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1.
Support Care Cancer ; 32(6): 329, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709308

RESUMO

BACKGROUND: Psychological distress is a prevalent unpleasant experience faced by many cancer patients. However, the psychological distress among gastrointestinal (GI) cancer patients is scarcely explored. Moreover, the association between psychological distress and quality of life in different genders has yet to be explored. AIMS: To explore the psychological distress among GI cancer patients and examine its association with quality of life among different genders. METHODS: This study was a cross-sectional study. A total of 237 gastrointestinal cancer patients completed the distress thermometer and the Functional Assessment of Chronic Illness Therapy-General. RESULTS: The mean score of psychological distress of the participants was 3.04 (SD = 2.90). A greater proportion of female gastrointestinal cancer patients (52.8%) had clinically relevant psychological distress compared to males (35.9%). The quality of life was negatively associated with their psychological distress (B = - 1.502, 95%CI: - 2.759 to - 0.245, p = 0.019) among gastrointestinal cancer patients. Such association was stronger among males compared to females in gastrointestinal cancer patients (Interaction term, B = - 1.713, 95%CI: - 3.123 to - 0.303, p = 0.017). CONCLUSIONS: These findings suggest that healthcare providers should attach their attention to gastrointestinal cancer patients' psychological distress, especially females. Longitudinal studies could adopted to track the changes in psychological distress and its association with quality of life over time among different genders. In future intervention studies, the focus of psychological interventions needs to be gender-specific.


Assuntos
Neoplasias Gastrointestinais , Angústia Psicológica , Qualidade de Vida , Humanos , Masculino , Neoplasias Gastrointestinais/psicologia , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Fatores Sexuais , Idoso , Adulto , Estresse Psicológico/epidemiologia , Estresse Psicológico/etiologia , Estresse Psicológico/psicologia , Inquéritos e Questionários
2.
Biochemistry ; 62(6): 1138-1144, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36821831

RESUMO

Poly-ADP-ribose (PAR) is a natural type of polymer derived from enzymatic reactions catalyzed by cellular poly(ADP-ribose) polymerases (PARPs). Given its notable solubility and biocompatibility, the PAR polymer may function as effective carriers for therapeutics in addition to modulating biomolecular interactions in cells. To explore its therapeutic potential, we herein developed a PAR polymer-based bispecific antibody targeting both human epidermal growth factor receptor 2 (HER2) and T-cell CD3 antigens. This was accomplished by conjugating anti-HER2 and anti-CD3 monoclonal antibodies to azido-functionalized PAR polymers through click chemistry. The generated PAR polymer-anti-HER2/anti-CD3 antibody conjugate could not only bind specifically to both HER2- and CD3-expressing target cells but also display potent cytotoxicity against HER2-positive breast cancer cells in the presence of non-activated human peripheral blood mononuclear cells (PBMCs). Functionalized PAR polymers provide a new strategy for synthesizing bispecific antibodies and may enable generation of PAR polymer-based conjugates with unique pharmacological activities for biomedical applications.


Assuntos
Anticorpos Biespecíficos , Poli Adenosina Difosfato Ribose , Humanos , Poli Adenosina Difosfato Ribose/metabolismo , Polímeros , Leucócitos Mononucleares , Poli(ADP-Ribose) Polimerases/metabolismo
3.
Support Care Cancer ; 31(4): 243, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36977842

RESUMO

PURPOSE: Spiritual well-being is a critical element of individuals' quality of life and is overestimated by healthcare providers. A body of evidence is conducted on the spiritual well-being of cancer patients, but few on gastrointestinal (GI) cancer patients, which constitute a great proportion of the cancer burden. This study aimed to investigate the spiritual well-being of GI cancer patients and its association with hope and meaning in life. METHODS: A cross-sectional study was conducted. A total of 237 GI cancer patients were recruited in this study by convenience sampling in 2022. All the participants completed the sociodemographic and clinical characteristics, Functional Assessment of Chronic Illness Therapy-Spiritual Wellbeing, Herth Hope Index, and Meaning in Life Questionnaire. Multiple linear regression analysis was conducted to explore the associated factors with spiritual well-being. RESULTS: The GI cancer patients experience a relatively low level of spiritual well-being (mean = 31.54, SD = 9.84). The presence of meaning (B = 0.847, 95% CI [0.640, 1.054], p < 0.001), inner positive readiness and expectancy (B = 1.033, 95% CI [0.548, 1.518], p < 0.001), residence (B = 2.828, 95% CI [1.045, 4.612], p = 0.002), and search for meaning (B = 0.247, 95% CI [0.072, 0.422], p = 0.006) were associated with the spiritual well-being of GI cancer patients. These four associated variables accounted for 57.8% of the variance in spiritual well-being (F = 81.969, p < 0.001). CONCLUSION: The spiritual well-being of GI cancer patients was relatively low and associated with the presence of meaning, inner positive readiness and expectancy, residence, and search for meaning. Healthcare professionals may consider improving GI patients' spiritual well-being by enhancing their sense of meaning in life and inner positive readiness and expectancy.


Assuntos
Neoplasias Gastrointestinais , Neoplasias , Humanos , Espiritualidade , Estudos Transversais , Qualidade de Vida , Inquéritos e Questionários
4.
Mol Ther ; 30(9): 3066-3077, 2022 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-35746867

RESUMO

Exosomes are cell-derived nanovesicles involved in regulating intercellular communications. In contrast to conventional nanomedicines, exosomes are characterized by unique advantages for therapeutic development. Despite their major successes in drug delivery, the full potential of exosomes for immunotherapy remains untapped. Herein we designed genetically engineered exosomes featured with surfaced-displayed antibody targeting groups and immunomodulatory proteins. Through genetic fusions with exosomal membrane proteins, Expi293F cell-derived exosomes were armed with monoclonal antibodies specific for human T-cell CD3 and epidermal growth factor receptor (EGFR) as well as immune checkpoint modulators, programmed death 1 (PD-1) and OX40 ligand (OX40L). The resulting genetically engineered multifunctional immune-modulating exosomes (GEMINI-Exos) can not only redirect and activate T cells toward killing EGFR-positive triple negative breast cancer (TNBC) cells but also elicit robust anti-cancer immunity, giving rise to highly potent inhibition against established TNBC tumors in mice. GEMINI-Exos represent candidate agents for immunotherapy and may offer a general strategy for generating exosome-based immunotherapeutics with desired functions and properties.


Assuntos
Antineoplásicos Imunológicos , Exossomos , Neoplasias de Mama Triplo Negativas , Animais , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Receptores ErbB/genética , Receptores ErbB/metabolismo , Exossomos/metabolismo , Humanos , Imunoterapia , Camundongos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapia
5.
Ecotoxicol Environ Saf ; 259: 115023, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37201425

RESUMO

In highly intensive greenhouse vegetable production, soil acidification was caused by excessive fertilization, increasing cadmium (Cd) concentrations in the vegetables, which bears environmental hazards and is a negative influence on vegetables and humans. Transglutaminases (TGases), a central mediator for certain physiological effects of polyamines (PAs) in the plant kingdom, play important roles in plant development and stress response. Despite increased research on the crucial role of TGase in protecting against environmental stresses, relatively little is known about the mechanisms of Cd tolerance. In this study, we found, TGase activity and transcript level, which was upregulated by Cd, and TGase-induced Cd tolerance related to endogenous bound PAs increase and formation of nitric oxide (NO). Plant growth of tgase mutants was hypersensitive to Cd, chemical complementation by putrescine, sodium nitroprusside (SNP, nitric oxide donor) or gain of function TGase experiments restore Cd tolerance. α-diflouromethylornithine (DFMO, a selective ODC inhibitor) and 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO, NO scavenger), were respectively found declined drastically endogenous bound PA and NO content in TGase overexpression plants. Likewise, we reported that TGase interacted with polyamine uptake protein 3 (Put3), and the silencing of Put3 largely reduced TGase-induced Cd tolerance and bound PAs formation. This salvage strategy depends on TGase-regulated synthesis of bound PAs and NO that is able to positively increase the concentration of thiol and phytochelatins, elevate Cd in the cell wall, as well as induce the levels of expression Cd uptake and transport genes. Collectively, these findings indicate that TGase-mediated enhanced levels of bound PA and NO acts as a vital mechanism to protect the plant from Cd-caused toxicity.


Assuntos
Óxido Nítrico , Solanum lycopersicum , Cádmio/toxicidade , Cádmio/metabolismo , Parede Celular/metabolismo , Óxido Nítrico/metabolismo , Fitoquelatinas , Plantas/metabolismo , Poliaminas/farmacologia , Solanum lycopersicum/genética
6.
BMC Nurs ; 22(1): 140, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37101145

RESUMO

OBJECTIVES: Many factors are related to oncology nurses' professional values. However, the evidence on the relevance of professional values among oncology nurses in China remains sparse. This study aims to investigate the relationship between depression, self-efficacy, and professional values among Chinese oncology nurses and analyze the mediating effect of self-efficacy on this association. METHODS: It was a multicenter cross-sectional study designed with the STROBE guidelines. An anonymous online questionnaire recruited 2530 oncology nurses from 55 hospitals in six provinces of China between March and June 2021. Measures included self-designed sociodemographic and fully validated instruments. Pearson correlation analysis was employed to explore the associations between depression, self-efficacy, and professional values. Bootstrapping analysis by the PROCESS macro was used to examine the mediating effect of self-efficacy. RESULTS: The total scores of depression, self-efficacy, and professional values of Chinese oncology nurses were 52.75 ± 12.62, 28.39 ± 6.33, and 101.55 ± 20.43, respectively. About 55.2% of Chinese oncology nurses were depressed. Chinese oncology nurses' professional values were generally intermediate. Their professional values were negatively related to depression and positively correlated with self-efficacy, while depression was negatively related to self-efficacy. Moreover, self-efficacy partially mediated the relationship between depression and professional values, accounting for 24.8% of the total effect. CONCLUSIONS: Depression negatively predicts self-efficacy and professional values, and self-efficacy positively predicts professional values. Meanwhile, depression in Chinese oncology nurses has an indirect effect on their professional values through self-efficacy. Nursing managers and oncology nurses themselves should develop strategies aimed at relieving depression and improving self-efficacy to strengthen their positive professional values.

7.
Biomacromolecules ; 23(12): 5267-5272, 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36350184

RESUMO

Poly-ADP-ribose (PAR) is a naturally occurring form of polymers synthesized through enzymatic reactions catalyzed by poly(ADP-ribose) polymerases (PARPs). It is known for regulating various important cellular signaling pathways and processes. As a water soluble and biocompatible type of polymer, PAR may hold promise for safe and efficient delivery of therapeutics. To explore the therapeutic potential of PAR polymers, we herein generate PAR polymers conjugated with human granulocyte colony-stimulating factor (GCSF) protein by harnessing human PARP1-catalyzed auto-poly-ADP-ribosylation and a clickable analogue of nicotinamide adenine dinucleotide (NAD+). The resulting PAR polymer-based conjugate with multivalent GCSF ligands exhibits a potent cell proliferative activity. Notably, mice treated with a single dose of the PAR polymer-GCSF conjugate show sustained high levels of neutrophil in blood for 11 days, demonstrating excellent in vivo efficacy. Functionalized PAR polymers may provide new scaffolds for conjugating with therapeutic proteins or peptides toward improved pharmacological activities.


Assuntos
Poli Adenosina Difosfato Ribose , Polímeros , Humanos , Camundongos , Animais , Poli Adenosina Difosfato Ribose/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , NAD/metabolismo , Fator Estimulador de Colônias de Granulócitos/farmacologia
8.
Support Care Cancer ; 30(10): 8441-8453, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35633413

RESUMO

PURPOSE: Family caregivers of palliative cancer patients experience various supportive care needs. Appropriate self-reported instruments with robust psychological properties are required to identify these needs of family caregivers. Therefore, we conducted a systematic review to identify self-reported supportive care needs assessment instruments for family caregivers of palliative cancer patients and assess their contents, psychometric properties, and applicability. METHODS: Systematic searches were conducted in six English databases and four Chinese databases from inception to October 2020 and updated in June 2021. The instruments identified were evaluated using an 18-item checklist consisting of six domains: conceptual model, content validity, reliability, construct validity, scoring and interpretation, and respondent burden and presentation. RESULTS: Six articles, describing four self-reported needs assessment instruments, were included in the review. These instruments varied significantly in terms of contents, constructs, scoring methods, and applicability. Three of these instruments were developed to assess the comprehensive supportive care needs of family caregivers, while one was specifically developed to assess the spiritual needs of family caregivers. With respect to psychometric properties, none of the instruments identified met all the criteria. Three major shortcomings were identified, namely, lack of longitudinal validity, lack of a strategy for interpreting missing data, and lack of a description of the literacy level required to understand the questions. Additionally, the instrument development processes assessed in this study lacked qualitative elements. CONCLUSIONS: End-users need to consider contents, psychometric properties, and applicability when choosing an appropriate needs assessment instrument according to individual purpose and context. Further evaluation or development of needs assessment for the family caregivers of palliative cancer patients is needed, with a particular emphasis on caregivers' perspectives.


Assuntos
Neoplasias , Cuidados Paliativos , Cuidadores/psicologia , Humanos , Avaliação das Necessidades , Neoplasias/psicologia , Neoplasias/terapia , Cuidados Paliativos/métodos , Psicometria/métodos , Reprodutibilidade dos Testes , Inquéritos e Questionários
9.
Methods ; 177: 95-102, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31568822

RESUMO

Extracellular vesicles (EVs) have been emerging as a new class of cell-free therapy for the treatment of a variety of diseases, including cancer, tissue injuries, and inflammatory diseases. Reprograming native EVs by genetic engineering and other approaches offers an attractive prospect of extending therapeutic capabilities of EVs beyond their natural functions and properties. In this review article, we survey the state-of-the-art methods of EVs engineering and summarize major therapeutic applications of the reprogrammed EVs.


Assuntos
Engenharia Química/métodos , Sistemas de Liberação de Medicamentos/métodos , Vesículas Extracelulares/metabolismo , Inflamação/terapia , Neoplasias/terapia , Engenharia de Proteínas/métodos , Antígenos de Superfície/genética , Antígenos de Superfície/metabolismo , Sistema Livre de Células/química , Sistema Livre de Células/metabolismo , Vesículas Extracelulares/química , Vesículas Extracelulares/transplante , Expressão Gênica , Humanos , Proteína 2 de Membrana Associada ao Lisossomo/genética , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Proteínas do Leite/genética , Proteínas do Leite/metabolismo , Terapia de Alvo Molecular/métodos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Ligação Proteica , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Tetraspaninas/genética , Tetraspaninas/metabolismo
10.
Support Care Cancer ; 29(5): 2319-2326, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32914328

RESUMO

PURPOSE: This study was conducted to evaluate the effects of meaning in life and individual characteristics on dignity in patients with advanced cancer. METHODS: One hundred sixty-seven patients with advanced cancer participated in this study. Dignity was assessed with the Patient Dignity Inventory (PDI), meaning in life was assessed with the Meaning in Life Scale (MiLS), and performance status was defined as the Karnofsky Performance Status (KPS). Sociodemographic and clinical variables were also measured. Independent T tests and one-way ANOVA were performed for the PDI scores and sociodemographic and clinical variables. Relationships among the PDI, MiLS, and KPS scores were evaluated with bivariate analyses (Spearman rank correlation). A multiple linear regression analysis was conducted to determine the predictors the of PDI score. RESULTS: Patients reported a mean of 4.2 (SD 4.9) problems affecting their sense of dignity; 21.6% reported moderate to severe loss of their sense of dignity. Multivariable regression analyses revealed that a lower MiLS score, younger age, inpatient status, and a lower KPS score predicted the loss of dignity. Stepwise regression showed that 49.8% of dignity-related distress could be explained by the MiLS score, age, inpatient status, and the KPS score. CONCLUSION: Self-perceived dignity is significantly negatively associated with meaning in life, age, inpatient status, and performance status. The early recognition of risk factors for the loss of dignity and interventions to enhance meaning in life may prevent the loss of dignity in patients with advanced cancer.


Assuntos
Individualidade , Neoplasias/psicologia , Respeito , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
11.
Mol Ther ; 28(2): 536-547, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-31843452

RESUMO

Exosomes are nanosized membranous vesicles secreted by a variety of cells. Due to their unique and pharmacologically important properties, cell-derived exosome nanoparticles have drawn significant interest for drug development. By genetically modifying exosomes with two distinct types of surface-displayed monoclonal antibodies, we have developed an exosome platform termed synthetic multivalent antibodies retargeted exosome (SMART-Exo) for controlling cellular immunity. Here, we apply this approach to human epidermal growth factor receptor 2 (HER2)-expressing breast cancer by engineering exosomes through genetic display of both anti-human CD3 and anti-human HER2 antibodies, resulting in SMART-Exos dually targeting T cell CD3 and breast cancer-associated HER2 receptors. By redirecting and activating cytotoxic T cells toward attacking HER2-expressing breast cancer cells, the designed SMART-Exos exhibited highly potent and specific anti-tumor activity both in vitro and in vivo. This work demonstrates preclinical feasibility of utilizing endogenous exosomes for targeted breast cancer immunotherapy and the SMART-Exos as a broadly applicable platform technology for the development of next-generation immuno-nanomedicines.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Neoplasias da Mama/imunologia , Neoplasias da Mama/terapia , Micropartículas Derivadas de Células , Engenharia Genética , Terapia de Alvo Molecular , Animais , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Imunoterapia , Ativação Linfocitária , Camundongos , Modelos Biológicos , Nanopartículas , Receptor ErbB-2/antagonistas & inibidores , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Appl Nurs Res ; 58: 151409, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33745557

RESUMO

AIMS AND OBJECTIVES: To explore the Chinese nurses' knowledge and attitudes concerning advance care planning (ACP) and their engagement in ACP practice. BACKGROUND: Nurses' knowledge, attitude, and practice of ACP are important in promoting ACP in patients, but little is known about knowledge, attitudes, and practice of ACP among nurses in countries where there are no national policies or regulations on ACP. DESIGN: A descriptive study with a cross-sectional design. METHODS: An online questionnaire survey was distributed to Chinese nurses who attended a national conference. RESULTS: A total of 531 nurses completed the survey and were included in the final analysis. No nurses answered all questions correctly, while 31 (5.8%) answered all the survey questions wrong. The participants were most knowledgeable about the item "Once ACP is made, the content of advance directives cannot be revoked" and were least knowledgeable about the item "ACP is valid only when the patients are well informed of the medical condition". The implementation of ACP was favored by 92.5% of participants, but only 3.4% of them had actually engaged in all 5 ACP practices listed in the survey. Experience of dealing with death was positively associated with nurses' knowledge concerning ACP. The number of dying patients cared for in the past 6 months, school education of palliative care, knowledge of ACP, and age were related to engagement in the practice of ACP. CONCLUSION: Chinese nurses have supportive attitudes towards ACP, but they have limited knowledge and little practice in ACP.


Assuntos
Planejamento Antecipado de Cuidados , Enfermeiras e Enfermeiros , Atitude do Pessoal de Saúde , China , Competência Clínica , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Inquéritos e Questionários
13.
BMC Nurs ; 20(1): 38, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676508

RESUMO

BACKGROUND: Collaboration between physicians and nurses is critical. However, a limited number of studies have provided insights into the status of physician-nurse collaboration in truth disclosure. METHODS: A cross-sectional survey was conducted using an electronic questionnaire among Chinese nurses who attended a provincial conference. The Nurse-Physician Collaboration Scale was administered to nurses to assess the collaboration in truth disclosure from their perspective. A multiple-choice question was asked to assess the perceived difficulties in truth disclosure. Descriptive statistics, univariate, and multiple stepwise regression analyses were performed to evaluate physician-nurse collaboration in truth disclosure. RESULTS: A total of 287 nurses completed the survey, and 279 of them reported that they had carried out truth disclosures among patients. The average score for physician-nurse collaboration in truth disclosure was 3.98 ± 0.72. The majority of nurses (73.1-81%) responded positively to different dimensions of collaboration in truth disclosure. The results of multiple stepwise regression analysis showed that seniority (B = - 0.111, 95% confidence interval [CI] = - 0.167-- 0.055, p < 0.001) and frequency of truth disclosure (B = 0.162, 95%CI = 0.076-0.249, p < 0.001) were the only two factors associated with collaboration in truth disclosure between physicians and nurses. The most common barrier perceived by nurses was fear of patients' negative emotions or their suicide attempts after truth telling. CONCLUSIONS: Most nurses responded positively to physician-nurse collaboration in truth disclosure. Various difficulties existed in the practice of truth-telling collaboration. Further studies are required to test the potential interventions to promote cooperation between nurses and physicians in truth disclosure.

14.
J Nurs Manag ; 29(2): 326-332, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32914508

RESUMO

AIMS: To explore the spiritual care competence among nurses in mainland China and determine its relationships with their self-efficacy and personal characteristics. BACKGROUNDS: Nurses' perception of competence in spiritual care has critical effects on their own practice. Having a view of the nurses' spiritual care competence would help nurse managers recognize the weakness of spiritual practice. METHODS: A descriptive cross-sectional study using online survey methods was carried out in 2,970 Chinese nurses. Spiritual care competence scale and General Self-Efficacy Scale were used to collect the data. RESULTS: The total score of spiritual care competence scale was 58.5 (16.05). The highest score on competence was for communication (3.48 (0.97)), and the lowest was referral to professionals (2.25 (0.93)). Positive correlation was found between spiritual care competence and self-efficacy (r = .490, p < .01). Results of multiple linear regression analysis showed that self-efficacy, whether or not trained, experience of caring terminal illness patients, working experiences and first degree were the five factors associated with spiritual care competence (F = 217.425, p < .001, R2  = 26.7%). CONCLUSIONS: Nurses showed different levels of competence in various dimensions of spiritual care. Their spiritual care competence was related to self-efficacy, whether or not received training, experience of caring terminal illness patients, working experiences and first degree of nursing education. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers have to realize that it is imperative to enhance the nurses' competence to address the spiritual care needs of patients. Appropriate ways to enhance the nurses' spiritual care competence are needed so as to improve spiritual practices.


Assuntos
Enfermeiros Administradores , Terapias Espirituais , China , Estudos Transversais , Humanos , Espiritualidade , Inquéritos e Questionários
15.
Biochemistry ; 59(14): 1420-1427, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32212642

RESUMO

Cathepsin B (CTSB) is an abundant cysteine protease that functions in both endolysosomal compartments and extracellular regions. A considerable number of preclinical and clinical studies indicate that CTSB is implicated in many human diseases. Expression levels and activity of CTSB significantly correlate with disease progression and severity. Current inhibitors of CTSB are lack of adequate specificity and pharmacological activities. Through structure-guided rational design, we hereby designed and generated a humanized antibody inhibitor targeting human CTSB. This was achieved by genetically fusing the propeptide of procathepsin B, a naturally occurring inhibitor of CTSB, into heavy chain complementarity-determining region 3 (CDR3H) of Herceptin that is used in the clinic for the treatment of breast cancer. The resulting antibody-propeptide fusion displayed high specificity for inhibiting CTSB proteolytic activity at nanomolar levels. Pharmacokinetic studies in mice revealed a plasma half-life of approximately 42 h for this anti-CTSB antibody inhibitor, comparable to that of the parental Herceptin scaffold. This study demonstrates a new approach for the efficient generation of humanized antibody inhibitors with high potency and specificity for human CTSB, which may be extended to develop antibody inhibitors against other disease relevant cathepsin proteases.


Assuntos
Anticorpos/química , Catepsina B/antagonistas & inibidores , Inibidores Enzimáticos/química , Animais , Anticorpos/administração & dosagem , Anticorpos/genética , Anticorpos/metabolismo , Catepsina B/química , Catepsina B/genética , Catepsina B/metabolismo , Desenho de Fármacos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/metabolismo , Feminino , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Domínios Proteicos
16.
Support Care Cancer ; 27(9): 3403-3409, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30648209

RESUMO

PURPOSE: This study aimed to explore the associated factors of spiritual well-being among cancer patients and the relationship between spiritual well-being (SWB) and quality of life (QOL). METHODS: This cross-sectional study was conducted in 200 Chinese cancer patients in a tertiary cancer hospital. Functional Assessment of Cancer Therapy-General (FACT-G) and the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being (FACIT-Sp) were used to measure SWB and QOL levels of participants. Multiple regression analyses were performed to determine the relationship between SWB and QOL. RESULTS: The mean score of QOL was 59.8 (SD 13.1) with a range of 27-106. The mean score of SWB was 24.4 (SD 6.5), with a range of 8-48. Hospitalization frequency was the only variable associated with SWB. In terms of the relationship between SWB and QOL, the meaning and peace subscales were significantly related to overall QOL. It was also observed that the meaning subscale was positively related to social/family well-being, emotional well-being, and functional well-being. The peace subscale was related to the physical well-being, social/family well-being, and functional well-being. Faith was negatively related to physical and emotional well-being, but it had a positive effect on functional well-being. CONCLUSIONS: Given that the meaning and peace subscales are related to a higher QOL level, it is important to find ways to improve these dimensions of spiritual well-being among cancer inpatients during treatment.


Assuntos
Neoplasias/psicologia , Qualidade de Vida/psicologia , Espiritualidade , Adolescente , Adulto , Idoso , Institutos de Câncer , Doença Crônica , Estudos Transversais , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Adulto Jovem
17.
J Am Chem Soc ; 140(48): 16413-16417, 2018 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-30452238

RESUMO

Exosomes are naturally occurring membranous vesicles secreted by various types of cells. Given their unique and important biological and pharmacological properties, exosomes have been emerging as a promising form of nanomedicine acting via efficient delivery of endogenous and exogenous therapeutics. Here we explore a new concept of utilizing endogenously derived exosomes as artificial controllers of cellular immunity to redirect and activate cytotoxic T cells toward cancer cells for killing. This was achieved through genetically displaying two distinct types of antibodies on exosomal surface. The resulting synthetic multivalent antibodies retargeted exosomes (SMART-Exos), which express monoclonal antibodies specific for T-cell CD3 and cancer cell-associated epidermal growth factor receptor (EGFR), were shown to not only induce cross-linking of T cells and EGFR-expressing breast cancer cells but also elicit potent antitumor immunity both in vitro and in vivo. This proof-of-concept study demonstrates a novel application of exosomes in cancer immunotherapy and may provide a general and versatile approach for the development of a new class of cell-free therapy.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Exossomos/imunologia , Imunidade Celular/imunologia , Animais , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Antineoplásicos Imunológicos/imunologia , Complexo CD3/imunologia , Linhagem Celular Tumoral , Receptores ErbB/imunologia , Feminino , Células HEK293 , Humanos , Imunoterapia/métodos , Camundongos Endogâmicos NOD , Estudo de Prova de Conceito , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/imunologia , Linfócitos T Citotóxicos/imunologia , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/terapia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Support Care Cancer ; 26(10): 3405-3412, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29663138

RESUMO

PURPOSE: Spiritual needs are important for many patients with life-limiting illnesses. Knowledge of spiritual needs is a first step to their fulfillment; however, such knowledge is lacking for patients with cancer in mainland China. This study evaluated spiritual needs among patients with cancer in China and analyzed their associations with demographic and clinical characteristics. METHODS: A descriptive, cross-sectional study was performed. A general information questionnaire and a Chinese version of the Spiritual Needs Scale were used to collect information about patients with cancer. A total of 200 participants were recruited, and 182 completed the survey. RESULTS: The overall average spiritual needs score was 3.15. Of five dimensions investigated, the highest and lowest scores were for "hope and peace" (mean = 3.31) and "relationship with transcendence" (mean = 2.96). Of specific needs, "to be accepted," "to take responsibility for my life," and "to alleviate my suffering" (means = 3.36-3.38) were valued as most important by participants. "To talk to someone," "to pray and participate in religious rituals and services," and "to feel God with me during my struggle against disease" (means = 2.71-2.91) were considered least important. Participants' spiritual needs differed significantly according to disease stage (p < 0.001), time since diagnosis (p = 0.002), and hospitalization frequency (p = 0.004). CONCLUSIONS: The spiritual needs of patients with cancer should receive more attention in China. Effective assessment tools and procedures should be established to evaluate the spiritual needs of patients and formulate appropriate interventions at an early stage.


Assuntos
Neoplasias/psicologia , Espiritualidade , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Chemistry ; 21(46): 16547-54, 2015 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-26405808

RESUMO

Platinum anticancer drugs are particularly in need of controlled drug delivery because of their severe side effects. Platinum(IV) agents are designed as prodrugs to reduce the side effects of platinum(II) drugs; however, premature reduction could limit the effect as a prodrug. In this work, a highly biocompatible, pH and redox dual-responsive delivery system is prepared by using hybrid nanoparticles of human serum albumin (HSA) and calcium phosphate (CaP) for the Pt(IV) prodrug of cisplatin. This conjugate is very stable under extracellular conditions, so that it protects the platinum(IV) prodrug in HSA. Upon reaching the acidic and hypoxic environment, the platinum drug is released in its active form and is able to bind to the target DNA. The Pt-HSA/CaP hybrid inhibits the proliferation of various cancer cells more efficiently than cisplatin. Different cell cycle arrests suggest different cellular responses of the Pt(IV) prodrug in the CaP nanocarrier. Interestingly, this delivery system demonstrates enhanced cytotoxicity to tumor cells, but not to normal cells.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Fosfatos de Cálcio/química , Cisplatino/química , Cisplatino/farmacologia , Nanopartículas/química , Compostos Organoplatínicos/química , Compostos Organoplatínicos/farmacologia , Pró-Fármacos/química , Albumina Sérica/química , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Humanos , Oxirredução
20.
Sci Rep ; 14(1): 4009, 2024 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-38369657

RESUMO

This qualitative study aimed to gain a deep understanding of the spiritual needs of patients with advanced cancer. A qualitative study using semi-structured interviews was conducted. The interviews were audio-recorded, transcribed verbatim, and subjected to thematic analysis. Two researchers coded the interviews independently in NVivo 12 plus and developed major themes and subthemes by inductive and constant comparison. This study was conducted in the inpatient ward of a tertiary cancer hospital in Hunan Province, Chinese Mainland. Eligible participants with advanced cancer were recruited using the purposive sampling method. The sample size was determined by data saturation. All interviews were conducted face-to-face individually from May 2021 to July 2021. A total of 13 patients with advanced cancer patients were interviewed. Six themes were identified, namely being treated as normal and independent individuals, receiving and giving love, seeking inner peace, connecting with spiritual sources, finding meaning and purpose, and preparing for death. Different categories of spiritual needs of patients with advanced cancer were identified in this study. Healthcare professionals need to develop interventions that aim to meet patients' spiritual needs.


Assuntos
Neoplasias , Humanos , Neoplasias/terapia , Pessoal de Saúde , Pacientes , Pesquisa Qualitativa , China
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