In the recent years the importance of the role played by non-coding RNA on the regulation of gene expression was increased by numerous studies. The research mainly focused on small ncRNAs, such as miRNAs, while the functions of long non-coding RNA (lncRNA) have been much less studied. lncRNAs can be transcribed from intergenic, intragenic or specific chromosomal regions. Compared to miRNAs, lncRNAs have a complex secondary and tertiary structure which allows to bind proteins, RNA, DNA and to carry out their regulatory functions. Several studies showed that extracellular ncRNAs can circulate in the blood of both healthy and diseased patients. Most of the circulating ncRNAs are included in lipid or lipoprotein vesicles, such as apoptotic bodies, macrovesicles or exosomes, in which they are highly stable. The presence of circulating ncRNAs in the blood of cancer patients versus normal subjects suggested the possibility that these molecules may represent new diagnostic markers. HOTAIR is a HOX transcript antisense RNA, located in the HOXC locus, able to repress transcription in the posterior region of the HOXD locus. HOTAIR has been involved in the evolution of several primary tumors, wherein increase of HOTAIR expression has endorsed invasion and metastasis. In this review, we describe the experimental evidences on the potential role as circulating marker of lncRNA HOTAIR.
The diagnostic criteria of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) are not well defined, and DIPNECH can be mistaken for carcinoids associated with neuroendocrine cell hyperplasia (NECH). In this study, we compared clinical, radiologic, histologic, immunohistochemical, and molecular features of DIPNECH and isolated carcinoids with/without NECH. The study population included 151 cases (77 female patients and 74 male patients), 19 with DIPNECH and 132 with carcinoids with/without NECH. None of the cases displayed molecular alterations or anaplastic lymphoma kinase expression. Compared with individuals with carcinoids with/without NECH, patients with DIPNECH were more likely to be female individuals (P<0.0001), nonsmokers (P=0.021), and symptomatic, and to have an obstructive/mixed respiratory defect, peripheral location of the lesions, and air trapping (P<0.0001) on chest computed tomography, and constrictive bronchiolitis on histology (P<0.0001). Among immunohistochemical markers, DIPNECH was associated with higher expression of thyroid transcription factor-1, CD10, and gastrin-releasing peptide/bombesin-like peptide (P<0.0001). Yet, when a purely histopathologic definition of DIPNECH was applied, 40% of isolated carcinoids also met the diagnostic criteria for DIPNECH, even in the absence of symptoms and/or radiologic abnormalities. Therefore, as DIPNECH represents a distinct clinical syndrome, we suggest the term DIPNECH be limited to cases presenting with respiratory symptoms, functional and/or radiologic abnormalities, and constrictive bronchiolitis on histology.
Onco-nephrology is an emerging field in medicine. Patients with cancer may suffer from kidney diseases because of the cancer itself and cancer-related therapy. It is critical for nephrologists to be knowledgeable of cancer biology and therapy in order to be fully integrated in the multidisciplinary team and optimally manage patients with cancer and kidney diseases. In a recent international meeting, the key issues in this challenging clinical interface were addressed, including many unresolved basic science questions, such as the high tumor incidence in kidney transplant recipients. To this end, 70 highly qualified faculty members were gathered from all over the world to discuss these issues in 8 plenary sessions, including 5 keynote lectures. In addition, 48 young nephrologists and oncologists were invited to present their original observations that were highlighted in 2 large poster sessions.
Ovarian metastases from renal cell carcinoma (RCC) are very rare. Over the past 16 years we have encountered 3 examples. The first 2 cases occurred in adults 49 and 50 years old, respectively, who had huge ovarian metastases, clinically detected 12 and 14 months, respectively, after diagnosis of RCC. The third case was a 17-year-old girl in whom a metastatic renal cell carcinoma was detected in an otherwise benign-appearing cystic ovarian mass. To the best of our knowledge only 11 cases of clinically detected ovarian metastases of RCC have been reported. We report 3 new cases and review the literature on the subject.
Chemotherapy and biological therapy with Interferon α (IFN-α) and cis retinoic acid are active but give limited results. Recently, strategies based on the use of molecularly target-based agents (MTA) have been used with promising results. Based on the available findings, we hypothesize that SCC cells can develop survival and resistance mechanisms to MTAs. The detection of these mechanisms could be useful in designing strategies able to overcome the latter and to potentiate the anticancer activity of MTAs. We describe the example of the EGF-dependent survival pathway elicited by IFN-α and the different strategies to abrogate this survival pathway. Other strategies to potentiate the antitumor activity of cytotoxic agents such as docetaxel or cisplatin are also discussed. Illuminating examples are the inhibition of multichaperone activity or the inactivation of the proteasome. In conclusion, a new dawn based upon the rationale use of MTAs is rising up in the treatment of advanced cSCC.
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