Rapid advance in oncology leads to increasing survival of oncologic patients. More and more of them live long enough to reach either the natural age of menopause or, as a side effect of their oncotherapy, experience the cessation of gonadal function, leading to premature ovarian insufficiency, with disturbing vasomotor symtoms and long-term negative cardiovascular and skeletal effects. Thus, an ever increasing number of cancer survivors search endocrinologic help in the form of hormone replacement therapy (HRT). The misinterpretation of the WHI (Women's Health Initiative) Study has lead to an irrational fear of female hormone replacement, both by the general population and medical professionals. It has seemed the logical and safe conclusion to many physicians to avoid HRT, supposing that this attitude definitely causes no harm, whereas the decision of prescribing estrogen alone or with progestins might bear oncologic and thromboembolic risks and may even lead to litigation in case of a potentially related complication. However, it was known even before the WHI results that premature menopause and hypogonadism decreases the life expectancy of women by years through its skeletal and cardiovascular effects, and this negative effect correlates with the length of the hypoestrogenaemic period. Therefore, the denial of HRT also needs to be supported by evidence and should be weighed againts the risks of HRT. Yet, the oncologic risk of HRT is extremely difficult to assess. In this work we review the latest evidence from in vitro experiments to clinical studies, regarding HRT in survivors of gynecologic and non-gynecologic cancers. Based on our literature research, we group tumours regarding the oncologic risk of properly chosen female hormone replacement therapy in cancer survivors as follows: 'HRT is advanageous' (e.g. endometrial cancer type I, cervical adenocarcinoma, haematologic malignancies, local cutaneous malignant melanoma, colorectal cancer, hepatocellular cancer); 'HRT is neutral' (e.g. BRCA 1/2 mutation carriers without cancer, endometrial cancer type II, uterinal carcinosarcoma and adenosarcoma, certain types of ovarian cancer, cervical, vaginal and vulvar squamous cell carcinoma, prolactinoma, kidney cancer, pancreatic cancer, thyroid cancer); 'HRT is relatively contraindicated' for various reasons (e.g. leiomyosarcoma, certain types of ovarian tumours, brain tumours, advanced metastatic malignant melanoma, lung cancer, gastric cancer, bladder cancer); 'HRT is diasadvantageous and thus contraindicated' (e.g. breast cancer, endometrial stroma sarcoma, meningioma, glioma, hormone receptor positive gastric and bladder cancer).
Purinergic signal transduction mechanisms have been appreciated as a complex intercellular signalling network that plays an important regulatory role in both short- and long-term processes in practically every living cell. One of the most intriguing aspects of the field is the participation of ATP and other purine nucleotides in the determination of cell fate and the way they direct cells towards proliferation, differentiation or apoptosis, thereby possibly taking part in promoting or preventing malignant transformation. In this review, following a very brief introduction to the historical aspects of purinergic signalling and a concise overview of the structure of and signal transduction pathways coupled to P2 purinergic receptors, the current theories concerning the possible ways how extracellular ATP can alter the function of tumour cells and the effectiveness of anticancer therapies are discussed, including pharmacological, nutritional, vasoactive and 'anti-antioxidant' actions of the nucleotide. The effects of ATP on animals inoculated with human tumours and on patients with cancer are looked over next, and then an overview of the literature regarding the expression and presumed functions of P2 purinoceptors on tumour cells in vitro is presented, sorted out according to the relevant special clinical fields. The article is closed by reviewing the latest developments in the diagnostic use of P2 purinergic receptors as tumour markers and prognostic factors, while discussing some of the difficulties and pitfalls of the therapeutic use of ATP analogues.
Ca2+‐signaling of human melanoma is in the focus of intensive research since the identification of the role of WNT‐signaling in melanomagenesis. Genomic and functional studies pointed to the important role of various Ca2+ channels in melanoma, but these data were contradictory. In the present study we clearly demonstrate, in a number of different ways including microarray analysis, DNA sequencing and immunocytochemistry, that various human melanoma cell lines and melanoma tissues overexpress ryanodine receptor type 2 (RyR2) and express P2X7 channel proteins as compared to melanocytes. These channels, although retain some of their usual characteristics and pharmacological properties, display unique features in melanoma cells, including a functional interaction between the two molecules. Unlike P2X7, RyR2 does not function as a calcium channel. On the other hand, the P2X7 receptor has an antiapoptotic function in melanoma cells, since ATP‐activation suppresses induced apoptosis, while knock down of the gene expression significantly enhances that. © 2007 Wiley‐Liss, Inc.
Aim To obtain palaeobotanical evidence enabling evaluation of the viability of the hypothesis that the 'oriental' element of the Balkan flora reached south-east Europe from Turkey prior to the Holocene, probably via the Thracian Plain during a late Quaternary glacial stage but no later than the late Weichselian.
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