RESUMEN

While telemedicine has been shown to improve the quality of care for cancer patients, it remains underused for older patients (OP), partly due to the assumption that OPs are unabled or unwilling to use digital tools. However, more than 50% of new cancers are diagnosed in people over 70. The ConnectElderlyPatientToDoctor study aimed to evaluate the OP compliance with the use of the digital telemonitoring platform Cureety in oncology. All cancer patients followed at the Military Hospital Bégin were eligible for the study. Patients were invited to respond to a symptomatology questionnaire personalized to their pathology and treatment. An algorithm evaluated the health status of the patient based on the reported adverse events. The population was divided into two groups, OP and younger patients (YP), based on a cut-off at 70 years. The primary endpoint was to assess the compliance of OPs with the use of the digital oncology platform Cureety, compared to YP. From July 2020 to September 2021, a total of 117 patients were included in our study. We found that 66% of the patients were compliant, with no difference between the two groups (71.2% of YP, 61.7% of OP, P = .29). In OPs, progression free survival (PFS) ratio at 6-months was 64.6% in the tolerant patients vs 23.4% in the nontolerant patients (HR = 0.1980, 95% CI = 0.04431-0.8845, P = .0339). The median PFS was 23.3 months in the tolerant group vs 3.3 months in the nontolerant group (P = .0339). The data of overall survival are immature. OPs had a clear benefit from using this platform, similar to what was observed for YP. Patients felt less isolated and felt that they benefited from personalized care with early ambulatory medical care of adverse events. We also found that the health indicators collected with the platform in the first month of treatment are predictive of the progression of the disease. This solution makes it possible to streamline and improve the care pathway of OP.

Asunto(s)

Neoplasias , Telemedicina , Humanos , Neoplasias/terapia

RESUMEN

BACKGROUND: Immunotherapy alone or in combination has clearly improved the survival of patients with lung cancer. However, it may also be responsible for adverse events impacting these patients' quality of life. The ToxImmune study aims to identify prognostic factors that can help to predict immune-related adverse events. METHODS: We included all patients aged 18 years and older who had received at least one dose of immune checkpoint inhibitors, with or without other therapy, between June 2015 and December 2020 and were diagnosed with nonsmall cell lung cancer or small-cell lung cancer. Patients' baseline demographic characteristics, biological blood markers, and imaging by PET-scanner were collected from electronic medical records. All adverse events (AEs) and immune-related AEs (irAEs) were recorded (Common Terminology Criteria For Adverse Events V.5.0). RESULTS: Sixty-four patients were included, of whom 60 (94%) presented at least one irAE. The incidence of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 and grade 3-4 was 34% and 8% respectively. Female sex, Primitive Tumor Standardized Uptake Value Max (SUVmax) <5, number of metastases ≥3 and immunotherapy received after the first line were found to be significant risk factors for immune-related adverse events. Based on the number of risk factors, the ToxImmune score predicts the risk of having a grade ≥2 adverse event (primitive tumor SUV ≥ 5 = 0 vs. primitive tumor SUV <5 = 1, number of metastases <3 = 0 vs. number of metastases ≥3 = 1 and L1 = 0 vs. L1 ≥ 1). The incidence of grade ≥2 adverse events was 20%, 55% and 90% with ToxImmune scores 0, 1 and = 2 respectively (p = .003). Median progression-free survival (PFS) times were 19.2 months, 6.64 months and 2.63 months for ToxImmune scores 0, 1 and = 2 respectively, p = .13. Median overall survival times were 22.6 months, 16.4 months and 9.8 months for ToxImmune scores 0, 1 and ≥2 respectively, p = .24. The disease control rate (DRR) was 78% in ToxIummune score 0 group, and 50% in ToxImmune score 1 and ≥2 groups (p = .363). CONCLUSION: The ToxImmune score, which is grounded on objective clinical parameters, indicates that cases with a high score had an advanced threat of severe adverse events. The ToxImmune score could therefore be used in clinical practice to identify patients treated for lung cancer with immunotherapy and at risk of severe AE.

Asunto(s)

Antineoplásicos Inmunológicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Femenino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Pronóstico , Calidad de Vida , Antineoplásicos Inmunológicos/uso terapéutico

RESUMEN

Background: Non-adherence to antipsychotics in schizophrenia is associated with an increased risk of psychotic relapse and hospitalization, a risk that is reduced with the use of long-acting injectable (LAI) antipsychotics. Randomized clinical trials (RCTs) have demonstrated the efficacy of paliperidone palmitate 3-monthly (PP3M) for psychotic relapse prevention in schizophrenia, but it remains poorly documented among individuals treated in real-life settings who can benefit the most out of LAIs. Objectives: The objective of this study was to evaluate the effectiveness of PP3M in relapse prevention among patients with schizophrenia. Methods: This is a multicentre retrospective study conducted in four outpatients' clinics across Canada. All consecutive patients with a main diagnosis of schizophrenia who initiated PP3M between June 2016 and March 2020 were included. The primary outcome was psychotic relapse, defined using broad and clinically relevant criteria. Results: Among 178 consecutive patients who were switched to PP3M, the 12-month relapse rate was 18.5% and the relapse-free survival probability was 0.788 (95% confidence interval [CI] = 0.725-0.856). Comorbid diagnoses of personality disorders and substance use disorders were associated with hazard rates (HRs) of 3.6 (95% CI = 1.8-7.3, p < 0.001) and 3.1 (95% CI = 1.6-6.2), respectively. Increased psychopathology severity was associated with an increased likelihood of relapse, while having a job or being in school was protective. Conclusion: These findings reinforce the necessity of conducting research in patients with comorbid psychiatric disorders who are typically underrepresented in RCTs, yet overrepresented in real-life settings, in order to better inform and guide clinical practice.

RESUMEN

Surfactants are crystallizing a certain focus for consumer interest, and their market is still expected to grow by 4 to 5% each year. Most of the time these surfactants are of petroleum origin and are not often biodegradable. Cashew Nut Shell Liquid (CNSL) is a promising non-edible renewable resource, directly extracted from the shell of the cashew nut. The interesting structure of CNSL and its components (cardanol, anacardic acid and cardol) lead to the synthesis of biobased surfactants. Indeed, non-ionic, anionic, cationic and zwitterionic surfactants based on CNSL have been reported in the literature. Even now, CNSL is absent or barely mentioned in specialized review or chapters talking about synthetic biobased surfactants. Thus, this review focuses on CNSL as a building block for the synthesis of surfactants. In the first part, it describes and criticizes the synthesis of molecules and in the second part, it compares the efficiency and the properties (CMC, surface tension, kraft temperature, biodegradability) of the obtained products with each other and with commercial ones.

Asunto(s)

Diseño de Fármacos , Descubrimiento de Drogas/métodos , Tensoactivos/química , Técnicas de Química Sintética , Tecnología Química Verde , Humanos , Estructura Molecular , Relación Estructura-Actividad , Tensoactivos/síntesis química , Tensoactivos/farmacología

RESUMEN

Small nucleolar RNAs (snoRNAs) are an omnipresent class of non-coding RNAs involved in the modification and processing of ribosomal RNA (rRNA). As snoRNAs are required for ribosome production, the increase of which is a hallmark of cancer development, their expression would be expected to increase in proliferating cancer cells. However, assessing the nature and extent of snoRNAs' contribution to cancer biology has been largely limited by difficulties in detecting highly structured RNA. In this study, we used a dedicated midsize non-coding RNA (mncRNA) sensitive sequencing technique to accurately survey the snoRNA abundance in independently verified high-grade serous ovarian carcinoma (HGSC) and serous borderline tumour (SBT) tissues. The results identified SNORA81, SNORA19 and SNORA56 as an H/ACA snoRNA signature capable of discriminating between independent sets of HGSC, SBT and normal tissues. The expression of the signature SNORA81 correlates with the level of ribosomal RNA (rRNA) modification and its knockdown inhibits 28S rRNA pseudouridylation and accumulation leading to reduced cell proliferation and migration. Together our data indicate that specific subsets of H/ACA snoRNAs may promote tumour aggressiveness by inducing rRNA modification and synthesis.

RESUMEN

Background: The mini-Balance Evaluation Systems Test (mini-BESTest) is a valid tool for assessing standing balance in people with spinal cord injury (SCI). Its reliability has not yet been investigated with this population. Objective: To assess the test-retest and inter-rater reliability of the mini-BESTest in adults with SCI in a rehabilitation setting. Methods: Twenty-three participants admitted in a rehabilitation center following an SCI (mean age = 52.2 years, SD = 14.5; 13/23 tetraplegia; 14/23 traumatic injury) and able to stand 30 seconds without help were recruited. They were evaluated twice with the mini-BESTest to establish the test-retest reliability (interval of 1 to 2 days). One of the two sessions was video-recorded to establish the inter-rater reliability (3 physiotherapists). Intraclass correlation coefficients (ICC2,1), weighted kappa (Kw) and Kendall's W were used to determine reliability of total score and individual items. Minimal detectable changes (MDC) were computed. Results. The mini-BESTest total scores showed excellent test-retest (ICC = 0.94) and inter-rater (ICC = 0.96) reliability. Reliability of 50% of the individual items was acceptable to excellent (Κw and W = 0.35-1.00). The MDC of the mini-BESTest total score was 4 points. Conclusion: The mini-BESTest is a reliable tool to assess standing balance in adults with an SCI. A minimal change of 4 points on the total scale is needed to be confident that the change is not a measurement error between two sessions or two raters.

Asunto(s)

Evaluación de la Discapacidad , Equilibrio Postural/fisiología , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/rehabilitación , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diferencia Mínima Clínicamente Importante , Estudios Prospectivos , Reproducibilidad de los Resultados , Adulto Joven

RESUMEN

OBJECTIVE: To describe the clinical, biological and pathological characteristics of patients with the association of SLE and thymic epithelial tumors (TET) in a retrospective multicenter series. METHODS: Cases diagnosed in France between 2000 and 2015 were collected after a call for observations from the French network for thymic epithelial tumors (RYTHMIC database) and the French National Society of Internal Medicine (SNFMI). RESULTS: Fourteen patients were identified, the majority were women (93%). The median age at diagnosis of lupus was 43.5 [range: 30-66] years and 43.5 [range: 26-73] years at diagnosis of thymoma. TET required chemotherapy and/or radiotherapy complementary to surgery in >90% cases. Lupus was diagnosed before, simultaneously, or after diagnosis of thymoma in 6, 3 and 5 cases, respectively. Among the lupus manifestations, joint involvement was predominant (78.6%), followed by autoimmune cytopenia (35.7%), cutaneous affections (28.6%), serositis (28.6%) and renal involvement (21.4%). SLE was associated with one or more AID in 5/14 patients. These characteristics were compared with those from 17 patients identified in the literature. Among them, joint and skin involvement as well as pleural/pericardial effusions occurred in >50%. SLE was controlled by prednisone and hydroxychloroquine in the majority of cases, but 7 out of 31 patients had an immunosuppressant. CONCLUSION: The association of SLE and TET is rare, and its clinical profile seems to be distinguished by the frequency of cytopenias. The management of these patients is complicated by the need to treat cancer, lupus and/or associated autoimmune diseases.

Asunto(s)

Lupus Eritematoso Sistémico/complicaciones , Timoma/complicaciones , Neoplasias del Timo/complicaciones , Adulto , Anciano , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos

RESUMEN

Variations in the activity, up to absolute deficiency, of the enzyme dihydropyrimidine dehydrogenase (DPD), result in the occurrence of adverse reactions to chemotherapy, and have been included among the pharmacogenetic factors underlying inter-individual variability in response to fluoropyrimidines. The study of single-nucleotide polymorphisms of the DPYD gene, which encodes the DPD enzyme, is one of the main parameters capable of predicting reduced enzymatic activity and the consequent influence on fluoropyrimidine treatment, in terms of reduction of both adverse reactions and therapeutic efficacy in disease control. In this paper, we describe a patient with metastatic breast cancer showing signs of increased toxicity following capecitabine therapy. The DPD enzyme activity analysis revealed a partial deficiency. The study of the most frequent polymorphisms of the DPYD gene suggested a wild-type genotype but indicated a novel variant c.1903A>G (p.Asn635Asp), not previously described, proximal to the splice donor site of exon 14. After excluding the potential pathogenic feature of the newly-identified variant, we performed cDNA sequencing of the entire DPYD coding sequence. This analysis identified the variants c.85T>C and c.496A>G, which were previously described as pivotal components of the haplotype associated with decreased enzyme activity and suggested that both variant alleles are related to DPD deficiency. The clinical case findings described in this study emphasize the importance of performing complete genetic analysis of the DPYD gene in order to identify rare and low frequency variants potentially responsible for toxic reactions to fluoropyrimidine treatment.

RESUMEN

The Mini BESTest has been developed to comprehensively examine postural control in individuals with various pathologies treated by rehabilitation professionals. However, no formal French version of the Mini BESTest is available. This study aimed to translate and transculturally adapt the Mini BESTest to French and verify its intra- and inter-rater reliability. Translation and transcultural adaptation was performed in accordance with established guidelines, which included 2 initial translations and transcultural adaptations of the Mini BESTest to French that were then merged, a backward English translation, a subsequent adapted French version resolving discrepancies between the English versions, and pilot testing the final version by French-speaking physical therapists. In total, 20 participants with sensorimotor impairments with various etiologies and able to stand for at least 30sec without human or technical assistance were video-recorded during evaluation with the Mini BESTest. From this video-recording, we calculated inter-rater and intrarater reliability (intraclass correlation coefficient=0.974-0.988), internal consistency (Cronbach alpha=0.895-0.929), standard error of measurement (1.05 and 1.63), and minimal detectable change at the 95% confidence interval (2.91 and 4.51). All values were comparable to those previously reported for the original version of the Mini BESTest. Furthermore, no significant ceiling or floor effect was detected. Therefore, the translated and transculturally adapted version of the Mini BESTest in French compares well to the original version and can be used by French-speaking rehabilitation professionals to examine postural control.

Asunto(s)

Comparación Transcultural , Evaluación de la Discapacidad , Equilibrio Postural/fisiología , Trastornos Somatosensoriales/fisiopatología , Trastornos Somatosensoriales/rehabilitación , Adulto , Anciano , Estudios Transversales , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Traducciones

Asunto(s)

Síndrome de Churg-Strauss/diagnóstico por imagen , Granulomatosis con Poliangitis/diagnóstico por imagen , Granulomatosis con Poliangitis/patología , Linfoma de Células T Periférico/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Biopsia con Aguja , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/tratamiento farmacológico , Síndrome de Churg-Strauss/patología , Diagnóstico Diferencial , Femenino , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/tratamiento farmacológico , Humanos , Linfadenopatía Inmunoblástica/diagnóstico por imagen , Linfadenopatía Inmunoblástica/patología , Inmunohistoquímica , Inmunosupresores/uso terapéutico , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/tratamiento farmacológico , Linfoma de Células T Periférico/patología , Persona de Mediana Edad , Medición de Riesgo

RESUMEN

Mesenchymal stem cells (MSCs) have gained increasing interest for tissue engineering and cellular therapy. MSC expansion on microcarriers (MCs) in stirred bioreactors has emerged as an attractive method for their scaled up production. Some MCs have been developed based on polyesters as a hydrophobic biodegradable core. However, most of these MCs are formulated by an emulsion/organic solvent evaporation (E/E) process using poly(vinyl alcohol) as a shell steric stabilizer, which is biocompatible but not degradable in vivo. Moreover, in most of these MCs, the polymer shell is only physically adsorbed at the particle surface. To the best of our knowledge, no study deals with the stability of such a shell when the MCs are in contact with competitive surfactants or with proteins contained in the culture medium. In this study, fully in vivo bioresorbable dextran-covered polylactide-based MCs were formulated using an E/E process, which allowed to control their surface chemistry. Different dextran derivatives with alkyne or ammonium groups were firstly synthesised. Then, on the one hand, some MCs (non-clicked MCs) were formulated with a physically adsorbed polysaccharide shell onto the core. On the other hand, the polysaccharide shell was linked to the core via in situ CuAAC click-chemistry carried out during the E/E process (clicked MCs). The stability of such coverage was first studied in the presence of competitive surfactants (sodium dodecyl sulfate-SDS, or proteins contained in the culture medium) using nanoparticles (NPs) exhibiting the same chemical composition (core/shell) as MCs. The results revealed the total desorption of the dextran shell for non-clicked NPs after treatment with SDS or the culture medium, while this shell desorption was greatly decreased for clicked NPs. A qualitative study of this shell stability was finally carried out on MCs formulated using a new fluorescent dextran-based surfactant. The results were in agreement with those observed for NPs, and showed that non-clicked MCs are characterized by poor shell stability in contact with a competitive surfactant, which could be quite an issue during MSC expansion. In contrast, clicked MCs possess better shell stability, which allow a better control of the MC surface chemistry, especially during cell culture.

RESUMEN

The impact of the chain stiffness on physicochemical properties has been studied by chemical modification of xanthan under both ordered and disordered conformations. Corresponding rheological properties were studied and results showed that amphiphilic xanthan exhibited completely different behaviors depending on its conformation during modification. Xanthan, when modified under ordered conformation, exhibits similar behavior to non-modified one, only the chain relaxation being strongly slowed down. Therefore, the high stiffness of xanthan helices does not allow hydrophobic moieties to associate. Oppositely, xanthan modified under its disordered conformation displayed a chemical gel-like behavior without any relaxation of the chain within the studied frequency range nor with temperature, which is unexpected for this length of alkyl chains. These different viscoelastic properties can be correlated to the regioselectivity of the grafting; the latter can be controlled by the conformation of xanthan during modification, thus by the synthesis conditions.

RESUMEN

Objectives. To quantify the association between performance-based manual wheelchair propulsion tests (20 m propulsion test, slalom test, and 6 min propulsion test), trunk and upper extremity (U/E) strength, and seated reaching capability and to establish which ones of these variables best predict performance at these tests. Methods. 15 individuals with a spinal cord injury (SCI) performed the three wheelchair propulsion tests prior to discharge from inpatient SCI rehabilitation. Trunk and U/E strength and seated reaching capability with unilateral hand support were also measured. Bivariate correlation and multiple linear regression analyses allowed determining the best determinants and predictors, respectively. Results. The performance at the three tests was moderately or strongly correlated with anterior and lateral flexion trunk strength, anterior seated reaching distance, and the shoulder, elbow, and handgrip strength measures. Shoulder adductor strength-weakest side explained 53% of the variance on the 20-meter propulsion test-maximum velocity. Shoulder adductor strength-strongest side and forward seated reaching distance explained 71% of the variance on the slalom test. Handgrip strength explained 52% of the variance on the 6-minute propulsion test. Conclusion. Performance at the manual wheelchair propulsion tests is explained by a combination of factors that should be considered in rehabilitation.

RESUMEN

OBJECTIVE: To quantify and compare the responsiveness and concurrent validity of 3 performance-based manual wheelchair propulsion tests among manual wheelchair users with subacute spinal cord injury (SCI) undergoing inpatient rehabilitation. DESIGN: Quasi-experimental repeated-measures design. SETTING: Publicly funded comprehensive inpatient SCI rehabilitation program. PARTICIPANTS: Consenting adult manual wheelchair users with a subacute SCI admitted and discharged from inpatient rehabilitation (N=14). INTERVENTION: Participants performed 20-m propulsion at both self-selected natural and maximal speeds, the slalom, and the 6-minute propulsion tests at rehabilitation admission and discharge. MAIN OUTCOME MEASURES: Time required to complete the performance-based wheelchair propulsion tests. Standardized response means (SRMs) were computed for each performance test and Pearson correlation coefficients (r) were calculated to explore the associations between performance tests. RESULTS: The slalom (SRM=1.24), 20-m propulsion at maximum speed (SRM=.99), and 6-minute propulsion tests (SRM=.84) were the most responsive. The slalom and 20-m propulsion at maximum speed were strongly correlated at both admission (r=.93) and discharge (r=.92). CONCLUSIONS: The slalom and 6-minute propulsion tests best document wheelchair propulsion performance change over the course of inpatient rehabilitation. Adding the 20-m propulsion test performed at maximal speed provides a complementary description of performance change.

Asunto(s)

Modalidades de Fisioterapia/normas , Traumatismos de la Médula Espinal/rehabilitación , Silla de Ruedas , Adulto , Suministros de Energía Eléctrica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Quebec , Reproducibilidad de los Resultados

Asunto(s)

Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos/efectos adversos , Melanoma/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Púrpura Trombocitopénica Idiopática/inducido químicamente , Neoplasias Cutáneas/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Adulto , Biomarcadores de Tumor/antagonistas & inhibidores , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Masculino , Melanoma/enzimología , Melanoma/genética , Melanoma/secundario , Persona de Mediana Edad , Mutación , Recuento de Plaquetas , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Púrpura Trombocitopénica Idiopática/sangre , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/inmunología , Inducción de Remisión , Neoplasias Cutáneas/enzimología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Resultado del Tratamiento

RESUMEN

CONTEXT: Trunk control is essential to engage in activities of daily living. Measuring trunk strength and function in persons with spinal cord injury (SCI) is difficult. Trunk function has not been studied in non-traumatic SCI (NTSCI). OBJECTIVES: To characterize changes in trunk strength and seated functional reach in individuals with NTSCI during inpatient rehabilitation. To determine if trunk strength and seated reach differ between walkers and wheelchair users. To explore relationships between trunk and hip strength and seated functional reach. DESIGN: Observational study. SETTING: Two SCI rehabilitation facilities. PARTICIPANTS: 32 subacute inpatients (mean age 48.0 ± 15.4 years). OUTCOME MEASURES: Isometric strength of trunk and hip and function (Multidirectional Reach Test: MDRT) were assessed at admission and within 2 weeks of discharge. Analysis of variance was conducted for admission measures (MDRT, hip and trunk strength) between walkers and wheelchair users. Changes in MDRT, hip and trunk strength were evaluated using parametric and non-parametric statistics. The level of association between changes in values of MRDT and strength was also examined. RESULTS: Significant differences between walkers and wheelchair users were found for strength measures (P < 0.05) but not for MDRT. Left- and right-sided reaches increased in wheelchair users only (P < 0.05). Associations between changes in hip strength, trunk strength, and reach distance were found (R = 0.67-0.73). CONCLUSION: In clinical settings, it is feasible and relevant to assess trunk, hip strength, and MRDT. Future studies require strategies to increase the number of participants assessed, in order to inform clinicians about relevant rehabilitation interventions.

Asunto(s)

Movimiento , Fuerza Muscular , Examen Físico/métodos , Traumatismos de la Médula Espinal/diagnóstico , Traumatismos de la Médula Espinal/fisiopatología , Torso/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rango del Movimiento Articular , Reproducibilidad de los Resultados , Sensibilidad y Especificidad

RESUMEN

Small nucleolar RNAs (snoRNAs) are among the first discovered and most extensively studied group of small non-coding RNA. However, most studies focused on a small subset of snoRNAs that guide the modification of ribosomal RNA. In this study, we annotated the expression pattern of all box C/D snoRNAs in normal and cancer cell lines independent of their functions. The results indicate that C/D snoRNAs are expressed as two distinct forms differing in their ends with respect to boxes C and D and in their terminal stem length. Both forms are overexpressed in cancer cell lines but display a conserved end distribution. Surprisingly, the long forms are more dependent than the short forms on the expression of the core snoRNP protein NOP58, thought to be essential for C/D snoRNA production. In contrast, a subset of short forms are dependent on the splicing factor RBFOX2. Analysis of the potential secondary structure of both forms indicates that the k-turn motif required for binding of NOP58 is less stable in short forms which are thus less likely to mature into a canonical snoRNP. Taken together the data suggest that C/D snoRNAs are divided into at least two groups with distinct maturation and functional preferences.

Asunto(s)

Proteínas Nucleares/fisiología , ARN Nucleolar Pequeño/metabolismo , Proteínas de Unión al ARN/fisiología , Proteínas Represoras/fisiología , Ribonucleoproteínas Nucleolares Pequeñas/fisiología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular , Línea Celular Tumoral , Femenino , Humanos , Células MCF-7 , Proteínas Nucleares/antagonistas & inhibidores , Conformación de Ácido Nucleico , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Factores de Empalme de ARN , ARN Nucleolar Pequeño/química , ARN Nucleolar Pequeño/clasificación , Ribonucleoproteínas Nucleolares Pequeñas/antagonistas & inhibidores

RESUMEN

Paraneoplastic syndromes (PNPs) refer to cancer-associated signs and symptoms arising in organs and tissues that are remote from the cancer and unrelated to metastasis. Currently the best described PNPs are attributed to tumor secretion of functional peptides and hormones or immune cross-reactivity between tumor and normal host tissues. Paraneoplastic hematologic syndromes are observed more rarely. Here we report a case of paraneoplastic granulocytosis in an advanced lung cancer patient.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Granulocitos/patología , Leucocitosis/diagnóstico , Neoplasias Pulmonares/diagnóstico , Síndromes Paraneoplásicos/diagnóstico , Neoplasias de las Glándulas Suprarrenales/secundario , Neoplasias Encefálicas/secundario , Proteína C-Reactiva/análisis , Carcinoma de Pulmón de Células no Pequeñas/secundario , Resultado Fatal , Humanos , L-Lactato Deshidrogenasa/análisis , Metástasis Linfática/diagnóstico , Masculino , Persona de Mediana Edad

RESUMEN

Hydrophobic octyl moieties have been grafted in various densities onto the carboxylic acid functions of xanthan under its ordered conformation. The outcoming amphiphilic and associative properties were studied by fluorescence spectroscopy and rheology. Results showed that the conformation of xanthan is not affected by the chemical modification and remains the same as the native one. Additionally, xanthan derivatives do not show any viscoelastic enhancement; nevertheless, their dynamics is strongly slowed down: the higher the grafting density, the slower the relaxation. We proved that hydrophobically modified xanthan, even being amphiphilic, does not exhibit any additional associating properties compared to the unmodified xanthan. The high stiffness of xanthan helices does not allow the derivatives to adopt the organization usually observed for flexible amphiphilic polymers. On the basis of these observations, a model depicting such a singular behavior is proposed.

Asunto(s)

Polisacáridos Bacterianos/química , Aminas/química , Interacciones Hidrofóbicas e Hidrofílicas , Espectroscopía de Resonancia Magnética , Polisacáridos Bacterianos/síntesis química , Reología , Espectrometría de Fluorescencia , Temperatura , Viscosidad