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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
3.
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
4.
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
5.
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
6.
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
7.
Biomater Adv ; 138: 212919, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35913232

RESUMEN

Photothermal therapy (PTT) usually causes hyperthermia and damages healthy tissues. Developing a PTT platform with enhanced therapeutic effects and reduced side effects to normal tissues attracts increasing attention. Herein, we developed a multifunctional theranostic nanoplatform using poly(lactic-co-glycolic acid) (PLGA) loaded with near-infrared (NIR) photothermal agent (new indocyanine green IR820), fluorescence imaging agent (ZnCdSe/ZnS quantum dots, QDs) and autophagy inhibitor (chloroquine, CQ). These PLGA/IR820/Fluorescence imaging agent/CQ co-loading nanoparticles (termed PIFC NPs) displayed photothermal effects, enhanced the stability of IR820 in vivo, and enabled QDs to have stable fluorescent signals in vitro and in vivo. The PIFC NPs with particle size around 240 nm aggregated to tumor sites through the high permeability and retention effects of solid tumors. The intracellular delivery of CQ molecules through PIFC NPs significantly attenuated the degradation of autophagic lysosomes in tumor cells and effectively inhibited the autophagy mediated repair of photothermal damaged cells. Under milder NIR irradiation conditions, PIFC NPs exhibited high antitumor effect. By regulating autophagy, PTT can be effectively sensitized, which will provide a new idea for future cancer treatment research.


Asunto(s)
Hipertermia Inducida , Neoplasias , Autofagia , Humanos , Neoplasias/terapia , Fototerapia/métodos , Terapia Fototérmica , Medicina de Precisión
8.
Biomater Adv ; 138: 212938, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35913234

RESUMEN

Photothermal nanoparticles are important in photothermal therapy. Combining different nanoparticles can achieve a high photothermal capacity. In this study, composite nanoparticles composed of black phosphorus nanosheets (BPNSs) and gold nanostars (BP-AuNSs) were synthesized by using BPNSs as the reductant. AuNSs were deposited on the BPNSs. The BP-AuNSs were further hybridized with porous gelatin scaffolds to prepare gelatin-BP-AuNS composite scaffolds. The gelatin-BP-AuNS composite scaffolds promoted cell migration and distribution. The synergistic effects of the BPNSs and AuNSs endowed the gelatin-BP-AuNS composite scaffolds with excellent photothermal properties. The gelatin-BP-AuNS composite scaffolds eliminated cancer cells after near infrared laser exposure and supported the adipogenic differentiation of human mesenchymal stem cells. Thus, this gelatin-BP-AuNS composite scaffold holds promise for breast cancer therapy.


Asunto(s)
Gelatina , Neoplasias , Diferenciación Celular , Oro , Humanos , Neoplasias/terapia , Fósforo , Células Madre
9.
Biomater Adv ; 138: 212867, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35913249

RESUMEN

Radiotherapy (RT) is frequently utilized for cancer treatment in clinical practice and has been proved to have immune stimulation potency in recent years. However, its inhibitory effect on tumor growth, especially on tumor metastasis, is still limited by many factors, including the complex tumor microenvironment (TME). Therefore, the TME - regulating SiO2@MnO2 nanoparticles (SM NPs) were prepared and applied to the combination of RT and immunotherapy. In a bilateral animal model, SM NPs not only enhanced the inhibitory effect of RT on primary tumor growth, but also strengthened the abscopal effect to inhibit the growth of distant untreated tumors. As for the distant untreated tumor, 40% of mice showed complete inhibition of tumor growth and 40% showed a suppressed tumor growth. Moreover, SM NPs showed modulation functions for TME through inducing the increase in intracellular levels of oxygen and reactive oxygen species after their reaction with hydrogen peroxide and the main antioxidative agent glutathione in TME. Lastly, SM NPs also effectively induced the increase in the amounts of cytokines secreted by macrophage - like cells, indicating modulation functions for immune responses. This work highlighted a potential strategy of simultaneously inhibiting tumor growth and metastasis through the regulation of TME and immune responses by SM NPs - enhanced radio - immunotherapy.


Asunto(s)
Neoplasias , Microambiente Tumoral , Animales , Inmunoterapia , Compuestos de Manganeso/farmacología , Ratones , Neoplasias/radioterapia , Óxidos/farmacología , Dióxido de Silicio/farmacología
10.
Biomater Adv ; 138: 212935, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35913256

RESUMEN

Parthenolide (PTL), a germacrane sesquiterpene lactone extracted from the "Yin" Chinese traditional herb feverfew, has gained interest due to its lethal effects on tumor cells and its pharmacological effects within traditional Chinese medicine theory. To overcome low, non-targeted accumulation and uncontrolled release of PTL administration, a dual-responsive PTL-liposomes@chitosan@gold nanoshells (PTL-Lips@CS@GNS) system was fabricated. Hyperthermia generated under light irradiation in the near-infrared region via local surface plasmon resonance of gold nanoshells induced photothermal therapy, which also stimulated PTL release due to the liposomes gel-to-liquid crystalline phase transition. Additionally, PTL-Lips@CS@GNS exhibited a pH-responsive release in the acidic tumor microenvironment. Collectively, this study provides a realistic strategy for an effective combination of traditional Chinese medicine and current nanotechnology for tumor therapy.


Asunto(s)
Antineoplásicos , Hipertermia Inducida , Neoplasias , Antineoplásicos/farmacología , Oro/química , Humanos , Liposomas/química , Fototerapia , Sesquiterpenos , Microambiente Tumoral
11.
Cancer Epidemiol Biomarkers Prev ; 31(8): 1517-1520, 2022 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-35916602

RESUMEN

The effectiveness and efficiency of cancer screening in real-world settings depend on many factors, including test sensitivity and specificity. Outside of select experimental studies, not everyone receives a gold standard test that can serve as a comparator in estimating screening test accuracy. Thus, many studies of screening test accuracy use the passage of time to infer whether or not cancer was present at the time of the screening test, particularly for patients with a negative screening test. We define the accuracy assessment interval as the period of time after a screening test that is used to estimate the test's accuracy. We describe how the length of this interval may bias sensitivity and specificity estimates. We call for future research to quantify bias and uncertainty in accuracy estimates and to provide guidance on setting accuracy assessment interval lengths for different cancers and screening modalities.


Asunto(s)
Detección Precoz del Cáncer , Neoplasias , Sesgo , Humanos , Tamizaje Masivo , Neoplasias/diagnóstico , Aceptación de la Atención de Salud , Sensibilidad y Especificidad
13.
Eur Rev Med Pharmacol Sci ; 26(14): 4997-5007, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35916796

RESUMEN

OBJECTIVE: Considering the impact of mental illness and cancer on the society, the relationship between the two diseases should be assessed. This study aimed at determining the association between mental illness and cancer. MATERIALS AND METHODS: The Embase and Medline databases were searched on October 21, 2020. Cohort, case-control, and cross-sectional studies were eligible for study inclusion. The Newcastle-Ottawa scale was used to qualitatively assess the risk of bias. Funnel plots were drawn to evaluate the risks of bias across the included studies. RESULTS: We included 58 studies from 16 countries, incorporating approximately 30 national databases and 25 million individuals. Patients with psychiatric disorders did not show an increased risk of developing cancer. However, patients with cancer had a significantly increased risk of developing mental illness. The survival rates of patients with mental illness according to cancer occurrence and patients with cancer according to mental illness occurrence were significantly decreased. CONCLUSIONS: Clinicians should conduct early screening to ensure that appropriate interventions for mental illness are administered in patients with cancer. Due to the high incidence of death in patients with mental illnesses due to unnatural causes, such as suicide, homicide, and accidents, clinicians should be aware of the importance of the treatment and management of these patients.


Asunto(s)
Trastornos Mentales , Neoplasias , Suicidio , Estudios Transversales , Homicidio , Humanos , Trastornos Mentales/epidemiología , Neoplasias/epidemiología
14.
JCO Clin Cancer Inform ; 6: e2200006, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35917480

RESUMEN

PURPOSE: The advancement of natural language processing (NLP) has promoted the use of detailed textual data in electronic health records (EHRs) to support cancer research and to facilitate patient care. In this review, we aim to assess EHR for cancer research and patient care by using the Minimal Common Oncology Data Elements (mCODE), which is a community-driven effort to define a minimal set of data elements for cancer research and practice. Specifically, we aim to assess the alignment of NLP-extracted data elements with mCODE and review existing NLP methodologies for extracting said data elements. METHODS: Published literature studies were searched to retrieve cancer-related NLP articles that were written in English and published between January 2010 and September 2020 from main literature databases. After the retrieval, articles with EHRs as the data source were manually identified. A charting form was developed for relevant study analysis and used to categorize data including four main topics: metadata, EHR data and targeted cancer types, NLP methodology, and oncology data elements and standards. RESULTS: A total of 123 publications were selected finally and included in our analysis. We found that cancer research and patient care require some data elements beyond mCODE as expected. Transparency and reproductivity are not sufficient in NLP methods, and inconsistency in NLP evaluation exists. CONCLUSION: We conducted a comprehensive review of cancer NLP for research and patient care using EHRs data. Issues and barriers for wide adoption of cancer NLP were identified and discussed.


Asunto(s)
Procesamiento de Lenguaje Natural , Neoplasias , Registros Electrónicos de Salud , Humanos , Almacenamiento y Recuperación de la Información , Neoplasias/diagnóstico , Neoplasias/terapia , Atención al Paciente
15.
JCO Glob Oncol ; 8: e2200043, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35917484

RESUMEN

PURPOSE: With successive infection waves and the spread of more infectious variants, the COVID-19 pandemic continues to have major impacts on health care. To achieve best outcomes for patients with cancer during a pandemic, efforts to minimize the increased risk of severe pandemic infection must be carefully balanced against unintended adverse impacts of the pandemic on cancer care, with consideration to available health system capacity. Cancer Australia's conceptual framework for cancer care during a pandemic provides a planning resource for health services and policy-makers that can be broadly applied globally and to similar pandemics. METHODS: Evidence on the impact of the COVID-19 pandemic on cancer care and health system capacity to June 2021 was reviewed, and the conceptual framework was developed and updated. RESULTS: Components of health system capacity vary during a pandemic, and capacity relative to pandemic numbers and severity affects resources available for cancer care delivery. The challenges of successive pandemic waves and high numbers of pandemic cases necessitate consideration of changing health system capacity in decision making about cancer care. Cancer Australia's conceptual framework provides guidance on continuation of care across the cancer pathway, in the face of challenges to health systems, while minimizing infection risk for patients with cancer and unintended consequences of delays in screening, diagnosis, and cancer treatment and backlogs because of service interruption. CONCLUSION: Evidence from the COVID-19 pandemic supports continuation of cancer care wherever possible during similar pandemics. Cancer Australia's conceptual framework, underpinned by principles for optimal cancer care, informs decision making across the cancer care continuum. It incorporates consideration of changes in health system capacity and capacity for cancer care, in relation to pandemic progression, enabling broad applicability to different global settings.


Asunto(s)
COVID-19 , Neoplasias , Atención a la Salud , Programas de Gobierno , Humanos , Neoplasias/terapia , Pandemias/prevención & control , SARS-CoV-2
16.
Acad Med ; 97(8): 1160-1163, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-35917543

RESUMEN

PROBLEM: Students eager to enter the medical field must develop perspective-taking skills that enhance their ability to connect with patients. Toward this goal, the authors developed a pilot workshop for undergraduate students that included an art activity during which they collaborated to design scalp tattoos to symbolize cancer patients' experiences with chemotherapy and hair loss. APPROACH: A 90-minute, arts-based workshop was held in April 2019. One author selected anonymous excerpts from previously conducted interviews with patients experiencing ovarian and uterine cancer. These excerpts were shared with students to humanize patients' perspectives and give context to the difficulty of coping with chemotherapy-induced alopecia. Students discussed these excerpts and images of scalp tattoos from the internet. Together, they then designed scalp tattoos representing their perspective on the experience of coping with chemotherapy and hair loss and drew them onto mannequin heads. OUTCOMES: Twenty members of the university community participated in this workshop, including 3 faculty members and 17 undergraduate students. Participants worked together to create 2 sets of scalp tattoos. Of the 20 participants, 75% (n = 15) responded to the postworkshop survey. All respondents were undergraduate students, and 73% (n = 11) reported an increase in empathy toward patients and 87% (n = 13) an increased connection with the patient experience. All respondents agreed that the art activity demonstrated the importance of taking the patient's perspective. NEXT STEPS: This arts-based workshop is effective and can be replicated for other audiences, including undergraduate students, medical students, and practicing clinicians, to encourage perspective-taking and compassion for patients. Further analysis of students' skill development using pre- and postworkshop data is needed.


Asunto(s)
Neoplasias , Estudiantes de Medicina , Tatuaje , Alopecia/inducido químicamente , Humanos , Neoplasias/tratamiento farmacológico , Cuero Cabelludo , Tatuaje/efectos adversos
17.
PLoS One ; 17(8): e0272740, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35930603

RESUMEN

Uninsured or underinsured individuals with cancer are likely to experience financial hardship, including forgoing healthcare or non-healthcare needs such as food, housing, or utilities. This study evaluates the association between health insurance coverage and financial hardship among cancer survivors during the COVID-19 pandemic. This cross-sectional analysis used Patient Advocate Foundation (PAF) survey data from May to July 2020. Cancer survivors who previously received case management or financial aid from PAF self-reported challenges paying for healthcare and non-healthcare needs during the COVID-19 pandemic. Associations between insurance coverage and payment challenges were estimated using Poisson regression with robust standard errors, which allowed for estimation of adjusted relative risks (aRR). Of 1,437 respondents, 74% had annual household incomes <$48,000. Most respondents were enrolled in Medicare (48%), 22% in employer-sponsored insurance, 13% in Medicaid, 6% in an Affordable Care Act (ACA) plan, and 3% were uninsured. Approximately 31% of respondents reported trouble paying for healthcare during the COVID-19 pandemic. Respondents who were uninsured (aRR 2.58, 95% confidence interval [CI] 1.83-3.64), enrolled in an ACA plan (aRR 1.86, 95% CI 1.28-2.72), employer-sponsored insurance (aRR 1.70, 95% CI 1.23-2.34), or Medicare (aRR 1.49, 95% CI 1.09-2.03) had higher risk of trouble paying for healthcare compared to Medicaid enrollees. Challenges paying for non-healthcare needs were reported by 57% of respondents, with 40% reporting trouble paying for food, 31% housing, 28% transportation, and 20% internet. In adjusted models, Medicare and employer-sponsored insurance enrollees were less likely to have difficulties paying for non-healthcare needs compared to Medicaid beneficiaries. Despite 97% of our cancer survivor sample being insured, 31% and 57% reported trouble paying for healthcare and non-healthcare needs during the COVID-19 pandemic, respectively. Greater attention to both medical and non-medical financial burden is needed given the economic pressures of the COVID-19 pandemic.


Asunto(s)
COVID-19 , Supervivientes de Cáncer , Neoplasias , Anciano , COVID-19/epidemiología , Estudios Transversales , Estrés Financiero/epidemiología , Humanos , Cobertura del Seguro , Seguro de Salud , Pacientes no Asegurados , Medicare , Neoplasias/epidemiología , Pandemias , Patient Protection and Affordable Care Act , Estados Unidos/epidemiología
18.
Sci Immunol ; 7(74): eabj9123, 2022 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-35930654

RESUMEN

Response rates to immunotherapy in solid tumors remain low due in part to the elevated prevalence of terminally exhausted T cells, a hypofunctional differentiation state induced through persistent antigen and stress signaling. However, the mechanisms promoting progression to terminal exhaustion in the tumor remain undefined. Using the low-input chromatin immunoprecipitation sequencing method CUT&RUN, we profiled the histone modification landscape of tumor-infiltrating CD8+ T cells throughout differentiation. We found that terminally exhausted T cells had unexpected chromatin features that limit their transcriptional potential. Terminally exhausted T cells had a substantial fraction of active chromatin, including active enhancers enriched for bZIP/AP-1 transcription factor motifs that lacked correlated gene expression, which was restored by immunotherapeutic costimulatory signaling. Reduced transcriptional potential was also driven by an increase in histone bivalency, which we linked directly to hypoxia exposure. Enforced expression of the hypoxia-insensitive histone demethylase Kdm6b was sufficient to overcome hypoxia, increase function, and promote antitumor immunity. Our study reveals the specific epigenetic changes mediated by histone modifications during T cell differentiation that support exhaustion in cancer, highlighting that their altered function is driven by improper costimulatory signals and environmental factors. These data suggest that even terminally exhausted T cells may remain competent for transcription in settings of increased costimulatory signaling and reduced hypoxia.


Asunto(s)
Cromatina , Neoplasias , Linfocitos T CD8-positivos , Cromatina/metabolismo , Histonas/metabolismo , Humanos , Hipoxia/metabolismo , Histona Demetilasas con Dominio de Jumonji/metabolismo , Microambiente Tumoral
19.
Nat Commun ; 13(1): 4553, 2022 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-35931666

RESUMEN

Combining immune checkpoint blockade (ICB) therapy with photodynamic therapy (PDT) holds great potential in treating immunologically "cold" tumors, but photo-generated reactive oxygen species (ROS) can inevitably damage co-administered ICB antibodies, hence hampering the therapeutic outcome. Here we create a ROS-responsive hydrogel to realize the sustained co-delivery of photosensitizers and ICB antibodies. During PDT, the hydrogel skeleton poly(deca-4,6-diynedioic acid) (PDDA) protects ICB antibodies by scavenging the harmful ROS, and at the same time, triggers the gradual degradation of the hydrogel to release the drugs in a controlled manner. More interestingly, we can visualize the ROS-responsive hydrogel degradation by Raman imaging, given the ultrastrong and degradation-correlative Raman signal of PDDA in the cellular silent window. A single administration of the hydrogel not only completely inhibits the long-term postoperative recurrence and metastasis of 4T1-tumor-bearing mice, but also effectively restrains the growth of re-challenged tumors. The PDDA-based ROS-responsive hydrogel herein paves a promising way for the durable synergy of PDT and ICB therapy.


Asunto(s)
Neoplasias , Fotoquimioterapia , Animales , Línea Celular Tumoral , Hidrogeles , Ratones , Neoplasias/tratamiento farmacológico , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo
20.
Sci Rep ; 12(1): 13480, 2022 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-35931709

RESUMEN

Bioengineered MS1 silk is derived from major ampullate spidroin 1 (MaSp1) from the spider Nephila clavipes. The MS1 silk was functionalized with the H2.1 peptide to target Her2-overexpressing cancer cells. The immunogenic potential of drug carriers made from MS1-type silks was investigated. The silk spheres were administered to healthy mice, and then (i) the phenotypes of the immune cells that infiltrated the Matrigel plugs containing spheres (implanted subcutaneously), (ii) the presence of silk-specific antibodies (after two intravenous injections of the spheres), (iii) the splenocyte phenotypes and their activity after restimulation ex vivo in terms of proliferation and cytokine secretion (after single intravenous injection of the spheres) were analyzed. Although the immunogenicity of MS1 particles was minor, the H2.1MS1 spheres attracted higher levels of B lymphocytes, induced a higher anti-silk antibody titer, and, after ex vivo restimulation, caused the activation of splenocytes to proliferate and express more IFN-γ and IL-10 compared with the PBS and MS1 groups. Although the H2.1MS1 spheres triggered a certain degree of an immunological response, multiple injections (up to six times) neither hampered the carrier-dependent specific drug delivery nor induced toxicity, as previously indicated in a mouse breast cancer model. Both findings indicate that a drug delivery system based on MS1-type silk has great potential for the treatment of cancer and other conditions.


Asunto(s)
Fibroínas , Neoplasias , Arañas , Animales , Ingeniería Biomédica , Portadores de Fármacos/farmacología , Sistemas de Liberación de Medicamentos , Inmunidad , Ratones , Neoplasias/tratamiento farmacológico
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