1,721,276 research outputs found
Finding a path to overcome chemoresistance
No full textMultidrug resistance is a significant obstacle to providing effective chemotherapy to many cancer patients, leading to failure of several medical treatments, with dramatic consequences for the patients. Resistance to chemotherapy is associated with the overexpression of P-glycoprotein (P-gp), resulting in increased efflux of chemotherapic agents from cancer cells. P-gp is a 170 Kd transmembrane glycoprotein, encoded by the multidrug resistance gene 1 (MDR1), which is expressed in many cancer cell lines and human tissues. Several reports describe the successful overcoming of drug resistance by inactivation of MDR1 function or expression, and, recently, an important role for cyclooxygenase-2 (COX-2) has been reported in modulating MDR1 function. Medullary thyroid carcinoma (MTC) is a malignant tumor originating from thyroid parafollicular C cells, which is highly resistant to chemotherapy, and, so far, nonsurgical approaches to MTC treatment have met with inconsistent results. Many other endocrine-related cancers (i.e. breast cancer), as well as endocrine gland cancers (i.e. adrenocortical cancer) may display chemoresistance or develop such phenotype after the first chemotherapy courses.
The aim of the proposed research is to explore the possible pathways for overcoming multidrug resistance by treatment with compounds inhibiting COX-2 activity. It has been demonstrated that COX-2 activity dose-dependently induces P-gp function
Pathological markers of aggressive pituitary tumour behaviour
No full textRecent advances in molecular pathology have improved our knowledge on the pathogenesis of pituitary tumors, as well as on their growth potential, likelihood of recurrence, and prognosis. The development of reliable and prognostically informative methods of assessing tumor behavior is particularly important in pituitary tumors, where no precise correlation exists between morphology and clinical aggressiveness. Specific morphologic features (macroscopic invasion of the perisellar tissues, number of mitoses, Ki-67 labelling index, p53 expression) may serve as predictive markers of tumor behavior.
Apoptosis and mitoses represent two adverse and asynchronous events, maintaining the optimal cell numbers, and, as well as cytogenetic analysis, may be useful in defining the biological aggressiveness of pituitary tumors. From the genetic point of view, MEN1 tumors seem more aggressive, invasive and resistant to treatment requiring a very careful long-life follow-up. Recently, several studies attempted to identify new molecular markers (i.e. cyclooxygenase-2, galectin-3, angiogenesis molecules, pituitary tumor-transforming gene), that need to be validated. Among these, several are represented by therapeutic targets of new (and old) molecularly targeted therapies. Immunohistochemical detection of somatostatin receptors is important, being their density directly related to the effectiveness of somatostatin analogues. Similarly, the outcome of treatment with temozolomide, an orally administered alkylating agent, has been related to the expression of O(6)-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme. Studies involving cDNA microarrays, stem cells and microenvironment may reveal additional important information to identify predictive markers in the near future
Pathogenesis of non-functioning pituitary adenomas
No full textThe pathogenesis of non functioning pituitary adenomas (NFPA) is a complex process involving several factors, from molecular to genetic and epigenetic modifications, where tumor suppressor genes, oncogenes, cell cycle derangements have been demonstrated to play an important role. MicroRNAs (miRNAs) have also been identified as possible players in NFPA tumorigenesis and pituitary stem cells have been investigated for their potential role in pituitary tumor initiation. However, a critical role for paracrine signalling has also been highlighted. This review focuses on the current knowledge on the involvement of these factors in NFPA pathogenesis
Regulation of the neuroendocrine system: C-cell of the thyroid
No full textDescrizione dell'anatomi a fisiologia delle cellule C parafollicolari della tiroid
MicroRNAs and possible role in pituitary adenoma
No full textThis review reports the current knowledge of microRNA (miRNA) expression in pituitary adenomas, focussing on recent microarray data. Moreover, discussion in provided concerning the possible role of validated and putative targets of the most dysregulated miRNA in pituitary adenoma pathogenesis
LUNG: SECRETORY PATTERN AND PARANEOPLASTIC SYNDROMES: NEUROENDOCRINE MARKERS, CUSHING, ACROMEGALY, OTHERS
No full textLUNG: SECRETORY PATTERN AND PARANEOPLASTIC SYNDROMES: NEUROENDOCRINE MARKERS, CUSHING, ACROMEGALY, OTHER
Uso di inibitori delle Cicloossigenasi di tipo 2 come agenti atti a modificare la farmacoresistenza cellulare
No full textUso degli inibitori delle cicloossigenasi di tipo 2 per prevenire la comparsa del fenomeno chemioresistenza nelle neoplasie endocrino-relate
The significance of new somatostatin analogs as therapeutic agents
No full textThe effects of somatostatin, or somatotropin release-inhibiting factor (SRIF), and SRIF analogs in human diseases have been widely investigated to potentially expand the therapeutic applications of commercially available and newly designed
compounds belonging to this class of agents. Several preclinical studies and clinical trials have demonstrated the antiproliferative and antisecretory effects of SRIF and its analogs. This review discusses results from studies investigating the secretory activity and cell viability of SRIF analogs, and the potential of
new therapeutic applications of these drugs in endocrine diseases and, in particular, as a treatment for endocrine neoplasia
Somatostatin receptors: from basic science to clinical approach-thyroid
No full textSomatostatin and its receptors are expressed in the thyroid gland, but somatostatin analogs which are currently available have provided contradictory results in the diagnosis and treatment of thyroid neoplasia. Somatostatin and its analogs fail to influence follicular thyroid function, whereas their administration in patients with medullary thyroid carcinoma induces a reduction of serum calcitonin concentrations and clinical symptoms, but fails to influence tumour size and patient survival rate. Radiolabelled somatostatin analogs can localise tumours expressing somatostatin receptors, but somatostatin receptor-targeted radiotherapy of thyroid malignancies has provided conflicting and inconclusive results. Our recent results indicate that somatostatin receptor 2 activation by somatostatin receptor 2 agonists inhibits cell proliferation in the human medullary thyroid carcinoma cell line, TT. This effect can be hampered by concurrent somatostatin receptor 5 selective agonist treatment, wh..
NUOVE FRONTIERE TERAPEUTICHE NEGLI ADENOMI IPOFISARI INVASIVI
No full textIN QUESTO CAPITOLO SI PRESENTANO LE NUOVE FRONTIERE TERAPEUTICHE NEGLI ADENOMI IPOFISARI INVASIV
- …
