11 research outputs found

    Multiple primary malignancies in renal transplant recipients: a single centre retrospective cohort study

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    BACKGROUND/AIMES: Renal transplant recipients are exposed to immunosuppressive treatment which may increase the risk for developing malignancies. Limited data exists concerning the occurrence of multiple primary malignancies (MPM) in renal transplant patients. ----- METHODS: All the patients who received a renal allograft at our institution from 1973 to 2017 were included in this investigation. Data from patients with more MPM were obtained from the charts and medical records. Malignancies were categorized as synchronous if the interval between occurrences was less than or equal to 6 months and metachronous if the interval was more than 6 months. ----- RESULTS: Out of the 1884 patients who received a renal allograft, 164 (8.7%) developed a malignant tumor. Twenty-two patients (13.4%; 6 females, 16 males) developed MPM, 7 synchronous (31.8%) and 15 metachronous types (68.2%). The most common initial primary tumors were skin cancers (8) and kidney cancers (3). Furthermore, skin cancers were the most common second primary malignancies (9). Log-rank analysis revealed significantly better survival in the synchronous group (113.3 months) than in the metachronous group (24.6 months) (p=0.04). ----- CONCLUSION: MPM are more frequent in renal transplant recipients than in the general population. It is associated with a high mortality rate, especially in the metachronous group. An increased awareness and frequent screening tests are necessary when managing this condition

    Immunosupprssants

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    ViŔestruke primarne malignosti u pacijenata s transplantiranim bubregom: retrospektivna kohortna studija

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    BACKGROUND/AIMS: Renal transplant recipients are exposed to immunosuppressive treatment which may increase the risk for developing malignancies. Limited data exists concerning the occurrence of multiple primary malignancies (MPM) in renal transplant patients. ----- METHODS: All the patients who received a renal allograft at our institution from 1973 to 2017 were included in this investigation. Data from patients with more MPM were obtained from the charts and medical records. Malignancies were categorized as synchronous if the interval between occurrences was less than or equal to 6 months and metachronous if the interval was more than 6 months. ----- RESULTS: Out of the 1884 patients who received a renal allograft, 164 (8.7%) developed a malignant tumor. Twenty-two patients (13.4%; 6 females, 16 males) developed MPM, 7 synchronous (31.8%) and 15 metachronous types (68.2%). The most common initial primary tumors were skin cancers (8) and kidney cancers (3). Furthermore, skin cancers were the most common second primary malignancies (9). Log-rank analysis revealed significantly better survival in the synchronous group (113.3 months) than in the metachronous group (24.6 months) (p=0.04). ----- CONCLUSION: MPM are more frequent in renal transplant recipients than in the general population. It is associated with a high mortality rate, especially in the metachronous group. An increased awareness and frequent screening tests are necessary when managing this condition

    Molecular mechanisms of neurodegeneration related to C9orf72 hexanucleotide repeat expansion

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    Two clinically distinct diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), have recently been classified as two extremes of the FTD/ALS spectrum. The neuropathological correlate of FTD is frontotemporal lobar degeneration (FTLD), characterized by tau-, TDP-43-, and FUS-immunoreactive neuronal inclusions. An earlier discovery that a hexanucleotide repeat expansion mutation in chromosome 9 open reading frame 72 (C9orf72) gene causes ALS and FTD established a special subtype of ALS and FTLD with TDP-43 pathology (C9FTD/ALS). Normal individuals carry 2-10 hexanucleotide GGGGCC repeats in the C9orf72 gene, while more than a few hundred repeats represent a risk for ALS and FTD. The proposed molecular mechanisms by which C9orf72 repeat expansions induce neurodegenerative changes are C9orf72 loss-of-function through haploinsufficiency, RNA toxic gain-of-function, and gain-of-function through the accumulation of toxic dipeptide repeat proteins. However, many more cellular processes are affected by pathological processes in C9FTD/ALS, including nucleocytoplasmic transport, RNA processing, normal function of nucleolus, formation of membraneless organelles, translation, ubiquitin proteasome system, Notch signalling pathway, granule transport, and normal function of TAR DNA-binding protein 43 (TDP-43). Although the exact molecular mechanisms through which C9orf72 repeat expansions account for neurodegeneration have not been elucidated, some potential therapeutics, such as antisense oligonucleotides targeting hexanucleotide GGGGCC repeats in mRNA, were successful in preclinical trials and are awaiting phase 1 clinical trials. In this review, we critically discuss each proposed mechanism and provide insight into the most recent studies aiming to elucidate the molecular underpinnings of C9FTD/ALS

    Radical Oā†’C Transposition: A Metal-Free Process for Conversion of Phenols into Benzoates and Benzamides

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    We report a metal-free procedure for transformation of phenols into esters and amides of benzoic acids via a new radical cascade. Diaryl thiocarbonates and thiocarbamates, available in a single high-yielding step from phenols, selectively add silyl radicals at the sulfur atom of the Cī—»S moiety. This addition step, analogous to the first step of the Bartonāˆ’McCombie reaction, produces a carbon radical which undergoes 1,2 Oā†’C transposition through an <i>O</i>-neophyl rearrangement. The usually unfavorable equilibrium in the reversible rearrangement step is shifted forward via a highly exothermic Cāˆ’S bond scission in the O-centered radical, which furnishes the final benzoic ester or benzamide product. The metal-free preparation of benzoic acid derivatives from phenols provides a potentially useful alternative to metal-catalyzed carbonylation of aryl triflates
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