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1.
Journal of Public Health and Preventive Medicine ; (6): 152-156, 2024.
Artículo en Chino | WPRIM | ID: wpr-1016435

RESUMEN

Objective To analyze the risk factors for survival in patients with hematological malignancies after hematopoietic stem cell transplantation (HSCT), to establish a risk prediction and survival prediction model, and to provide a reference for clinical diagnosis and treatment. Methods A total of 237 patients with malignant hematological diseases who underwent HSCT at West China Hospital of Sichuan University from January 2017 to April 2019 were selected as the study subjects. The survival of all patients after HSCT was statistically analyzed. The influencing factors of survival were analyzed by multivariate regression analysis, and the prediction model was constructed. Results A total of 237 patients with hematological malignancies were included in this study. After 3 years of follow-up, 85 patients died, with a mortality rate of 35.86%. Multivariate logistic analysis showed that diabetes mellitus (OR=4.358, P=0.007), infection (OR=3.522, P=0.000), neutropenia time >7d (OR=2.734, P=0.009), incomplete HLA matching (OR=5.688, P=0.000), cGVHD (OR=2.593, P=0.007) and HCT-CI (OR=6.701, P=0.000) were independent risk factors affecting the survival of patients with hematological malignancies after HSCT (P(3.192 + 01.259 + 1.472 ×(diabetes mellitus) + 1.259×(infection) + 1.006 ×(neutropenia time) + 1.738 ×(HLA matching) + 0.953 ×(cGVHD) + 1.902 ×(HCT-CI)), Hosmer-Lemeshow χ2=6.692, P=0.462. AUC and 95%CI of the model for predicting survival were 0.836 and 0.783-0.888, showing good fit and predictive efficiency. Conclusion Diabetes mellitus, infection, neutropenia time >7d, incomplete HLA matching, cGVHD and HCT-CI are all high-risk factors of survival in patients with malignant hematologic disease after HSCT. Clinically, attentions should be paid to these patients and intervention measures should be taken to improve their survival after HSCT.

2.
Cancer Research on Prevention and Treatment ; (12): 140-146, 2024.
Artículo en Chino | WPRIM | ID: wpr-1011512

RESUMEN

The biosynthesis and maturation of proteins are primarily regulated by the endoplasmic reticulum in its physiological state. Thus, the disruption of physiological homeostasis initiates the buildup of unfolded and misfolded proteins in the endoplasmic reticulum, resulting in endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). One of the important pathways by which UPR maintains intracellular homeostasis under ERS is activating protein kinase R-like endoplasmic reticulum kinase (PERK). The activation of the PERK pathway stimulates eukaryotic translation initiation factor 2 subunit-α (eIF2α) phosphorylation and the selective translation of active transcription factor 4 (ATF4), and PERK induces cell apoptosis by directly binding to the promoter of pro-apoptotic transcription factor C/EBP homologous protein (CHOP). This signaling pathway is also one of the important mechanisms by which UPR participates in the regulation of hematological malignancies and immune cells in a tumor microenvironment. This article provides an overview of advancements in research into the PERK-eIF2α-ATF4-CHOP signaling pathway in hematological malignancies and the potential therapeutic benefits of targeting this signaling pathway.

3.
Rev. cuba. invest. bioméd ; 432024. tab
Artículo en Español | CUMED, LILACS | ID: biblio-1559797

RESUMEN

Introducción: La infiltración del sistema nervioso central por células malignas constituye una complicación grave de algunas neoplasias hematológicas, principalmente leucemias agudas y linfomas agresivos. Objetivo: Resumir la base científica y la significación clínica de los métodos de estudio del líquido cefalorraquídeo para el diagnóstico y el seguimiento de la infiltración neuromeníngea en pacientes con neoplasias hematológicas. Métodos: Se buscó información durante abril de 2021 en las bases de datos PubMed, ScienceDirect y SciELO. Se seleccionaron las publicaciones en base a su tipología, actualidad, alcance y las limitaciones de los estudios. Conclusiones: El estudio citomorfológico del líquido cefalorraquídeo se considera el método estándar para el diagnóstico y el seguimiento de la infiltración neuromeníngea. La citometría de flujo resulta más sensible para la detección de infiltración oculta que la citología convencional; pero aún existen reservas sobre su significación clínica. Se investiga también la sensibilidad de otros estudios moleculares como el uso de la reacción en cadena de la polimerasa y la detección de biomarcadores(AU)


Introduction: Infiltration of the central nervous system by malignant cells constitutes a serious complication of some hematological malignancies, mainly acute leukemias and aggressive lymphomas. Objective: To summarize the scientific basis and clinical significance of cerebrospinal fluid study methods for the diagnosis and follow-up of neuromeningeal infiltration in patients with hematologic malignancies. Methods: Information was searched during April 2021 in PubMed, ScienceDirect and SciELO databases. Publications were selected based on their typology, timeliness, scope, and study limitations. Conclusions: The cytomorphological study of cerebrospinal fluid is considered the standard method for the diagnosis and follow-up of neuromeningeal infiltration. Flow cytometry is more sensitive for the detection of occult infiltration than conventional cytology, but there are still reservations about its clinical significance. The sensitivity of other molecular studies such as the use of PCR and biomarker detection is also investigated(AU)


Asunto(s)
Humanos , Neoplasias Hematológicas/líquido cefalorraquídeo , Biomarcadores , Sistema Nervioso Central , Reacción en Cadena de la Polimerasa , Citometría de Flujo
4.
Braz. j. infect. dis ; 28(1): 103718, 2024. tab
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1550137

RESUMEN

Abstract Invasive fungal infection (IFI) is frequent in patients with hematologic malignancies or submitted hematopoietic stem cell transplantation (HSCT). Objectives To evaluate the role of the GM (galactomannan) test in prescribing therapeutic antifungals; to determine invasive aspergillosis (IA) frequency, the factors associated with positive GM test, and the in-hospital mortality. Methods We conducted a retrospective observational study including patients aged 18 or over with hematological malignancy or submitted to HSCT. GM test was measured twice weekly. The hypothesis of IFI was considered in patients with neutropenia and persistent fever despite broad-spectrum antibiotics. Results A total of 496 patients were evaluated; the mean of GM tests performed per patient was 4.2 (+3.1), and 86 (17.3 %) had positive results. IFI was diagnosed in 166 (33.5 %) and IA in 22 (24.6 %) patients. Positive GM test was more frequent in patients with IFI (72.2 % and 25.1 %; OR 8.1; 95 % CI 4.8 - 13.8), and was associated with therapeutic antifungals prescription (52, 9 % and 20.5 %; OR 4.3, 95CI% 2.0 - 9.4), as well as lung abnormalities on HRCT (45.3% vs. 21.5 %; OR 3.0, 95 %CI 1.4 - 6.5). Mortality was 31.6 %. In the multivariate analysis, the variables associated with mortality were the hypothesis of IFI (OR 6.35; 95 % CI 3.63-11.12.0), lung abnormalities on HRCT (57.9 % and 26.9 %; OR 2 0.6; 95 % CI 1.5 - 4.4), and positive GM test (57.9 % and 26.9 %; OR 2.7 95 % CI 1.6 - 4.5). Conclusions Positive GM test was associated with lung abnormalities on HRCT and with the introduction of therapeutic antifungals. If adequate anti-mold prophylaxis is available, the GM test should not be used as screening, but to investigate IFI in high-risk patients. The diagnosis of IFI, positive GM test and lung abnormalities on HRCT were predictors of hospital mortality in patients with hematological malignancies or undergoing HSCT.

5.
Rev. chil. infectol ; 40(6): 665-674, dic. 2023. tab, graf
Artículo en Español | LILACS | ID: biblio-1529997

RESUMEN

INTRODUCCIÓN: Las infecciones fúngicas invasoras (IFI) en pacientes con neoplasias hematológicas (NH) representan un desafío diagnóstico y terapéutico. OBJETIVOS: Describir la etiología, características clínicas, diagnóstico y evolución de los episodios de IFI probadas y probables en pacientes con NH y trasplante de progenitores hematopoyéticos (TPH). PACIENTES Y MÉTODOS: Estudio descriptivo, retrospectivo y de cohorte que incluyó IFI probadas y probables en pacientes adultos con NH y TPH. Se realizó seguimiento hasta el día 90. RESULTADOS: Se incluyeron 80 episodios de IFI: 49% probadas y 51% probables, 67,5% por hongos filamentosos (HF), 30% por hongos levaduriformes (HL) y 2,5% por hongos dimorfos. Los tipos de IFI más frecuentes fueron aspergilosis invasoras pulmonares (AP) y candidiasis invasoras (CI), en su mayoría por Candida spp. no albicans. Todos los casos de AP se diagnosticaron por detección de galactomanano en sangre y/o lavado broncoalveolar, y solamente 22,2% presentaban nódulos con halo en la tomografía computada (TC) de tórax, siendo los infiltrados inespecíficos los hallazgos más frecuentes. Tuvieron coinfección bacteriana y viral el 30 y 17,5%, respectivamente. El 50% fueron IFI de brecha, y la mortalidad global y mortalidad relacionada a la IFI fue 51 y 24%, respectivamente. CONCLUSIÓN: Los HF fueron la principal causa de IFI, con una gran proporción de IFI de brecha, y presentaron elevada mortalidad. Para el diagnóstico, resulta importante la utilización de biomarcadores y jerarquizar cualquier imagen patológica en la TC.


BACKGROUND: Invasive fungal infections (IFI) in patients with hematological malignancies (HM) represent a diagnostic and therapeutic challenge. AIM: To describe the etiology, clinical characteristics, diagnosis and evolution of proven and probable IFI episodes in patients with HM and hematopoietic stem cell transplantation (HSCT). METHODS: Retrospective, descriptive, cohort study performed in adult patients with HM and HSCT, who developed proven and probable IFI. Follow-up was carried out until day 90. RESULTS: A total of 80 IFI episodes were included: 49% proven and 51% probable, 67,5% due to mold (M), 30% to yeast-like fungi (Y) and 2,5% to dimorphic fungi. The most frequent causes were probable pulmonary aspergillosis (PA) and invasive candidiasis (IC), mainly due to non-albicans Candida species. PA were all diagnosed by detection of galactomannan (GM) in blood and bronchoalveolar lavage, and only 22,2% presented halo sign on chest CT. Bacterial and viral coinfections were reported in 30% and 17,5% respectively. Breakthrough IFI occurred in 50%, and global and IFI-related mortality were 51% and 24% respectively. CONCLUSION: Mold was the main cause of IFI, with a large proportion of breakthrough IFI, presenting high mortality. The use of biomarkers and the classification of any pathological image on CT contribute to the diagnosis.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Neoplasias Hematológicas/complicaciones , Infecciones Fúngicas Invasoras/diagnóstico , Infecciones Fúngicas Invasoras/etiología , Argentina , Evolución Clínica , Estudios Retrospectivos , Factores de Riesgo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Neoplasias Hematológicas/mortalidad , Infecciones Fúngicas Invasoras/mortalidad , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Hospitales Universitarios , Antifúngicos/uso terapéutico
6.
Hematol., Transfus. Cell Ther. (Impr.) ; 45(supl.2): S68-S75, July 2023. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1514186

RESUMEN

ABSTRACT Introduction: The data on the pattern of primary hematologic malignancies in Bahrain is sparse, although previously published studies suggested rising trends in their incidence. This study aimed to compare with regional and world data and identify any changing trends. Methods: A retrospective cross-sectional chart analysis study was done on all cases of primary hematologic malignancies of bone marrow origin of Bahraini nationals presenting during the 10-year period from January 2005 to December 2014 at the sole oncology referral center in Bahrain during the study period. Results: In a total of 272 cases, the primary hematologic malignancies in decreasing order of frequency with respective median ages at diagnosis were: acute myeloid leukemia (AML; 26.1%, 39 years), acute lymphoblastic leukemia (ALL; 22.8%, 9 years), multiple myeloma (MM, 16.2%, 57 years), chronic myeloid leukemia (CML, 14%, 39.5 years), myelodysplastic syndromes (MDS; 12.5%, 56 years) and chronic lymphocytic leukemia (CLL; 5.5%, 65 years). The overall crude annual incidence rate of these malignancies was 4.8/105 population. Age-specific incidence rates were found to increase dramatically with age, except for ALL, for which it peaked in the pediatric age group. The age-standardized incidence rates (ASIRs) per 105 per year were 1.47 (AML), 1.13 (MM), 0.93 (ALL), 0.85 (MDS), 0.81 (CML) and 0.44 (CLL). Conclusion: The pattern of primary hematologic malignancies in Bahrain shows unique features that distinguish it from trends reported in Eastern and Western world populations.

7.
Arch. argent. pediatr ; 121(3): e202202714, jun. 2023. ilus
Artículo en Inglés, Español | LILACS, BINACIS | ID: biblio-1436134

RESUMEN

El sarcoma sinovial pleuropulmonar (SSPP) es un tumor primario de pulmón, maligno, infrecuente en pediatría (prevalencia 0,1-0,5 %) que afecta predominantemente a adolescentes y adultos jóvenes. Se ha descrito una sobrevida global cercana al 30 % a los 5 años. Se reporta el caso de un paciente de 12 años de edad, previamente sano, que presentó tos, dolor torácico y disnea de comienzo súbito, como manifestación inicial de neumotórax izquierdo, el que persistió a los 4 días y requirió resección quirúrgica de lesión bullosa pulmonar. Se realizó diagnóstico histológico de sarcoma sinovial pleuropulmonar confirmado por estudio molecular, que evidenció la translocación cromosómica entre el cromosoma X y el 18: t(X;18) (p11.2;q11.2) de la pieza quirúrgica extirpada. Ante pacientes con neumotórax persistente o recidivante, es importante descartar causas secundarias, entre ellas, sarcoma sinovial pleuropulmonar. Su ominoso pronóstico determina la necesidad de arribar a un diagnóstico temprano e implementar un tratamiento agresivo


Pleuropulmonary synovial sarcoma (PPSS) is a primary malignancy of the lung, uncommon in pediatrics (prevalence: 0.1­0.5%) that predominantly affects adolescents and young adults. Overall survival has been reported to be close to 30% at 5 years. Here we report the case of a previously healthy 12-year-old male patient who presented with cough, chest pain, and dyspnea of sudden onset as initial manifestation of left pneumothorax, which persisted after 4 days and required surgical resection of pulmonary bullous lesion. A histological diagnosis of pleuropulmonary synovial sarcoma was made and confirmed by molecular study, which showed chromosomal translocation between chromosomes X and 18: t(X;18) (p11.2;q11.2) in the surgical specimen removed. In patients with persistent or recurrent pneumothorax, it is important to rule out secondary causes, including pleuropulmonary synovial sarcoma. Such poor prognosis determines the need for early diagnosis and aggressive treatment.


Asunto(s)
Humanos , Masculino , Niño , Neumotórax/complicaciones , Neumotórax/etiología , Sarcoma Sinovial/complicaciones , Sarcoma Sinovial/diagnóstico , Sarcoma Sinovial/patología , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico , Tos , Pulmón/patología
8.
Artículo | IMSEAR | ID: sea-218343

RESUMEN

Although breast carcinoma is common, metastatic deposits to the breast from extramammary neoplasms are rare. Clinically and radiologically, metastatic neoplasms may mimic primary benign and malignant neoplasms of the breast. A correct diagnosis of metastasis to the breast is of considerable importance since the treatment of primary and secondary malignancies of the breast is different. We report 4 cases of extra mammary primary cancers metastasizing to the breast, diagnosed by biopsy, in a period of 5 years in our tertiary care centre. Each of the cases had different characteristics. A good knowledge of cytomorphology and histomorphology, together with clinical correlation and comparison with previous histopathological evidence, will prevent a misdiagnosis and aid in optimal management and therapy.

9.
Cancer Research on Prevention and Treatment ; (12): 1010-1014, 2023.
Artículo en Chino | WPRIM | ID: wpr-997695

RESUMEN

With a deepened understanding of the pathophysiology and pathogenesis of thoracic malignancies, the treatment has been transited from traditional treatment on the basis of surgery, radiotherapy, and chemotherapy to individualized and precise targeted therapy and immunotherapy. As an antitumor immunotherapy, chimeric antigen receptor gene-modified T (CAR-T) cells have been approved by the FDA for the treatment of hematological malignancies in five CAR-T products. They have also achieved good therapeutic effects in solid tumors. However, significant challenges remain in the clinical application of CAR-T cell immunotherapy in thoracic malignancies. In this review, the latest research progress of CAR-T cell immunotherapy in the treatment of thoracic malignancies were summarized, including the basic characteristics of CAR-T cells, the popular target antigens, and the existing problems and challenges, to provide new ideas and strategies for clinical immunotherapy of thoracic malignancies.

10.
Chinese Journal of Laboratory Medicine ; (12): 866-871, 2023.
Artículo en Chino | WPRIM | ID: wpr-995803

RESUMEN

N6-Methyladenosine (m6A) is one of the most prevalent RNA modifications in mammals. The m6A modification is catalyzed by m6A writers or erasers and involved in various RNA metabolic processes with the recognition by m6A readers. Recently, emerging studies have shown m6A modification is pivotal in fundamental bioprocesses including cell homeostasis and oxidative stress, programmed cell death, cell metabolism, and immune regulation, and accounts for tumoral occurrence and development. To date, abnormal m6A levels and dysregulated related enzymes participate in tumorigenesis and chemoresistance among acute leukemias, chronic myeloid leukemia, multiple myeloma, lymphomas, thus influencing patient prognosis. The mechanisms of m6A modification are sophisticated and varied in different types of malignancies or subtypes. Screening appropriate patients to apply m6A-targeted inhibitors is instructive to the precise treatment of hematological malignancies.

11.
China Tropical Medicine ; (12): 392-2023.
Artículo en Chino | WPRIM | ID: wpr-979698

RESUMEN

@#Abstract: Objective To investigate the epidemiological characteristics of pathogens causing bloodstream infection in hematology patients during treatment and to compare the effects of allogeneic hematopoietic stem cell transplantation (HSCT) on them, so as to provide evidence for the diagnosis and treatment of bloodstream infection. Methods A total of 292 cases with bloodstream infection in hematology wards of the PLA General Hospital were collected from 2017 to 2021, which were divided into HSCT group and N-HSCT group according to whether performed HSCT or not. The epidemiological characteristics and influence of pathogenic bacteria in blood stream infection were analyzed and compared between the two groups. Results A total of 362 strains of pathogenic bacteria were collected from 292 cases, including 106 strains in HSCT group (84 cases) and 256 strains in N-HSCT group (208 cases). Bloodstream infections were more common in acute myeloid leukemia (130/392, 44.52%), followed by non-Hodgkin's lymphoma (74/292, 25.34%). The rate of once bloodstream infection in HSCT group was higher than that in N-HSCT Group, but the rate of twice bloodstream infections in N-HSCT group was higher. Gram-negative Bacilli were the most common pathogens (56.08%), with Escherichia coli being absolutely dominant (109/362, 30.11%), followed by Klebsiella pneumoniae (39/362, 10.77%). Coagulase-negative staphylococci (CoNS) (107/362, 29.56%) were the most common Gram-positive cocci. The detection rate of fungi in HSCT group (10/106, 9.43%) was significantly higher than that in N-HSCT Group (3.52%). The drug resistance rate of the common pathogenic bacteria was at a high level, and there was a certain proportion of multi-drug resistant strains (except for Pseudomonas aeruginosa). The resistance rates of CoNS to penicillin, gentamicin, moxifloxacin, clindamycin and rifampicin in HSCT group were higher than those in N-HSCT Group. The resistance rate of Escherichia coli to piperacillin/tazobactam, cephalosporins and etapenem in HSCT group was significantly higher than that in N-HSCT group. Conclusions The pathogens of blood stream infection in hematology patients are complicated and various. It is difficult for clinical diagnosis and treatment to detect multiple infections and multiple pathogens. HSCT patients have a higher risk of fungal bloodstream infection and more multi-drug resistant strains detected. Therefore, the identification of bloodstream infection and multi-drug resistant strains associated with HSCT patients should prompt surveillance.

12.
Journal of Leukemia & Lymphoma ; (12): 249-252, 2023.
Artículo en Chino | WPRIM | ID: wpr-988978

RESUMEN

Patients with lymphoid hematologic malignancies have a poor prognosis after developing SARS-CoV-2 infection, and their seropositivity rate after SARS-CoV-2 vaccination is lower than that of the healthy population. Since most clinical trials of SARS-CoV-2 vaccines do not include immunodeficient populations, the safety and efficacy of various types of SARS-CoV-2 vaccines for patients with lymphoid hematologic malignancies are unclear. Therefore, physicians should decide whether patients with lymphoid hematologic malignancies receive SARS-CoV-2 vaccination and the timing, type and dose of vaccine after taking into full consideration the patient's immune status, type of treatment and the risk of SARS-CoV-2 infection.

13.
Journal of Leukemia & Lymphoma ; (12): 193-198, 2023.
Artículo en Chino | WPRIM | ID: wpr-988970

RESUMEN

With the wide application of high-throughput next-generation sequencing (NGS) and other molecular genetic detection technologies, researchers have a more and more in-depth understanding of the pathogenesis of hematologic malignancies, especially of the myeloid hematologic malignancies, which makes the diagnosis and treatment of myeloid hematologic malignancies into an era of precision medicine. At the 64th American Society of Hematology (ASH) Annual Meeting in 2022, there were a series of new progresses regarding the application of NGS in the diagnosis and classification, risk stratification, treatment guidance, and minimal residual disease monitoring of myeloid hematologic malignancies. This article focuses on the progress of NGS application in acute myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms.

14.
Journal of Leukemia & Lymphoma ; (12): 12-17, 2023.
Artículo en Chino | WPRIM | ID: wpr-988946

RESUMEN

Minimal residual disease (MRD) has been used for warning of relapse and guiding the therapy selection for hematological malignancies including acute leukemia. Based on MRD-related content reported at the 64th American Society of Hematology (ASH) Annual Meeting, this article discusses the progress of MRD-directed individualized therapy for hematological malignancies with a primary focus on acute myeloid leukemia.

15.
Journal of Leukemia & Lymphoma ; (12): 8-11, 2023.
Artículo en Chino | WPRIM | ID: wpr-988945

RESUMEN

Minimal residual disease (MRD) has been used not only for relapse prediction, prognosis re-classification and directing pre-emptive therapy of patients with acute leukemia, but also in the field of therapy for patients with other hematological malignancies or solid tumors. A deep understanding of the intension and extension of MRD is important for exploring novel methods for accurate prediction of relapse and consummating the individualized intervention strategies for malignant tumors.

16.
Journal of Experimental Hematology ; (6): 306-310, 2023.
Artículo en Chino | WPRIM | ID: wpr-971142

RESUMEN

Long non-coding RNA (lncRNA) is a hot topic in the field of researching tumor pathogenesis, and the importance in hematologic malignancies has been gradually being elucidated. LncRNA not only regulates hematological tumorigenesis and progression through affecting various biological processes such as cell proliferation, differentiation, pluripotency and apoptosis; moreover, abnormal expression and mutation of lncRNA are closely related to drug resistance and prognosis. Thus lncRNA can be used as novel biomarker and potential therapeutic target for hematological tumors. In this review, we will focus on the latest progress of lncRNA in hematological tumors to provide new ideas for the clinical diagnosis, prognostic evaluation together with research and development of target drugs for hematologic malignancies.


Asunto(s)
Humanos , ARN Largo no Codificante/metabolismo , Neoplasias Hematológicas/genética , Neoplasias , Carcinogénesis/patología , Transformación Celular Neoplásica/genética , Regulación Neoplásica de la Expresión Génica
17.
JOURNAL OF RARE DISEASES ; (4): 414-419, 2023.
Artículo en Inglés | WPRIM | ID: wpr-1004968

RESUMEN

The research and development of somatostatin analogues is a hot area in endocrinology and metabolism. The first generation octreotide, lanreotide and the second generation pareotide have been approved to be effective for the treatment of neuroendocrine tumors such as acromegaly. However, paltusotine, a somatostatin receptor ligand, is a novel non-peptide small molecule drug which can be administered orally and inhibits excessive secretion of growth hormone and insulin-like growth factor 1. This review summarizes the research progress of the pharmacokinetics, pharmacodynamics, clinical efficacy, telerability, and safety of paltusotine.

18.
Journal of Experimental Hematology ; (6): 1921-1924, 2023.
Artículo en Chino | WPRIM | ID: wpr-1010061

RESUMEN

Proteolysis-targeting chimeras (PROTACs) are heterobifunctional small molecules by utilizing the ubiquitin proteasome system (UPS) to degrade proteins of interest. PROTACs have exhibited unprecedented efficacy and specificity in degrading various oncogenic proteins because of their unique mechanism of action, ability to target "undruggable" and mutant proteins. A series of PROTACs have been developed to degrade multiple key protein targets for the treatment of hematologic malignancy. Notably, PROTACs that target BCL-XL, IRAK4, STAT3 and BTK have entered clinical trials. The known PROTACs that have the potential to be used to treat various hematological malignancies are systematically summarized in this review.


Asunto(s)
Humanos , Neoplasias Hematológicas/tratamiento farmacológico , Complejo de la Endopetidasa Proteasomal/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Quimera Dirigida a la Proteólisis
19.
Journal of Experimental Hematology ; (6): 992-998, 2023.
Artículo en Chino | WPRIM | ID: wpr-1009954

RESUMEN

OBJECTIVE@#To detect the gene mutations in patients with myeloid malignancies by high-throughput sequencing and explore the correlation between gene mutations and prognosis.@*METHODS@#A retrospective analysis was performed on 56 patients with myeloid malignancies who were hospitalized in the department of hematology, Peking University International Hospital from January 2020 to May 2021. The genetic mutations of the patients were detected by next-generation sequencing technology, and the correlation between the genetic mutations and prognosis of myeloid malignancies was analyzed.@*RESULTS@#In 56 patients, the number of mutated genes detected in a single patient is 0-9, with a median of 3. Sequencing results showed that the most common mutated genes were RUNX1(21.4%), TET2(17.9%), DNMT3A(17.9%), TP53(14.3%) and ASXL1(14.3%), among which the most common mutations occurred in the signaling pathway-related genes (23.3%) and the transcription factor genes (18.3%). 84% of the patients carried multiple mutated genes (≥2), and correlation analysis showed there were obvious co-occurring mutations between WT1 and FLT3, NPM1 and FLT3-ITD, and MYC and FLT3. TP53 mutation was more common in MDS patients.The overall survival time of patients with NRAS mutation was significantly shortened (P =0.049). The prognosis of patients with TP53 mutation was poor compared with those without TP53 mutation, but the difference wasn't statistically significant (P =0.08).@*CONCLUSION@#The application of next-generation sequencing technology is of great significance in myeloid malignancies, which is helpful to better understand the pathogenesis of the disease, to judge the prognosis and to find possible therapeutic targets.


Asunto(s)
Humanos , Leucemia Mieloide Aguda/genética , Nucleofosmina , Pronóstico , Estudios Retrospectivos , Secuenciación de Nucleótidos de Alto Rendimiento , Trastornos Mieloproliferativos , Mutación
20.
Chinese Journal of Hematology ; (12): 479-483, 2023.
Artículo en Chino | WPRIM | ID: wpr-984647

RESUMEN

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.


Asunto(s)
Humanos , Bacteriemia/epidemiología , Cefoperazona , Sulbactam , Estudios Retrospectivos , Farmacorresistencia Bacteriana , Pruebas de Sensibilidad Microbiana , Neoplasias Hematológicas , Sepsis , Antibacterianos/farmacología , Bacterias Gramnegativas , Bacterias Grampositivas , Combinación Piperacilina y Tazobactam , Escherichia coli
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