Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 397.801
Filtrar
1.
Mol Cancer ; 21(1): 32, 2022 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-35090469

RESUMEN

N6-methyladenosine (m6A) methylation, the most common form of internal RNA modification in eukaryotes, has gained increasing attention and become a hot research topic in recent years. M6A plays multifunctional roles in normal and abnormal biological processes, and its role may vary greatly depending on the position of the m6A motif. Programmed cell death (PCD) includes apoptosis, autophagy, pyroptosis, necroptosis and ferroptosis, most of which involve the breakdown of the plasma membrane. Based on the implications of m6A methylation on PCD, the regulators and functional roles of m6A methylation were comprehensively studied and reported. In this review, we focus on the high-complexity links between m6A and different types of PCD pathways, which are then closely associated with the initiation, progression and resistance of cancer. Herein, clarifying the relationship between m6A and PCD is of great significance to provide novel strategies for cancer treatment, and has a great potential prospect of clinical application.


Asunto(s)
Adenosina , Neoplasias , Adenosina/análogos & derivados , Adenosina/metabolismo , Apoptosis/genética , Humanos , Metilación , Neoplasias/genética , Neoplasias/metabolismo
2.
Cell Commun Signal ; 20(1): 14, 2022 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-35090497

RESUMEN

Programmed cell death 1 ligand 1 (PD-L1) is the ligand for programmed death protein-1 (PD-1), is associated with immunosuppression. Signaling via PD-1/PD-L1 will transmits negative regulatory signals to T cells, inducing T-cell inhibition, reducing CD8+ T-cell proliferation, or promoting T-cell apoptosis, which effectively reduces the immune response and leads to large-scale tumor growth. Accordingly, many antibody preparations targeting PD-1 or PD-L1 have been designed to block the binding of these two proteins and restore T-cell proliferation and cytotoxicity of T cells. However, these drugs are ineffective in clinical practice. Recently, numerous of studies have shown that, in addition to the surface of tumor cells, PD-L1 is also found on the surface of extracellular vesicles secreted by these cells. Extracellular vesicle PD-L1 can also interact with PD-1 on the surface of T cells, leading to immunosuppression, and has been proposed as a potential mechanism underlying PD-1/PD-L1-targeted drug resistance. Therefore, it is important to explore the production, regulation and tumor immunosuppression of PD-L1 on the surface of tumor cells and extracellular vesicles, as well as the potential clinical application of extracellular vesicle PD-L1 as tumor biomarkers and therapeutic targets. Video Abstract.


Asunto(s)
Vesículas Extracelulares , Neoplasias , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Linfocitos T CD8-positivos , Vesículas Extracelulares/metabolismo , Humanos , Neoplasias/metabolismo , Microambiente Tumoral
4.
J Immunol Res ; 2022: 8052212, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35340585

RESUMEN

With the huge therapeutic potential, cancer immunotherapy is expected to become the mainstream of cancer treatment. In the current field of cancer immunotherapy, there are mainly five types. Immune checkpoint blockade therapy is one of the most promising directions. Adoptive cell therapy is an important component of cancer immunotherapy. The therapy with the cancer vaccine is promising cancer immunotherapy capable of cancer prevention. Cytokine therapy is one of the pillars of cancer immunotherapy. Oncolytic immunotherapy is a promising novel component of cancer immunotherapy, which with significantly lower incidence of serious adverse reactions. The recent positive results of many clinical trials with cancer immunotherapy may herald good clinical prospects. But there are still many challenges in the broad implementation of immunotherapy. Such as the immunotherapy cannot act on all tumors, and it has serious adverse effects including but not limited to nonspecific and autoimmunity inflammation. Here, we center on recent progress made within the last 5 years in cancer immunotherapy. And we discuss the theoretical background, as well as the opportunities and challenges of cancer immunotherapy.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Vacunas contra el Cáncer/uso terapéutico , Humanos , Factores Inmunológicos , Inmunoterapia/métodos , Inmunoterapia Adoptiva
5.
J Clin Pharmacol ; 62(2): 206-219, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34435684

RESUMEN

Population pharmacokinetic (PK) and exposure-safety analyses of alisertib were performed in children enrolled in 2 clinical trials: NCT02444884 and NCT01154816. NCT02444884 was a dose-finding study in children with relapsed/refractory solid malignancies (phase 1) or neuroblastomas (phase 2). Patients received oral alisertib 45 to 100 mg/m2 as powder-in-capsule once daily or twice daily for 7 days in 21-day cycles. Serial blood samples were collected up to 24 hours after dosing on cycle 1, day 1. NCT01154816 was a phase 2 single-arm study evaluating efficacy in children with relapsed/refractory solid malignancies or acute leukemias. Patients received alisertib 80 mg/m2 as enteric-coated tablets once daily for 7 days in 21-day cycles. Sparse PK samples were collected up to 8 hours after dosing on cycle 1, day 1. Sources of alisertib PK variability were characterized and quantified using nonlinear mixed-effects modeling to support dosing recommendations in children and adolescents. A 2-compartment model with oral absorption described by 3 transit compartments was developed using data from 146 patients. Apparent oral clearance and central distribution volume were correlated with body surface area across the age range of 2 to 21 years, supporting the use of body surface area-based alisertib dosing in the pediatric population. The recommended dose of 80 mg/m2 once daily enteric-coated tablets provided similar alisertib exposures across pediatric age groups and comparable exposure to that in adults receiving 50 mg twice daily (recommended adult dose). Statistically significant relationships (P < .01) were observed between alisertib exposures and incidence of grade ≥2 stomatitis and febrile neutropenia, consistent with antiproliferative mechanism-related toxicities.


Asunto(s)
Antineoplásicos/farmacocinética , Azepinas/farmacocinética , Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacocinética , Pirimidinas/farmacocinética , Adolescente , Antineoplásicos/efectos adversos , Azepinas/efectos adversos , Superficie Corporal , Niño , Preescolar , Esquema de Medicación , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Modelos Biológicos , Estadificación de Neoplasias , Neoplasias/patología , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/efectos adversos , Adulto Joven
6.
Psychooncology ; 31(1): 107-115, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34425036

RESUMEN

OBJECTIVE: CanCope is an internet-delivered, cognitive-behavioural intervention adapted from the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders to improve emotion regulation and support the mental health of cancer survivors. Four separate pilot studies evaluated each of CanCope's modules for (1) feasibility and participant satisfaction, and changes in (2) module-specific outcomes, and (3) global measures of emotion dysregulation and anxiety and depressive symptoms, from pre-to-post module delivery. METHODS: Eligible cancer survivors self-selected into one two-week online module designed to improve a specific aspect of emotion regulation ([1] understanding emotions, [2] mindfulness of emotions, [3] cognitive reappraisals, [4] challenging emotion-driven behaviours). RESULTS: Across modules, post-intervention surveys were completed by 17-19 participants, (58.1%-90.5% completion rate for participants who received the intervention). Each module was feasible and participants reported high satisfaction. Moderate-to-large pre-to-post effect sizes in mean differences were observed in module-specific target outcomes (p's < 0.05). Emotion dysregulation significantly decreased across modules 1 to 3 (p's < 0.05) with a non-significant decrease for module 4 (p = 0.13). Anxiety symptoms significantly decreased across all modules (p's < 0.05). Depressive symptoms significantly decreased across modules 1 and 3 (p's < 0.05), with non-significant decreases across modules 2 (p = 0.08) and 4 (p = 0.06). CONCLUSIONS: Each CanCope module demonstrated promise in targeting emotion regulation skills and supporting the mental health of cancer survivors. Randomised controlled trials are required to test the efficacy of CanCope as an intervention in its entirety.


Asunto(s)
Supervivientes de Cáncer , Terapia Cognitivo-Conductual , Intervención basada en la Internet , Neoplasias , Trastornos de Ansiedad/terapia , Supervivientes de Cáncer/psicología , Terapia Cognitivo-Conductual/métodos , Humanos , Salud Mental , Neoplasias/terapia
7.
In Vivo ; 36(2): 898-906, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35241548

RESUMEN

BACKGROUND/AIM: An early evaluation concerning the effectiveness of supportive oligonucleotide therapy (SOT) in cancer as a monotherapy and in combination with other types of treatment. PATIENTS AND METHODS: This study evaluated the clinical condition and performance status (Karnofsky-Index) of 95 patients, post-SOT administration. Furthermore, circulating tumor cells (CTCs) from 47 patients' pre- and post-SOT administration were measured and analyzed by repeated-measures ANOVA. RESULTS: Improvement of the clinical condition was observed in all patients who used SOT (77.89%), SOT in combination with other therapy (69.77%) and SOT as a monotherapy or no information was given concerning another therapy (84.31%). Positive results for Karnofsky-Index were also observed in 71.58%, 61.36%, and 80.39%, respectively. Finally, statistically significant reductions in CTCs were observed for both SOT as a monotherapy and SOT as an adjunctive therapy. CONCLUSION: The preliminary results indicate that SOT therapy can be used both as monotherapy as well as in combination with other therapies for cancer.


Asunto(s)
Neoplasias , Oligonucleótidos , Humanos , Neoplasias/terapia , Oligonucleótidos/uso terapéutico
8.
BMC Public Health ; 22(1): 902, 2022 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-35524227

RESUMEN

BACKGROUND: National mortality statistics are only based on the underlying cause of death, which may considerably underestimate the effects of some chronic conditions. METHODS: The sensitivity, specificity, and positive and negative predictive values for diabetes (a common precursor to multimorbidity), dementia (a potential accelerant of death) and cancer (expected to be well-recorded) were calculated from death certificates for 9 056 women from the 1921-26 cohort of the Australian Longitudinal Study on Women's Health. Log binomial regression models were fitted to examine factors associated with the sensitivity of death certificates with these conditions as underlying or contributing causes of death. RESULTS: Among women who had a record of each of these conditions in their lifetime, the sensitivity was 12.3% (95% confidence interval, 11.0%, 13.7%), 25.2% (23.7%, 26.7%) and 57.7% (55.9%, 59.5%) for diabetes, dementia and cancer, respectively, as the underlying cause of death, and 40.9% (38.8%, 42.9%), 52.3% (50.6%, 54.0%) and 67.1% (65.4%, 68.7%), respectively, if contributing causes of death were also taken into account. In all cases specificity (> 97%) and positive predictive value (> 91%) were high, and negative predictive value ranged from 69.6% to 84.6%. Sensitivity varied with age (in different directions for different conditions) but not consistently with the other sociodemographic factors. CONCLUSIONS: Death rates associated with common conditions that occur in multimorbidity clusters in the elderly are underestimated in national mortality statistics, but would be improved if the multiple causes of death listed on a death certificate were taken into account in the statistics.


Asunto(s)
Demencia , Diabetes Mellitus , Neoplasias , Anciano , Australia/epidemiología , Causas de Muerte , Estudios de Cohortes , Certificado de Defunción , Demencia/epidemiología , Diabetes Mellitus/epidemiología , Femenino , Humanos , Estudios Longitudinales , Masculino
9.
J Nanobiotechnology ; 20(1): 214, 2022 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-35524277

RESUMEN

Immunotherapy has gradually emerged as the most promising anticancer therapy. In addition to conventional anti-PD-1/PD-L1 therapy, anti-CTLA-4 therapy, CAR-T therapy, etc., immunotherapy can also be induced by stimulating the maturation of immune cells or inhibiting negative immune cells, regulating the tumor immune microenvironment and cancer vaccines. Lipid nanovesicle drug delivery system includes liposomes, cell membrane vesicles, bacterial outer membrane vesicles, extracellular vesicles and hybrid vesicles. Lipid nanovesicles can be used as functional vesicles for cancer immunotherapy, and can also be used as drug carriers to deliver immunotherapy drugs to the tumor site for cancer immunotherapy. Here, we review recent advances in five kinds of lipid nanovesicles in cancer immunotherapy and assess the clinical application prospects of various lipid nanovesicles, hoping to provide valuable information for clinical translation in the future.


Asunto(s)
Inmunoterapia , Neoplasias , Sistemas de Liberación de Medicamentos , Humanos , Lípidos , Neoplasias/tratamiento farmacológico , Microambiente Tumoral
10.
Methods Enzymol ; 667: 1-35, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35525538

RESUMEN

The PEAK family of pseudokinases, which comprises PEAK1, PEAK2 and PEAK3, are newly identified scaffolds that dynamically assemble oncogenic signaling pathways known to contribute to the development of several aggressive cancers. A striking feature of this unique family of pseudokinase scaffolds is their large multi-domain structure, which allows them to achieve protein complex assemblies through their structural plasticity and functional versatility. Recent structural advances have begun to reveal the critical regulatory elements that control their function. Specifically, the dimer-dependent scaffolding activity of PEAK pseudokinases is emerging as a critical mechanism for their signaling function, in addition to their ability to hetero-associate to form higher-order regulatory networks to diversify and amplify their signaling output. Here, we present a suite of techniques that enable the efficient expression and purification of PEAK proteins for functional characterization.


Asunto(s)
Neoplasias , Transducción de Señal , Carcinogénesis , Humanos
11.
Methods Enzymol ; 667: 79-99, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35525562

RESUMEN

Human Tribbles 2 (TRIB2) is a cancer-associated pseudokinase with a broad human protein interactome, including the well-studied AKT, C/EBPα and MAPK modules. Several lines of evidence indicate that human TRIB2 promotes cell survival and drug-resistance in solid tumors and blood cancers and is therefore of interest as a potential therapeutic target, although its physiological functions remain relatively poorly understood. The unique TRIB2 pseudokinase domain lacks the canonical 'DFG' motif, and subsequently possesses very low affinity for ATP in both the presence and absence of metal ions. However, TRIB2 also contains a unique cysteine-rich αC-helix, which interacts with a conserved peptide motif in its own carboxyl-terminal tail. This regulatory flanking region drives regulated interactions with distinct E3 ubiquitin ligases that serve to control the stability and turnover of TRIB2 client proteins. TRIB2 is also a low-affinity target of several known small-molecule protein kinase inhibitors, which were originally identified using purified recombinant TRIB2 proteins and a thermal shift assay. In this chapter, we discuss laboratory-based procedures for purification, stabilization and analysis of human TRIB2, including screening procedures that can be used for the identification of both reversible and covalent small molecule ligands.


Asunto(s)
Proteínas Quinasas Dependientes de Calcio-Calmodulina , Neoplasias , Proteínas Quinasas Dependientes de Calcio-Calmodulina/genética , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias/patología , Ubiquitina-Proteína Ligasas/metabolismo
12.
BMC Cancer ; 22(1): 484, 2022 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-35501771

RESUMEN

BACKGROUND: The capacity for invasive tissue biopsies followed by histopathology diagnosis in sub-Saharan Africa is severely limited. Consequently, many cancer patients are diagnosed late and outcomes are poor. Here, we propose to evaluate circulating tumour (ct) DNA analysis ("liquid biopsy"), a less invasive and faster approach to diagnose endemic EBV-driven lymphomas (EBVL) in East Africa. METHODS: We will evaluate the clinical utility of an already validated ctDNA test prospectively in a head-to-head comparison against histopathology. The primary endpoint is the time from presentation to the specialist centre to a final diagnosis of EBV- Lymphoma. Secondary endpoints include the sensitivity and specificity of liquid biopsy and health economic benefits over histopathology. One hundred forty-six patients will be recruited over 18 months. Patients will be eligible if they are 3-30 years of age and have provided written consent or assent as per IRB guidelines. Tissue and venous blood samples will be processed as per established protocols. Clinical data will be captured securely and in real-time into a REDCap database. The time from presentation to diagnosis will be documented. The sensitivity and specificity of the methods can be estimated within 5% error margin with 95% confidence level using 73 cases and 73 controls. Health-economic assessment will include micro-costing of ctDNA test and histopathology. All results will be reviewed in a multidisciplinary tumour board. DISCUSSION: The study evaluates the clinical utility of ctDNA in improving the speed of diagnostic pathways for EBVL in sub-Saharan Africa. Our results would provide proof-of-principle that ctDNA can be used as a diagnostic tool in areas without access to regular pathology, that transfer of the tool is feasible, and that it leads to an earlier and faster diagnosis. The potential clinical and economic impact of this proposal is thus significant. If successful, this study will provide appropriate, and cost-effective diagnostic tools that will promote earlier diagnosis of EBVL and potentially other cancers in countries with restricted healthcare resources. TRIAL REGISTRATION: Pan African Clinical Trials Registry:  PACTR202204822312651 , registered on 14th-April-2022.


Asunto(s)
ADN Tumoral Circulante , Linfoma no Hodgkin , Neoplasias , África Oriental , Biomarcadores de Tumor/genética , Niño , Herpesvirus Humano 4/genética , Humanos , Biopsia Líquida/métodos , Neoplasias/diagnóstico , Adulto Joven
13.
Cancer Prev Res (Phila) ; 15(5): 279-284, 2022 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-35502553

RESUMEN

The COVID-19 pandemic overloaded health care systems around the globe and brought travel restrictions and other mandates. These effects critically impacted cancer care and conduct of clinical trials, and required medical and research communities to incorporate changes and novel flexible workflows within clinical trials and regulations to improve efficiency. We report the impact of the pandemic on cancer prevention clinical trials managed by the Division of Cancer Prevention within the NCI, focusing on participant-centric, study staff-centric and regulatory elements. Learning lessons from this challenging period, the cancer prevention community has the opportunity to incorporate many of these necessitated novel approaches to future design of clinical trials, to streamline and improve clinical trial efficiency and impact.


Asunto(s)
COVID-19 , Ensayos Clínicos como Asunto , Neoplasias , COVID-19/epidemiología , Atención a la Salud , Humanos , National Cancer Institute (U.S.) , Neoplasias/prevención & control , Pandemias , Proyectos de Investigación , Estados Unidos/epidemiología
14.
PLoS One ; 17(5): e0267741, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35511918

RESUMEN

INTRODUCTION: In radiotherapy, the presence of air gaps near a tumour can lead to underdose to the tumour. In this study, the impact of air gaps on dose to the surface was evaluated. 3D-printing was used to construct a Eurosil-4 Pink bolus customised to the patient and its dosimetric properties were compared with that of Paraffin wax bolus. METHODS: Surface dose was measured for flat sheets of Eurosil-4 Pink bolus with different thicknesses. Different air gap thicknesses were inserted between the bolus and the surface, and dose was measured for each air gap using 10 cm × 10 cm fields. This was repeated with the effective field size calculated from the patient plan. Surface dose was measured for varying angles of incidence. A customised chest phantom was used to compare dose for two customised Eurosil-4 Pink boluses, and commonly used Paraffin wax bolus. RESULTS: The surface dose was found to be highest for 1.1 cm thick bolus. The decrease in surface dose for the Eurosil-4 Pink bolus was minimal for the 10 cm × 10 cm field, but higher for the effective field size and larger angles of incidence. For instance, the dose was reduced by 6.2% as a result of 1 cm air gap for the effective field size and 60 degree angle of incidence. The doses measured using Gafchromic film under the customised Eurosil-4 Pink boluses were similar to that of the Paraffin wax bolus, and higher than prescribed dose. CONCLUSIONS: The impact of air gaps can be significant for small field sizes and oblique beams. A customised Eurosil-4 Pink bolus has promising physical and dosimetric properties to ensure sufficient dose to the tumour, even for treatments where larger impact of air gaps is suspected.


Asunto(s)
Neoplasias , Pared Torácica , Humanos , Neoplasias/radioterapia , Parafina , Fantasmas de Imagen , Radiometría , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador
15.
Medicine (Baltimore) ; 101(17): e29143, 2022 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-35512070

RESUMEN

BACKGROUND: Mesenteric panniculitis (MP) is a non-specific, localized inflammation at the mesentery of small intestines which often gets detected on computed tomography. An association with malignant neoplasms remains unclear. We performed a systematic review and meta-analysis to examine the association of malignancy with MP. METHODS: MEDLINE, EMBASE, Web of Science, and Cochrane databases were searched for articles published from inception to 2020 that evaluated the association of malignant neoplasms with MP in comparison with control groups. Using random-effects method, a summary odds ratio (OR) estimate with 95% confidence intervals for malignant neoplasms in MP was estimated. RESULTS: Four case-control studies reporting data on 415 MP patients against 1132 matched-controls met inclusion criteria and were analyzed. The pooled OR for finding a malignant neoplasm in patients with MP was 0.907 (95% CI: 0.688-1.196; P = .489). The heterogeneity was mild and non-significant. Also, there was no heightened risk of any specific type of malignancy with MP. Three more case-series with unmatched-control groups (MP: 282, unmatched-controls: 17,691) were included in a separate analysis where the pooled OR of finding a malignant neoplasm was 2.963 (95% CI: 1.434-6.121; P = .003). There was substantial heterogeneity in this group. CONCLUSION: This meta-analysis of matched controlled studies proves absence of any significant association of malignant neoplasms with MP. Our study also demonstrates that the putative association of malignancy with MP is mainly driven by uncontrolled studies or case-series.


Asunto(s)
Neoplasias , Paniculitis Peritoneal , Bases de Datos Factuales , Humanos , Mesenterio , Paniculitis Peritoneal/complicaciones , Paniculitis Peritoneal/epidemiología , Tomografía Computarizada por Rayos X
16.
Medicine (Baltimore) ; 101(17): e29207, 2022 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-35512078

RESUMEN

BACKGROUND AIMS: At present, increasing reports have shown that latent transforming growth factor-ß-binding protein 2 (LTBP2) was associated with the prognosis of many types of cancer. We performed rounded analysis to comprehensively analyze and evaluate the prognostic significance of LTBP2 for patients with malignant tumors. METHODS: We identified relevant studies by searching database including PubMed, Embase, Cochrane Library, and Web of Science. The odds ratio with its 95% confidence interval (CI) was used to assess the correlation between LTBP2 and clinicopathologic features or overall survival of patients with cancer. Hazard ratio with its 95% CI was used to explore the prognostic risk factors. The analysis was performed and assessed using Review Manager 5.2. RESULTS: A total of 11 studies including 2322 participants were included in this systematic review. Pooled results showed that malignant tissues experienced higher incidence of high LTBP2 expression when compared with adjacent or normal tissues. Patients with high LTBP2 expression experienced significantly lower 1-year, 2-year, 3-year, and 4-year overall survival rate, with the pooled odds ratios being 0.26 (95% CI 0.13-0.53; P = .0002), 0.27 (95% CI 0.14-0.50; P < .0001), 0.26 (95% CI 0.13-0.53; P = .0002), and 0.21 (95% CI 0.06-0.73; P = .01) respectively. Univariate analysis showed high LTBP2 expression, tumor node metastasis stage, T stage, and N stage were prognostic factors of patients with tumors. Multivariate analysis indicated high LTBP2 expression was an independent prognostic factor. CONCLUSIONS: The present analysis suggested that LTBP2 may have significant association with survival of patients with cancer. High LTBP2 expression was an independent prognostic factor and indicated poor survival.


Asunto(s)
Neoplasias , Biomarcadores de Tumor/metabolismo , Humanos , Proteínas de Unión a TGF-beta Latente , Pronóstico , Modelos de Riesgos Proporcionales , Tasa de Supervivencia
18.
Acta Orthop Belg ; 88(1): 73-85, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35512157

RESUMEN

The evidence for the functional outcome of endo- prosthetic replacement (EPR) after tumour resection has been from few cohort studies. A scoping search revealed no systematic review on patient reported outcome measures after EPR around the knee. The purpose of this study was to evaluate the functional outcome of distal femoral and proximal tibial EPR after tumour resection. A systematic review was conducted using the PRISMA guidelines. The search identified 2560 articles from MEDLINE, EMBASE, CINAHL, and Web of Science. 36 studies satisfying the selection criteria were included for data synthesis. Pooled analysis was performed for homogenous studies. Narrative synthesis was performed for all the studies due to heterogeneity in methodological and statistical analysis. Amongst the overall patient population of 2930, mean ages ranged from 18-66 years and the mean follow up periods in the studies ranged from 12 - 180 months. The weighted mean functional outcome was similar for patients who had DFEPR and PTEPR. The functional outcome scores of Rotating Hinge Knee implants (RHK) were significantly greater than that for Fixed Hinge Knee implants (FHK). The weighted mean functional outcome scores were higher after cemented fixation and after primary EPR procedures. The current evidence suggests that functional out- come after EPR in the knee is good, and RHK implants are better than FHK implants. Functional outcome after primary EPR was significantly better than following revision EPR, and this underscores the importance of minimising complications at the primary surgery.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Neoplasias , Artroplastia de Reemplazo de Rodilla/métodos , Preescolar , Humanos , Lactante , Articulación de la Rodilla/cirugía , Prótesis de la Rodilla/efectos adversos , Falla de Prótesis , Reoperación/métodos , Resultado del Tratamiento
19.
Inquiry ; 59: 469580221098754, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35502985

RESUMEN

The Youth and Young Adults Cancer Knowledge Attitudes and Practices (C-KAP) exploratory study in 2 rural underserved areas in a border community. C-KAP is an interdisciplinary research pilot project led by university scholars in psychology and social work in partnership with community partners. The exploratory cross-sectional mix-method study recruited 141 (n=141) youth and young adults (ages 18-39). This study was informed on empirical research and a bilingual online questionnaire was field-tested, and data was collected via QuestionPro Software. Quantitative analysis was conducted using SPSS version 27. Descriptive statistics and frequency analysis were used for demographics and basic statistics. Chi square tests and Fisher's exact tests between variables were ran to find statistically significant associations. For the qualitative data, independent coders conducted recurrent content analysis to identify themes. Salient themes include knowledge about cancer types; access to health care; prevention; and the perceived impact of COVID-19 pandemic. Findings highlight a lack of knowledge and orientation on cancer in youth and young adults suggesting the need for community tailored education and screening interventions. Other findings reflect gender differences in knowledge and practices, which indicates that a gender-specific lens is needed when delivering education.


Asunto(s)
COVID-19 , Neoplasias , Adolescente , Adulto , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Humanos , Pandemias , Proyectos Piloto , Población Rural , Encuestas y Cuestionarios , Texas , Adulto Joven
20.
Elife ; 112022 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-35503721

RESUMEN

Genotoxic agents remain the mainstay of cancer treatment. Unfortunately, the clinical benefits are often countered by a rapid tumor adaptive response. Here, we report that the oncoprotein B cell lymphoma 6 (BCL6) is a core component that confers solid tumor adaptive resistance to genotoxic stress. Multiple genotoxic agents promoted BCL6 transactivation, which was positively correlated with a weakened therapeutic efficacy and a worse clinical outcome. Mechanistically, we discovered that treatment with the genotoxic agent etoposide led to the transcriptional reprogramming of multiple pro-inflammatory cytokines, among which the interferon-α and interferon-γ responses were substantially enriched in resistant cells. Our results further revealed that the activation of interferon/signal transducer and activator of transcription 1 axis directly upregulated BCL6 expression. The increased expression of BCL6 further repressed the tumor suppressor PTEN and consequently enabled resistant cancer cell survival. Accordingly, targeted inhibition of BCL6 remarkably enhanced etoposide-triggered DNA damage and apoptosis both in vitro and in vivo. Our findings highlight the importance of BCL6 signaling in conquering solid tumor tolerance to genotoxic stress, further establishing a rationale for a combined approach with genotoxic agents and BCL6-targeted therapy.


Asunto(s)
Daño del ADN , Neoplasias , Línea Celular Tumoral , Etopósido/farmacología , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Proteínas Oncogénicas/genética , Proteínas Proto-Oncogénicas c-bcl-6/genética , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...