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1.
Cancer Epidemiol ; 93: 102656, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39217827

RESUMO

BACKGROUND: Haematological ('blood') cancers are a diverse group of non-solid cancers with varying incidence, mortality and survival. While there is some evidence that Maori experience disparities in blood cancer outcomes relative to New Zealand's majority European population, there is a need for a comprehensive overview of the current state of evidence in this context. METHODS: Blood cancer registrations were derived from the NZ Cancer Registry for the 2007-2019 period (combined blood cancers: 2653 Maori, 20,458 Europeans), and linked to Mortality records. We calculated age-sex-standardised incidence and mortality rates, and conducted cancer-specific survival analysis, for four main categories of blood cancers (leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma and myeloma) as well as for sub-types of leukaemia non-Hodgkin lymphoma. RESULTS: We found that Maori are more likely to be diagnosed with (incidence) and to die from (mortality) both leukaemia and myeloma, and similarly likely to be diagnosed or die from Hodgkin and non-Hodgkin lymphoma, compared to Europeans. Maori had demonstrably poorer cancer-specific survival outcomes across most blood cancer types (age-sex-adjusted hazard ratios [HRs], Maori vs European: leukaemia 1.77, 95 % CI 1.57-2.00; Hodgkin lymphoma 1.18, 95 % CI 0.65-2.16; non-Hodgkin lymphoma 1.71, 95 % CI 1.50-1.95; myeloma 1.40, 95 % CI 1.19-1.64). CONCLUSION: Blood cancers are a common cancer type for Maori, and we found evidence of disparities in incidence, mortality and survival compared to Europeans. Further research is required to further pinpoint exactly where interventions should be aimed to reduce blood cancer incidence and address survival disparities for Maori.

2.
Heliyon ; 10(17): e36552, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39263069

RESUMO

Chronic myeloid leukemia (CML) is a cancer in the bone marrow caused by the proliferation of granulocyte cells at all the maturation stages. Late diagnosis of CML decreases the patient survival rate, makes diagnosing CML is mandatory before entering the blastic phase. CD 19 is an important target for CML and is effectively utilized for therapeutic and diagnosis purposes. This research was focused on developing an aptamer-mediated circular interdigitated electrode (IDE) sensor for detecting the level of CD 19 and measured at 0-2 V with the step of 0.1 V. To improve the surface functionalization on IDE, the surface of IDE was modified with a single-walled carbon nanotube (SWCN) to enhance the aptamer immobilization. SWCN increased the aptamer attachment and also enhanced the analytical performances on IDE. This SWCN-aptamer modified IDE detected the CD 19 as low as 10 nM on a linear co-regression range from 10 to 100 nM [y = 2.0126x - 2.3857; R2 = 0.9749]. Furthermore, control performances with CD 33, and complementary aptamer did not show the increment of current, and CD 19 spiked human serum increased the current flow without significant interference, demonstrating the specific and selective detection of CD 19. This biosensor quantifies CD 19 biomarker at its lower level and diagnoses CML and its associated complications.

3.
J Natl Cancer Inst ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39276159

RESUMO

BACKGROUND: Many uninsured patients do not receive Medicaid coverage until a cancer diagnosis, potentially delaying access to care for early cancer detection and treatment. We examine the association of Medicaid enrollment timing and patterns with survival among children and adolescents/young adults (AYAs) diagnosed with blood cancers, where disease onset can be acute and early detection is critical. METHODS: We identified 28,750 children and AYAs (0-39 years) newly diagnosed with blood cancers from the 2006-2013 SEER-Medicaid data. Enrollment patterns included continuous Medicaid (preceding through diagnosis), newly gained Medicaid (at/shortly after diagnosis), other noncontinuous Medicaid enrollment, and private/other insurance. We assessed cumulative incidence of death from diagnosis, censoring at last follow-up, five years post-diagnosis, or December 2018, whichever occurred first. Multivariable survival models estimated the association of insurance enrollment patterns with risk of death. RESULTS: One-fourth (26.1%) of the cohort were insured by Medicaid; of these, 41.1% had continuous Medicaid, 34.9% had newly gained Medicaid, and 24.0% had other noncontinuous enrollment. The cumulative incidence of all-cause death five-year post-diagnosis was highest in patients with newly gained Medicaid (30.2%, 95%CI = 28.4-31.9%), followed by other noncontinuous enrollment (23.2%, 95%CI = 21.3-25.2%), continuous Medicaid (20.5%, 95%CI = 19.1-21.9%), and private/other insurance (11.2%; 95%CI = 10.7-11.7%). In multivariable models, newly gained Medicaid was associated with a higher risk of all-cause (hazard ratio = 1.39, 95%CI = 1.27-1.53) and cancer-specific death (hazard ratio = 1.50, 95%CI = 1.35-1.68), compared to continuous Medicaid. CONCLUSIONS: Continuous Medicaid coverage is associated with survival benefits among pediatric and AYA patients diagnosed with blood cancers; however, less than half of Medicaid-insured patients have continuous coverage before diagnosis.

4.
J Cancer Policy ; 41: 100501, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39142605

RESUMO

BACKGROUND: Whole genome sequencing (WGS) has transformative potential for blood cancer management, but reimbursement is hindered by uncertain benefits relative to added costs. This study employed scenario planning and multi-criteria decision analysis (MCDA) to evaluate stakeholders' preferences for alternative reimbursement pathways, informing future health technology assessment (HTA) submission of WGS in blood cancer. METHODS: Key factors influencing WGS reimbursement in blood cancers were identified through a literature search. Hypothetical scenarios describing various evidential characteristics of WGS for HTA were developed using the morphological approach. An online survey, incorporating MCDA weights, was designed to gather stakeholder preferences (consumers/patients, clinicians/health professionals, industry representatives, health economists, and HTA committee members) for these scenarios. The survey assessed participants' approval of WGS reimbursement for each scenario, and scenario preferences were determined using the geometric mean method, applying an algorithm to improve reliability and precision by addressing inconsistent responses. RESULTS: Nineteen participants provided complete survey responses, primarily clinicians or health professionals (n = 6; 32 %), consumers/patients and industry representatives (both at n = 5; 26 %). "Clinical impact of WGS results on patient care" was the most critical criterion (criteria weight of 0.25), followed by "diagnostic accuracy of WGS" (0.21), "cost-effectiveness of WGS" (0.19), "availability of reimbursed treatment after WGS" (0.16), and "eligibility criteria for reimbursed treatment based on actionable WGS results" and "cost comparison of WGS" (both at 0.09). Participants preferred a scenario with substantial clinical evidence, high access to reimbursed targeted treatment, cost-effectiveness below $50,000 per quality-adjusted life year (QALY) gained, and affordability relative to standard molecular tests. Reimbursement was initially opposed until criteria such as equal cost to standard tests and better treatment accessibility were met. CONCLUSION: Payers commonly emphasize acceptable cost-effectiveness, but strong clinical evidence for many variants and comparable costs to standard tests are likely to drive positive reimbursement decisions for WGS.


Assuntos
Técnicas de Apoio para a Decisão , Sequenciamento Completo do Genoma , Humanos , Avaliação da Tecnologia Biomédica , Mecanismo de Reembolso , Análise Custo-Benefício , Inquéritos e Questionários
5.
Best Pract Res Clin Haematol ; 37(2): 101551, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39098795

RESUMO

Biobanking provides benefit for future generations by facilitating medical research and subsequent translation and application of research findings. Long-term storage and research involving biological material and associated data necessitate the proper implementation of ethical and legal standards. A key principle includes recognizing informed consent as a crucial element for legitimizing the collection of biological material and data. Furthermore, any collected material and data must be employed exclusively for the research framework that aligns with the explicit consent provided by the participants. Last but not least, data privacy and security are essential in biobanking. This review elucidates chances and limitations of biobanking in the field of allogeneic hematopoietic cell transplantation. We discuss the practical implementation of the requirements, illustrated by the Collaborative Biobank, a collaborative research platform for research in blood cancer.


Assuntos
Bancos de Espécimes Biológicos , Transplante de Células-Tronco Hematopoéticas , Humanos , Doadores de Tecidos , Consentimento Livre e Esclarecido , Aloenxertos
6.
Clin Transl Med ; 14(8): e1780, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39162183

RESUMO

While paediatric blood cancers are deadly, modern medical advances have enabled clinicians to measure levels of residual cancer cells to manage therapeutic strategies for patients. However, blood cancers, including leukaemias and lymphomas, are highly heterogeneous and is comprised of complex clonal populations that can hinder efforts in detecting the cancer cells as well as managing treatments. Furthermore, the tumour microenvironment is comprised of heterogenous immune dynamics that may be different between patients. High-throughput sequencing has constributed to new discoveries in genetic and transcriptomic alterations underpinning cancer, including blood cancers, and has changed how patients are monitored and managed. Here we discuss the recent efforts using single-cell approach, particularly on efforts to track clonal heterogenity of paediatric blood cancer and the underlying immune response, highlighting avenues for novel biomarker discovery that may have significant impact on clinical oncology practice.


Assuntos
Neoplasias Hematológicas , Análise de Célula Única , Humanos , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/imunologia , Análise de Célula Única/métodos , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética
7.
Asian Pac J Cancer Prev ; 25(8): 2605-2613, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39205557

RESUMO

BACKGROUND: Sphingosine kinase 1 (SphK1) is a lipid enzyme whose role in the etiology of cancer has been well explored. Here, a systematic review and meta-analysis were conducted to evaluate the association of SphK1 expression with hematological malignancy. MATERIALS AND METHODS: Relevant studies were identified through electronic databases (PubMed, Scopus, Embase, and OVID) and evaluated based on predefined inclusion and exclusion criteria. Quality assessment using the Newcastle-Ottawa Scale (NOS) was conducted, and pooled odds ratio (OR) was calculated to assess the association between SphK1 expression and hematological malignancy. RESULTS: Nine studies meeting the inclusion criteria were included in the systematic review. These studies utilized various techniques to assess SphK1 expression in hematological malignancies. The quality assessment reported that the included studies were of moderate quality. Meta-analysis of eligible studies revealed a positive association between SphK1 expression and hematological malignancies at the protein level (OR = 52.37, 95% CI = 10.10 to 271.47, and P = 0.00001). The funnel plot indicated no publication bias among the included studies. However, the certainty of the evidence was low according to the GRADE assessment. CONCLUSION: Our study's findings support the link between SphK1 expression and hematological malignancies. SphK1 gene dysregulation may contribute to various malignancies, suggesting it could be a therapeutic target to improve patient outcomes. Further research is needed to understand SphK1's mechanistic role in hematological malignancies and its therapeutic potential.


Assuntos
Neoplasias Hematológicas , Fosfotransferases (Aceptor do Grupo Álcool) , Humanos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/patologia , Fosfotransferases (Aceptor do Grupo Álcool)/análise , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Prognóstico
8.
Cytotherapy ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970613

RESUMO

Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells has shown promising results in early-phase clinical studies. However, advancing CAR-NK cell therapeutic efficacy is imperative. In this study, we investigated the impact of a fourth-generation CD19-targeted CAR (CAR.19) coexpressing IL-27 on NK-92 cells. We observed a significant improvement in NK-92 cell proliferation and cytotoxicity activity against B-cell cancer cell lines, both in vitro and in a xenograft mouse B-cell lymphoma model. Our systematic transcriptome analysis of the activated NK-92 CAR variants further supports the potential of IL-27 in fourth-generation CARs to overcome limitations of NK cell-based targeted tumor therapies by providing essential growth and activation signals. Integrating IL-27 into CAR-NK cells emerges as a promising strategy to enhance their therapeutic potential and elicit robust responses against cancer cells. These findings contribute substantially to the mounting evidence supporting the potential of fourth-generation CAR engineering in advancing NK cell-based immunotherapies.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38979549

RESUMO

Background: Administrative burdens have been identified as a major issue impacting patient care, professional practice, and the overall efficiency of healthcare systems. The aim of this study is to assess the administrative burden faced by Italian hematologists. Methods: A cross-sectional survey that included both closed-ended quantitative questions and open-ended free text answer options was administered to 1,570 hematologists working with malignancies and members of Italian GIMEMA Foundation - Franco Mandelli ONLUS and the Italian Linfomi Foundation (FIL). The survey was conducted online from May 24 to June 30, 2023. Descriptive statistics were computed for the quantitative data to clearly summarize the responses and descriptive analysis of free text responses was carried out. Results: Surveyed hematologists spend an average of 47.07% of their time on administrative tasks, with 63.22% (n = 110) of respondents reporting spending at least half of their time on these activities. More than half (57.47%, n = 100) reported that "Patient care" is the medical task most affected by a lack of time. Additionally, 55.17% (n = 96) reported experiencing burnout in the past 6 months, with filling out "Forms" being identified as the top contributing administrative task by 27.59% (n = 48) of respondents, followed by "Scheduling" (24.71%, n = 43) and "Managing IT system failures" (21.84%, n = 38). Nearly half of the surveyed hematologists (45.40%, n  =  = 79) identified patient care as the top priority requiring more time. Conclusions: The study confirms that the administrative workload of hematologists has a significant impact on patient care, communication, and burnout risk, reducing the time available for patient care, leading to exhaustion and concern about clinical errors.

10.
Front Immunol ; 15: 1384509, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846951

RESUMO

Introduction: The Philadelphia chromosome-negative myeloproliferative neoplasms are a group of slowly progressing haematological malignancies primarily characterised by an overproduction of myeloid blood cells. Patients are treated with various drugs, including the JAK1/2 inhibitor ruxolitinib. Mathematical modelling can help propose and test hypotheses of how the treatment works. Materials and methods: We present an extension of the Cancitis model, which describes the development of myeloproliferative neoplasms and their interactions with inflammation, that explicitly models progenitor cells and can account for treatment with ruxolitinib through effects on the malignant stem cell response to cytokine signalling and the death rate of malignant progenitor cells. The model has been fitted to individual patients' data for the JAK2 V617F variant allele frequency from the COMFORT-II and RESPONSE studies for patients who had substantial reductions (20 percentage points or 90% of the baseline value) in their JAK2 V617F variant allele frequency (n = 24 in total). Results: The model fits very well to the patient data with an average root mean square error of 0.0249 (2.49%) when allowing ruxolitinib treatment to affect both malignant stem and progenitor cells. This average root mean square error is much lower than if allowing ruxolitinib treatment to affect only malignant stem or only malignant progenitor cells (average root mean square errors of 0.138 (13.8%) and 0.0874 (8.74%), respectively). Discussion: Systematic simulation studies and fitting of the model to the patient data suggest that an initial reduction of the malignant cell burden followed by a monotonic increase can be recapitulated by the model assuming that ruxolitinib affects only the death rate of malignant progenitor cells. For patients exhibiting a long-term reduction of the malignant cells, the model predicts that ruxolitinib also affects stem cell parameters, such as the malignant stem cells' response to cytokine signalling.


Assuntos
Janus Quinase 2 , Transtornos Mieloproliferativos , Nitrilas , Pirazóis , Pirimidinas , Humanos , Pirazóis/uso terapêutico , Pirazóis/farmacologia , Pirimidinas/uso terapêutico , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/genética , Janus Quinase 2/genética , Janus Quinase 2/antagonistas & inibidores , Células-Tronco Neoplásicas/efeitos dos fármacos , Modelos Teóricos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia
11.
Front Oncol ; 14: 1391429, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863644

RESUMO

Background: Hematological cancers impose a complex burden on individuals, affecting their physical health and mental and emotional well-being. This study evaluated the health-related Quality of Life (HRQOL) and its determinants among adults with hematological cancers in Qatar in 2023. Methods: A cross-sectional study used a validated structured questionnaire conducted among adult patients diagnosed with hematological cancers. All adult patients who attended The National Centre for Cancer Care and Research (NCCCR) in Qatar during the Data collection period (January to March 2023) and agreed to participate were included in the study. Results: A total of 257 participants were enrolled in the study. The highest median (IQR) score of the HRQOL domain was observed in the functionating score of 90.6 (13.8), followed by the global health score of 83.3(25. 0). The median (IQR) of the symptoms burden score was 07.4(12.3). Gender significantly affects HRQOL, with males reporting better functioning and lower symptom burden than females. Employment status is positively associated with functioning scores. Regular exercise correlates with higher global health and functioning scores and lower symptom burden, while depressive symptoms are linked to poorer HRQOL outcomes. Patients experiencing cancer recurrence or active disease report lower global health and functioning scores and higher symptom burden. Treatment modalities such as chemotherapy and bone marrow transplant (BMT) timing also influence HRQOL, with recent treatment recipients showing lower global health and higher symptom burden scores. Depressive symptoms were the primary factor, lowering the global health score by 15.2%. Regarding the low functioning score predictors, female gender, depressive symptoms, and cancer recurrence emerged as significant predictors of the low functioning score. Furthermore, Regular exercise increased the functioning score by 03.4 units (p-value=0.018). Finally, Multiple linear regression analysis reinforced the significance of depressive symptoms, active disease status, and recurrence within the past five years as substantial predictors of higher symptom scores. Conclusions: The study emphasizes the profound impact of depressive symptoms on all aspects of Health-Related Quality of Life (HRQOL), mainly affecting global health. It highlights the positive role of regular exercise in enhancing global health, functioning, and symptom burden scores.

12.
Cureus ; 16(4): e58488, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38765438

RESUMO

Introduction The National Institutes of Health and the American Medical Association recommend patient education materials (EMs) be at or below the sixth-grade reading level. The American Cancer Society, Leukemia & Lymphoma Society, and National Comprehensive Cancer Network have accurate blood cancer EMs. Methods One hundred one (101) blood cancer EMs from the above organizations were assessed using the following: Flesch Reading Ease Formula (FREF), Flesch-Kincaid Grade Level (FKGL), Gunning Fog Index (GFI), Simple Measure of Gobbledygook Index (SMOG), and the Coleman-Liau Index (CLI). Results Only 3.96% of patient EMs scored at or below the seventh-grade reading level in all modalities. Healthcare professional education materials (HPEMs) averaged around the college to graduate level. For leukemia and lymphoma patient EMs, there were significant differences for FKGL vs. SMOG, FKGL vs. GFI, FKGL vs. CLI, SMOG vs. CLI, and GFI vs. CLI. For HPEMs, there were significant differences for FKGL vs. GFI and GFI vs. CLI. Conclusion The majority of patient EMs were above the seventh-grade reading level. A lack of easily readable patient EMs could lead to a poor understanding of disease and, thus, adverse health outcomes. Overall, patient EMs should not replace physician counseling. Physicians must close the gaps in patients' understanding throughout their cancer treatment.

13.
Am J Hosp Palliat Care ; : 10499091241254523, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38803232

RESUMO

Background: Palliative care can enhance quality of life during a terminal hospitalization. Despite advances in diagnostic and treatment tools, blood cancers lag behind solid malignancies in palliative use. It is not clear what factors affect palliative care use in blood cancer. Methods: We used the 2016 to 2019 National Inpatient Sample to identify demographic and socioeconomic factors associated with receiving palliative care among patients over age 18 with any malignant hematological diagnosis during a terminal hospitalization lasting at least 3 days, excluding those receiving a stem cell transplant. Results: Palliative care use was documented 54% of the time among 49,720 weighted cases (9944 distinct individual hospitalizations), approximately evenly distributed across the years 2016-2019. Palliative care use was lowest in 2016 (51%) and highest in 2018 (58%), and increased with age, reaching 58% for those 80 years and older. Men and women were similarly likely to receive care. Patients of Hispanic ethnicity and African Americans received less palliative care (47% and 49%, respectively), as did those insured by Medicaid (48%), and those admitted to small or rural hospitals (52% and 47%, respectively). Charges for hospitalizations with palliative care were 19% lower than for those without it. Conclusions: This study highlights disparities in palliative care use among blood-cancer patients who died in the hospital. It seems likely that many of the 46% who did not receive palliative care could have benefitted from it. Interventions are likely needed to achieve equitable access to ideal levels of palliative care services in late-stage blood cancer.

14.
Noncoding RNA Res ; 9(3): 695-703, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38577021

RESUMO

AKT2 is crucial for cancer cells' invasion, metastasis, and survival. It is a possible downstream gene target of cancer glycolysis-related microRNAs. The study investigated the role of miRNA-4716-3p, rs2304186, and the AKT2 gene in blood cancer pathogenesis. RT-qPCR was used to analyze AKT2 gene mRNA and miRNA-4716-3p expression in 200 blood cancer samples and 200 healthy controls. Furthermore, Tetra-ARMS PCR was used to examine the rs2304186 AKT2 SNP in 300 patients and 290 control samples. miRNA-4716-3p was shown to be significantly downregulated (p = 0.0294), whereas mRNA expression of the AKT2 gene was found to be significantly upregulated (p = 0.0034) in blood cancer patients compared to healthy individuals. miRNA-4716-3p downregulation (p = 0.0466) was more pronounced, while AKT2 upregulation was non-significant (p = 0.1661) in untreated patients compared to chemotherapy-treated patients. Blood cancer risk was significantly associated with the rs2304186 GT genotype (p = 0.0432), TT genotype (p = 0.0502), and mutant allele (T) frequency (p = 0.0008). Polymorphism rs2304186 was associated with an increased risk of blood cancer in dominant (p = 0.0011), recessive (p = 0.0502), and additive (p = 0.0008) genetic models. The results suggested that the rs2304186 and the deregulated expression of miRNA-4716-3p and AKT2 gene at the mRNA level may significantly increase the incidence of blood cancer, particularly in the Pakistani population. Therefore, these may function as suitable biomarkers for blood cancer diagnosis and prognosis. Additional, larger-scale investigations may be required to affirm these results.

15.
Eur J Pharmacol ; 974: 176618, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38679117

RESUMO

Cancer poses a formidable challenge in the field of medical science, prompting the exploration of innovative and efficient treatment strategies. One revolutionary breakthrough in cancer therapy is Chimeric Antigen Receptor (CAR) T-cell therapy, an avant-garde method involving the customization of a patient's immune cells to combat cancer. Particularly successful in addressing blood cancers, CAR T-cell therapy introduces an unprecedented level of effectiveness, offering the prospect of sustained disease management. As ongoing research advances to overcome current challenges, CAR T-cell therapy stands poised to become an essential tool in the fight against cancer. Ongoing enhancements aim to improve its effectiveness and reduce time and cost, with the integration of Artificial Intelligence (AI) and Internet of Things (IoT) technologies. The synergy of AI and IoT could enable more precise tailoring of CAR T-cell therapy to individual patients, streamlining the therapeutic process. This holds the potential to elevate treatment efficacy, mitigate adverse effects, and expedite the overall progress of CAR T-cell therapies.


Assuntos
Inteligência Artificial , Imunoterapia Adotiva , Internet das Coisas , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/imunologia , Neoplasias/terapia , Neoplasias/imunologia , Animais
16.
Cancer Cell ; 42(5): 850-868.e9, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38670091

RESUMO

TP53-mutant blood cancers remain a clinical challenge. BH3-mimetic drugs inhibit BCL-2 pro-survival proteins, inducing cancer cell apoptosis. Despite acting downstream of p53, functional p53 is required for maximal cancer cell killing by BH3-mimetics through an unknown mechanism. Here, we report p53 is activated following BH3-mimetic induced mitochondrial outer membrane permeabilization, leading to BH3-only protein induction and thereby potentiating the pro-apoptotic signal. TP53-deficient lymphomas lack this feedforward loop, providing opportunities for survival and disease relapse after BH3-mimetic treatment. The therapeutic barrier imposed by defects in TP53 can be overcome by direct activation of the cGAS/STING pathway, which promotes apoptosis of blood cancer cells through p53-independent BH3-only protein upregulation. Combining clinically relevant STING agonists with BH3-mimetic drugs efficiently kills TRP53/TP53-mutant mouse B lymphoma, human NK/T lymphoma, and acute myeloid leukemia cells. This represents a promising therapy regime that can be fast-tracked to tackle TP53-mutant blood cancers in the clinic.


Assuntos
Apoptose , Proteínas de Membrana , Proteína Supressora de Tumor p53 , Proteína Supressora de Tumor p53/genética , Humanos , Animais , Camundongos , Proteínas de Membrana/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Mutação , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Fragmentos de Peptídeos/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas/genética
17.
Eur J Oncol Nurs ; 70: 102544, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38513454

RESUMO

PURPOSE: This study examines how blood cancer impacts patients' sexuality and sense of gendered identity. METHODS: An interpretive epistemological framework necessitated a qualitative study design. Participants (6 male and 6 female), recruited from a hospital Haematology department in a large Northern English City, took part in semi-structured in-depth interviews to gather rich data about their subjective experiences. RESULTS: A key theme from the qualitative data was a sense of disruption in relation to several aspects of their gendered identities and sexual life. Participants explained disruption to their sexual function and sexual sense of self. They narrated concerns about future imagined relationships. The emotional burden of sexuality related concerns was strongly articulated. A gendered perspective enabled the similarities and differences between men and women to be explored. CONCLUSION: This study, drawing on rich qualitative data, documents the sexuality concerns of blood cancer patients; for some such concerns arise many years post treatment. The findings highlight the need for gender appropriate care around sexuality which should continue to be accessible well after diagnosis and treatment phases have ceased.


Assuntos
Identidade de Gênero , Pesquisa Qualitativa , Sexualidade , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Sexualidade/psicologia , Neoplasias Hematológicas/psicologia , Neoplasias Hematológicas/terapia , Inglaterra , Comportamento Sexual/psicologia
18.
Eur J Cancer ; 201: 113603, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38359496

RESUMO

BACKGROUND: People with blood cancer have increased risk of severe COVID-19 outcomes and poor response to vaccination. We assessed the safety and effectiveness of COVID-19 vaccines in this vulnerable group compared to the general population. METHODS: Individuals aged ≥12 years as of 1st December 2020 in the QResearch primary care database were included. We assessed adjusted COVID-19 vaccine effectiveness (aVE) against COVID-19-related hospitalisation and death in people with blood cancer using a nested matched case-control study. Using the self-controlled case series methodology, we compared the risk of 56 pre-specified adverse events within 1-28 days of a first, second or third COVID-19 vaccine dose in people with and without blood cancer. FINDINGS: The cohort comprised 12,274,948 individuals, of whom 81,793 had blood cancer. COVID-19 vaccines were protective against COVID-19-related hospitalisation and death in people with blood cancer, although they were less effective, particularly against COVID-19-related hospitalisation, compared to the general population. In the blood cancer population, aVE against COVID-19-related hospitalisation was 64% (95% confidence interval [CI] 48%-75%) 14-41 days after a third dose, compared to 80% (95% CI 78%-81%) in the general population. Against COVID-19-related mortality, aVE was >80% in people with blood cancer 14-41 days after a second or third dose. We found no significant difference in risk of adverse events 1-28 days after any vaccine dose between people with and without blood cancer. INTERPRETATION: Our study provides robust evidence which supports the use of COVID-19 vaccinations for people with blood cancer.


Assuntos
COVID-19 , Neoplasias Hematológicas , Neoplasias , Humanos , Vacinas contra COVID-19/efeitos adversos , Estudos de Casos e Controles , COVID-19/prevenção & controle , Neoplasias/terapia , Vacinação/efeitos adversos
19.
Hematology ; 29(1): 2306444, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38305210

RESUMO

Acute myeloid leukemia (AML) is the common blood cancer in hematopoietic system-related diseases and has a poor prognosis. Studies have shown that long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of a variety of diseases, including AML. However, the specific molecular mechanism remains unclear. Hence, the objective of this study was to investigate the effect and mechanism of lncRNA X inactive specific transcript (lncRNA XIST) on AML. To achieve our objective, some tests were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of lncRNA XIST, miR-142-5p and the platelet isoform of phosphofructokinase (PFKP). The targeting relationship between miR-142-5p and lncRNA XIST and PFKP was verified by Pearson correlation analysis, dual-luciferase reporter assay, and pull-down assay. Functional experiments were used to analyze the effect and mechanism of action of knocking down lncRNA XIST on THP-1 and U937 cells. Compared with bone marrow cells, lncRNA XIST and PFKP expression levels were up-regulated and miR-142-5p expression levels were down-regulated in AML. Further analysis revealed that lncRNA XIST targeted and bound to miR-142-5p, and PFKP was a target gene of miR-142-5p. Knockdown of lncRNA XIST significantly promoted miR-142-5p expression to down-regulate PFKP in THP-1 and U937 cells, while the cell proliferation, cell viability, and cell cycle arrest were inhibited and apoptosis was increased. Knockdown of miR-142-5p reversed the functional impact of lncRNA XIST knockdown on AML cells. In conclusion, down-regulation of lncRNA XIST can affect the progression of AML by regulating miR-142-5p.


Assuntos
Leucemia Mieloide Aguda , MicroRNAs , RNA Longo não Codificante , Humanos , Apoptose/genética , Proliferação de Células/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfofrutoquinases , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Técnicas de Silenciamento de Genes
20.
Curr Treat Options Oncol ; 25(4): 465-495, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38372853

RESUMO

OPINION STATEMENT: Cardiotoxicity has emerged as a serious outcome catalyzed by various therapeutic targets in the field of cancer treatment, which includes chemotherapy, radiation, and targeted therapies. The growing significance of cancer drug-induced cardiotoxicity (CDIC) and radiation-induced cardiotoxicity (CRIC) necessitates immediate attention. This article intricately unveils how cancer treatments cause cardiotoxicity, which is exacerbated by patient-specific risks. In particular, drugs like anthracyclines, alkylating agents, and tyrosine kinase inhibitors pose a risk, along with factors such as hypertension and diabetes. Mechanistic insights into oxidative stress and topoisomerase-II-B inhibition are crucial, while cardiac biomarkers show early damage. Timely intervention and prompt treatment, especially with specific agents like dexrazoxane and beta-blockers, are pivotal in the proactive management of CDIC.


Assuntos
Antineoplásicos , Neoplasias Hematológicas , Neoplasias , Humanos , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/etiologia , Antineoplásicos/efeitos adversos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Antraciclinas/efeitos adversos , Neoplasias Hematológicas/complicações
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