Publication date: Available online 27 November 2016
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Natalie Orlovetskie, Raphael Serruya, Ghada Abboud-Jarrous, Nayef Jarrous
WRN helicase has several roles in genome maintenance, such as replication, base excision repair, recombination, DNA damage response and transcription. These processes are often found upregulated in human cancers, many of which display increased levels of WRN. Therefore, directed inhibition of this RecQ helicase could be beneficial to selective cancer therapy. Inhibition of WRN is feasible by the use of small-molecule inhibitors or application of RNA interference and EGS/RNase P targeting systems. Remarkably, helicase depletion leads to a severe reduction in cell viability due to mitotic catastrophe, which is triggered by replication stress induced by DNA repair failure and fork progression arrest. Moreover, we present new evidence that WRN depletion results in early changes of RNA polymerase III and RNase P activities, thereby implicating chromatin-associated tRNA enzymes in WRN-related stress response. Combined with the recently discovered roles of RecQ helicases in cancer, current data support the targeting prospect of these genome guardians, as a means of developing clinical phases aimed at diminishing adaptive resistance to present targeted therapies.
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Κυριακή 27 Νοεμβρίου 2016
Targeted inhibition of WRN helicase, replication stress and cancer
“Facing spousal cancer during child-rearing years: the short-term effects of the Cancer-PEPSONE programme - a single-center randomized controlled trial.”
Abstract
Objective
To measure the short-term effects of the Cancer-PEPSONE programme (CPP) on the partners' received and perceived social support, psychological distress and quality of life (QOL), as well as explore the role of received social support as a mediator of the intervention effects.
Methods
Open single-center randomized controlled trial, trial number 15982171(ISRCTN). Eligible participants were partners of cancer patients who were concomitantly caring for minors (the well parents). The sample consisted of 35 participants randomly allocated to receive either intervention (n = 17) or support as usual (n = 18). At the three-month follow-up (approximately one month after intervention), 24 continued to participate (intervention n = 13, control n = 11). The intervention group selected supporters to participate in CPP (N = 130). Data were obtained using validated questionnaires.
Results
The multivariate analysis of covariance revealed significant intervention effects (p = .03, η2p = 0.42), with main effects on received and perceived social support. A mediational analysis suggested that CPP may have indirect effects on QOL through received social support.
Conclusions
Even though the long-term effects are yet to be studied, CPP seems to increase social support for the well parents short-term, which in turn may improve their quality of life. Given the study's low sample size, further replications in larger samples are required.
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“Facing spousal cancer during child-rearing years: the short-term effects of the Cancer-PEPSONE programme - a single-center randomized controlled trial.”
Abstract
Objective
To measure the short-term effects of the Cancer-PEPSONE programme (CPP) on the partners' received and perceived social support, psychological distress and quality of life (QOL), as well as explore the role of received social support as a mediator of the intervention effects.
Methods
Open single-center randomized controlled trial, trial number 15982171(ISRCTN). Eligible participants were partners of cancer patients who were concomitantly caring for minors (the well parents). The sample consisted of 35 participants randomly allocated to receive either intervention (n = 17) or support as usual (n = 18). At the three-month follow-up (approximately one month after intervention), 24 continued to participate (intervention n = 13, control n = 11). The intervention group selected supporters to participate in CPP (N = 130). Data were obtained using validated questionnaires.
Results
The multivariate analysis of covariance revealed significant intervention effects (p = .03, η2p = 0.42), with main effects on received and perceived social support. A mediational analysis suggested that CPP may have indirect effects on QOL through received social support.
Conclusions
Even though the long-term effects are yet to be studied, CPP seems to increase social support for the well parents short-term, which in turn may improve their quality of life. Given the study's low sample size, further replications in larger samples are required.
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Abnormal heavy/light chain ratio after treatment is associated with shorter survival in patients with IgA myeloma
Abstract
Immunoglobulin (Ig) heavy/light chain (HLC) assays enable the separate quantification of the different light chain types of each Ig class. We retrospectively analyzed the correlation of heavy/light chain ratio (HLCR) with clinical status and its impact on outcome in 120 patients with multiple myeloma (MM). Abnormal HLCR was seen more frequently in patients with poorer myeloma response, and it appeared to be more sensitive for detecting clonality in IgA myeloma compared to IgG myeloma after treatment. Among the 85 patients who achieved ≥VGPR, the patients remained HLCR abnormal were showed significantly shorter overall survival (OS) compared to those achieving a normal HLCR (not reached vs. 55.5 months, P = 0.032). This correlation was seen in IgA myeloma patients (not reached vs. 30.1 months, P = 0.014), but not in IgG myeloma patients when patients were analysed separately. Univariate and multivariate analysis of factors that may affect survival identified abnormal HLCR at the best response as the only independent risk factor (hazard ratio, 4.7; 95% confidence interval, 1.4 – 15.26; P = 0.012) for shorter OS in this subset of patients. This study highlighted the HLC assay as a prognostic predictor in patients with IgA myeloma.
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Σάββατο 26 Νοεμβρίου 2016
Analysis of Carcinogenic Heavy Metals in Gallstones and its Role in Gallbladder Carcinogenesis
Abstract
Purpose
Gallstone is a high-risk factor for gallbladder pre-malignancy or malignancy (GB PM-M) but which substances of gallstones definitely assist to turn out in to GB PM-M, remains unclear. This study aimed to find out the presence of carcinogenic heavy metals in gallstones and to explore the aetiopathogenesis of gallbladder pre-malignancy and malignancy.
Methods
Presence of elements in gallstones was detected by energy dispersive X-ray spectroscopy (EDS) with scanning electron microscopy (SEM) and then level of carcinogenic heavy metals was estimated in gallstones using atomic absorption spectroscopy (AAS). The experiment was carried out in gallstone samples of 46 patients with gallbladder pre-malignant and malignant condition (PM-M group) and 65 sex and age-matched patients with chronic cholecystitis (C-C group). Gallstones were also classified in to three types such as cholesterol stone, mixed stone, and black pigment stone.
Results
EDS analysis detected presence of mercury, lead, and cobalt elements in all types of gallstones of both PM-M and C-C groups. AAS analysis revealed significantly higher amount of mercury (p < 0.001), lead (p < 0.0001), cobalt (p < 0.01), and cadmium (p < 0.01) in the gallstones of PM-M than C-C groups. The presence of these heavy metals also varied among stone types of both groups. EDS phase analysis showed 'dense deposits' of these metals in gallstones.
Conclusions
Presence of significantly higher amount of mercury, lead, cobalt, and cadmium in gallstones may play a pivotal role as risk factors in the development of gallbladder malignancy or pre-malignancy. 'Dense deposits' of these metals in the gallstones which is the first observation, may act as crucial doses of carcinogens.
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