Preventive and therapeutic effects of oleuropein against carbon tetrachloride-induced liver damage in mice

Olives and olive products, an inevitable part of the Mediterranean diet, possess various beneficial effects, such as a decreased risk of cardiovascular disease and cancer. Oleuropein is a non-toxic secoiridoid found in the leaves and fruits of olive (Olea europaea L.). In this study, we have investigated the hepatoprotective activity of oleuropein in carbon tetrachloride (CCl(4))-induced liver injury in male BALB/cN mice. Oleuropein in doses of 100 and 200mg/kg was administered intraperitoneally (ip) once daily for 3 consecutive days, prior to CCl(4) administration (the preventive treatment), or once daily for 2 consecutive days 6h after CCl(4) intoxication (the curative treatment). CCl(4) intoxication resulted in a massive hepatic necrosis and increased plasma transaminases. Liver injury was associated with oxidative/nitrosative stress evidenced by increased nitrotyrosine formation as well as a significant decrease in superoxide dismutase activity and glutathione levels. CCl(4) administration triggered inflammatory response in mice livers by inducing expression of nuclear factor-kappaB, which coincided with the induction of tumor necrosis factor-alpha, cyclooxygenase-2 and inducible nitric oxide synthase. In both treatment protocols, oleuropein significantly attenuated oxidative/nitrosative stress and inflammatory response and improved histological and plasma markers of liver damage. Additionally, in the curative regimen, oleuropein prevented tumor necrosis factor-beta1-mediated activation of hepatic stellate cells, as well as the activation of caspase-3. The hepatoprotective activity of oleuropein was, at least in part, achieved through the NF-E2-related factor 2-mediated induction of heme oxygenase-1. The present study demonstrates antioxidant, anti-inflammatory, antiapoptotic, and antifibrotic activity of oleuropein, with more pronounced therapeutic than prophylactic effects.     

Neurocysticercosis causing sudden death: a case report

We report an acute case of a native man from Bolivia suffered from cephalalgia which rapidly worsened and ended in his sudden and unexpected death. Magnetic resonance imaging (MRI) of the brain was obtained. Features demonstrated on brain MRI scan were consistent with a diagnosis of neurocysticercosis (NCC). An autopsy showed the presence of intraventricular Taenia solium (T. solium) cysts which caused blockage of cerebrospinal fluid and secondary hydrocephalus. Due to the increasing travel movements of people neurocysticercosis must be considered as a cause of unexplained sudden death.     

Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis

Background:

In pancreatic ductal adenocarcinoma (PDAC), fractalkine receptor CX3CR1 contributes to perineural invasion (PNI). We investigated whether CX3CR1 expression occurs early in PDAC and correlates with tumour features other than PNI.

Methods:

We studied CX3CR1 and CX3CL1 expression by immunohistochemistry in 104 human PDAC and coexisting Pancreatic Intraepithelial Neoplasia (PanIN), and in PdxCre/LSL-Kras^G12D mouse model of PDAC. CX3CR1 expression in vitro was studied by a spheroid model, and in vivo by syngenic mouse graft of tumour cells.

Results:

In total, 56 (53.9%) PDAC expressed CX3CR1, 70 (67.3%) CX3CL1, and 45 (43.3%) both. CX3CR1 expression was independently associated with tumour glandular differentiation (P=0.005) and PNI (P=0.01). Pancreatic Intraepithelial Neoplasias were more frequently CX3CR1+ (80.3%, P<0.001) and CX3CL1+ (86.8%, P=0.002) than matched cancers. The survival of PDAC patients was better in those with CX3CR1+ tumour (P=0.05). Mouse PanINs were also CX3CR1⁺ and -CL1⁺. In vitro, cytokines significantly increased CX3CL1 but not CX3CR1 expression. Differently, CX3CR1 was upregulated in tumour spheroids, and in vivo only in well-differentiated tumours.

Conclusion:

Tumour differentiation, rather than inflammatory signalling, modulates CX3CR1 expression in PanINs and PDAC. CX3CR1 expression pattern suggests its early involvement in PDAC progression, outlining a potential target for interfering with the PanIN transition to invasive cancer.     

A retrospective study on 73 elderly patients (≥ 75 years) with aggressive B-cell non Hodgkin lymphoma: Clinical significance of treatment intensity and comprehensive geriatric assessment

ObjectiveThe clinical outcome of elderly (≥ 75 years) patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL) is not firmly established because few studies have specifically addressed this issue. In addition, the usefulness of a comprehensive geriatric assessment (CGA) in B-NHL still needs to be deeply explored.Materials and MethodsWe evaluated the prognostic factors of 73 patients aged ≥ 75 years (median age: 78) with B-NHL treated by clinical judgment with curative anthracycline-based approaches (n = 36) or with conservative treatments without anthracyclines (n = 37). Analysis of clinical outcomes also included baseline CGA stratification.ResultsThe curative approaches resulted in a better clinical outcome than conservative approaches [overall response rate: 91.2% vs. 69.7%, P = 0.003; 2-year progression-free survival: 47.2% vs. 21.6%, P = 0.006; and 2-year overall survival (OS): 58.3% vs 24.3%, P = 0.003] with similar safety profiles. Independent of treatment type, patients classified as “fit” and “intermediate” by CGA presented with better OS compared to patients classified as “frail” (P < 0.001). Patients classified as “fit” and “intermediate” who were receiving curative treatments presented with a significantly better OS when compared with those treated conservatively on the basis of clinical judgment. A curative anthracycline-based therapy (P = 0.048), the response to treatment (P = 0.017) and a “frail” condition (P = 0.031) were the only factors affecting OS in multivariate analysis.ConclusionsPresent data indicates that even in elderly patients with B-NHL curative anthracycline-based therapies are more effective than conservative approaches. However, choice of treatment should rely more on objective than on subjective parameters. Therefore, further prospective trials are warranted to better define the CGA role in hematopoietic malignancies.     

Formation en curiethérapie

Treatment technique training needs theoretical and practical knowledge allowing proposing the right treatment for the right patient, but also allowing performing the technical gesture in the best conditions for an optimal result with a maximal security. The evolution of the brachytherapy techniques needs the set up of specific theoretical and practical training sessions. The present article focuses on the importance of the brachytherapy training as well as the different means currently available for the young radiation oncologist community for perfecting their education. National and international trainings are presented. The role of the simulation principle in the frame of brachytherapy is also discussed. Even if brachytherapy is not always an easy technique, its efficacy and its medico-economical impact need to be passed down to motivated students with the implementation of relevant educational means.     

Sarcomes d’Ewing localisés du rachis chez l’enfant : étude préliminaire d’escalade de dose comparant les techniques innovantes

PurposeAlthough radiosensitive, spinal locations of Ewing's sarcomas are challenging for the radiation oncologist due to poor radiation tolerance of the spinal cord. However, some favorable anatomical compartments – that may represent more than 20% – were associated with a better outcome and could benefit from a radiation dose escalation using the most recent radiation therapy techniques.Materials and methodsWe performed a dose escalation study on one patient, declined in two scenarios: (1) a tumour located within a single vertebral body and (2) a locally advanced disease involving the vertebral foramen and paraspinal soft tissues. Five dose-levels are proposed: 44.8 Gy, 54.4 Gy, 59.2 Gy, 65.6 Gy and 70.4 Gy (1.6 Gy per session, 8 Gy per week). The 3D-conformational technique is compared with static intensity modulated radiation therapy (IMRT), helical tomotherapy, volumetric modulated arc therapy (VMAT), stereotactic body robotic radiation therapy (SBRT) and protontherapy (passive scattering). Two constraints had to be respected in order to skip to the next level: the planned target volume (PTV) coverage must exceed 95% and the D_2% on the spinal cord shall not exceed a given constraint set at 50 Gy in case 1 and 44 Gy in case 2 due to initial neurological sufferance.ResultsOnly protontherapy, SBRT, helical tomotherapy and VMAT appear able to reach the last dose level while respecting the constraints in case 1. On the other hand, only helical tomotherapy seems capable of reaching 59.2 Gy on the PTV in case 2.ConclusionWith the most recent radiation therapy techniques, it becomes possible to deliver up to 70.4 Gy in a favorable compartment in this sham patient. Unfavorable compartments can receive up to 59.2 Gy. Definitive radiation therapy may be an interesting local treatment option to be validated in an early phase trial.     

Antiphospholipid antibodies and necrotizing purpura

A 30-year-old woman with recurrent necrotizing purpura on the legs which did not fit, to our knowledge, within any distinctive pathological entity, is described. Laboratory investigations disclosed a mild thrombocytopenia and antiphospholipid antibodies, i.e. lupus anticoagulant and anticardiolipin. Cutaneous lesions may be an early marker of the antiphospholipid antibody syndrome.