Chemotherapy accelerates immune-senescence and functional impairments of Vδ2pos T cells in elderly patients affected by liver metastatic colorectal cancer.

Human (gamma delta) γδ T cells are unconventional innate-like lymphocytes displaying a broad array of anti-tumor activities with promising perspectives in cancer immunotherapy. In this context, Vδ2pos T cells represent the preferential target of several immunotherapy protocols against solid tumors. However, the impact of both aging and chemotherapy (CHT) on Vδ2pos T cells is still unknown. The present study evaluates with multi-parametric flow cytometry the frequencies, terminal differentiation, senescence and effector-functions of peripheral blood and tumor infiltrating Vδ2pos T cells purified from liver metastases (CLM) of patients affected by colorectal cancer (CRC) compared to those of sex- and age-matched healthy donors. The peripheral blood of CLM patients underwent CHT is characterized by decreased amounts of Vδ2pos T cells showing a relative increase of terminally-differentiated CD27neg/CD45RApos (TEMRA) cells. The enrichment of this latter subset is associated with an increased expression of the senescent marker CD57. The acquisition of CD57 on TEMRA Vδ2pos T cells is also coupled with impairments in cytotoxicity and production of TNF-α and IFN-γ. These features resemble the acquisition of an immune-senescent profile by Vδ2pos T cells from CLM patients that received CHT, a phenomenon that is also associated with the loss of the co-stimulatory marker CD28 and with the induced expression of CD16. The group of CLM patients underwent CHT and older than 60 years old showed higher frequencies of CD57pos and TEMRA Vδ2pos T cells. Similar results were found for tumor infiltrating Vδ2pos T cell subset purified from CLM specimens of patients treated with CHT. The toxicity of CHT regimens also affects the homeostasis of Vδ2pos T cells by inducing higher frequencies of circulating CD57pos TEMRA subset in CLM underwent CHT and younger than 60 years old. Taken together, our data demonstrate that the enrichment of senescent Vδ2pos T cells in CLM patients is not only induced by patients' aging but also by the toxicity of CHT that further accelerates the accumulation of CD57pos TEMRA cells highly dysfunctional in their anti-tumor activities. These results are important to both predict the clinical outcome of CLM and to optimize those protocols of cell cancer immunotherapy employing unconventional Vδ2pos T cells

Hepatobiliary surgeons meet immunologists : the case of colorectal liver metastases patients

The burgeoning field of cancer immunology demands a change in the paradigm of cancer patient management. The understanding of the course of a given malignant disease should also include the host immune system as one of the key factors in determining the patient's prognosis. Surgical and medical oncologists need to understand the basic and advanced applications of immunotherapies, which are rapidly evolving, and are nowadays an integral part of the armamentarium for the treatment of cancer patients. In the present work, we review the current knowledge concerning the immune landscape of colorectal cancer (CRC) patients with liver metastases, as recently discovered

A Three-Dimensional Ply Failure Model for Composite Structures

A fully 3D failure model to predict damage in composite structures subjected to multiaxial loading is presented in this paper. The formulation incorporates shear nonlinearities effects, irreversible strains, damage and strain rate effects by using a viscoplastic damageable constitutive law. The proposed formulation enables the prediction of failure initiation and failure propagation by combining stress-based, damage mechanics and fracture mechanics approaches within an unified energy based context. An objectivity algorithm has been embedded into the formulation to avoid problems associated with strain localization and mesh dependence. The proposed model has been implemented into ABAQUS/Explicit FE code within brick elements as a userdefined material model. Numerical predictions for standard uniaxial tests at element and coupon levels are presented and discussed

Multiple focal nodular hyperplasias induced by oxaliplatin-based chemotherapy

that affects normal liver with low prevalence. Recently, the extensive use of oxaliplatin to treat patients with colorectal cancer has been reported to be associated with the development of different liver injuries, as well as focal liver lesions. The present work describes two patients with multiple bilateral focal liver lesions misdiagnosed as colorectal liver metastases, and treated with liver resection. The first patient had up to 15 small bilateral focal liver lesions, with magnetic resonance imaging consistent with colorectal liver metastases (CLM), and fluorodeoxyglucose (FDG)-positron emission tomography (PET) negative. The second patient had up to 5 small focal liver lesions, with computed tomography consistent with CLM, and FDG-PET negative. They had parenchyma sparing liver surgery, with uneventful postoperative course. At the histology the diagnosis was multiple FNHs. The risks of oxaliplatinbased chemotherapy regimens in development of liver injuries, such as FNH, should not be further denied. The value of the modern multidisciplinary management of patients with colorectal cancer relies also on the precise estimation of the risk/benefit for each patien

An experimental investigation of trailing-edge noise reduction due to elasticity

The proximity of the source and an edge can make the acoustic scattering by wings a significant source of aerodynamic sound. Theoretical results have shown that elastic edges lead to reductions of acoustic scattering; however, experimental confirmation of theoretical trends is difficult, since surface vibrations modify both the source structure and the scattering properties. A simplified, controlled setting for measurements of acoustic scattering, allowing the evaluation of fluid-structure interactions, would thus be desirable to study how elastic edges modify the radiated sound. We present an experimental procedure to isolate the scattered field using a loudspeaker in the vicinity of at plates. The methodology is applied to three different plates, made of steel, aluminum and carbon fiber, as a demonstration. The responses of these elastic plates are studied for a sound source of dipole type near the trailing edge. The method is based on the experimental determination of frequency response functions between source and radiated sound for experiments with and without the plate; subtraction of results, accounting for amplitude and phase, isolates the scattered field. Experimental results treated with the developed procedure were compared with predictions made by numerical simulations performed with a Boundary Element Method (BEM), coupling the acoustic problem with the plate vibration. The comparison between experimental and numerical results revealed that a two-dimensional model can predict satisfactorily the reductions in scattered field by elastic plates observed in the experiment. The present methods can be used to support the choice between different materials for edges focusing on their respective acoustic benefit

Morphophenotypic changes in human multistep hepatocarcinogenesis with translational implications

BACKGROUND & AIMS: Human hepatocarcinogenesis in cirrhosis is thought to be multistep and characterized by a spectrum of nodular lesions, ranging from low to high grade dysplastic nodules (LGDN and HGDN) to early and progressed hepatocellular carcinoma (eHCC and pHCC). Aim of this study was to investigate the morpho-phenotypical changes of this sequence and their potential translational significance. METHODS: We scored the vascular profile, ductular reaction/stromal invasion and overexpression of 5 biomarkers (GPC3, HSP70, GS, CHC, and EZH2), in a series of 100 resected nodules (13 LGDN, 16 HGDN, 42 eHCC and 29 small pHCC). RESULTS: The score separated the 4 groups of nodules as individual entities (p<0.01). In the sequence, biomarkers overexpression progressively increased with parallel decrease of ductular reaction; the vascular remodeling started very early (LGDN) but did not further develop in a proportion of HCC. eHCC was the most heterogeneous entity, with marginal overlap with HGDN and pHCC. Liver environment (fibrosis, etiology) did not impact on the phenotype of the different nodules. A subclass of eHCC (16/42) without evidence of stromal invasion was identified, suggesting a "preinvasive stage" (p<0.05). For diagnosis, the application of 4 and 5 biomarkers (rather than the usual 3) improved the sensitivity of the assay for the detection of eHCC (76% and 93% vs. 52%); biomarkers in alternative combinations also increased the sensitivity of the assay (GS+CHC+EZH2: 76%; GS+CHC+EZH2+HSP70: 90%). CONCLUSIONS: This study supports the multistep nature of human hepatocarcinogenesis, suggests that eHCC is more heterogeneous than previously thought and provides information of potential translational significance into the clinical practice

Anatomical resection of segment 8 by means of ultrasound-guided vessel compression

BACKGROUND: Anatomical resection is the gold standard for liver resection in patients with hepatocellular carcinoma (HCC). Bimanual hepatic vessel compression has been already described, although segmental and subsegmental resection of segment 8 (S8) remain challenging by this technique. We demonstrate how to obtain a S8 demarcation by means of ultrasound-guided vessel compression. METHODS: Two patients with HCC with hepatitis C virus-related cirrhosis partially or fully located in S8 without portal thrombosis underwent liver resection. In the first patient with a HCC fed by subsegmental glissonian pedicles to S4 superior (P4sup) and S8 ventral (P8v), the resection area was disclosed by direct compression of the aforementioned feeding pedicles. A second patient had a HCC located in S8 ventral with a satellite in S8 dorsal; the patient had a pedicle to the right anterior sector originating from the left portal vein. The resection area was obtained by means of direct compression of the P8d and countercompression of the left portal vein (peripherally to the origin of the pedicle to the anterior sector), and P5. Countercompression was needed because of the peculiar trajectory of P8v passing across the middle hepatic vein. RESULTS: In neither case was there a congested area. In the first patient, hepatic veins were not exposed because it was a resection conducted in a subsegmental fashion. There was no morbidity, and no blood transfusions were needed. Patients were both discharged on day 8 after surgery. CONCLUSIONS: Disclosure of subsegmental portions of S8 by means of intraoperative ultrasound-guided compression technique is feasible and confirms the reliability of this approach

Avaliação sensorial de farinhas de bocaiuva produzidas por processo artesanal e mecanizado.

Na região de Corumbá-MS, junto a comunidades extrativistas, de modo a tornar o processo artesanal de extração da polpa e obtenção da farinha de bocaiuva menos penoso e mais rápido, vem sendo avaliado processo mecânico de extração da polpa para obtenção de farinha. O maior desafio é a obtenção de farinha com qualidade similar àquela obtida artesanalmente, a qual é tradicionalmente aceita pelos apreciadores de bocaiuva. Neste trabalho foram comparadas, por meio de avaliação sensorial, farinhas de bocaiuva obtidas por processos artesanal e mecanizado. Foram atribuídas notas maiores para a farinha mecanizada, destacando-se os parâmetros de cor e textura. Ambos os tipos de farinha (mecanizada e artesanal) foram bem aceitas, comprovando sua similaridade e, consequentemente, seu potencial de utilização como ingrediente na elaboração de produtos alimentícios. Amplia-se a possibilidade de geração de trabalho e renda junto às comunidades extrativistas da bocaiuva no Mato Grosso do Sul.Agroecol 2016. 1 CD-ROM. Publicado também em: Cadernos de Agroecologia, v. 11, n. 2, 2016