Molecular oncology focus - Is carcinogenesis a 'mitochondriopathy'?

Mitochondria are sub-cellular organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As suggested over 70 years ago by Otto Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and in mitochondrial DNA (mtDNA) appear to be common features of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells, and some reports document the prevalence of inherited mitochondrial DNA polymorphisms in cancer patients. Nevertheless, a careful reanalysis of methodological criteria and methodology applied in those reports has shown that numerous papers can't be used as relevant sources of data for systematic review, meta-analysis, or finally for establishment of clinically applicable markers

Waga wczesnego rozpoznania i leczenia obturacyjnego bezdechu podczas snu w grupie pacjentów obciążonych kardiologicznie

Obturacyjny bezdech podczas snu (OSA) jest jednym z najczęściej występujących zaburzeń oddychania we śnie. Nowe badania epidemiologiczne wskazują na dużo większe rozpowszechnienie schorzenia w ogólnej populacji niż wcześniej sądzono. Szczególną grupą chorych są pod tym względem pacjenci obciążeni chorobą układu sercowo-naczyniowego, wśród których OSa występuje zdecydowanie częściej niż w ogólnej populacji oraz może stanowić izolowany czynnik ryzyka rozwoju niektórych schorzeń kardiologicznych. W artykule omówiono metody diagnostyki OSA, epidemiologię w poszczególnych schorzeniach kardiologicznych oraz perspektywy rozwoju badań przesiewowych.Obturacyjny bezdech podczas snu (OSA) jest jednym z najczęściej występujących zaburzeń oddychania we śnie. Nowe badania epidemiologiczne wskazują na dużo większe rozpowszechnienie schorzenia w ogólnej populacji niż wcześniej sądzono. Szczególną grupą chorych są pod tym względem pacjenci obciążeni chorobą układu sercowo-naczyniowego, wśród których OSa występuje zdecydowanie częściej niż w ogólnej populacji oraz może stanowić izolowany czynnik ryzyka rozwoju niektórych schorzeń kardiologicznych. W artykule omówiono metody diagnostyki OSA, epidemiologię w poszczególnych schorzeniach kardiologicznych oraz perspektywy rozwoju badań przesiewowych

The importance of early diagnosis and treatment of obstructive sleep apnoea in patients with cardiovascular diseases

Obstructive sleep apnoea (OSA) is one of the most common sleep-related breathing disorders. New epidemiological studies show that the disease is much more prevalent in the general population than previously believed. Individuals with cardiovascular diseases are a special group of patients suffering from OSA as the prevalence of the disorder among them is much greater than in the general population, and it can constitute an isolated risk factor for the development of some cardiovascular diseases. This article will discuss methods for diagnosing OSA, its epidemiology among patients with particular cardiovascular diseases and the prospects for the development of screening examinations

Successful treatment of postoperative, radiation-associated wound dehiscence around tracheostomy with negative pressure wound therapy.

We present case report of 62-year-old man who underwent total laryngectomy, bilateral neck dissection and radiotherapy due to laryngeal cancer. After 11 months he was reoperated because of a local recurrence. The second procedure was complicated with postoperative wound dehiscence in tracheostomy site which was successfully treated with negative pressure wound therapy. We indicate the difficulties and point technical solutions for negative pressure dressing around the airway

Selected ALKBH dioxygenases are overexpressed in salivary gland tumours.

Salivary gland tumours (SGTs) are a heterogeneous group of benign tumours of various origins and pathologies, showing a number of DNA modifications. Previously, in malignant head and neck cancer (HNSCC), we found overexpression of ALKBH proteins, the homologs of Escherichia coli AlkB 2-oxoglutarate and Fe(II) dependent dioxygenase. Moreover, we proved the connection of some of these dioxygenases with cancer development. Here, we studied the expression of five of these ALKBH dioxygenases: 1, 3, 4, 5, and FTO in benign SGTs. Using Western blot analysis, we found overexpression of three proteins: ALKBH1, 4, and FTO in SGT as compared to the surrounding, unaffected tissue. ALKBH4 was overexpressed in 76% of patient samples, whereas ALKBH1 and FTO in 65% of the samples. These results differ from those obtained in HNSCC, where FTO overexpression has been observed in 90% of patient samples. We also investigated the relationships between ALKBHs’ expression levels in normal and SGT tissues and identified two correlated pairs: ALKBH1-ALKBH3 and ALKBH1-ALKBH5. Additionally, in tumour tissue ALKBHs: ALKBH1, ALKBH3, ALKBH4, and ALKBH5 levels were correlated with each other. Together, these findings show that the ALKBH proteins exhibit pro cancerogenic action in SGT, even though the levels ALKBHs are generally lower in benign SGT than in malignant HNSCC. We suggest that the overexpression of the ALKBHs, especially FTO, may be used as a cancer marker and for its grading

Mitochondrial genotype in vulvar carcinoma - cuckoo in the nest

Vulvar squamous cell carcinoma (VSCC) is a rare female genital neoplasm. Although numerous molecular changes have been reported in VSCC, biomarkers of clinical relevance are still lacking. On the other hand, there is emerging evidence on the use of mtDNA as a diagnostic tool in oncology. In order to investigate mtDNA status in VSCC patients, haplogroup distribution analysis and D-loop sequencing were performed. The results were compared with available data for the general Polish population, cancer free-centenarians as well as patients with endometrial and head and neck cancer. The obtained data were also compared with the current status of mitochondrial databases. Significant differences in haplogroup distribution between VSCC cohort, general Polish population and cancer-free centenarians cohort were found. Moreover, a correlation between the VSCC patients haplogroup and HPV status was observed. Finally, a specific pattern of mtDNA polymorphisms was found in VSCC. Our results suggest that the mitochondrial genetic background may influence the risk of VSCC occurrence as well as susceptibility to HPV infection

ALKBH overexpression in head and neck cancer: potential target for novel anticancer therapy

The nine identified human homologues of E. coli AlkB 2-oxoglutarate (2OG) and Fe(II)-dependent dioxygenase, ALKBH1-8 and FTO, display different substrate specificities and diverse biological functions. Here we discovered the combined overexpression of members of the ALKBH family in head and neck squamous cell carcinomas (HNSCC). We found direct correlation of ALKBH3 and FTO expression with primary HNSCC tumor size. We observed unidentified thus far cytoplasmic localization of ALKBH2 and 5 in HNSCC, suggesting abnormal role(s) of ALKBH proteins in cancer. Further, high expression of ALKBHs was observed not only in HNSCC, but also in several cancerous cell lines and silencing ALKBH expression in HeLa cancer cells resulted in dramatically decreased survival. considering the discovered impact of high expression of ALKBH proteins on HNSCC development, we screened for ALKBH blockers among newly synthetized anthraquinone derivatives and demonstrated their potential to support standard anticancer therapy

Diagnosis and treatment of rhabdomyosarcomas

Rhabdomyosarcoma (RMS) is a soft tissue sarcoma. The primary tumor is most commonly localized in the head and neck, the urogenital system, or the limbs. Classification by the World Health Organization has distinguished four histopathological RMS subtypes: embryonal, alveolar, pleomorphic, and spindle cell/sclerosing. Differential diagnosis of RMS includes melanoma, malignant neoplasm of peripheral nerve sheaths, liposarcoma, and PEComa. Among typical cytogenetic changes in RMS are chromosomal translocations t(2;13)(q35;q14) and t(1;13) (p36;q14). They lead to the formation of fusion genes that have a prognostic value. In the course of RMS, changes may also be present in signaling pathways, including RAS-PI3K, Wnt/b-catenin, receptor tyrosine kinase pathways, and myogenesis regulation. In 30% of patients at the time of diagnosis of RMS, distant metastases are present, most commonly to lungs, lymph nodes, bones, and bone marrow. Treatment of patients with RMS requires a multidisciplinary approach, and steadily perfected diagnostic techniques contribute to the individualization of therapeutic strategies. Optimal treatment of localized RMS is based on surgery combined with radiotherapy and chemotherapy. If distant metastases are present, the basic therapeutic method is multidrug chemotherapy, most frequently based on vincristine, dactinomycin, ifosfamide/cyclophosphamide, and etoposide. Despite intensive treatment, the 5-year survival index for RMS is not greater than 50%. There are still no unequivocal guidelines concerning the treatment in patients with local or distant recurrences