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1.
Methods Mol Biol ; 2519: 127-140, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36066718

RESUMO

Hi-C is a method that analyzes genome-wide chromatin structure using next-generation sequencer. Chromatin structure is crucial for regulating transcription or replication, and Hi-C has revealed the hierarchical chromatin structures, such as loop, domain , and compartment structures. Aberrant alteration of these structures causes disease, and a number of structural aberrations in cancer cells have been reported recently. Besides, Hi-C can identify chromosome rearrangements that frequently occurred in cancer. Therefore, Hi-C is a powerful technique to analyze epigenomic and genomic aberrations in tumorigenesis. Here we will introduce the basic protocol of Hi-C in experimental and analytical aspects.


Assuntos
Cromatina , Neoplasias , Cromatina/genética , Cromossomos , Genoma , Genômica/métodos , Humanos , Neoplasias/genética
2.
Mol Cancer ; 21(1): 32, 2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-35090469

RESUMO

N6-methyladenosine (m6A) methylation, the most common form of internal RNA modification in eukaryotes, has gained increasing attention and become a hot research topic in recent years. M6A plays multifunctional roles in normal and abnormal biological processes, and its role may vary greatly depending on the position of the m6A motif. Programmed cell death (PCD) includes apoptosis, autophagy, pyroptosis, necroptosis and ferroptosis, most of which involve the breakdown of the plasma membrane. Based on the implications of m6A methylation on PCD, the regulators and functional roles of m6A methylation were comprehensively studied and reported. In this review, we focus on the high-complexity links between m6A and different types of PCD pathways, which are then closely associated with the initiation, progression and resistance of cancer. Herein, clarifying the relationship between m6A and PCD is of great significance to provide novel strategies for cancer treatment, and has a great potential prospect of clinical application.


Assuntos
Adenosina , Neoplasias , Adenosina/análogos & derivados , Adenosina/metabolismo , Apoptose/genética , Humanos , Metilação , Neoplasias/genética , Neoplasias/metabolismo
3.
Cell Commun Signal ; 20(1): 14, 2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-35090497

RESUMO

Programmed cell death 1 ligand 1 (PD-L1) is the ligand for programmed death protein-1 (PD-1), is associated with immunosuppression. Signaling via PD-1/PD-L1 will transmits negative regulatory signals to T cells, inducing T-cell inhibition, reducing CD8+ T-cell proliferation, or promoting T-cell apoptosis, which effectively reduces the immune response and leads to large-scale tumor growth. Accordingly, many antibody preparations targeting PD-1 or PD-L1 have been designed to block the binding of these two proteins and restore T-cell proliferation and cytotoxicity of T cells. However, these drugs are ineffective in clinical practice. Recently, numerous of studies have shown that, in addition to the surface of tumor cells, PD-L1 is also found on the surface of extracellular vesicles secreted by these cells. Extracellular vesicle PD-L1 can also interact with PD-1 on the surface of T cells, leading to immunosuppression, and has been proposed as a potential mechanism underlying PD-1/PD-L1-targeted drug resistance. Therefore, it is important to explore the production, regulation and tumor immunosuppression of PD-L1 on the surface of tumor cells and extracellular vesicles, as well as the potential clinical application of extracellular vesicle PD-L1 as tumor biomarkers and therapeutic targets. Video Abstract.


Assuntos
Vesículas Extracelulares , Neoplasias , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Linfócitos T CD8-Positivos , Vesículas Extracelulares/metabolismo , Humanos , Neoplasias/metabolismo , Microambiente Tumoral
4.
J Immunol Res ; 2022: 8052212, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35340585

RESUMO

With the huge therapeutic potential, cancer immunotherapy is expected to become the mainstream of cancer treatment. In the current field of cancer immunotherapy, there are mainly five types. Immune checkpoint blockade therapy is one of the most promising directions. Adoptive cell therapy is an important component of cancer immunotherapy. The therapy with the cancer vaccine is promising cancer immunotherapy capable of cancer prevention. Cytokine therapy is one of the pillars of cancer immunotherapy. Oncolytic immunotherapy is a promising novel component of cancer immunotherapy, which with significantly lower incidence of serious adverse reactions. The recent positive results of many clinical trials with cancer immunotherapy may herald good clinical prospects. But there are still many challenges in the broad implementation of immunotherapy. Such as the immunotherapy cannot act on all tumors, and it has serious adverse effects including but not limited to nonspecific and autoimmunity inflammation. Here, we center on recent progress made within the last 5 years in cancer immunotherapy. And we discuss the theoretical background, as well as the opportunities and challenges of cancer immunotherapy.


Assuntos
Vacinas Anticâncer , Neoplasias , Vacinas Anticâncer/uso terapêutico , Humanos , Fatores Imunológicos , Imunoterapia/métodos , Imunoterapia Adotiva
5.
Psychooncology ; 31(1): 107-115, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34425036

RESUMO

OBJECTIVE: CanCope is an internet-delivered, cognitive-behavioural intervention adapted from the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders to improve emotion regulation and support the mental health of cancer survivors. Four separate pilot studies evaluated each of CanCope's modules for (1) feasibility and participant satisfaction, and changes in (2) module-specific outcomes, and (3) global measures of emotion dysregulation and anxiety and depressive symptoms, from pre-to-post module delivery. METHODS: Eligible cancer survivors self-selected into one two-week online module designed to improve a specific aspect of emotion regulation ([1] understanding emotions, [2] mindfulness of emotions, [3] cognitive reappraisals, [4] challenging emotion-driven behaviours). RESULTS: Across modules, post-intervention surveys were completed by 17-19 participants, (58.1%-90.5% completion rate for participants who received the intervention). Each module was feasible and participants reported high satisfaction. Moderate-to-large pre-to-post effect sizes in mean differences were observed in module-specific target outcomes (p's < 0.05). Emotion dysregulation significantly decreased across modules 1 to 3 (p's < 0.05) with a non-significant decrease for module 4 (p = 0.13). Anxiety symptoms significantly decreased across all modules (p's < 0.05). Depressive symptoms significantly decreased across modules 1 and 3 (p's < 0.05), with non-significant decreases across modules 2 (p = 0.08) and 4 (p = 0.06). CONCLUSIONS: Each CanCope module demonstrated promise in targeting emotion regulation skills and supporting the mental health of cancer survivors. Randomised controlled trials are required to test the efficacy of CanCope as an intervention in its entirety.


Assuntos
Sobreviventes de Câncer , Terapia Cognitivo-Comportamental , Intervenção Baseada em Internet , Neoplasias , Transtornos de Ansiedade/terapia , Sobreviventes de Câncer/psicologia , Terapia Cognitivo-Comportamental/métodos , Humanos , Saúde Mental , Neoplasias/terapia
6.
In Vivo ; 36(2): 898-906, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35241548

RESUMO

BACKGROUND/AIM: An early evaluation concerning the effectiveness of supportive oligonucleotide therapy (SOT) in cancer as a monotherapy and in combination with other types of treatment. PATIENTS AND METHODS: This study evaluated the clinical condition and performance status (Karnofsky-Index) of 95 patients, post-SOT administration. Furthermore, circulating tumor cells (CTCs) from 47 patients' pre- and post-SOT administration were measured and analyzed by repeated-measures ANOVA. RESULTS: Improvement of the clinical condition was observed in all patients who used SOT (77.89%), SOT in combination with other therapy (69.77%) and SOT as a monotherapy or no information was given concerning another therapy (84.31%). Positive results for Karnofsky-Index were also observed in 71.58%, 61.36%, and 80.39%, respectively. Finally, statistically significant reductions in CTCs were observed for both SOT as a monotherapy and SOT as an adjunctive therapy. CONCLUSION: The preliminary results indicate that SOT therapy can be used both as monotherapy as well as in combination with other therapies for cancer.


Assuntos
Neoplasias , Oligonucleotídeos , Humanos , Neoplasias/terapia , Oligonucleotídeos/uso terapêutico
7.
Clin. transl. oncol. (Print) ; 24(10): 1833–1843, octubre 2022.
Artigo em Inglês | IBECS | ID: ibc-207940

RESUMO

Chimeric antigen receptor (CAR) T cell therapy is a novel therapeutic approach that uses gene editing techniques and lentiviral transduction to engineer T cells so that they can effectively kill tumors. However, CAR T cell therapy still has some drawbacks: many patients who received CAR T cell therapy and achieve remission, still had tumor relapse and treatment resistance, which may be due to tumor immune escape and CAR T cell dysfunction. To overcome tumor relapse, more researches are being done to optimize CAR T cell therapy to make it more precise and personalized, including screening for more specific tumor antigens, developing novel CAR T cells, and combinatorial treatment approaches. In this review, we will discuss the mechanisms as well as the progress of research on overcoming plans. (AU)


Assuntos
Humanos , Antígenos , Neoplasias , Imunoterapia Adotiva , Linfócitos T , Microambiente Tumoral
8.
Clin. transl. oncol. (Print) ; 24(10): 1844–1855, octubre 2022.
Artigo em Espanhol | IBECS | ID: ibc-207941

RESUMO

Epithelial-to-mesenchymal transition (EMT) confers the most lethal characteristics to cancer cells i.e., metastasis and resistance to chemo-and-radio-therapy, and therefore exhibit an appealing target in the field of oncology. Research in the past decade has demonstrated the crucial role of aerobic glycolysis in EMT, which is generally credited as the glucose metabolism for the creation of biomass such as fatty acids, amino acids, and nucleotides thereby providing building blocks for limitless proliferation. In the present review, apart from discussing EMT’s evident role in the metastatic process and cancer stemness, we also talked about the vital role of glycolytic enzymes viz. GLUTs, HKs, PGI, PFK-1, aldolase, enolase, PK, LDHA, etc. in the induction of the EMT process in cancerous cells. (AU)


Assuntos
Humanos , Carcinogênese , Transição Epitelial-Mesenquimal , Glicólise , Células-Tronco Neoplásicas , Neoplasias
9.
Clin. transl. oncol. (Print) ; 24(10): 1856–1864, octubre 2022.
Artigo em Inglês | IBECS | ID: ibc-207942

RESUMO

Due to the bottlenecks encountered in traditional treatment for tumor, more effective drug targets need to be developed. Cell division cycle 7 kinase plays an important role in DNA replication, DNA repair and recombination signaling pathways. In this review, we first describe recent studies on the role of CDC7 in DNA replication in normal human tissues, and then we integrate new evidence focusing on the important role of CDC7 in replication stress tolerance of tumor cells and its impact on the prognosis of clinical oncology patients. Finally, we comb through the CDC7 inhibitors identified in recent studies as a reference for further research in clinical practice. (AU)


Assuntos
Humanos , Biomarcadores , Proteínas de Ciclo Celular , DNA , Proteínas Serina-Treonina Quinases , Neoplasias
11.
Clin. transl. oncol. (Print) ; 24(10): 2044-2044, octubre 2022.
Artigo em Inglês | IBECS | ID: ibc-207960

RESUMO

Histone lysine methylation plays a key role in gene activation and repression. The trimethylation of histone H3 on lysine-27 (H3K27me3) is a critical epigenetic event that is controlled by Jumonji domain-containing protein-3 (JMJD3). JMJD3 is a histone demethylase that specifically removes methyl groups. Previous studies have suggested that JMJD3 has a dual role in cancer cells. JMJD3 stimulates the expression of proliferative-related genes and increases tumor cell growth, propagation, and migration in various cancers, including neural, prostate, ovary, skin, esophagus, leukemia, hepatic, head and neck, renal, lymphoma, and lung. In contrast, JMJD3 can suppress the propagation of tumor cells, and enhance their apoptosis in colorectal, breast, and pancreatic cancers. In this review, we summarized the recent advances of JMJD3 function in cancer cells. (AU)


Assuntos
Humanos , Metilação , Neoplasias , Apoptose
12.
Oncol Nurs Forum ; 49(5): 445-453, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36067244

RESUMO

OBJECTIVES: Hematologic malignancies (HMs) are life-threatening cancers that frequently entail aggressive, long, inpatient treatment protocols. This can result in numerous concurrent symptoms and decreased quality of life for patients and can affect family caregivers (FCs). This study examined the impact of an HM diagnosis on patients and on their FCs. SAMPLE & SETTING: A descriptive design was used to explore the experiences of 28 newly diagnosed patients and their FCs. All patients were receiving treatment on an inpatient acute oncology unit at a National Cancer Institute-designated cancer center. METHODS & VARIABLES: Semistructured, separate interviews with patients and FCs were recorded and transcribed verbatim. Textual and content analyses were conducted to generate common themes. RESULTS: Patients and FCs reported how diagnosis and treatment affected them physically, emotionally, logistically, and financially. They described the effects of their experiences with the health system and providers in areas such as diagnostic process, trust in the medical team, support needs, and hospitalization. IMPLICATIONS FOR NURSING: Understanding the parallel experiences of patients with HMs and their designated FCs allows researchers to develop targeted interventions and enables clinicians to provide personalized patient- and family-centered care.


Assuntos
Neoplasias Hematológicas , Neoplasias , Monofosfato de Adenosina , Cuidadores/psicologia , Família/psicologia , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Humanos , Neoplasias/psicologia , Cuidados Paliativos/psicologia , Qualidade de Vida/psicologia
13.
Oncol Nurs Forum ; 49(5): 433-443, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36067243

RESUMO

OBJECTIVES: Patients with advanced cancer and minor children experience high rates of depression and anxiety. However, associations between parental status and other aspects of the patient experience are not well understood. This study compared patient-reported outcomes of patients with and without minor children. SAMPLE & SETTING: This was a retrospective analysis of 448 adults with stage III or IV solid tumors from a public research registry. METHODS & VARIABLES: Multiple linear regression models or modified Poisson regression models were fitted to evaluate differences in health-related quality of life, global health, and patient satisfaction scores between patients living with and without minors. RESULTS: One in five patients lived with minor children. They reported significantly worse health-related quality of life, global physical health, and global mental health. They also expressed lower satisfaction with time spent with their provider, communication, and financial aspects. IMPLICATIONS FOR NURSING: Patients with minor children may benefit from earlier identification and support for their psychosocial needs and concerns.


Assuntos
Neoplasias , Qualidade de Vida , Monofosfato de Adenosina , Adulto , Criança , Humanos , Neoplasias/psicologia , Satisfação do Paciente , Satisfação Pessoal , Qualidade de Vida/psicologia , Estudos Retrospectivos
14.
Oncol Nurs Forum ; 49(5): 455-460, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36067245

RESUMO

OBJECTIVES: To evaluate preliminary efficacy, fidelity, and integrity of data collection of a nurse-led, telemedicine-delivered video visit intervention aimed at improving management of rural survivors' cancer-related distress symptoms. SAMPLE & SETTING: 21 rural survivors participated in a nurse-led telemedicine intervention delivered six weeks after the end of active cancer treatment. METHODS & VARIABLES: Participants' symptom management was measured with the Short Form Survivor Unmet Needs Survey, a four-factor, 30-item instrument that measures the unmet needs of adult survivors. Data were collected preintervention and six weeks postintervention. RESULTS: The mean difference between pre- and postintervention survey scores was -0.24, representing an overall improvement in management of unmet needs. The unmet emotional needs domain had the highest mean preintervention score and the largest mean reduction. All effect sizes were small. IMPLICATIONS FOR NURSING: A nurse-led, telemedicine-delivered video visit intervention may improve rural survivors' symptom management during early survivorship. Comparison with a control group using a sample size powered to detect clinically meaningful differences is an important next step to fully evaluate the impact of this model of care.


Assuntos
Neoplasias , Telemedicina , Monofosfato de Adenosina , Adulto , Humanos , Neoplasias/terapia , Qualidade de Vida/psicologia , População Rural , Sobreviventes/psicologia , Telemedicina/métodos
15.
Oxid Med Cell Longev ; 2022: 9614819, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046686

RESUMO

Protein disulfide isomerase A3 (PDIA3) is a kind of thiol oxidoreductase with a wide range of functions, and its expression is elevated in a variety of tumors, which is closely related to the invasion and metastasis of tumor cells, and has a significant impact on the immunogenicity of tumor cells. Although more and more studies have shown that PDIA3 plays an important role in the occurrence and development of many tumors, there is no systematic pan-cancer study on PDIA3. Therefore, in this study, the differential expression of PDIA3 in 33 kinds of tumors was analyzed to explore its ability to regulate tumor immunity as a biomarker and evaluate its role in different cancer onset stages or clinical prognosis. In this paper, by analyzing the multilevel data including 33 kinds of cancers in the databases of Cancer Genome Atlas (TCGA), UCSC Xena, Cancer Cell Encyclopedia (CCLE), Genotypic Tissue Expression (GTEx), Human Protein Atlas (HPA), cBioPortal, and GDC; the differential expression level of PDIA3 in different types of malignant tumors and its relationship with prognosis and the potential correlation between PDIA3 expression and microsatellite instability (MSI), tumor mutation load (TMB), mismatch repair gene (MMR), DNA methylation level, and immune infiltration level were analyzed with bioinformatics. The results showed that PDIA3 was highly expressed in 19 types of cancers, but downregulated only in THCA. Next, PDIA3 in different tumors was positively or negatively correlated with patient outcome, Kaplan-Meier survival analysis showed that PDIA3 plays an important role in the prognosis of patients with KIRP, KICH, and CESC and may be used as a prognostic biomarker, and the methylation level of PDIA3 promoter region was closely related to patient outcome in eight tumors. The expression level of PDIA3 was correlated with TMB in 13 tumors and MSI in 9 tumors. Among them, the expression level of PDIA3 in THYM has the strongest correlation with TMB, and the expression level of PDIA3 in READ has the strongest correlation with MSI. In addition, the expression of PDIA3 in eight kinds of tumors, including BRCA, HNSC, THYM, LGG, LUAD, LUSC, PRAD, and THCA, had the highest correlation with the infiltration degree of immune cells, and the expression of PDIA3 had the highest correlation with the infiltration degree of 11 kinds of immune cells, including regulatory T cell and macrophages. And LGG is the tumor most likely to be affected by the tumor microenvironment to affect its development and prognosis. To sum up, this study suggests that PDIA3 plays an important role in the occurrence and development of KIRP, KICH, and CESC and in the immunotherapeutic response of THYM, READ, and LGG and can be used as a prognostic biomarker for these tumors.


Assuntos
Neoplasias , Isomerases de Dissulfetos de Proteínas , Biomarcadores/metabolismo , Metilação de DNA/genética , Humanos , Fatores Imunológicos , Imunoterapia , Neoplasias/genética , Neoplasias/terapia , Isomerases de Dissulfetos de Proteínas/genética , Isomerases de Dissulfetos de Proteínas/metabolismo , Microambiente Tumoral
16.
Biomark Med ; 16(13): 959-970, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36052661

RESUMO

Aim: To investigate potential DNA methylation in methylcytosine dioxygenases and correlation of TET genes with vitamin B12/ferritin levels in cancer patients. Materials & methods: 200 blood samples were obtained from both cancer patients and healthy individuals. Results: The expression of DNMT1, DNMT3a and DNMT3b was increased in patients with low vitamin B12 and ferritin levels, while the expression of MTR, TET1 and TET3 significantly decreased. DNA methylation analysis in patients with deficient vitamin B12/ferritin levels showed methylomic changes within the location 318/CG and 385/CG in the promoter region of TET1 and TET3, respectively. Conclusion: Vitamin B12/ferritin deficiency contributes to DNA methylation progress in cancer patients.


Assuntos
Dioxigenases , Neoplasias , 5-Metilcitosina/metabolismo , Metilação de DNA , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dioxigenases/genética , Dioxigenases/metabolismo , Epigênese Genética , Ferritinas/metabolismo , Humanos , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Neoplasias/complicações , Neoplasias/genética , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas/genética , Vitamina B 12
17.
Cancer Imaging ; 22(1): 44, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057635

RESUMO

AIM: We aimed to evaluate the prevalence of incidental 68 Ga-DOTA-conjugated somatostatin receptor-targeting peptide PET/CT (SSTR PET/CT) findings, their clinical significance in the need for follow-up, and their risk of malignancy. MATERIALS AND METHODS: Studies reporting incidental SSTR PET/CT findings were systematically searched in PubMed, Cochrane, Embase and Web of Science literature published prior to 1st of May 2020. Studies were filtered by two independent readers for eligibility based on title and abstract, and subsequently on full text. The main exclusion criteria were: 1) pathological findings that matched scan indication, 2) known organ specific disease and/or incidental findings confirmed on other scan modality prior to SSTR PET/CT, 3) lack of diagnosis and/or follow up, and 4) results published in proceedings or conference abstracts. RESULTS: Twenty-one studies, comprising a total of 2906 subjects, were eligible for the analysis. Studies included were retrospective cohort studies on incidental SSTR PET/CT findings in a specific organ (n = 2888, 7/21) or case reports (n = 18, 14/21). A total of 133 subjects had incidental SSTR PET/CT findings. Incidental findings were predominantly seen in the thyroid gland (n = 65), spine (n = 30), brain (n = 26) and breast (n = 6). Seventeen of 133 (13%) incidental findings were malignant on final diagnosis. Incidental breast findings were associated with the highest risk of malignancy (67%). In the thyroid, incidental SSTR uptake was caused by malignancy in 8%, all presenting as focal uptake. The lowest risk was seen in the spine with a malignancy rate of 3% in patients with incidental SSTR uptake and benign cases were interpreted as vertebral hemangiomas on CT. Incidental SSTR PET/CT findings in other locations were of malignant etiology in two out of six cases (33%) and should be evaluated individually. CONCLUSION: The most incidental SSTR PET/CT findings were found in the thyroid gland, spine, and brain. The risk of malignancy was greatest in incidental SSTR PET/CT findings in the breast, cranially, and thyroid gland. The results of the present study can prove useful in the interpretation of atypical findings on SSTR PET/CT and in the counseling of clinicians.


Assuntos
Neoplasias , Receptores de Somatostatina , Compostos Heterocíclicos com 1 Anel , Humanos , Achados Incidentais , Neoplasias/diagnóstico por imagem , Neoplasias/epidemiologia , Peptídeos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prevalência , Estudos Retrospectivos
18.
Mol Med ; 28(1): 101, 2022 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-36058921

RESUMO

BACKGROUND: Deregulated translation initiation is implicated extensively in cancer initiation and progression. It is actively pursued as a viable target that circumvents the dependency on oncogenic signaling, a significant factor in current strategies. Eukaryotic translation initiation factor (eIF) 4A plays an essential role in translation initiation by unwinding the secondary structure of messenger RNA (mRNA) upstream of the start codon, enabling active ribosomal recruitment on the downstream genes. Several natural product molecules with similar scaffolds, such as Rocaglamide A (RocA), targeting eIF4A have been reported in the last decade. However, their clinical utilization is still elusive due to several pharmacological limitations. In this study we identified new eIF4A1 inhibitors and their possible mechanisms. METHODS: In this report, we conducted a pharmacophore-based virtual screen of RocA complexed with eIF4A and a polypurine RNA strand for novel eIF4A inhibitors from commercially available compounds in the MolPort Database. We performed target-based screening and optimization of active pharmacophores. We assessed the effects of novel compounds on biochemical and cell-based assays for efficacy and mechanistic evaluation. RESULTS: We validated three new potent eIF4A inhibitors, RBF197, RBF 203, and RBF 208, which decreased diffuse large B-cell lymphoma (DLBCL) cell viability. Biochemical and cellular studies, molecular docking, and functional assays revealed that thosenovel compounds clamp eIF4A into mRNA in an ATP-independent manner. Moreover, we found that RBF197 and RBF208 significantly depressed eIF4A-dependent oncogene expression as well as the colony formation capacity of DLBCL. Interestingly, exposure of these compounds to non-malignant cells had only minimal impact on their growth and viability. CONCLUSIONS: Identified compounds suggest a new strategy for designing novel eIF4A inhibitors.


Assuntos
Linfoma , Neoplasias , Fator de Iniciação 4A em Eucariotos/química , Fator de Iniciação 4A em Eucariotos/genética , Fator de Iniciação 4A em Eucariotos/metabolismo , Humanos , Linfoma/tratamento farmacológico , Simulação de Acoplamento Molecular , RNA Mensageiro/metabolismo
19.
World J Surg Oncol ; 20(1): 245, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36058927

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is a threat to the prognosis of tumor patients, especially for critically ill patients. No uniform standard model of VTE risk for critically ill patients with tumors was formatted by now. We thus analyzed risk factors of VTE from the perspectives of patient, tumor, and treatment and assessed the predictive value of the ICU-VTE score, which consisted of six independent risk factors (central venous catheterization, 5 points; immobilization ≥ 4 days, 4 points; prior VTE, 4 points; mechanical ventilation, 2 points; lowest hemoglobin during hospitalization ≥ 90 g/L, 2 points; and baseline platelet count > 250,000/µL, 1 points). METHODS: We evaluated the data of tumor patients admitted to the intensive care unit of the Peking University Cancer Hospital between November 2011 and January 2022; 560 cases who received VTE-related screening during hospitalization were chosen for this retrospective study. RESULTS: The inhospital VTE occurrence rate in our cohort was 55.7% (312/560), with a median interval from ICU admission to VTE diagnosis of 8.0 days. After the multivariate logistic regression analysis, several factors were proved to be significantly associated with inhospital VTE: age ≥ 65 years, high tumor grade (G3-4), medical diseases, fresh frozen plasma transfusion, and anticoagulant prophylaxis. The medium-high risk group according to the ICU-VTE score was positively correlated with VTE when compared with the low-risk group (9-18 points vs. 0-8 points; OR, 3.13; 95% CI, 2.01-4.85, P < 0.001). The AUC of the ICU-VTE scores according to the ROC curve was 0.714 (95% CI, 0.67-0.75, P < 0.001). CONCLUSIONS: The ICU-VTE score, as well as tumor grade, might assist in the assessment of inhospital VTE risk for critically ill patients with tumors. The predictive accuracy might be improved when combining two of them; further follow-up researches are needed to confirm it.


Assuntos
Neoplasias , Tromboembolia Venosa , Idoso , Transfusão de Componentes Sanguíneos , Estado Terminal/terapia , Humanos , Unidades de Terapia Intensiva , Neoplasias/complicações , Neoplasias/terapia , Plasma , Estudos Retrospectivos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia
20.
Pathol Oncol Res ; 28: 1610401, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061145

RESUMO

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-mediated senescence-associated secretory phenotype (SASP) pathway has recently been identified in the suppression and promotion of cancers. However, its practical role in carcinogenesis remains to be comprehensively elucidated. Here, we describe an investigation analysing SASP activity and its correlations with DNA damage response (DDR), genomic mutations, and cell proliferation in gastric carcinogenesis among 30 cases with available endoscopic submucosal dissection (ESD) specimens of early neoplastic lesions (including low-grade dysplasia [LGD], high-grade dysplasia [HGD], and intramucosal carcinoma). The positive cells of senescence-associated ß-galactosidase staining and cGAS, STING, interferon-regulatory factor 3 (IRF3), and signal transducer and activator of transcription 6 (STAT6) expression levels using immunostaining were elevated in HGD and in cancers. Similarly, increased expression of the Fanconi anemia group D2 (FANCD2) protein, tumour suppressor p53 binding protein 1 (TP53BP1), and replication protein A (RPA2) (i.e., primary DDR factors) was detected in HGD and in cancers; these increased expression levels were closely correlated with high expression of Ki67 and minichromosome maintenance complex component 7 (MCM7) proteins. Moreover, genomic mutations in TP53 gene were detected in 56.67% of the evaluated cases (17/30) using next-generation sequencing, and positive staining was verified in HGD and in cancers. Statistical analysis revealed that cell proliferation closely correlated with the expression of DDR factors, of which TP53BP1 was positively associated with SASP factors and IRF3 was positively correlated with cell proliferation. In addition, an analysis evaluating clinical features demonstrated that STAT6-positive cases showed a longer progression-free survival time than STAT6-negative cases. Our evaluation, conducted using a limited number of specimens, suggests SASP may be prevalent in early gastric neoplastic lesions and could be activated by accelerated cell proliferation-induced DDR. The clinical significance of SASP still needs to be determined.


Assuntos
Senescência Celular , Neoplasias , Carcinogênese , Proliferação de Células/genética , Senescência Celular/genética , Dano ao DNA/genética , Humanos , Proteínas de Membrana , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo
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