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1.
Compr Child Adolesc Nurs ; : 1-19, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38995682

RESUMEN

Progression of ill health and death trajectories is different for children with a non-oncology diagnosis. As previous research has focused primarily on children with cancer diagnoses, this scoping review explored what factors influence the parent and/or child's choice of place of death for a child with a non-oncological complex care condition, when death is expected. Eighteen papers were identified considering the preferred place of death. The findings were themed into 1. Diagnostic Factors; 2. Home Factors; 3. Socio-economic Factors; 4. Parent Factors. In conclusion, informed discussions with families that recognize the reason for, and the impact of their choices, are necessary not only for the preferred place of death but also end of life care.

2.
Hum Vaccin Immunother ; 19(2): 2251839, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37814513

RESUMEN

Recently, the remarkable success of chimeric antigen receptor T cell (CAR-T) therapy in treating certain tumors has led to numerous studies exploring its potential application to treat non-oncology diseases. This review discusses the progress and evolution of CAR-T cell therapies for treating non-oncology diseases over the past 5 years. Additionally, we summarize the advantages and disadvantages of CAR-T cell therapy in treating non-oncological diseases and identify any difficulties that should be overcome. After conducting an in-depth analysis of the most recent studies on CAR-T technology, we discuss the key elements of CAR-T therapy, such as developing an effective CAR design for non-oncological diseases, controlling the rate and duration of response, and implementing safety measures to reduce toxicity. These studies provide new insights into different delivery strategies, the discovery of new target molecules, and improvements in the safety of CAR-T therapy for non-oncological diseases.


Asunto(s)
Neoplasias , Receptores Quiméricos de Antígenos , Humanos , Linfocitos T Reguladores , Neoplasias/terapia , Inmunoterapia Adoptiva/efectos adversos , Receptores de Antígenos de Linfocitos T/genética , Tratamiento Basado en Trasplante de Células y Tejidos
3.
Cancers (Basel) ; 15(20)2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37894273

RESUMEN

Background: Multidisciplinary management is crucial in cancer diagnosis and treatment. Multidisciplinary teams include specialists in surgery, medical therapies, and radiation therapy (RT), each playing unique roles in oncology care. One significant aspect is RT, guided by radiation oncologists (ROs). This paper serves as a detailed primer for non-oncologists, medical students, or non-clinical investigators, educating them on contemporary RT practices. Methods: This report follows the process of RT planning and execution. Starting from the decision-making in multidisciplinary teams to the completion of RT and subsequent patient follow-up, it aims to offer non-oncologists an understanding of the RO's work in a comprehensive manner. Results: The first step in RT is a planning session that includes obtaining a CT scan of the area to be treated, known as the CT simulation. The patients are imaged in the exact position in which they will receive treatment. The second step, which is the primary source of uncertainty, involves the delineation of treatment targets and organs at risk (OAR). The objective is to ensure precise irradiation of the target volume while sparing the OARs as much as possible. Various radiation modalities, such as external beam therapy with electrons, photons, or particles (including protons and carbon ions), as well as brachytherapy, are utilized. Within these modalities, several techniques, such as three-dimensional conformal RT, intensity-modulated RT, volumetric modulated arc therapy, scattering beam proton therapy, and intensity-modulated proton therapy, are employed to achieve optimal treatment outcomes. The RT plan development is an iterative process involving medical physicists, dosimetrists, and ROs. The complexity and time required vary, ranging from an hour to a week. Once approved, RT begins, with image-guided RT being standard practice for patient alignment. The RO manages acute toxicities during treatment and prepares a summary upon completion. There is a considerable variance in practices, with some ROs offering lifelong follow-up and managing potential late effects of treatment. Conclusions: Comprehension of RT clinical effects by non-oncologists providers significantly elevates long-term patient care quality. Hence, educating non-oncologists enhances care for RT patients, underlining this report's importance.

4.
Eur J Med Res ; 28(1): 345, 2023 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-37710280

RESUMEN

Cancer poses a significant global health challenge, with predictions of increasing prevalence in the coming years due to limited prevention, late diagnosis, and inadequate success with current therapies. In addition, the high cost of new anti-cancer drugs creates barriers in meeting the medical needs of cancer patients, especially in developing countries. The lengthy and costly process of developing novel drugs further hinders drug discovery and clinical implementation. Therefore, there has been a growing interest in repurposing approved drugs for other diseases to address the urgent need for effective cancer treatments. The aim of this comprehensive review is to provide an overview of the potential of approved non-oncology drugs as therapeutic options for cancer treatment. These drugs come from various chemotherapeutic classes, including antimalarials, antibiotics, antivirals, anti-inflammatory drugs, and antifungals, and have demonstrated significant antiproliferative, pro-apoptotic, immunomodulatory, and antimetastatic properties. A systematic review of the literature was conducted to identify relevant studies on the repurposing of approved non-oncology drugs for cancer therapy. Various electronic databases, such as PubMed, Scopus, and Google Scholar, were searched using appropriate keywords. Studies focusing on the therapeutic potential, mechanisms of action, efficacy, and clinical prospects of repurposed drugs in cancer treatment were included in the analysis. The review highlights the promising outcomes of repurposing approved non-oncology drugs for cancer therapy. Drugs belonging to different therapeutic classes have demonstrated notable antitumor effects, including inhibiting cell proliferation, promoting apoptosis, modulating the immune response, and suppressing metastasis. These findings suggest the potential of these repurposed drugs as effective therapeutic approaches in cancer treatment. Repurposing approved non-oncology drugs provides a promising strategy for addressing the urgent need for effective and accessible cancer treatments. The diverse classes of repurposed drugs, with their demonstrated antiproliferative, pro-apoptotic, immunomodulatory, and antimetastatic properties, offer new avenues for cancer therapy. Further research and clinical trials are warranted to explore the full potential of these repurposed drugs and optimize their use in treating various cancer types. Repurposing approved drugs can significantly expedite the process of identifying effective treatments and improve patient outcomes in a cost-effective manner.


Asunto(s)
Reposicionamiento de Medicamentos , Neoplasias , Humanos , Antibacterianos , Antifúngicos , Antivirales , Apoptosis , Neoplasias/tratamiento farmacológico
5.
Front Oncol ; 13: 1157366, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37274234

RESUMEN

Emerging evidence suggests that chemotherapeutic agents and targeted anticancer drugs have serious side effects on the healthy cells/tissues of the patient. To overcome this, the use of non-oncology drugs as potential cancer therapies has been gaining momentum. Herein, we investigated one non-oncology drug named meticrane (a thiazide diuretic used to treat essential hypertension), which has been reported to indescribably improve the therapeutic efficacy of anti-CTLA4 in mice with AB1 HA tumors. In our hypothesis-driven study, we tested anti-cancer potential meticrane in hematological malignance (leukemia and multiple myeloma) and liver cancer cell lines. Our analysis showed that: 1) Meticrane induced alteration in the cell viability and proliferation in leukemia cells (Jurkat and K562 cells) and liver cancer (SK-hep-1), however, no evidence of apoptosis was detectable. 2) Meticrane showed additive/synergistic effects with epigenetic inhibitors (DNMT1/5AC, HDACs/CUDC-101 and HDAC6/ACY1215). 3) A genome-wide transcriptional analysis showed that meticrane treatment induces changes in the expression of genes associated with non-cancer associated pathways. Of importance, differentially expressed genes showed favorable correlation with the survival-related genes in the cancer genome. 4) We also performed molecular docking analysis and found considerable binding affinity scores of meticrane against PD-L1, TIM-3, CD73, and HDACs. Additionally, we tested its suitability for immunotherapy against cancers, but meticrane showed no response to the cytotoxicity of cytokine-induced killer (CIK) cells. To our knowledge, our study is the first attempt to identify and experimentally confirm the anti-cancer potential of meticrane, being also the first to test the suitability of any non-oncology drug in CIK cell therapy. Beyond that, we have expressed some concerns confronted during testing meticrane that also apply to other non-oncology drugs when considered for future clinical or preclinical purposes. Taken together, meticrane is involved in some anticancer pathways that are passively targeting cancer cells and may be considered as compatible with epigenetic inhibitors.

6.
Expert Opin Ther Pat ; 33(5): 349-369, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37249104

RESUMEN

INTRODUCTION: Histone deacetylase (HDAC) inhibitors have been considered as an attractive strategy to reverse aberrant epigenetic changes associated with cancer treatments. The use of HDAC inhibitors in various cancer types has continued to develop for decades, bringing several novel HDAC inhibitors successfully into clinical trials. The combination use of HDAC inhibitors with other agents have also been developed and have demonstrated superior efficacy compared to that of monotherapy in recent studies. Hence, development of new anticancer treatment and therapeutic regimen is necessary. AREAS COVERED: This review summarizes a comprehensive review of the patent literature from 2020 to 2022 including HDAC inhibitors and their use as anticancer agents (searched from European Patent Office, 2020-2022). The approved and developing HDAC inhibitors are described. It also provides perspectives on the challenges and future opportunities. EXPERT OPINION: Although hundreds of clinical trials of HDAC inhibitors are still going on, the application for HDAC inhibitors has been limited at present . Not only in the anticancer treatment, but also non-oncology disease therapies are being investigated eagerly. Recently, applications of HDAC inhibitors in non-oncology diseases have also been revealed and proceeded to clinical trials. New indications for HDAC inhibitors are needed urgently in the future.


Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Patentes como Asunto , Neoplasias/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Histona Desacetilasas/uso terapéutico
7.
J Cardiovasc Pharmacol Ther ; 28: 10742484231171579, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37131338

RESUMEN

OBJECTIVE: To investigate the safety and effectiveness of catheter-based therapy (CBT) compared to conventional catheter-directed thrombosis (CDT) for non-oncological patients with inferior vena cava thrombosis (IVCT), as well to evaluate the differences between CBTs using AngioJet rheolytic thrombectomy (ART) and large lumen catheter aspiration (LLCA). METHODS: This retrospective single-center study included eligible patients with IVCT treated with CBTs coupled with/without CDT or CDT alone as the first-line treatment between January 3, 2015 and January 28, 2022. The baseline demographics, comorbidities, clinical characteristics, treatment details, course data were all reviewed. RESULTS: A total of 106 patients (128 limbs) were included, with 42 cases were treated with ART, 30 with LLCA, and 34 with CDT alone. Technical success rates were 100% (128/128), and 95.5% (84/88) limbs treated with CBT subsequently underwent CDT. The mean duration of CDT time and total infusion agent dosage in patients with CBTs were lower than those who underwent CDT alone (P < .05). Similarities were observed in ART compared to LLCA (P < .05). At the end of CDT, clinical success was achieved in 85.2% (75/88) of limbs treated with CBTs and 77.5% (31/40) of limbs with CDT alone, and 88.5% (46/52) in ART and 80.6% (29/36) in LLCA. The 12-month follow-up showed slightly lower incidences of recurrent thrombosis (7.7% vs 15.2%) and post-thrombotic syndrome (14.1% vs 21.2%), which persisted in patients who underwent ART compared to LLCA (4.3% vs 12.9% and 8.5% vs 22.6%). Patients who underwent CBTs tended to have lower minor complications (5.6% vs 17.6%) but were at higher risk of transient macroscopic hemoglobinuria (58.3% vs 0%) and recoverable acute kidney injury (11.1% vs 2.9%) compared to CDT alone. These findings were similar in ART compared to LLCA (2.4% vs 10.0%, 100% vs 0%, and 16.7% vs 3.3%, respectively). LLCA seemed to have more hemoglobin losses (10.50 ± 9.20 vs 5.57 ± 10. 42 g/L, P < .05). CONCLUSION: CBTs coupled with/without CDT are safe and effective in patients with IVCT, reducing the clot burden in a moderate time, restoring blood flow rapidly, minimizing thrombolytic drug requirement and lowering minor bleeding complication compared to CDT alone. ART and LLCA have comparable outcomes but with different adverse event profiles.


Asunto(s)
Terapia Trombolítica , Trombosis de la Vena , Humanos , Estudios Retrospectivos , Terapia Trombolítica/efectos adversos , Vena Cava Inferior/diagnóstico por imagen , Resultado del Tratamiento , Trombectomía/efectos adversos , Trombosis de la Vena/terapia , Trombosis de la Vena/tratamiento farmacológico , Fibrinolíticos , Catéteres/efectos adversos
8.
J Pain Symptom Manage ; 64(6): e341-e346, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36031081

RESUMEN

BACKGROUND: Expanding specialty palliative care within complex health systems involves consideration of patients' unmet needs, clinicians' perceptions of palliative care, and the availability of palliative care resources. Prior to this quality improvement (QI) project, palliative care services in our health system primarily served oncology patients. INTERVENTION: We undertook a prospective strategic planning process that included executive sponsorship and engagement of institutional leaders and clinicians to help define which palliative care services were most needed by the health system. MEASURES: We interviewed and surveyed a broad range of clinicians including physicians, nurse practitioners, and social workers. OUTCOMES: The two most prominent themes that emerged from the stakeholder engagement process were clinicians' wish for specialty-aligned interprofessional palliative care teams and for expansion of nononcology palliative care access. CONCLUSION: Careful needs assessment and stakeholder engagement can result in goal-directed and data-driven expansion of palliative care services within tertiary health care systems.


Asunto(s)
Enfermería de Cuidados Paliativos al Final de la Vida , Cuidados Paliativos , Humanos , Atención Terciaria de Salud , Estudios Prospectivos , Oncología Médica
9.
Acta Pharm Sin B ; 12(2): 532-557, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35256933

RESUMEN

Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.

10.
Cells ; 11(3)2022 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-35159385

RESUMEN

Despite some significant advancements, breast cancer has become the most prevalent cancer in the world. One of the main reasons for failure in treatment and metastasis has been attributed to the presence of cancer initiating cells-cancer stem cells. Consequently, research is now being focussed on targeting cancer cells along with their stem cell population. Non-oncology drugs are gaining increasing attention for their potent anticancer activities. Metformin, a drug commonly used to treat type 2 diabetes, is the best example in this regard. It exerts its therapeutic action by activating 5' adenosine monophosphate-activated protein kinase (AMPK). Activated AMPK subsequently phosphorylates and targets several cellular pathways involved in cell growth and proliferation and the maintenance of stem-like properties of cancer stem cells. Therefore, AMPK is emerging as a target of choice for developing effective anticancer drugs. Vanadium compounds are well-known PTP inhibitors and AMPK activators. They find extensive applications in treatment of diabetes and obesity via PTP1B inhibition and AMPK-mediated inhibition of adipogenesis. However, their role in targeting cancer stem cells has not been explored yet. This review is an attempt to establish the applications of insulin mimetic vanadium compounds for the treatment of breast cancer by AMPK activation and PTP1B inhibition pathways.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Neoplasias de la Mama , Células Madre Neoplásicas , Compuestos de Vanadio , Proteínas Quinasas Activadas por AMP/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Humanos , Células Madre Neoplásicas/metabolismo , Compuestos de Vanadio/uso terapéutico
11.
Contemp Clin Trials ; 115: 106715, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35217187

RESUMEN

BACKGROUND: Enrollment in non-oncology clinical trials is often challenging and social determinants that may serve as motivators or barriers to clinical trial enrollment are largely unexplored. We sought to assess engagement in non-oncology clinical trials with a focus on social determinants of health as barriers or motivators toward participation. METHODS: A cross-sectional analysis of non-cancer respondents was conducted using the Health Information National Trends Survey (HINTS) administered in 2020. Our analytic cohort was comprised of respondents with no reported history of cancer. Our primary outcome of interest was trial engagement defined as receiving an invitation to participate in a clinical trial. Secondary outcomes included participation in a clinical trial and reported motivators and barriers to clinical trial participation. RESULTS: A total of 3113 respondents with no reported history of cancer were included. Overall, 8.1% of respondents reported being invited to participate in a clinical trial. Amongst those invited to participate, 47.7% reported participating in a clinical trial. Respondents reported that clinical trial participation was motivated "somewhat" or "a lot" by "wanting to get better" (80.5%), "helping other people" (61.4%), "physician encouragement" (60.6%), "getting a chance to try new care" (60.2%), "family friend encouragement" (54.2%), or "getting paid" (50.0%). Overall, 82.5% of all respondents "don't know anything" or have "a little knowledge" about clinical trials. Reported barriers to clinical trial participation including getting transportation, childcare or paid time off work (48.4%) and standard of care not covered by insurance (62.0%) influenced the decision to participate "somewhat" or "a lot." CONCLUSION: Amongst a nationally representative sample, non-oncology clinical trial invitation is low, but participation amongst those invited is nearly 50%. This highlights the need for clinician engagement in clinical trials. Identifying modifiable social determinants of non-oncologic clinical trial participation may help promote improved engagement.


Asunto(s)
Ensayos Clínicos como Asunto , Participación del Paciente , Estudios de Cohortes , Estudios Transversales , Humanos , Encuestas y Cuestionarios
12.
J Clin Pharmacol ; 62(4): 486-493, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34608640

RESUMEN

Race and ethnicity can contribute to differences in drug exposure and/or response. Here, we report that about 10% of the new molecular entities (NMEs) approved between 2014 and 2019 by the US Food and Drug Administration's Center for Drug Evaluation and Research showed differences in exposure and/or response based on race/ethnicity or pharmacogenetic factors known to vary in frequency across global populations. Fewer NMEs (10%) reported differences in the labeling in 2014 to 2019 when compared to about 21% of NMEs approved between 2008 and 2013 that had differences in pharmacokinetics, safety, response, and/or pharmacogenetics. Understanding the underlying mechanisms that lead to such differences and adequate enrollment of racial and ethnic subgroups is essential to obtain sufficient information on exposure and response. Though drug development is global, when heterogeneous populations are not adequately enrolled, the risk-benefit assessments can remain incomplete for certain subgroups. Consequently, this can result in regional differences in drug approval, population-specific prescribing recommendations, or need for additional postmarketing studies to address concerns related to exposure, response, or lack of representation that lead to gaps in information.


Asunto(s)
Aprobación de Drogas , Etnicidad , Desarrollo de Medicamentos , Humanos , Preparaciones Farmacéuticas , Farmacogenética , Estados Unidos , United States Food and Drug Administration
13.
Acta Pharmaceutica Sinica B ; (6): 532-557, 2022.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-929313

RESUMEN

Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.

14.
Methods Mol Biol ; 2078: 23-36, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31643047

RESUMEN

The majority of ADCs in preclinical and clinical development are for oncology indications where cytotoxic payloads are targeted to antigen-expressing cancer cells. However, the modulation of pathogenic cellular activity via ADC-mediated delivery of bioactive small molecules is also an attractive concept for non-oncology indications leading to an expanded application of the technology. Here we summarize those ADCs that have been described so far for non-oncology applications and which cover a variety of payload mechanisms beyond cell killing, from early in vitro proof-of-concept experiments to clinical trials. As our understanding of ADC technology continues to grow, it is anticipated that the development of ADCs as therapeutics for disease areas outside of oncology will also increase.


Asunto(s)
Desarrollo de Medicamentos , Inmunoconjugados/química , Inmunoconjugados/farmacología , Animales , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Biomarcadores , Humanos , Inmunoconjugados/uso terapéutico , Terapia Molecular Dirigida , Relación Estructura-Actividad
16.
Patient Prefer Adherence ; 8: 755-61, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24876769

RESUMEN

PURPOSE: Direct feedback from patients about their preferred modes of medication administration has been increasingly sought by providers to develop care programs that best match patient goals. Multispecialty infusion centers generally provide care to hematology-oncology (HO) and non-HO patients in one unit, with the same nursing staff. Our staff perceived that this was dissatisfying to our non-HO patients. We assessed patient satisfaction, as well as nursing and physician perceptions of patient preference/satisfaction with our infusion center, to determine whether a separate unit should be recommended when designing our new Cancer Institute Infusion Center. PATIENTS AND METHODS: A seven-question Likert scale satisfaction survey for patients, and a separate survey to assess nurses' and physicians' perception of patient satisfaction, were developed. The survey was administered to non-HO patients receiving infusions, doctors prescribing infusions, and nurses administering infusions. Results of the survey were compared between groups to assess differences in responses. RESULTS: Responses were received from 52 non-HO patients, 18 physicians, and 13 nurses. Patients had more satisfaction, on all survey items, with the multispecialty infusion center than had been realized by physicians and nurses. Analysis demonstrated that patients were satisfied with care in a multispecialty infusion unit and were in favor of continuing their care in this combined center. Total scores of patient surveys were significantly different (P<0.001) from those of physicians and nurses, who had assumed patients would prefer to have their care in a non-HO infusion setting. CONCLUSION: Understanding patient preferences is an important step in deciding the structure of infusion centers. Based on these survey conclusions, a combined multispecialty infusion center has been continued at our institution, thus improving quality by including patients in decision-making affecting their care.

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