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1.
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
2.
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.

3.
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.

4.
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.

5.
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
6.
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.

7.
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.

8.
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.

9.
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
10.
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
11.
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
12.
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
13.
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
14.
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
15.
Acta Haematol ; 147(4): 435-446, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38228094

RESUMO

INTRODUCTION: Blood cancer survivors are at increased risk for medical complications. METHODS: Our questionnaire-based study involved 1,551 blood cancer survivors with a ≥3-year interval since the last intense treatment. Its goal was to quantify health-related complications during follow-up and assess their impact on the patients' lives. RESULTS: A total of 20.4% of the responding survivors reported a disease relapse, most often in indolent lymphomas. Second primary malignancies occurred in 14.1%, primarily in lymphoma and allogeneic transplantation survivors. The most frequent malignancy was basal cell carcinoma of the skin, but myeloid malignancies, melanoma, bladder, head-and-neck, and thyroid cancer also appeared disproportionately frequent. An increased infection rate was reported by 43.7%, most often after allogeneic transplantation. New cardiovascular diseases were reported by 30.2%, with a high rate of thromboembolic events in multiple myeloma (MM) and myeloproliferative diseases. Polyneuropathies were reported by 39.1%, most often by survivors with a history of MM or aggressive lymphoma. Disease relapse was perceived as the highest burden, followed by second primary malignancy, increased infection frequency, and polyneuropathy. In each area investigated, the range of perceived severities was wide. CONCLUSIONS: Health-related complications are frequent during blood cancer follow-up, with significant repercussions on the patients' lives.


Assuntos
Sobreviventes de Câncer , Neoplasias Hematológicas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Seguimentos , Adulto , Idoso , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/mortalidade , Inquéritos e Questionários , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/epidemiologia , Assistência ao Convalescente
16.
Obes Rev ; 25(3): e13674, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38092420

RESUMO

Obesity has taken the face of a pandemic with less direct concern among the general population and scientific community. However, obesity is considered a low-grade systemic inflammation that impacts multiple organs. Chronic inflammation is also associated with different solid and blood cancers. In addition, emerging evidence demonstrates that individuals with obesity are at higher risk of developing blood cancers and have poorer clinical outcomes than individuals in a normal weight range. The bone marrow is critical for hematopoiesis, lymphopoiesis, and myelopoiesis. Therefore, it is vital to understand the mechanisms by which obesity-associated changes in BM adiposity impact leukemia development. BM adipocytes are critical to maintain homeostasis via different means, including immune regulation. However, obesity increases BM adiposity and creates a pro-inflammatory environment to upregulate clonal hematopoiesis and a leukemia-supportive environment. Obesity further alters lymphopoiesis and myelopoiesis via different mechanisms, which dysregulate myeloid and lymphoid immune cell functions mentioned in the text under different sequentially discussed sections. The altered immune cell function during obesity alters hematological malignancies and leukemia susceptibility. Therefore, obesity-induced altered BM adiposity, immune cell generation, and function impact an individual's predisposition and severity of leukemia, which should be considered a critical factor in leukemia patients.


Assuntos
Neoplasias Hematológicas , Leucemia , Humanos , Medula Óssea/patologia , Medula Óssea/fisiologia , Adiposidade , Obesidade/complicações , Obesidade/patologia , Inflamação/patologia , Leucemia/etiologia , Leucemia/patologia , Neoplasias Hematológicas/patologia
17.
Med Res Rev ; 44(1): 5-22, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37265248

RESUMO

Cancer treatment brings about a phenomenon not fully clarified yet, termed chemobrain. Its strong negative impact on patients' well-being makes it a trending topic in current research, interconnecting many disciplines from clinical oncology to neuroscience. Clinical and animal studies have often reported elevated concentrations of proinflammatory cytokines in various types of blood cancers. This inflammatory burst could be the background for chemotherapy-induced cognitive deficit in patients with blood cancers. Cancer environment is a dynamic interacting system. The review puts into close relationship the inflammatory dysbalance and oxidative/nitrosative stress with disruption of the blood-brain barrier (BBB). The BBB breakdown leads to neuroinflammation, followed by neurotoxicity and neurodegeneration. High levels of intracellular reactive oxygen species (ROS) induce the progression of cancer resulting in increased mutagenesis, conversion of protooncogenes to oncogenes, and inactivation of tumor suppression genes to trigger cancer cell growth. These cell alterations may change brain functionality, as well as morphology. Multidrug chemotherapy is not without consequences to healthy tissue and could even be toxic. Specific treatment impacts brain function and morphology, functions of the immune system, and metabolism in a unique mixture. In general, a chemo-drug's effects on cognition in cancer are not direct and/or in-direct, usually a combination of effects is more probable. Last but not least, chemotherapy strongly impacts the immune system and could contribute to BBB disruption. This review points out inflammation as a possible mechanism of brain damage during blood cancers and discusses chemotherapy-induced cognitive impairment.


Assuntos
Comprometimento Cognitivo Relacionado à Quimioterapia , Neoplasias Hematológicas , Neoplasias , Animais , Humanos , Comprometimento Cognitivo Relacionado à Quimioterapia/metabolismo , Comprometimento Cognitivo Relacionado à Quimioterapia/patologia , Neoplasias/tratamento farmacológico , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Encéfalo/metabolismo , Sistema Imunitário
18.
Cureus ; 15(10): e46382, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37927646

RESUMO

INTRODUCTION: Cancer is characterized by the rapid proliferation of abnormal cells that exceed their normal boundaries, infiltrating other body parts and leading to metastasis, a distinctive feature setting it apart from other diseases. Metastasis is the primary cause of cancer-related deaths, with nearly 10 million global fatalities, making it the leading cause of mortality. Leukemia, a type of cancer originating in the bone marrow or blood cells, presents significant complications and is associated with various risk factors, including a positive family history, smoking, and obesity. This study aims to evaluate the general knowledge of leukemia and its associated risks among the inhabitants of the Eastern Province, Saudi Arabia. METHODS: A cross-sectional survey was conducted targeting all residents of the Eastern Province, Saudi Arabia, who were Saudi nationals, spanning both genders and aged 15 to 59 years. The questionnaire was distributed electronically through social networking applications, and responses were collected via Google Forms (Google, Mountain View, CA). RESULTS: The study findings indicated that the most frequently identified risk factors for leukemia included blood disorders, genetic disorders, and extensive exposure to radiation and chemicals. The most prevalent leukemia symptoms were bruising and bleeding, followed by vomiting, nausea, and headache. The most commonly reported side effects of leukemia treatment were dizziness, followed by anorexia and exhaustion. CONCLUSION: The study revealed a lack of awareness about leukemia and its associated risks among participants. This underscores the need for continued educational initiatives and awareness campaigns to improve leukemia knowledge and early detection rates, potentially leading to better outcomes for affected individuals. Future research should aim to overcome study limitations and provide a broader perspective on leukemia awareness throughout Saudi Arabia.

19.
AAPS PharmSciTech ; 24(8): 233, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37973643

RESUMO

Blood cancer, also known as hematological malignancy, is one of the devastating types of cancer that has significantly paved its mortality mark globally. It persists as an extremely deadly cancer type and needs utmost attention owing to its negligible overall survival rate. Major challenges in the treatment of blood cancer include difficulties in early diagnosis, as well as severe side effects resulting from chemotherapy. In addition, immunotherapies and targeted therapies can be prohibitively expensive. Over the past two decades, scientists have devised a few nanoparticle-based drug delivery systems aimed at overcoming this challenge. These therapeutic strategies are engineered to augment the cellular uptake, pharmacokinetics, and effectiveness of anticancer drugs. However, there are still numerous types of nanoparticles that could potentially improve the efficacy of blood cancer treatment, while also reducing treatment costs and mitigating drug-related side effects. To the best of our knowledge, there has been limited reviews published on the use of nano-based drug delivery systems for the treatment of hematological malignancies. Therefore, we have made a concerted effort to provide a comprehensive review that draws upon recent literature and patents, with a focus on the most promising results regarding the use of nanoparticle-based approaches for the treatment of hematological malignancies. All these crucial points covered under a common title would significantly help researchers and scientists working in the area.


Assuntos
Antineoplásicos , Neoplasias Hematológicas , Nanopartículas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Hematológicas/tratamento farmacológico
20.
Heliyon ; 9(11): e21461, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38027970

RESUMO

The consistent increase in multidrug resistance among pathogens and increased cancer incidence are serious public health concerns and threaten humans by killing countless lives. In the present study, Talaromyces pinophilus CJ15 was characterized and evaluated for its antibacterial, candidicidal and cytotoxic activities. The selected isolate Talaromyces pinophilus CJ15 with 18S rRNA gene sequence of 1021 base pairs exhibited antifungal activity on plant pathogens via dual culture. The GC-MS profiling of crude extract illustrated the existence of many bioactive macromolecules which include squalene belonging to the terpenoids family. The biological macromolecules in the bioactive fraction of CJ15 exhibited increasing antibacterial activity with an increase in concentration such that the highest activity was recorded against Shigella flexneri with 15, 18, 20, and 24 mm inhibition zones at 25, 50, 75 and 100 µl concentrations, respectively. The squalene, having a molecular weight of 410.718 g/mol, displayed candidicidal activity with a right-side shifted log phase in the growth curve of all the treated Candida species, indicating delayed exponential growth. In cytotoxic activity, the extracted squalene exhibited an IC50 concentration of 26.22 µg/ml against JURKAT cells and induced apoptosis-induced cell death. This study's outcomes encourage the researchers to explore further the development of new and improved bioactive macromolecules that could help to prevent infections and human blood cancer.

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