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Among protein oxidative damages, di-tyrosine bridges formation has been evidenced in many neuropathological diseases. Combining oxidative radical production by gamma radiolysis with very performant chromatographic separation coupled to mass spectrometry detection, we brought into light new insights of tyrosine dimerization. Hydroxyl and azide radical tyrosine oxidation leading to di-tyrosine bridges formation was studied for different biological compounds a full-length protein (Δ25-centrin 2), a five amino acid peptide (KTSLY) and free tyrosine. We highlighted that both radicals generate high proportion of dimers even for low doses. Surprisingly, no less than five different di-tyrosine isomers were evidenced for the protein and the peptide. For tyrosine alone, at least four distinct dimers were evidenced. These results raise some questions about their respective role in vivo and hence their relative toxicity. Also, as di-tyrosine is often used as a biomarker, a better knowledge of the type of dimer detected in vivo is now required.The purpose was to explore the intrinsic dysconnectivity pattern of whole-brain functional networks in Parkinson’s disease patients with mild cognitive impairment (PD-MCI) using a voxel-wise degree centrality (DC) analysis approach. The resting-state functional magnetic resonance imaging (rs-fMRI) scanning was performed in all subjects including PD-MCI, PD patients with no cognitive impairment (PD-NCI), and healthy controls (HCs). DC mapping was used to identify functional connectivity (FC) alterations among these groups. Correlation between abnormal DC and clinical features was performed. Secondary seed-based FC analyses and voxel-based morphometry (VBM) analyses were also conducted. Compared with HCs, PD-MCI and PD-NCI showed DC abnormalities mainly in the right temporal lobe, thalamus, left cuneus, middle frontal gyrus, and corpus callosum. Compared with PD-NCI, PD-MCI showed abnormal DC in the left fusiform gyrus (FFG) and left cerebellum lobule VI, left cuneus, right hippocampus, and bilateral precuneus. In PD-MCI patients, correlation analyses revealed that DC in the left FFG was positively correlated with the Montreal Cognitive Assessment (MoCA) scores, and DC in the left precuneus was negatively correlated with the MoCA scores. Secondary seed-based FC analysis further revealed FC changes mainly in the default mode network, right middle cingulum, right supramarginal gyrus, and right postcentral/precentral gyrus. However, no significant difference was found in the secondary VBM analysis. The findings suggest that dysfunction in extensive brain areas is involved in PD-MCI. Among these regions, the left precuneus, FFG, and cerebellum VI may be the key hubs in the pathogenesis of PD-MCI.

The pattern of lower motor neuron (LMN) degeneration in amyotrophic lateral sclerosis (ALS), i.e., dying-back (from the nerve ending to cell body) or dying-forward (from the cell body to nerve ending), has been widely discussed. In this study, we aimed to evaluate LMN loss using compound muscle action potential (CMAP), motor unit number index (MUNIX), and MScan-fit-based motor unit number estimation (MUNE) to understand the pattern of neurodegeneration in ALS.

Twenty-five patients were compared with 25 controls using CMAP amplitude and area, MUNIX, and MScan-fit MUNE in three proximal and distal muscles innervated by the ulnar nerve.

Unlike the controls, the CMAP area, MScan-fit MUNE, and MUNIX recorded in ALS patients showed more neurodegeneration in distal muscles than proximal muscles. In ALS patients with unaffected CMAP amplitudes (n = 13), the CMAP area, MScan-fit MUNE, and MUNIX showed subtle motor unit loss of 30.7 %, 53.8 %, and 38.4 %, respectively.

The CMAP area, MScan-fit MUNE, and MUNIX showed neurodegeneration earlier than the reduction in CMAP amplitude. These tests confirmed dying-back neurodegeneration, while only MUSIX showed re-innervation in ALS.

The CMAP area, MScan-fit MUNE, and MUNIX showed neurodegeneration earlier than the reduction in CMAP amplitude. These tests confirmed dying-back neurodegeneration, while only MUSIX showed re-innervation in ALS.Zaleya decandra is a prostrate, glabrous, succulent herb of the family Aizoaceae. In recent years the pharmacological efficacy of the plant such as the hepatoprotective, antimicrobial, antidiabetic, anti-inflammatory and anticancer activities has been reported. However, a long-term toxicity study of Z. decandra is yet to be carried out. In the present study, the acute dose of 2000 mg/kg b.w. of ethanolic extract of Z. decandra (EEZD) administered orally to Wistar rats gained gradual weight with time and appeared healthy without any record of mortality. In the sub-chronic toxicity study, the rats showed no remarkable increase or decrease in their weight even at the highest dose of 500 mg/kg b.w. The haematological, biochemistry and serum marker enzyme parameters did not show any dose dependent change in the values. Further, the histology micrographs confirmed that the tissue architecture of all the vital organs were not affected by EEZD treatment. Hence, the EEZD (500 mg/kg b.w.) is considered safe for a 90-day period. Therefore, the present study warrants extensive investigation of EEZD using higher pre-clinical model system to substantiate the findings. The GC-MS analysis revealed the presence of 39 phytoconstituents including octadecenoic acid, hexadecanoic and phytosterols such as campesterol, sitosterol and stigmasterol.

To report the long-term outcome of a multicenter phase II study with FOLFIRINOX followed by stereotactic body radiotherapy (LAPC-1 trial) in patients with locally advanced pancreatic cancer (LAPC).

Patients with histological confirmation of LAPC inoperable at diagnosis were enrolled. Induction therapy with 8 cycles of FOLFIRINOX was administered. If no disease progression was found after chemotherapy, patients received stereotactic body radiotherapy (SBRT) at a total dose of 40 Gy in 5 fractions.

In LAPC-1 trial, 50 patients were included, but due to disease progression in 11 patients under chemotherapy, 39 patients received stereotactic SBRT after FOLFIRINOX treatment. In whole population, the 1- and 3-year overall survival (OS) were 62% and 10%, respectively. Median follow-up was 13 months. The SBRT group had median OS of 18 months (95% CI 13.2-21.5) versus 5 months (95% CI 4.1-6.7) in non-SBRT group (p<0.001). After chemoradiotherapy, seven patients underwent surgery achieving a radical resection. Patients who underwent surgery had a 3-years OS of 43% compared to 6.5% in the unresected group (p=0.03). Four patients developed grade ≥ 3 adverse events during SBRT.

Long-term survival has been found in patients with LAPC underwent FOLFIRINOX followed by SBRT. This approach increased the probability of a radical surgery. The resected patients achieved a significant better survival compared to unresected group.

Long-term survival has been found in patients with LAPC underwent FOLFIRINOX followed by SBRT. This approach increased the probability of a radical surgery. The resected patients achieved a significant better survival compared to unresected group.

To introduce a contouring guideline for the taste bud bearing tongue mucosa for head and neck cancer patients receiving radiotherapy.

CT simulation images of oropharyngeal cancer patients were used to delineate both the whole tongue (extrinsic/intrinsic tongue muscles, floor of mouth) and the taste bud bearing tongue mucosa (method A adaptation of the whole tongue structure; method B axial adaptation of a mid-sagittal contour). TCPOBOP cell line Volumetric and dosimetric parameters of the whole tongue and the two methods of mucosal delineation, spatial overlap between methods A and B, and inter-observer variability for method B were calculated.

The study cohort was comprised of 70 patients with T1-4 N0-1 tonsillar (83%) and base of tongue (17%) cancers. Most of the comparative parameters between the whole tongue and mucosa (method A) significantly differed (mean, minimum, and maximum dose, V5-V70, D40-D90). The mean dose calculated for the whole tongue deviated on average 3.77Gy compared to method A. No significant differences were found between methods A and B of the taste bud bearing tongue mucosa structure, and none of the dosimetric parameters differed more than 1.03Gy on average. The mean Dice similarity coefficient for both mucosal structures was 0.79±0.05, and 0.63±0.12 for the inter-observer analysis of method B.

We defined two methods for delineating the taste bud bearing mucosa and both are equally satisfactory procedures. Either method is preferable over delineation of the whole tongue as organ at risk for taste impairment.

We defined two methods for delineating the taste bud bearing mucosa and both are equally satisfactory procedures. Either method is preferable over delineation of the whole tongue as organ at risk for taste impairment.

Following resection of pancreatic cancer, risk of positive margins and local recurrence remain high, especially for borderline-resectable pancreatic cancer (BRPC). We aimed to establish the maximum tolerated dose of a margin-intensified five-fraction stereotactic body radiotherapy (SBRT) regimen designed to treat the region at risk.

We conducted a prospective multicentre phase-1 rolling-six dose-escalation study. BRPC patients received pre-operative SBRT, with one dose to the primary tumour and an integrated boost to the region where tumour was in contact with vasculature. Four dose-levels were proposed, with starting dose 30Gy to primary PTV and 45Gy to boost volume (PTV_R), in five daily fractions. Primary endpoint was maximum tolerated dose (MTD), defined as highest dose where zero of three or one of six patients experienced dose-limiting toxicity (DLT).

Twelve patients were registered, eleven received SBRT. Radiotherapy was well tolerated with all treatment completed as scheduled. Dose was escalated one level up from starting dose without encountering any DLT (prescribed 32.5Gy PTV, 47.5Gy PTV_R). Nine serious adverse reactions or events occurred (seven CTCAE Grade 3, two Grade 4). Two patients went on to have surgical resection. Median overall survival for SBRT patients was 8.1months. The study closed early when it was unable to recruit to schedule.

Toxicity of SBRT was low for the two dose-levels that were tested, but MTD was not established. Few patients subsequently underwent resection of pancreatic tumour after SBRT, and it is difficult to draw conclusions regarding the safety or toxicity of these therapies in combination.

Toxicity of SBRT was low for the two dose-levels that were tested, but MTD was not established. Few patients subsequently underwent resection of pancreatic tumour after SBRT, and it is difficult to draw conclusions regarding the safety or toxicity of these therapies in combination.

Adoption of single-fraction radiation therapy (SFRT) has not been universal in the palliative treatment of bone metastases, despite evidence supporting its safety and efficacy. The aim of this study was to assess SFRT use for bone metastases in New South Wales (NSW), Australia, and the rate of 30-day mortality (30DM).

This is a population-based cohort of patients who received palliative radiation therapy (RT) for bone metastases (2009-2014), as captured in the NSW Central Cancer Registry. A logistic regression model was used to identify factors associated with fractionation type. The proportion of patients dying within 30-days from treatment start date was calculated.

Of the 14,602 courses of palliative RT delivered for bone metastases, 30% were SFRT. SFRT was more likely to be delivered to older patients ≥80 years (34%) versus < 60 years (28%). Patients with lower socioeconomic status (SES) (35%) were more likely to receive SFRT compared with higher SES (25%). SFRT delivered to patients from outer regional area of residence (34%) were higher compared to those from the major city (29%).