[MicroRNA Analysis in Epithelial Ovarian Cancer]. / Analýza mikroRNA u epiteliálního karcinomu vajecníku.

BACKGROUND: Ovarian carcinoma is a type of cancer with high mortality, which is often diagnosed in late stages indicating the necessity to identify new non-invasive biomarkers for detection this malignancy in early stages of the disease. MicroRNAs (miRNAs) seem to be one of the potential possibilities. MiRNAs are small noncoding RNA molecules, which regulate gene expression and are involved in many cellular processes including carcinogenesis. PATIENTS AND METHODS: Total RNA was isolated from sera of nine ovarian cancer patients treated at Masaryk Memorial Cancer Institute. As a control samples, we used sera from six cancer-free women. Purified RNA was subjected to reverse transcription followed by cDNA preamplification. MiRNA expression was determined using TaqMan MicroRNA Assays. For statistical analysis was used nonparametric Mann-Whitney U test. RESULTS: MiRNAs miR-30a-5p and miR-26b were identified as significantly overexpressed miRNAs in sera from ovarian cancer patients. Other miRNAs showing elevated level were identified as miR-628-5p, 520c-3p, miR-486 and let-7b. On the other hand, miR-596 showed reduced levels in sera from ovarian cancer patients. CONCLUSION: A significantly different level of at least two miRNAs (miR-30a-5p a miR-26b) has been observed in cancer patients in comparison with healthy individuals. These miRNAs would serve as a powerful non-invasive diagnostic tool to detect ovarian epithelial cancer in so called liquid biopsies.Key words: microRNA - biomarkers - ovarian epithelial cancer - qPCR This work was supported by MEYS - NPS I - LO1413. 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: 13. 3. 2017Accepted: 26. 3. 2017.

[Malignant melanoma treated with radical chemotherapy, resemblance histology of melanoma to soft tissue sarcomas, case report]. / Maligní melanom lécený intenzivní chemoterapií, podobnost histologického obrazu maligního melanomu a nádoru mekkých tkání, kazuistika pacientky.

BACKGROUND: Malignant melanoma is considered to be highly resistant to chemotherapy, radiotherapy, hormonotherapy and standard immunotherapy (interleukin 2, interferon alpha). Radical surgery in the early stages of the disease is still the most efficient method. Since the development of immunotherapy and targeted therapy, the role of palliative chemotherapy for advanced disease may be changing. CASE: A case report regarding 44-year-old woman with extensive tumor of the pectoral wall with contralateral axillary lymphadenopathy is presented. On the basis of imaging methods, histology and immunohistochemistry, the tumor was defined as a sarcoma. Due to PAX7-FKHR fusion gene positivity, rhabdomyosarcoma was the most probable classification. The patient was treated with radical chemotherapy including iphosphamide, vincristine, actinomycin D and doxorubicin with the effect of partial regression of the tumor. This enabled radical surgery of the chest wall tumor. Pathology proved 70% necrosis of the tumor. A contralateral axillary dissection was performed with a finding of two lymph nodes infiltrated with melanoma. The immunohistochemistry markers S100, HMB-45 and Melan A were positive. This resulted in a reclassification of the chest wall tumor to malignant melanoma. The following PET/CT scan was negative. A massive progression of the disease occurred after 5 months. B-RAF mutation leads to a plan of targeted therapy with vemurafenib. CONCLUSION: The case demonstrates the limits of the sensitivity and specificity of immunohistochemical markers of melanoma and the ability of this tumor to imitate various tumors including soft tissue sarcomas. A rare -PAX7-FKHR fusion gene positivity considered specific for rhabdomyosarcoma was found. An extraordinary response to radical chemotherapy with surgical resection led to an improvement of the quality of life and to a prolonged survival comparable with the effect of new targeted treatment for malignant melanoma.

[Liver function assessment in oncology practice]. / Hodnocení jaterní funkce v onkologické praxi.

The overall condition and prognosis of a patient can be affected by impaired liver function. It applies to anticancer pharmacotherapy, liver surgery and radiological interventions. The liver condition is usually assessed by common laboratory tests and clinical examination in daily practice. Liver tests consist of aminotransferases - alanine transaminase, aspartate transaminase, bilirubin, alkaline phosphatase, gamma glutamyl transpeptidase, lactate dehydrogenase, albumin and prothrombin time, less frequently prealbumin and cholinesterase. The alkaline phosphatase and aspartate transaminase are markers of a liver damage, the alkaline phosphatase and gamma glutamyl transpeptidase are most useful as markers for cholestatic liver injury. Albumin, prealbumin, cholinesterase and prothrombin time are the markers of synthetic liver function. Bilirubin and bile acids are related to the liver transport and excretory capacity. The Child-Pugh score is used to assess prognosis of chronic liver disease, mainly cirrhosis. The examination of liver function using indocyanine green helps to determinate the extent of possible liver resection. A mathematical analysis of dynamic cholescintigraphy and a calculation of hepatic extraction fraction enables quantification of liver function. Other liver function tests are of little use in oncology.

Uncommon EGFR Mutations in Non-Small Cell Lung Cancer and Their Impact on the Treatment.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations play an important role in the pathogenesis of non-small cell lung cancer. Because these alterations are so-called targetable mutations, their identification is important in daily clinical practice. The diagnostic standard of EGFR mutations is currently based on polymerase chain reaction methods, particularly the quantitative real-time polymerase chain reaction. In recent years, new generation sequencing has become increasingly important. In patients with EGFR mutations, a significant improvement in therapeutic outcomes was achieved with the administration of targeted therapy using tyrosine kinase inhibitors. EGFR is composed of four domains: extracellular with a ligand binding site, a transmembrane domain, a cytoplasmic tyrosine kinase catalytic domain, and a C-terminal domain. The key structures of the tyrosine kinase domain responsible for signal activation and transmission are encoded within exons 18-21 on chromosome 7. EGFR mutations are highly heterogeneous. About 90% of EGFR mutations are deletions of exon 19 and point mutation L858R in exon 21. These are referred to as classic mutations. Approximately 10% of the total number of EGFR mutations is attributable to less frequent alterations in the EGFR gene. Due to the low incidence of non-small cell lung cancer with less frequent EGFR mutations, information on their predictive significance is still incomplete. Most of the data for the treatment of cases with uncommon mutations were gathered from retrospective analyses and evaluations of small cohorts. PURPOSE: The aim of this review is to summarise the current options for diagnosing and treating non-small cell lung cancer patients with uncommon EGFR mutations. This work was supported by the MEYS - NPS I - LO1413 and MH CR - DRO (MMCI, 00209805). 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: 2. 6. 2019 Accepted: 26. 8. 2019.