RESUMO
Balneotherapy and spa therapy have been used in the treatment of ailments since time immemorial. Moreover, there is evidence to suggest that the beneficial effects of thermal water continue for months following the completion of treatment. The mechanisms through which thermal water exerts its healing effects remain unknown. Both balneological and hydroponic therapy at 'the oldest spa in the world', namely, the Nitrodi spring on the Island of Ischia (Southern Italy) are effective in a number of diseases and conditions. The aim of the present study was to investigate the molecular basis underlying the therapeutic effects of Nitrodi spring water in lowgrade inflammation and stressrelated conditions. For this purpose, an in vitro model was devised in which RKO colorectal adenocarcinoma cells were treated with phosphatebuffered saline or phosphatebuffered saline prepared with Nitrodi water for 4 h daily, 5 days a week for 6 weeks. The RKO cells were then subjected to the following assays: 3(4,5Dimethylthiazol2yl)2,5diphenyl2Htetrazolium bromide assay, Transwell migration assay, western blot analysis, the fluorimetric detection of protein Snitrosothiols and Snitrosylation western blot analysis. The results revealed that Nitrodi spring water promoted cell migration and cell viability, and downregulated protein Snitrosylation, probably also the nitrosylated active form of the cyclooxygenase (COX)2 protein. These results concur with all the previously reported therapeutic properties of Nitrodi spring water, and thus reinforce the concept that this natural resource is an important complementary therapy to traditional medicine.
Assuntos
Adenocarcinoma/terapia , Neoplasias Colorretais/terapia , Regulação para Baixo/fisiologia , Proteínas/metabolismo , S-Nitrosotióis/metabolismo , Água/fisiologia , Balneologia/métodos , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Sobrevivência Celular/fisiologia , Temperatura Alta , HumanosRESUMO
Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary precancerous condition caused by germline pathogenetic variants in the tumor suppressor adenomatous polyposis coli (APC) gene. Patients with FAP develop multiple gastrointestinal adenomatous polyps usually at the age of ~20 years, which, if untreated, become cancerous in 100% of cases. Genotype-phenotype associations have been extensively described; however, inter- and intra-familial variability exists. It is crucial to characterize the causative pathogenetic variant in each pedigree in order to develop a cancer prevention program and follow-up strategy for at-risk families. The present report describes a severe case of sporadic FAP that was diagnosed when the patient was ~2 years old. The patient was a carrier of the de novo pathogenic c.4132 C>T (p.Gln1378X) variant. Additionally, the patient was a carrier of the homozygous c.5465 T>A (p.Asp1822Val) polymorphism, inherited from both parents. However, it remains unclear whether or not this polymorphism is involved in the phenotypic manifestation. This case highlights the need to extend molecular screening to very young children when they show iron-deficiency, anaemia and/or rectal bleeding, even in the absence of a familial history of disease.
RESUMO
Colorectal cancer (CRC) is the third most prevalent type of cancer worldwide. It is also the second most common cause of cancerassociated mortality; it accounted for about 9.2% of all cancer deaths in 2018, most of which were due to resistance to therapy. The main treatment for CRC is surgery, generally associated with chemotherapy, radiation therapy and combination therapy. However, while chemoradiotherapy kills differentiated cancer cells, mesenchymal stemlike cells are resistant to this treatment, and this can give rise to therapyresistant tumors. Our previous study isolated T88 primary colon cancer cells from a patient with sporadic colon cancer. These cells exhibited mesenchymal and epithelial features, high levels of epithelialtomesenchymal transition transcription factors, and stemness markers. In addition, it was revealed that lithium chloride (LiCl), a specific glycogen synthase kinase (GSK)3ß inhibitor, induced both the mesenchymaltoepithelial transition and differentiation, and also reduced cell migration, stemness features and cell plasticity in these primary colon cancer cells. The aim of the present study was to investigate the effect of LiCl treatment on the viability of primary colon cancer cells exposed to 7 Gy delivered by highenergy photon beams, which corresponds to 6 megavolts of energy. To achieve this aim, the viability of irradiated T88 cells was compared with that of irradiated T88 cells pretreated with LiCl. As expected, it was observed that LiCl sensitized primary colon cancer cells to highenergy photon irradiation treatment. Notably, the decrease in cell viability was greater with combined therapy than with irradiation alone. To explore the molecular basis of this response, the effect of LiCl on the expression of Bax, p53 and Survivin, which are proteins involved in the apoptotic mechanism and in death escape, was analyzed. The present study revealed that LiCl upregulated the expression of proapoptotic proteins and downregulated the expression of proteins involved in survival. These effects were enhanced by highenergy photon irradiation, suggesting that LiCl could be used to sensitize colon cancer cells to radiation therapy.