Synchronous hepatocellular carcinoma and renal cell carcinoma in young woman with sarcoidosis: A case report.

Hepatocellular carcinoma (HCC) and clear cell renal carcinoma are both frequent cancers, especially in patients with risk factors such as cirrhosis in the first case or genetic mutations such as Li-Fraumeni syndrome in the second case; however, their synchronous appearance is very rare especially in young patients with no apparent predisposing factors. We describe the case of a 33-year-old woman with acute pain onset in right hypochondrium. The ultrasound (US) imaging and the contrast-enhanced computed tomography (CECT) of the abdomen revealed 2 abdominal masses: one in the VI-VII segments of the liver and the other one in the right kidney. The chest CECT study, acquired for staging purpose, detected multiple micronodules with patchy peri-bronchial distribution at both lungs. At the histological examination, the tumor arising from the right kidney was finally diagnosed as clear cell renal carcinoma, whereas the tumor arising from the right lateral hepatic lobe as HCC. The histological examination of lung lesions revealed sarcoidosis granulomas. The patient is still being followed up for the occurrence of lung and lymph node metastases from HCC 14 months later.

Genetic Tools for Analyzing Foxp3+ Treg Cells: Fluorochrome-Based Transcriptional Reporters and Genetic Fate-Mapping.

The lack of unambiguous Foxp3+ Treg cell-specific surface markers has prompted the development of various transgenic mouse lines with Foxp3-dependent reporter activity, which involved different fluorochromes and transgenic strategies, including coexpression of multiple transgenes, such as Cre recombinase. Since then, Foxp3 transcriptional reporter has proven to be an indispensable tool to identify and isolate viable Foxp3+ Treg cell populations. However, the physiologic Treg cell pool is functionally heterogeneous and consists of intrathymically (tTreg) and peripherally (pTreg) induced Treg cells, which may confound interpretation of data relying on indiscriminatory Foxp3-fluorochrome reporter expressed in all Treg cells. In this chapter, we describe how the dual Foxp3RFP/GFP reporter can be exploited to discriminate both developmental sublineages based on tTreg cell lineage-specific GFP/Cre recombinase activity, in conjunction with Foxp3-driven RFP expression in all Foxp3+ Treg cells, and provide guidelines for experimental design and implementation. We also elaborate on the possibility to exploit GFP/Cre expression of Foxp3RFP/GFP reporter mice for the manipulation of gene expression (activation and inactivation), such as lineage tracing and in vivo ablation of tTreg cells, while sparing pTreg cells.

Segmental Distribution of Hepatocellular Carcinoma in Cirrhotic Livers.

Background: To evaluate the segmental distribution of hepatocellular carcinoma (HCC) according to Couinaud's anatomical division in cirrhotic patients. Methods: Between 2020 and 2021, a total of 322 HCC nodules were diagnosed in 217 cirrhotic patients who underwent computed tomography (CT) or magnetic resonance imaging (MRI) for the evaluation of suspicious nodules (>1 cm) detected during ultrasound surveillance. For each patient, the segmental position of the HCC nodule was recorded according to Couinaud's description. The clinical data and nodule characteristics were collected. Results: A total of 234 (72.7%) HCC nodules were situated in the right lobe whereas 79 (24.5%) were detected in the left lobe (p < 0.0001) and only 9 nodules were in the caudate lobe (2.8%). HCC was most common in segment 8 (n = 88, 27.4%) and least common in segment 1 (n = 9, 2.8%). No significant differences were found in the frequencies of segmental or lobar involvement considering patient demographic and clinical characteristics, nodule dimension, or disease appearance. Conclusions: The intrahepatic distribution of HCC differs among Couinaud's segments, with segment 8 being the most common location and segment 1 being the least common. The segmental distribution of tumour location was similar to the normal liver volume distribution, supporting a possible correlation between HCC location and the volume of hepatic segments and/or the volumetric distribution of the portal blood flow.

Prevention of EAE by tolerogenic vaccination with PEGylated antigenic peptides.

BACKGROUND: Therapeutic treatment options for chronic autoimmune disorders such as multiple sclerosis (MS) rely largely on the use of non-specific immunosuppressive drugs, which are not able to cure the disease. Presently, approaches to induce antigen-specific tolerance as a therapeutic approach; for example, by peptide-based tolerogenic 'inverse' vaccines have regained great interest. We have previously shown that coupling of peptides to carriers can enhance their capacity to induce regulatory T cells in vivo. METHOD: In this present study, we investigated whether the tolerogenic potential of immunodominant myelin T-cell epitopes can be improved by conjugation to the synthetic carrier polyethylene glycol (PEG) in an experimental autoimmune encephalomyelitis (EAE) mouse model for chronic MS (MOG C57BL/6). RESULTS: Preventive administration of the PEGylated antigenic peptide could strongly suppress the development of EAE, accompanied by reduced immune cell infiltration in the central nervous system (CNS). Depletion of regulatory T cells (Tregs) abrogated the protective effect indicating that Tregs play a crucial role in induction of antigen-specific tolerance in EAE. Treatment during the acute phase of disease was safe and did not induce immune activation. However, treatment at the peak of disease did not affect the disease course, suggesting that either induction of Tregs does not occur in the highly inflamed situation, or that the immune system is refractory to regulation in this condition. CONCLUSION: PEGylation of antigenic peptides is an effective and feasible strategy to improve tolerogenic (Treg-inducing) peptide-based vaccines, but application for immunotherapy of overt disease might require modifications or combination therapies that simultaneously suppress effector mechanisms.

Tolerogenic Immunomodulation by PEGylated Antigenic Peptides.

Current treatments for autoimmune disorders rely on non-specific immunomodulatory and global immunosuppressive drugs, which show a variable degree of efficiency and are often accompanied by side effects. In contrast, strategies aiming at inducing antigen-specific tolerance promise an exclusive specificity of the immunomodulation. However, although successful in experimental models, peptide-based tolerogenic "inverse" vaccines have largely failed to show efficacy in clinical trials. Recent studies showed that repetitive T cell epitopes, coupling of peptides to autologous cells, or peptides coupled to nanoparticles can improve the tolerogenic efficacy of peptides, suggesting that size and biophysical properties of antigen constructs affect the induction of tolerance. As these materials bear hurdles with respect to preparation or regulatory aspects, we wondered whether conjugation of peptides to the well-established and clinically proven synthetic material polyethylene glycol (PEG) might also work. We here coupled the T cell epitope OVA323-339 to polyethylene glycols of different size and structure and tested the impact of these nano-sized constructs on regulatory (Treg) and effector T cells in the DO11.10 adoptive transfer mouse model. Systemic vaccination with PEGylated peptides resulted in highly increased frequencies of Foxp3+ Tregs and reduced frequencies of antigen-specific T cells producing pro-inflammatory TNF compared to vaccination with the native peptide. PEGylation was found to extend the bioavailability of the model peptide. Both tolerogenicity and bioavailability were dependent on PEG size and structure. In conclusion, PEGylation of antigenic peptides is an effective and feasible strategy to improve Treg-inducing, peptide-based vaccines with potential use for the treatment of autoimmune diseases, allergies, and transplant rejection.

Papillary Fibroelastoma of the Left Ventricle in a Radiation-treated Cancer Patient.

We present the case of a 69-year-old female patient with a history of endometrial carcinoma in 1996, who underwent a total hysterectomy and bilateral adnexectomy. The patient also received chemotherapy and mediastinal radiotherapy followed by cancer remission. Ten years later she presented with heart failure and her Doppler-echocardiogram showed severe mitral regurgitation with pulmonary hypertension and a papillary fibroelastoma in the left ventricle. In 2011, she underwent a mitral valve replacement with a biological prosthesis and the pathology exam revealed valve damage consistent with radiotherapy- induced changes and confirmed the presence of a papillary fibroelastoma. This unusual mechanism of papillary fibroelastoma should be disseminated among cardiology physicians and in patients who have survived for long periods after radiotherapy. It is important to remember that cardiac complications may indeed occur, and the treating physician is responsible for detecting them.

Autopercepción de pacientes oncológicos en cuidados paliativos y la visión de sus familiares / Self-perception of cancer patients in palliative care and the view of their relatives

INTRODUCCIÓN Conocer la percepción sobre la alimentación y el estado nutricional de los pacientes oncológicos en cuidados paliativos y la de sus familias es fundamental para llevar adelante intervenciones nutricionales orientadas a mejorar su calidad de vida y en general su sensación de bienestar. OBJETIVO Determinar si existe concordancia en la percepción de la alimentación y del estado nutricional entre los pacientes oncológicos en cuidados paliativos y sus familiares. Describir los diferentes síntomas que presentaron los pacientes durante el transcurso de la enfermedad. METODOLOGÍA En relación al primer objetivo, se diseñó un estudio comparativo, intersujeto con mediciones cegadas e independientes; con respecto al segundo objetivo, el diseño fue observacional, prospectivo, transversal y descriptivo. Se realizó un cuestionario de elaboración propia a 98 pacientes y sus familiares que se encontraban en seguimiento por el Equipo de Cuidados Paliativos del Hospital Dr. Cosme Argerich. RESULTADOS Se encontraron concordancias de grado insignificante o directamente no se halló concordancia en las percepciones entre los pacientes y sus familiares para la mayoría de los ítems evaluados. Se encontró una concordancia de grado leve entre las percepciones de los pacientes y sus familiares sobre el peso corporal de los pacientes (Kappa= 0,394; p=0,000), su apetito (Kappa=0,217; p=0,000) y la valoración del soporte nutricional parenteral (Kappa=0,348; p=0,000). Además, se halló una concordancia moderada en la percepción sobre si el paciente debería realizar cambios en su peso (Kappa=0,481; p=0,000). Tanto la falta de apetito, la falta de percepción del gusto a las comidas como las náuseas resultaron ser los síntomas con mayor prevalencia. DISCUSIÓN El análisis de las percepciones de los pacientes y sus familiares debería formar parte de cualquier intervención nutricional para optimizar así la adecuación a las necesidades y expectativas del paciente

Severe mitral regurgitation after radiotherapy.

We present the case of a 69-year-old patient with a history of gynecological neoplasia and a pulmonary metastasis, who in 1996 underwent chemotherapy and mediastinal radiotherapy followed by cancer remission. Ten years later she presented with heart failure and her Doppler echocardiogram showed severe mitral regurgitation with pulmonary hypertension. In 2011, she underwent a mitral valve replacement with a biological prosthesis and the pathology exam revealed valve damage consistent with radiotherapy-induced changes. This unusual mechanism of mitral regurgitation can be demonstrated clearly by echocardiography and should be disseminated among cardiology physicians and in patients who have survived for long periods after radiotherapy, it is important to remember that cardiac complications may indeed occur, and the treating physician is responsible for detecting them.

Structural motifs in the maturation process of peptide hormones. The somatostatin precursor. I. A CD conformational study.

Synthetic peptides reproducing both the native domain around the dibasic cleavage site of prosomatostatin, and mutated sequences there of, previously assayed in site-directed mutagenesis experiments, have been studied by CD in different solvent systems, such as water, TFE/H2O, MeCN/H2O and aqueous SDS, in order to ascertain the ability of each solvent to stabilize secondary structural motifs. A combination of deconvolution methods and empirical calculations, that allow subtraction of the contributions due to unordered structures from the spectra, suggests that mainly two distinct families of ordered conformers containing alpha-helix and/or structurally different beta-turns are present in solution, the relative stability of the different conformers depending on the nature of the solvent. The presence of beta-turns is in line with a previous NMR study in DMSO and DMSO/H2O. Comparison of the CD spectra in aqueous SDS of peptides undergoing processing with a sequence not processed in vivo shows that only the latter possesses a stable and detectable alpha-helix population. This observation suggests that the structuration involving beta-turns but no alpha-helix, which was observed by CD both in SDS and organic solvent/H2O mixtures at high water contents, might be of biological significance. The similarity of this structuration to molecular models obtained from NMR data in DMSO and DMSO/H2O is discussed.