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This study presents a comprehensive analysis of mitochondrial DNA (mtDNA) variations in dogs diagnosed with primary and recurrent tumours, employing Oxford Nanopore Technologies (ONT) for sequencing. Our investigation focused on mtDNA extracted from blood and tumour tissues of three dogs, aiming to pinpoint polymorphisms, mutations, and heteroplasmy levels that could influence mitochondrial function in cancer pathogenesis. Notably, we observed the presence of mutations in the D-loop region, especially in the VNTR region, which may be crucial for mitochondrial replication, transcription, and genome stability, suggesting its potential role in cancer progression. The study is pioneering in its use of long-read sequencing to explore the mutational landscape of mtDNA in canine tumours, revealing that while the overall mutational load did not differ between primary and recurrent tumours, specific changes in m.16168A/G, m.16188G/A, and m.16298A/G are linked with tumour tissues. Interestingly, the heteroplasmy outside the D-loop region was not specific to tumour tissues and did not provoke any malignant damage in protein-coding sequences, which in turn may be a tolerant effect of the reactive oxygen species (ROS) cellular stress mechanism. [ABSTRACT FROM AUTHOR]

The ability to undergo neoangiogenesis is a common feature with all cancers. Signaling related to vascular endothelial growth factors (VEGF) and their receptors (VEGFR) plays a key role in the process of tumor neoangiogenesis. A close relationship has been demonstrated between excessive VEGF levels and the induction of immunosuppression in the tumor microenvironment. The use of drugs blocking the VEGF function, apart from the anticancer effect, also result in adverse effects, in particular related to the circulatory system and kidneys. Cardiac toxicity associated with the use of such therapy manifests itself mainly in the form of hypertension, thromboembolic episodes and ischemic heart disease. In the case of renal complications, the most common symptoms include renal arterial hypertension, proteinuria and microangiopathy. Although these complications are reversible in 60–80% of cases after cessation of VSP (VEGF pathway inhibitor) therapy, in some cases they can lead to irreversible changes in renal function, whereas cardiac complications may be fatal. Also, the use of PD-1/PD-L1 inhibitors may result in kidney and heart damage. In the case of cardiac complications, the most common symptoms include myocarditis, pericarditis, arrhythmia, acute coronary syndrome and vasculitis, while kidney damage most often manifests as acute kidney injury (AKI), nephrotic syndrome, pyuria or hematuria. The decision whether to resume treatment after the occurrence of cardiovascular and renal complications remains a problem. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this retrospective study was to present the prevalence of early and late radiation-induced reaction and factors affecting its formation and severity in patients after adjuvant radio- or radiochemotherapy in salivary gland cancer. Material and methods: A total of 113 patients with early and 91 with late radiation-induced reaction, irradiated in 2006-2016 were enrolled in the study. The frequency of acute mucosal radiation-induced reaction, time of onset, intensity, healing time, as well as incidence of late radiation-induced reaction from the skin and subcutaneous tissue were analysed. Factors that could influence the development and intensity of reaction were identified. R esults: Acute severity and the presence of late radiation-induced reaction do not affect overall survival. Dosage in the tumour bed site as well as the dosage in the nodal region affect the severity of acute radiation-induced mucosal reaction. The severity of early radiation-induced reaction is higher in men, more advanced patients (higher T and N+ in TNM classification), irradiated into a larger area, and those in whom two-dimensional planning and complementary chemoradiotherapy were applied. The late reaction of the skin and subcutaneous tissue was dominated by patients irradiated in the nodal regions and those with a higher intensity of early radiation-induced reaction. C onclusions: Supplementary radiotherapy or radiochemotherapy in salivary gland cancer is associated with acceptable toxicity which has no effect on overall survival. [ABSTRACT FROM AUTHOR]

Introduction. The aim of the study was to analyse the survival and progression rates in patients with recurrent salivary gland cancer after surgery and adjuvant radio- or chemoradiotherapy. Material and methods. The study included 43 patients treated in 2006-2016 and evaluated in terms of PFS and OS. Results. The 6-, 12- and 24-month OS rates were: 51%, 41%, and 14%, respectively, while the 6-, 12- and 24-month PFS rates were: 44%, 27%, and 14%, respectively. Any treatment improves OS and PFS, with surgery having the greatest effect on improving PFS, followed by chemotherapy and radiotherapy. A multivariate analysis has shown that predictors of PFS are: irradiated volume and radiation technique, while irradiated volume is the predictor of OS. Conclusions. Prognosis in patients with recurrent gland cancer is poor and does not depend on the type of relapse, but rather on further management. [ABSTRACT FROM AUTHOR]

The aim of the study was to retrospectively analyze 7 cases of penile cancer treated with HDR brachytherapy and to review the literature on the usage of brachytherapy in this disease. Material and methods. The analysis involves 5 patients treated with interstitial brachytherapy and 2 patients treated with contact brachytherapy in 2012-2017. Two patients received adjuvant treatment due to non-radical surgery, while the remaining patients were treated for a local relapse after surgery. Partial penectomy was conducted in 3 cases, while only local resection was performed also in 3 cases. The patients treated with interstitial brachytherapy alone were irradiated to the total dose of 42-45 Gy twice daily in fractions of 3 Gy. The patient treated with contact brachytherapy alone was irradiated to the total dose of 45 Gy once daily in 15 fractions of 3 Gy. The patients treated with brachytherapy combined with teleradiotherapy were irradiated to the total dose of 60-66 Gy. Results. During the mean follow-up of 21 months (from 4 to 44 months), there were no cases of local recurrence in the treated region. Organ preservation was possible in all cases. The disease recurred in the form of metastases in two cases. One of them developed lung metastases, and the other - bilateral inguinal lymph node metastases. Acute toxicity was graded at maximally grade III in the RTOG (Radiation Therapy Oncology Group) system and concerned the skin and mucous membranes. Late complications (RTOG grade I only) included fibrosis and penile skin discoloration. Conclusions. Brachytherapy is an effective and safe treatment method and may be an alternative to mutilating surgery. [ABSTRACT FROM AUTHOR]

Copyright of Onkologia i Radioterapia is the property of Wydawnictwo SALVE and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Onkologia i Radioterapia is the property of Wydawnictwo SALVE and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background. Brain metastases from tonsillar cancers are extremely rare and only about 0.4% cases of tonsil cancer result in metastasis to the central nervous system. Methods and Results. Here we describe a case of 69 years old man with primary tonsillar cancer who achieved loco-regional control after surgical treatment and adjuvant radiotherapy. Two years after the treatment 2 metastastatic lesions in cerebellar hemispheres were detected. After the surgical removal of metastatic lesions patient was treated by radiotherapy. Whole brain radiation therapy was conducted applying the dose of 20 Gy in 5 fraction. 12 months later no disease progression and further metastases was observed either in the primary tumor site or in the central nervous system. Conclusions. Tonsillar cancers seen with cerebellar metastases are extremely rare. Whole brain radiation after the radical resection of brain metastases from tonsillar cancer may be favourable for patients without other metastases or local recurrence. [ABSTRACT FROM AUTHOR]

Neoplasms of large salivary glands are a highly differentiated group of diseases in terms of their histology. There are 24 histological types of these tumors, the most common of which are mucoepidermoid carcinoma and adenoid cystic carcinoma. The mainstay of radical treatment is surgical removal of the salivary gland, which, in certain patients, is supplemented with radiation therapy or chemoradiotherapy. There are no large randomized prospective studies that would show an overall survival or local control benefit in individual types of this disease. Research demonstrates that salivary gland tumors are generally resistant to radiation. Despite this, adjuvant radiotherapy is applied in patients without radical surgical margins and with highly advanced disease in most of these histological types. However, scientific investigations do not confirm the influence of adjuvant treatment on LC and OS in the mucoepidermoid type. Nevertheless, this treatment increases local control and prolongs overall survival in patients with adenoid cystic carcinoma and adenocarcinoma. As for acinic cell carcinoma and malignant mixed tumor, the benefit from radiotherapy is unclear. Irradiation in these diseases may improve local control and prolong survival in more advanced cases. As in other head and neck cancers, radiation therapy and chemoradiotherapy should be applied in patients with squamous cell carcinoma of the salivary glands. Due to the rare occurrence of other histological types, data on the benefit from radiotherapy are lacking. Adjuvant radiotherapy has been shown to improve survival only in patients with more advanced basal cell carcinoma. [ABSTRACT FROM AUTHOR]

Copyright of Onkologia i Radioterapia is the property of Wydawnictwo SALVE and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Onkologia i Radioterapia is the property of Wydawnictwo SALVE and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Next to thermoablation, radioembolization or chemoembolization, radiation therapy is one of non-surgical methods of local treatment for primary and secondary liver cancers. Brachytherapy is a radiotherapy technique which enables highdose irradiation with relatively low doses delivered to the remaining, healthy liver parenchyma owing to appropriate arrangement and number of applicators. The aim of the study was to assess the impact of various doses in the healthy hepatic parenchyma on early biochemical toxicity in patients undergoing brachytherapy for liver tumors. Material and methods. The analysis involved values of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (BIL) in 16 patients within the period of 6 months after brachytherapy. Six patients (37.5%) were administered 20 Gy, 7 (43.75%) 15 Gy (43.75%), and 3 (18.75%) 10 Gy. Toxicity was assessed based on the most common clinical liver function parameters: ALT, AST and BIL. Results. None of the patients demonstrated statistically significant differences in biochemical liver function markers (ALT, AST and BIL) for the first, second and third time periods. A statistically significant correlation was found between the maximum dose delivered to the liver and ALT levels in the second (p = 0.002) and third time periods (p = 0.014). Also, a correlation existed between CTV with the AST value in the first time period at a borderline significance level (p = 0.04). There were no statistically significant correlations between other physical parameters (Dmax, D1/3, D2/3, D50%, D10cm3, D100cm3, D500cm3, D100%, D90%, liver volume) and levels of biochemical liver function markers in individual time periods (p>0.05). Conclusions. Hepatotoxicity of brachytherapy depends on the volume of the irradiated tumor. This correlates with an increase in transaminases and indicates the existence of a certain tumor volume at which the toxicity of brachytherapy is not acceptable. Further studies are needed to assess the influence of brachytherapy conducted for the treatment of liver tumors on hepatotoxicity. [ABSTRACT FROM AUTHOR]

Background: Research has revealed the presence of somatic mutations in mitochondrial DNA (mtDNA) of certain types of tumours. As this has not been studied for canine mast cell tumours, the aim of this study was to identify mutations in the hypervariable region of mtDNA in mast cell tumours in dogs and determine their association with the process of neoplastic transformation. Results: Samples from 17 dogs with histopathologically confirmed mast cell tumours were analysed. The samples consisted of tumour tissues (n = 17), normal tissues (n = 17), and blood (n = 17). Amplicons of the displacement loop (D-loop) were sequenced and the obtained nucleotide sequences were subjected to bioinformatics analyses. Somatic mutations were detected in seven positions of the D-loop nucleotide sequences in 47 % of the dogs, while polymorphisms were identified in 94 % of the dogs. Most of these changes were homoplasmic, while heteroplasmy was detected in two individuals. Six new haplotypes were established as being characteristic for canine mast cell tumours. There was no association between the presence of the mutations and sex, haplotype, or malignancy grade assessed in 3 and 2-grade scales. Conclusions: Differences in the frequency of somatic mutations imply their direct association with the neoplastic transformation. However, their functional consequences and clinical significance are not clear. The mutations may be used for diagnosis and prognosis of canine mast cell tumours in the future. [ABSTRACT FROM AUTHOR]

Abstract. A series of 1,6-bis(3-substituted 1,5-dihydro-5-oxo-4H-1,2,4-triazol- -4-yl)hexanes 3a--g were synthesized by the cyclization reaction of 1,6-bis{[(2- -substituted hydrazinyl)carbonyl]amino}hexanes 2a--g in alkaline medium. The new derivatives 3a--c were screened in vitro for their antiproliferative and anticancer activity in human tumor cell lines derived from breast and lung carcinoma cells. Compounds 3a (at a concentration of 0.18 mM), 3b (at concentrations of 0.12 and 0.02 mM) and 3c (at concentrations of 0.23 and 0.11 mM) were found to be the most effective against the lung cell line. Compound 3a had the greatest antiproliferative effect on the breast carcinoma cell line. Representative compounds were established and evaluated as antimicrobial agents. All the tested derivatives showed minimum inhibitory concentrations (MIC) in the range 1.87--7.5 µg mL-1. Compound 3b was the most effective against Candida albicans (MIC 1.87 µg mL-1). [ABSTRACT FROM AUTHOR]

Aim: Identification of mutations and polymorphisms in the cytochrome b gene (Cyb) of mitochondrial DNA (mtDNA) in canine mast cell tumours and determinatiion of their association with the process of neoplastic transformation., Materials and Methods: The samples comprised tumour tissues and blood obtained from 34 dogs of various breeds. Mutations and polymorphisms in the Cyb gene were detected using amplification and sequencing methods., Results: Heteroplasmic mutations were detected at seven positions of mtDNA in 86% of the individuals. Blood and tumour heteroplasmy were recorded at five nucleotide positions of the Cyb gene, whereas tumour heteroplasmy was detected at two positions. Polymorphisms were detected at 14 Cyb gene positions in in the blood of 91% of dogs with mast cell tumours., Conclusion: The presence of numerous mutations and polymorphisms of Cyb in the blood and tumour tissues and the high frequency of heteroplasmy indicate their involvement in the process of neoplastic transformation in dogs., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Malignant peripheral nerve sheath tumor (MPNST) is a rare malignant counterpart to benign neurogenes tumors such as schwannomas and neurofibromas and account for approximately 5-10 % of all soft tissue sarcomas. This neoplasm is also referred to older designations as a malignant schwannoma, malignant neurilemmoma or neurogenic sarcoma. A patient was a woman of 59 years old with a diagnosed malignant neurilemmoma, treated since 1993. Operated several times and subjected to radiotherapy due to the local recurrence of the tumors located in the soft tissues of the back until 2002; Treated with chemotherapy (doxorubicin) and operated due to a lung metastases. The therapy resulted in a total remission that lasted 12 months. In 2004 a new small tumor was diagnosed in the right lung, which had been followed up until 2006. The patient did not give permission to a second surgery, treated with ifosfamide. In 2006 she was operated for renal cell carcinoma of the left kidney. In 2009, due to a following progression of neurilemmoma and a worsening overall condition, she was subsequently treated with a combination of gemcitabine and docetaxel. The treatment resulted in a slight improvement, but was stopped due to complications (pancytopenia). In 2010 another progression of the disease occurred, which resulted in pleural metastases and osteolytic lesions in the vertebrae (Th6 and L2).

Prognostic survival rate is one of the factors decisive about the kind of the local therapy at patients with bone metastases. The work evaluates chosen prognostic parameters such as age, sex, the presence of extra-skeletal metastases, the existence of pathological fracture and the applications of bisphosphonates and/or systemic treatment at 305 patients irradiated due to bone metastases. The median survival rate was 6.2 months and was significantly depended from primary location of the disease. The sex, age and number of metastatic foci had no significant influence on the median survival rate however the remaining prognostic factors depended on the primary location of the neoplasm.

Background. Bisphosphonates are form of medical therapy for bone metastases. Morbidity from bone metastases including hypercalcemia episodes, pain, pathological fractures and appearance of new metastases in skeletal system is decreased by bisphosphonate therapy. The aim of this article is to determine the influence of bisphosphonate therapy on survival time of patients irradiated due to bone metastases., Material and methods. 305 patients irradiated due to bone metastases were assessed in this retrospective study. 94 of them were additional treated by bisphosphonates. Median survival time counted from the end of radiotherapy to the death of patients was assessed. Using U Mann Whitney test the influence of bisphosphonates therapy on survival time was determined. The significance level of p = 0,05 was accepted., Results. The median survival time of patients irradiated due to bone metastases and treated by bisphosphonates was 8,1 month and 5,24 month in the group treated only by radiotherapy. Median survival time of pts with breast cancer and with unknown primary site of cancer who were treated by radiotherapy and bisphosphonates was significantly longer (respectively p = 0,001 and p = 0,016) as compared with the group with irradiated bone metastases only., Conclusions. 1. Bisphosphonates therapy improved the median survival time in the whole group of patients irradiated due to bone metastases. 2. Statisticaly significant prolonged survival time was observed in groups of patients with breast cancer and with unknown primary site of cancer. Median survival time was prolonged in these groups about 5 months and 3,5 months respectively.