Improving the Nuclear-Localized Androgen Receptor Splice Variant 7 Test

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Prognostic significance of tyrosinase expression in sentinel lymph node biopsy for ultra-thin, thin, and thick melanomas

Abstract. – BACKGROUND: Investigate if the tyrosinase mRNA expression may be predictive of the outcome on ultra-thin, thin, and thick melanoma patients. AIM: In our study, we sought to correlate tyrosinase mRNA expression to the outcome in a group of 71 patients with thick, thin and ultra-thin melanomas. MATERIALS AND METHODS: 71 patients with melanomas underwent a SLNB (sentinel lymph node biopsy) at the “Sapienza” University of Rome. Among these, 38 patients had thin melanomas, while the other 33 patients had thick melanomas. In every patient’s sample histology, immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) was completed. We then correlated tyrosinase mRNA expression to the statistical analysis of the outcome of patients. RESULTS: Positivity of histology was found in one patient (1.4%), immunohistochemistry in five patients (7%), and tyrosinase in 52/71 (73.2%). Thickness and tyrosinase positivity were predictive for disease progression (p < 0.05). The median follow-up was 58.24 months. There were recurrences and/or deaths in both groups of patients. CONCLUSIONS: Nodal metastasis in melanoma is uncommon, especially in patients with thin melanomas. In this study, histology and immunohistochemistry were found to be non predictive for the risk of nodal metastases, while instead, tyrosinase m-RNA expression appeared to play a role in highlighting those patients with a risk of disease progression. Moreover, no differences among the thin melanoma groups of patients (0.30-0.75 mm and 0.76-1.00 mm) were observed

Prognostic value of circulating tumor cells in nonmuscle invasive bladder cancer: a CellSearch analysis

Background: Circulating tumor cells (CTCs) provide prognostic information in patients with metastatic tumors. Recent studies have shown that CTCs are released in circulation in an early phase of cancer disease so that their presence is under investigation in the adjuvant setting. Few studies investigated the prognostic significance of CTCs enumeration in patients with metastatic and advanced bladder cancer. The current study has analyzed the presence of CTC in patients with nonmuscle-invasive bladder cancer (NMIBC). Patients and methods: Forty-four NMIBC patients were enrolled and included in a 24-month follow-up program. Blood drawings were carried out in all patients at the first diagnosis. CellSearch system (Veridex; LLC, Raritan, NJ) was used for CTCs enumeration. Results: CTC were detectable in 8/44 patients (18%). Presence of CTC was found significantly associated to shorter time to first recurrence (6.5 versus 21.7 months, P &lt; 0.001). Median time to progression was not reached, due to the short follow-up period. CTC presence was found associated to concomitant carcinoma in situ and higher T category. Conclusion: The detection of CTC in this setting of disease may allow to distinguish patients with high risk of recurrence from those with high risk of progression, as well as to early identify patients candidate for adjuvant treatment

Use of hormones in doping and cancer risk

Hormones with anabolic properties such as growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are commonly abused among professional and recreational athletes to enhance physical ability. Despite their adverse effects are well-documented, the use of GH and IGF-1 has recently grown. This article highlights the anabolic activity related to mechanisms of cancer development and progression. GH/IGF-1 axis is able to activate cellular mechanisms that modulate every key stage of cancer formation and progression, such as inhibition of apoptosis, resistance to treatments, and induction of angiogenesis, metastatic process and cell proliferation. Results from pre-clinical studies and epidemiological observations in patients with an excess of GH and IGF-1 production or treated with these hormones showed a positive association with the risk to develop several types of cancer. In conclusion, athletes should be made aware that long-term treatment with doping agents might increase the risk of developing cancer, especially if associated with other licit or illicit drugs and/or high-protein diet

The role of primary cilia in cancer

Primary cilia are microtubule based organelles that sense and transduce multiple extracellular signals to the interior of the cell through several signaling pathways. Ciliary defects lead to different pathologies. Interestingly, decreased ciliary expression has been associated with different types of cancer. In this review, we discuss the function and dynamics of primary cilia, their relation to different diseases and in particular their role in cancer, and how they can be explored as potential therapeutic targets.Sociedad Argentina de Fisiologí

Sibling relationships and family functioning in siblings of early adolescents, adolescents and young adults with autism spectrum disorder

The purpose of the study was to investigate how family functioning (defined as the ability that family members hold to manage stressful events, and intimate and social relationships), the degree to which family members feel happy and fulfilled with each other (called family satisfaction), and the demographical characteristics of siblings (age and gender) impacted on sibling relationships. The Circumplex Model of Marital and Family Systems and Behavioral Systems constituted the theoretical frameworks that guided our study. Eighty-six typically developing adolescents and young adults having a sister or a brother with autism spectrum disorder were enrolled. Results indicated that the youngest age group (early adolescents) reported to engage more frequently in negative behaviors with their siblings with ASD than the two older age groups (middle adolescents and young adults). No significant differences were found among the three age groups regarding behaviors derived from attachment, caregiving and affiliative systems. Family satisfaction and age significantly predicted behaviors during sibling interactions. Suggestions on prevention and intervention programs were discussed in order to prevent parentification among typically developing siblings and decrease episodes of quarrels and overt conflicts between brothers and sisters with and without AS

Synthetic Conjugates of Ursodeoxycholic Acid Inhibit Cystogenesis in Experimental Models of Polycystic Liver Disease

Altres ajuts: Suported by IKERBASQUE, Basque foundation for Science (M.J. Perugorria and J.M. Banales), Spain; "Junta de Castilla y Leon" (J.J.G. Marin: SA06P17); "Diputación Foral Gipuzkoa" (J.M. Banales: DFG15/010, DFG16/004; M.J. Perugorria: DFG18/114, DFG19/081), BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD to J.M. Banales), Department of Health of the Basque Country (J.M. Banales: 2017111010; M.J. Perugorria: 2019111024), and Euskadi RIS3 (J.M. Banales: 2016222001, 2017222014, and 2018222029; 2019222054); La Caixa Scientific Foundation (J.M. Banales: HR17-00601); "Fundación Científica de la Asociación Española Contra el Cáncer" (AECC Scientific Foundation, to J.M. Banales and J.J.G. Marin); and "Centro Internacional sobre el Envejecimiento", Spain (J.J.G. Marin: OLD-HEPAMARKER, 0348-CIE-6-E). A. Santos-Laso by the Basque Government (PRE_2018_2_0195), and Pui Y. Lee-Law by the European Association for the Study of the Liver (EASL; Sheila Sherlock Award). Basque Government (F.P. Cossío: IT-324-07). I. Rivilla had a postdoctoral contract from the Donostia International Physics Center.Background and Aims: Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive development of symptomatic biliary cysts. Current surgical and pharmacological approaches are ineffective, and liver transplantation represents the only curative option. Ursodeoxycholic acid (UDCA) and histone deacetylase 6 inhibitors (HDAC6is) have arisen as promising therapeutic strategies, but with partial benefits. Approach and Results: Here, we tested an approach based on the design, synthesis, and validation of a family of UDCA synthetic conjugates with selective HDAC6i capacity (UDCA-HDAC6i). Four UDCA-HDAC6i conjugates presented selective HDAC6i activity, UDCA-HDAC6i #1 being the most promising candidate. UDCA orientation within the UDCA-HDAC6i structure was determinant for HDAC6i activity and selectivity. Treatment of polycystic rats with UDCA-HDAC6i #1 reduced their hepatomegaly and cystogenesis, increased UDCA concentration, and inhibited HDAC6 activity in liver. In cystic cholangiocytes UDCA-HDAC6i #1 restored primary cilium length and exhibited potent antiproliferative activity. UDCA-HDAC6i #1 was actively transported into cells through BA and organic cation transporters. Conclusions: These UDCA-HDAC6i conjugates open a therapeutic avenue for PLDs