin komplikace MeSH
- renální hypertenze etiologie MeSH
- věkové faktory MeSH
- Wilmsův nádor komplikace MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- kazuistiky MeSH
- MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- glomangiom diagnóza genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory kůže diagnóza genetika MeSH
- rodokmen MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
There is discussed case of malignant paraganglioma with cervical lymph node metastasis that was complicated by mistake during peroperative histology. Peroperative histological examination revealed metastasis of medular carcinoma of thyroid gland. Total thyroidectomy was performed. Postoperative histological assessment revealed metastasis of carotic paraganglioma. Tumour was resected together with carotic arteries. Their reconstruction was performed during second procedure.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- nádory štítné žlázy sekundární MeSH
- tumor karotického glomu diagnóza patologie chirurgie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- kazuistiky MeSH
BACKGROUND: The tumor microenvironment plays an important role in tumorigenesis and the tumor-host relationship. An important part of the tumor microenvironment is inflammatory infiltration. Its evaluation in solid tumors has prognostic meaning and appears also to be predictive of outcome, which is particularly important for predicting responses to immune checkpoint inhibitors. However, the methodology used to assess inflammatory infiltration is problematic, because it has been standardized only for certain types of tumors. OBJECTIVE: The present study provides an overview of current issues related to the evaluation of inflammatory cells (tumor infiltrating lymphocytes) in solid tumors, specifically in tumors of the breast, lung, head and neck, gastrointestinal tract, female genital tract, urogenital tract, brain, malignant mesothelioma, and malignant melanoma. Various methodologies for evaluation are mentioned, including the efforts that are being made to standardize these methodologies and the importance of immunophenotyping inflammatory infiltrates. With regard to clinical meaning, prognostic and predictive significance are also discussed. CONCLUSION: The evaluation of TILs in solid tumors often has predictive value; however, the results have been equivocal. There is also ambiguity about the predictive use of this marker. Despite all the methodological developments, which have resulted in the implementation of complicated technologies (image analysis, multiplex fluorescence immunohistochemistry, and mass spectrometry) for the evaluation of the various aspects of inflammatory infiltrates present in tumors, including their functional characteristics, there is still a need for standardization and development of inexpensive and universally available methodologies to enable the wide use of TIL evaluations in clinical settings. The recently proposed unified methodology may be used in all solid tumors and could help resolve one of the main limitations of the routine use of TIL, i.e., the inconsistent approach to assessment.Key words: solid tumors - tumor-infiltratig lymphocytes - inflammatory cells This work was supported by program of the Czech Ministry of Health No. RVO-VFN 64165 and AZV project No. 16-30954A, Charles University and OPPK (CZ.2.16/3.1.00/24509). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 24. 9. 2017Accepted: 3. 10. 2017.
- MeSH
- lidé MeSH
- nádory imunologie MeSH
- tumor infiltrující lymfocyty imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Klíčová slova
- ADENOLYMPHOMA, SALIVARY *, PAROTID GLAND/neoplasms *,
- MeSH
- adenolymfom * MeSH
- lidé MeSH
- nádory příušní žlázy * MeSH
- nádory slinných žláz * MeSH
- nádory * MeSH
- parotis * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- dospělí MeSH
- gliom * diagnóza patologie MeSH
- lidé MeSH
- mozek patologie MeSH
- nádory mozku * komplikace diagnóza patologie MeSH
- náhlá smrt etiologie MeSH
- poruchy v puerperiu * diagnóza patologie MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
The evaluation of inflammatory infiltrate (tumor infiltrating lymphocytes - TIL) should be a standard part of biopsy examination for malignant melanoma. Currently, the most commonly used assessment method according to Clark is not optimal and there have been attempts to find an alternative system. Here we present an overview of possible approaches involving five different evaluation methods based on hematoxylin-eosin staining, including the recent suggestion of unified TIL evaluation method for all solid tumors. The issue of methodology, prognostic and predictive significance of TIL determination as well as the importance of immunohistochemical subtyping of inflammatory infiltrate is discussed.
- Klíčová slova
- malignant melanoma - tumor infiltrating lymphocytes - prediction - prognosis.,
- MeSH
- biopsie MeSH
- lidé MeSH
- melanom * imunologie terapie MeSH
- nádory kůže * imunologie terapie MeSH
- prognóza MeSH
- tumor infiltrující lymfocyty * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Mutations 657del5 and R215W in exon 6 of tumor suppressor gene NBS I are found in 1% Slavic populations. Increased occurrence of cancer was repeatedly reported in adult relatives of patients with Nijmegen breakage syndrome. Among children with oncological problematic, nonsignificantly increased frequency of NBS1 heterozygotes was found, which seems not to play any important role in cancerogenesis in childhood. However, the proportion of NBS heterozygotes among adult patients with malignancies could be significant and their therapy and follow up should respect their hyperradiosensitivity. METHODS AND RESULTS: Mutations in exon were studied in 706 adult patients with malignancies. We found 5 NBS heterozygotes, which not more than the population prevalence (1:129-165). Increased frequency of NBS heterozygotes was found among patients with colon and rectal cancer (2/101), breast cancer (1/60), skin malignancies (1/98). CONCLUSIONS: Surprisingly only one NBS heterozygote was found among 228 patients with nonHodgkin lymphoma, the malignancy which is a common complication in NBS homozygotes. Other types of malignancies were uncommon and only one R215W heterozygote was found. Comparison frequency of NBS heterozygotes with incidence NBS among person older than 70 years shows significant difference. Prevention of malignancies by avoidance from ionisation could be realized also in relatives of patients after identification of their genotype.
- MeSH
- dospělí MeSH
- heterozygot MeSH
- jaderné proteiny genetika MeSH
- lidé MeSH
- mutace * MeSH
- nádory genetika MeSH
- proteiny buněčného cyklu genetika MeSH
- tumor supresorové geny * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- jaderné proteiny MeSH
- NBN protein, human MeSH Prohlížeč
- proteiny buněčného cyklu MeSH