Ludmiła Grzybowska-Szatkowska

Polymorphisms in genes encoding mt-tRNA in female breast cancer in Poland

Recently, there have been indications of participation of mitochondria in the carcinogenic process and the role of polymorphisms in increasing the risk of cancer. The aim of the study was to detect possible changes in the sequence of 22 genes encoding mitochondrial tRNA in breast cancer carcinoma, which take part in protein synthesis in the translation process. The analysis of tumour tissue and blood material sampled from 50 patients revealed that few mutations have been found. It cannot be excluded that, through their impact on the secondary and tertiary tRNA structure, polymorphisms may cause mitochondrial dysfunction and contribute to appearance of other changes in mtDNA. Mutations in tRNA genes in breast cancer may affect the cell and cause its dysfunction, as in mitochondrial diseases.

Mitochondrial D-loop mutations and polymorphisms are connected with canine malignant cancers

Abstract The aim of the conducted investigations was to identify differences in the D-loop nucleotide sequence between neoplastic tissue, normal tissue, and blood and to determine their correlation with the type of cancer in dogs. In 62.5% of the analyzed tumors of epithelial origin and 25% tumors of mesenchymal origin, substitution was detected within the D-loop sequence between the neoplastic tissue, normal tissue, and blood. Two mutations occurring in the carcinogenic process in position T15620C have been identified in epithelioma glandulae sebacei and carcinoma planoepithelialae keratodes. Blood and cancer heteroplasmy was diagnosed for carcinoma planoepithelialae keratodes and “Comedo” carcinoma. The results of the study indicate that polymorphic changes in the D-loop sequence promote carcinogenesis in dogs. Heteroplasmy diagnosed in blood and tumor cells and absence thereof in normal tissue may imply mtDNA recombination. High prevalence of mtDNA mutations in canine tumors may suggest mtDNA genetic instability, which is likely to play a role in carcinogenesis.

Mitochondrial DNA polymorphism in genes encoding ND1, COI and CYTB in canine malignant cancers

Abstract The aim of the study was to identify DNA changes in mitochondrial gene fragments: NADH dehydrogenase subunit 1 (ND1), cytochrome c oxidase subunit I (COI) and cytochrome b (CYTB) in tumor tissue, normal tissue and blood, and to define their association with the tumor type in dogs. Molecular analysis included 144 tests in total. A functional effect of the non-synonymous protein coding SNP was predicted. The presence of polymorphisms in all tested gene fragments in individual tissues of dogs was observed. Heteroplasmic changes were found in ND1 and CYTB in epithelioma glandulae sebacei and in CYTB in lymphoma centroblasticum. The results of in silico analysis show the impact of these alleles (COI: 507, ND1: 450, 216, CYTB: 748) on the functioning of proteins and thus their potential role in carcinogenesis. The possible harmful effects of changes in polypeptides in positions T193N, V98M, V118M and H196P were evaluated. It seems that polymorphisms occurring in cells can have a negative impact on functioning of proteins. This promotes disorders of the energy level in cells.

Novel mitochondrial mutations in the ATP6 and ATP8 genes in patients with breast cancer

The role of the mitochondria in the process of carcinogenesis, mainly oxidative phosphorylation, mostly concerns their participation in the production of free radicals and ATP and in the process of apoptosis. The purpose of this study was to detect potential changes in the genes encoding the subunits 6 and 8 of the ATP synthase and their impact on the enzyme’s biochemical properties, structure and function in patients with breast tumors. The tested material was mitochondrial DNA (mtDNA) isolated from specimens of ductal carcinoma (carcinoma ductale) Tp1-2Np0-1Mp0, blood and non-cancerous tissue of mammary gland (control), sampled from 50 patients who had been operated for breast cancer. In the case of missense-type changes in the mtDNA, protein prediction software was used to assess their effect on the biochemical properties of the protein, its structure and function. We identified 8 changes in the ATP6 gene in 36/50 examined breast cancer cell samples and 5 changes in the ATP8 gene (10/50). Most of them were homoplasmic changes of missense type. Four of the changes (A8439C, G8858C, C9130G and T9119G) had not been described in the literature before. The identified mutations and polymorphisms, especially those of missense type, can affect mitochondrial functions, especially if the conservative domain of the protein is concerned. Replacement of ‘wild-type’ mtDNA by mutated mtDNA can be an important event in carcinogenesis.

Adjuvant Radiochemotherapy with a 23-Month Overall Survival Time in a Patient after a Surgery due to Splenic Hemangiosarcoma Rupture: A Case Report with the Literature Review

Spleen sarcoma is one of the most rare soft tissue malignancies. The annual incidence is 0.14–0.25/1,000,000 and the average age of diagnosis is 50 to 73 years. The incidence of this cancer has been increasing. Treatment of choice is surgical splenectomy, which rarely gives good results due to the aggressive course of the disease as well as the high potential for metastasis. Overall survival in primary spleen sarcomas as described by various authors is between 4 and 14 months. 80% of patients after spleen rupture do not survive 6 months. We report the case of a 42-year-old male diagnosed with spleen angiosarcoma. The patient underwent surgery in an emergency mode because of rapid rupture of the organ. Due to positive surgical margins, he underwent adjuvant radiochemotherapy followed by chemotherapy. Overall survival time was relatively long (23 months). The international guidelines provide information based on limited data. The role of postoperative radiotherapy in angiosarcomas remains controversial. Postoperative radiotherapy may increase local disease control, especially after nonradical operation, but this does not translate into improvement in overall survival time of these patients. The case shows that adjuvant radiotherapy as part of cancer treatment strategy may prolong the overall survival.

Retrospective Analysis of Intravaginal Brachytherapy in Adjuvant Treatment of Early Endometrial Cancer

The aim of this study was to determine the role of adjuvant endovaginal brachytherapy HDR (High Dose Rate) or observation, as well as identification of risk factors of tumor recurrence. The study included 178 women after radical hysterectomy. All patients belonged to the group of low- and medium-risk stage I FIGO. Analysis consisted of 3-, 5-, and 10-year OS, DFS, and LRFS in both groups. Follow-up was more than 6.5 years. The 5-OS, 5-DFS, and 5-LRFS were 93%, 96%, and 98% in the treated group and 95%, 94%, and 96% in the observed group, respectively. These differences were not statistically significant. There was a statistically significant difference in 5-OS in the treated group, between low- and medium-risk subgroups (100% versus 87.55%, p = 0.018). There was a better prognosis among the patients with FIGO IA compared to FIGO IB (5-DFS, 97 versus 86%, p = 0.047). Among the risk factors, there were only statistically significant differences in the 5-OS, between the ages of ≤ 70 years and >70 years. Use of brachytherapy may affect the reduction in the number of local recurrences at the vaginal stump (6% versus 2%). This is particularly noticeable in the low-risk subgroup (9% versus 0%).