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PURPOSE: The purpose of this study was to explore latent profiles of illness perception among cancer patients and its influencing factors. METHODS: This study was a cross-sectional study adopting convenience sampling to select cancer patients from two hospitals in China. A total of 286 patients completed Brief Illness Perception Questionnaire, Post-traumatic Growth Inventory, Fear of Disease Progression Questionnaire and Psychosocial Adjustment to Illness Scale. Latent profile analysis and multiple linear regression were performed to explore the subgroups and factors influencing classification. RESULTS: Three subgroups were identified, which were labelled as "Moderate Illness Perception Group" (16.8%; C1), "High Illness Perception with Heightened Concerns Group" (68.5%; C2) and "High Resilience and Low Symptomatic Impact Group" (14.7%; C3). Specifically, "Normal", "Mild symptom" and "Bed time during the day <50%" of "Functional Status" were more associated with C3. "Worker", "Farmer" and "Self-employed" were more associated with C1 and C2. Patients who had more "knowledge of the disease" were more associated with C2 and C3, who had less "post-traumatic growth" were more associated with C1, and who had less "fear of disease progression" and more "psychosocial adjustment" were more associated with C3 (all P < 0.05). CONCLUSIONS: There was significant variability of illness perception among three subgroups of cancer patients, which emphasized the complexity of psychological condition. The insights derived from these distinct profiles enables tailored interventions and patient-centered communication strategies. However, integrating objective measures or biomarkers is needed to complement self-reported data.
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Adaptação Psicológica , Neoplasias , Humanos , Estudos Transversais , Inquéritos e Questionários , Percepção , Progressão da DoençaRESUMO
Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen for the global pork industry. Although modified live virus (MLV) vaccines are commonly used for PRRSV prevention and control, they still carry a risk of infecting the host and replicating in target cells, thereby increasing the likehood of virus recombination and reversion to virulence. In this study, we inserted the target sequence of miR-142 into the nsp2 hypervariable region of PRRSV to inhibit viral replication in its host cells of pigs, with the aim of achieving virus attenuation. The chimeric virus RvJX-miR-142t was successfully rescued and retained its growth characteristics in MARC-145 cells. Furthermore, it did not replicate in MARC-145 cells transfected with miRNA-142 mimic. We also observed limited replication ability of RvJX-miR-142t in pulmonary alveolar macrophages, which are the main cell types that PRRSV infects. Our animal inoculation study showed that pigs infected with RvJX-miR-142t displayed less severe clinical symptoms, lower viremia titers, lighter lung lesions, and significantly lower mortality rates during the first 7 days post-inoculation, in comparison to pigs infected with the backbone virus RvJXwn. We detected a partially deletion of the miR-142 target sequence in the RvJX-miR-142t genome at 14 dpi. It is highly possible that the reversion of viral virulence observed in the later timepoints of our animal experiment was caused by that. Our study provided a new strategy for attenuating PRRSV and confirmed its effectiveness. However, further studies are necessary to increase the stability of this virus under host selection pressure.
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BACKGROUND: Next-generation sequencing (NGS) is maturely applied for gene fusion detection. Although tumor fusion burden (TFB) has been identified as an immune marker for cancer, the relationship between these fusions and the immunogenicity and molecular characteristics of gastric cancer (GC) patients remains unclear. GCs have different clinical significance depending on their subtypes, and thus, this study aimed to investigate the characteristics and clinical relevance of TFB in non-Epstein-Barr-virus-positive (EBV+) GC with microsatellite stability (MSS). METHODS: A total of 319 GC patients from The Cancer Genome Atlas stomach adenocarcinoma (TCGA-STAD) and a cohort of 45-case from ENA (PRJEB25780) were included. The cohort characteristics and distribution of TFB among the patients were analyzed. Additionally, the correlations of TFB with mutation characteristics, pathway differences, relative abundance of immune cells, and prognosis were examined in the TCGA-STAD cohort of MSS and non-EBV (+) patients. RESULTS: We observed that in the MSS and non-EBV (+) cohort, the TFB-low group exhibited significantly lower gene mutation frequency, gene copy number, loss of heterozygosity score, and tumor mutation burden than in the TFB-high group. Additionally, the TFB-low group exhibited a higher abundance of immune cells. Furthermore, the immune gene signatures were significantly upregulated in the TFB-low group, 2-year disease-specific survival was markedly increased in the TFB-low group compared with to the TFB-high group. The rates of TFB-low cases were significantly higher TFB-than high cases in durable clinical benefit (DCB) and response groups with pembrolizumab treatment. Low TFB may serve as a predictor of GC prognosis, and the TFB-low group exhibits higher immunogenicity. CONCLUSION: In conclusion, this study reveals that the TFB-based classification of GC patient may be instructive for individualized immunotherapy regimens.
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Adenocarcinoma , Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Relevância Clínica , Prognóstico , Mutação , Adenocarcinoma/patologiaRESUMO
PURPOSE: To investigate the efficacy and safety of the novel orally active PI3Kδ inhibitor in relapsed and/or refractory patients with follicular lymphoma (FL) who had received at least two prior systemic treatments. PATIENTS AND METHODS: Histologically confirmed relapsed and/or refractory patients with FL with disease progression after receiving second-line or greater systemic therapy were enrolled. Linperlisib was administered at 80 mg every day, orally in a 28-day cycle until disease progression or intolerable toxicity occurred. The primary outcome for the study was the objective response rate (ORR), with secondary outcomes including the duration of response (DOR), progression-free survival (PFS), overall survival (OS), disease control rate, and drug safety profile. RESULTS: Of 114 screened relapsed and/or refractory patients with FL, 84 were enrolled in the full analysis set (FAS). The ORR of the 84 FAS patients was 79.8% [95% confidence interval (CI), 69.6-87.8, 67 patients], with 13 patients (15.5%) achieving a complete response and 54 patients (64.3%) with a partial response. The median DOR was 12.3 months (95% CI, 9.3-15.9). The median PFS was 13.4 months (95% CI, 11.1-16.7). The 12-month OS rate was 91.4% (95% CI, 82.7-95.8) and a median OS not reached by 42 months. The most frequent (>3%) treatment-related adverse events Grade ≥3 were infectious pneumonia (19.0%), neutropenia (15.5%), decreased lymphocyte count (4.8%), decreased leukocyte count (4.8%), increased lipase (3.6%), decreased platelet count (3.6%), hypertriglyceridemia (3.6%), and interstitial lung disease (3.6%). CONCLUSIONS: Linperlisib demonstrated compelling clinical activity and manageable tolerability for relapsed and/or refractory patients with FL who had received at least two prior systemic therapies.
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Linfoma Folicular , Humanos , Linfoma Folicular/patologia , Inibidores da Angiogênese/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Progressão da Doença , Resultado do TratamentoRESUMO
PURPOSE: Recent studies have revealed an increase in the incidence rate of non-alcoholic fatty liver disease-related hepatocellular carcinoma (NAFLD-HCC). Furthermore, the association of Sphingosine 1-phosphate receptor 2 (S1PR2) with various types of tumours is identified, and the metabolism of conjugated bile acids (CBAs) performs an essential function in the onset and development of HCC. However, the association of CBA and S1PR2 with NAFLD-HCC is unclear. METHODS: The relationship between the expression of S1PR2 and the prognosis of patients suffering from NAFLD-HCC was investigated by bioinformatics techniques. Subsequently, the relationship between S1PR2 and the biological behaviours of HCC cell lines Huh 7 and HepG2 was explored by conducting molecular biology assays. Additionally, several in vivo animal experiments were carried out for the elucidation of the biological impacts of S1PR2 inhibitors on HCC cells. Finally, We used Glycodeoxycholic acid (GCDA) of CBA to explore the biological effects of CBA on HCC cell and its potential mechanism. RESULTS: High S1PR2 expression was linked to poor prognosis of the NAFLD-HCC patients. According to cellular assay results, S1PR2 expression could affect the proliferation, invasion, migration, and apoptosis of Huh 7 and HepG2 cells, and was closely associated with the G1/G2 phase of the cell cycle. The experiments conducted in the In vivo conditions revealed that the overexpression of S1PR2 accelerated the growth of subcutaneous tumours. In addition, JTE-013, an antagonist of S1PR2, effectively inhibited the migration and proliferation of HCC cells. Furthermore, the bioinformatics analysis highlighted a correlation between S1PR2 and the PI3K/AKT/mTOR pathway. GCDA administration further enhanced the expression levels of p-AKT, p-mTOR, VEGF, SGK1, and PKCα. Moreover, both the presence and absence of GCDA did not reveal any significant change in the levels of S1PR2, p-AKT, p-mTOR, VEGF, SGK1, and PKCα proteins under S1PR2 knockdown, indicating that CBA may regulates the PI3K/AKT/mTOR pathway by mediating S1PR2 expression. CONCLUSION: S1PR2 is a potential prognostic biomarker in NAFLD-HCC. In addition, We used GCDA in CBAs to treat HCC cell and found that the expression of S1PR2 was significantly increased, and the expression of PI3K/AKT/mTOR signalling pathway-related signal molecules was also significantly enhanced, indicating that GCDA may activate PI3K/AKT/mTOR signalling pathway by up-regulating the expression of S1PR2, and finally affect the activity of hepatocellular carcinoma cells. S1PR2 can be a candidate therapeutic target for NAFLD-HCC. Collectively, the findings of this research offer novel perspectives on the prevention and treatment of NAFLD-HCC.
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BACKGROUND: Few reliable methods to simulate and evaluate the intersegmental plane have been reported. We introduce intersegmental plane simulation based on the bronchus-vein-artery triad in three-dimensionally reconstructed images from patients who underwent segmentectomy for early lung cancer. METHODS: We collected clinical data of consecutive patients with early-stage lung cancer who underwent three-dimensional imaging-guided single-port thoracoscopic segmentectomy at Department No. 1 of Thoracic Surgery at Fujian Medical University Fujian Union Hospital from January 2019 to July 2019. Patients were divided into two groups according to the application of intersegmental plane simulation and nodule analysis: the intersegmental plane group and the non-intersegmental plane group. General clinical characteristics, operation status, and postoperative recovery were compared between groups. The three-dimensional reconstruction results in the intersegmental plane group were analyzed and summarized. RESULTS: A total of 120 patients were included (61 in the intersegmental plane group and 59 in the non-intersegmental plane group). There were no significant differences between the two groups in general characteristics (all P>0.05). All target lesions were resected in both groups. There were no significant differences between groups in operation characteristics or postoperative recovery, with the exception of the duration of chest drainage and the rate of gross margin insufficiency. There were five cases of gross margin insufficiency in the non-intersegmental plane group. With three-dimensional imaging reconstruction, a total of 131 intersegmental veins could be used to evaluate the simulated intersegmental plane in 61 patients, with an average of 2.1±0.5 veins per patient. Two patients (3.3%) had one vein that could be used to evaluate the intersegmental plane, 50 patients (82.3%) had two, seven patients (11.3%) had three, and two patients (3.3%) had four. The total number of intersegmental veins located on the simulated intersegmental plane was 124 (94.7%), with an average of 2.0±0.6 veins per patient. The accuracy of intersegmental plane simulation was 91.8% (56/61). CONCLUSIONS: The bronchus-vein-artery triad in intersegmental plane simulation can assist surgeons in preoperative planning and can facilitate complete resection of early lung cancer with sufficient surgical margins.
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Chromatin-associated RNA (caRNA) has been proposed as a type of epigenomic modifier. Here, we test whether environmental stress can induce cellular dysfunction through modulating RNA-chromatin interactions. We induce endothelial cell (EC) dysfunction with high glucose and TNFα (H + T), that mimic the common stress in diabetes mellitus. We characterize the H + T-induced changes in gene expression by single cell (sc)RNA-seq, DNA interactions by Hi-C, and RNA-chromatin interactions by iMARGI. H + T induce inter-chromosomal RNA-chromatin interactions, particularly among the super enhancers. To test the causal relationship between H + T-induced RNA-chromatin interactions and the expression of EC dysfunction-related genes, we suppress the LINC00607 RNA. This suppression attenuates the expression of SERPINE1, a critical pro-inflammatory and pro-fibrotic gene. Furthermore, the changes of the co-expression gene network between diabetic and healthy donor-derived ECs corroborate the H + T-induced RNA-chromatin interactions. Taken together, caRNA-mediated dysregulation of gene expression modulates EC dysfunction, a crucial mechanism underlying numerous diseases.
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Cromatina/fisiologia , Células Endoteliais/metabolismo , RNA/metabolismo , Estresse Fisiológico/fisiologia , DNA/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Epigenômica , Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes , Glucose/metabolismo , Glucose/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
OBJECTIVE: Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers, but its pathogenesis has not been fully elucidated. Therefore, it is valuable to explore the pathogenesis of NSCLC to improve diagnosis and identify novel treatment biomarkers. METHODS: Circular (circ)RNA, micro (mi)RNA, and gene expression datasets of NSCLC were analyzed to identify those that were differentially expressed between tumor and healthy tissues. Common genes were found and pathway enrichment analyses were performed. Survival analysis was used to identify hub genes, and their level of methylation and association with immune cell infiltration were analyzed. Finally, an NSCLC circRNA-miRNA-mRNA network was constructed. RESULTS: Eight miRNAs and 211 common genes were identified. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that cell projection morphogenesis, blood vessel morphogenesis, muscle cell proliferation, and synapse organization were enriched. Ten hub genes were found, of which the expression of DTL and RRM2 was significantly related to NSCLC patient prognosis. Significant methylation changes and immune cell infiltration correlations with DTL and RRM2 were also detected. CONCLUSIONS: hsa_circ_0001947/hsa-miR-637/RRM2 and hsa_circ_0072305/hsa-miR-127-5p/DTL networks were constructed, and identified molecules may be involved in the occurrence and development of NSCLC.
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Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Biologia Computacional , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Humanos , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Prognóstico , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/genética , RNA Circular/metabolismo , RNA Mensageiro/metabolismo , Análise de SobrevidaRESUMO
BACKGROUND: The accurate detection of cancer-associated venous thromboembolism (VTE) can avoid unnecessary diagnostic imaging or laboratory tests. OBJECTIVE: We sought to determine clinical and cancer-related risk factors of VTE that can be used as predictors for oncology patients presenting to the emergency department (ED) with suspected VTE. METHODS: We retrospectively analyzed all consecutive patients who presented with suspicion of VTE to The University of Texas MD Anderson Cancer Center ED between January 1, 2009, and January 1, 2013. Logistic regression models were used to identify risk factors that were associated with VTE. The ability of these factors to predict VTE was externally validated using a second cohort of patients who presented to King Hussein Cancer Center ED between January 1, 2009, and January 1, 2016. RESULTS: Cancer-related covariates associated with the occurrence of VTE were high-risk cancer type (odds ratio [OR] 3.64 [95% confidence interval {CI} 2.37-5.60], p < 0.001), presentation within 6 months of the cancer diagnosis (OR 1.92 [95% CI 1.62-2.28], p < 0.001), active cancer (OR 1.35 [95% CI 1.10-1.65], p = 0.003), advanced stage (OR 1.40 [95% CI 1.01-1.94], p = 0.044), and the presence of brain metastasis (OR 1.73 [95% CI 1.32-2.27], p < 0.001). When combined, these factors along with other clinical factors showed high prediction performance for VTE in the external validation cohort. CONCLUSIONS: Cancer risk group, presentation within 6 months of cancer diagnosis, active and advanced cancer, and the presence of brain metastases along with other related clinical factors can be used to predict VTE in patients with cancer presenting to the ED.
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Neoplasias , Tromboembolia Venosa , Serviço Hospitalar de Emergência , Humanos , Neoplasias/complicações , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologiaRESUMO
BACKGROUND The aim of this study was to construct a nomogram to predict the prognosis of patients with gastrointestinal stromal tumor (GIST). MATERIAL AND METHODS We enrolled 4086 GIST patients listed in the SEER database from 1998 to 2015. They were separated to 2 groups: an experimental group (n=2862) and a verification group (n=1224). A nomogram was constructed by using statistically significant prognostic factors. RESULTS A nomogram that included age, sex, marital status, tumor location, grade, SEER stage, tumor size, and surgical management was developed. It can be used to predict overall survival (OS), while adding AJCC 7th TNM stage can predict cancer-specific survival (CSS). The C-index used to forecast OS and CSS nomograms was 0.778 (95% CI, 0.76-0.79) and 0.818 (95% CI, 0.80-0.84), respectively. CONCLUSIONS The nomogram can effectively predict 3- and 5-year CSS in patients with GIST, and its use can improve clinical practice.
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Tumores do Estroma Gastrointestinal/mortalidade , Idoso , Feminino , Tumores do Estroma Gastrointestinal/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Gradação de Tumores , Estadiamento de Neoplasias , Nomogramas , Prognóstico , Modelos de Riscos Proporcionais , Programa de SEERRESUMO
Fusion transcripts are used as biomarkers in companion diagnoses. Although more than 15,000 fusion RNAs have been identified from diverse cancer types, few common features have been reported. Here, we compared 16,410 fusion transcripts detected in cancer (from a published cohort of 9,966 tumor samples of 33 cancer types) with genome-wide RNA-DNA interactions mapped in two normal, noncancerous cell types [using iMARGI, an enhanced version of the mapping of RNA-genome interactions (MARGI) assay]. Among the top 10 most significant RNA-DNA interactions in normal cells, 5 colocalized with the gene pairs that formed fusion RNAs in cancer. Furthermore, throughout the genome, the frequency of a gene pair to exhibit RNA-DNA interactions is positively correlated with the probability of this gene pair to present documented fusion transcripts in cancer. To test whether RNA-DNA interactions in normal cells are predictive of fusion RNAs, we analyzed these in a validation cohort of 96 lung cancer samples using RNA sequencing (RNA-seq). Thirty-seven of 42 fusion transcripts in the validation cohort were found to exhibit RNA-DNA interactions in normal cells. Finally, by combining RNA-seq, single-molecule RNA FISH, and DNA FISH, we detected a cancer sample with EML4-ALK fusion RNA without forming the EML4-ALK fusion gene. Collectively, these data suggest an RNA-poise model, where spatial proximity of RNA and DNA could poise for the creation of fusion transcripts.
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DNA/genética , Genoma Humano/genética , Proteínas de Fusão Oncogênica/genética , RNA/genética , Humanos , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias/genética , Neoplasias/patologia , Análise de Sequência de RNARESUMO
Human T-cell leukemia virus type 1 (HTLV-1) is the first retrovirus that has conclusively been shown to cause human diseases. In HIV-1, specific interactions between the nucleocapsid (NC) domain of the Gag protein and genomic RNA (gRNA) mediate gRNA dimerization and selective packaging; however, the mechanism for gRNA packaging in HTLV-1, a deltaretrovirus, is unclear. In other deltaretroviruses, the matrix (MA) and NC domains of Gag are both involved in gRNA packaging, but MA binds nucleic acids with higher affinity and has more robust chaperone activity, suggesting that this domain may play a primary role. Here, we show that the MA domain of HTLV-1, but not the NC domain, binds short hairpin RNAs derived from the putative gRNA packaging signal. RNA probing of the HTLV-1 5' leader and cross-linking studies revealed that the primer-binding site and a region within the putative packaging signal form stable hairpins that interact with MA. In addition to a previously identified palindromic dimerization initiation site (DIS), we identified a new DIS in HTLV-1 gRNA and found that both palindromic sequences bind specifically the NC domain. Surprisingly, a mutant partially defective in dimer formation in vitro exhibited a significant increase in RNA packaging into HTLV-1-like particles, suggesting that efficient RNA dimerization may not be strictly required for RNA packaging in HTLV-1. Moreover, the lifecycle of HTLV-1 and other deltaretroviruses may be characterized by NC and MA functions that are distinct from those of the corresponding HIV-1 proteins, but together provide the functions required for viral replication.
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Vírus Linfotrópico T Tipo 1 Humano/química , RNA Viral/metabolismo , Proteínas de Ligação a RNA/química , Montagem de Vírus , Produtos do Gene gag do Vírus da Imunodeficiência Humana/química , Dimerização , Proteínas do Vírus da Imunodeficiência Humana/química , Proteínas do Vírus da Imunodeficiência Humana/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Nucleocapsídeo/genética , Proteínas de Ligação a RNA/fisiologia , Replicação ViralRESUMO
Adrenocortical carcinoma is a rare malignancy with poor prognosis and limited response to chemotherapy. Hepatocyte growth factor (HGF) and its receptor cMET augment cancer growth and resistance to chemotherapy, but their role in adrenocortical carcinoma has not been examined. In this study, we investigated the association between HGF/cMET expression and cancer hallmarks of adrenocortical carcinoma. Transcriptomic and immunohistochemical analyses indicated that increased HGF/cMET expression in human adrenocortical carcinoma samples was positively associated with cancer-related biologic processes, including proliferation and angiogenesis, and negatively correlated with apoptosis. Accordingly, treatment of adrenocortical carcinoma cells with exogenous HGF resulted in increased cell proliferation in vitro and in vivo while short hairpin RNA-mediated knockdown or pharmacologic inhibition of cMET suppressed cell proliferation and tumor growth. Moreover, exposure of cells to mitotane, cisplatin, or radiation rapidly induced pro-cMET expression and was associated with an enrichment of genes (e.g., CYP450 family) related to therapy resistance, further implicating cMET in the anticancer drug response. Together, these data suggest an important role for HGF/cMET signaling in adrenocortical carcinoma growth and resistance to commonly used treatments. Targeting cMET, alone or in combination with other drugs, could provide a breakthrough in the management of this aggressive cancer.
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Neoplasias do Córtex Suprarrenal/metabolismo , Carcinoma/metabolismo , Fator de Crescimento de Hepatócito/fisiologia , Proteínas de Neoplasias/fisiologia , Proteínas Proto-Oncogênicas c-met/fisiologia , Transdução de Sinais/fisiologia , Adenoma/tratamento farmacológico , Adenoma/metabolismo , Adenoma/patologia , Neoplasias do Córtex Suprarrenal/irrigação sanguínea , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anilidas/farmacologia , Anilidas/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma/irrigação sanguínea , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Divisão Celular , Linhagem Celular Tumoral , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos da radiação , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Mitotano/farmacologia , Terapia de Alvo Molecular , Neovascularização Patológica/fisiopatologia , Piridinas/farmacologia , Piridinas/uso terapêutico , Interferência de RNA , RNA Interferente Pequeno/farmacologia , Transcriptoma , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Docetaxel, a lipophilic drug, is indicated for castration-resistant metastatic prostate cancer. Most men with such disease would have had androgen-deprivation therapy, which decreases muscle and increases body fat. Obesity and body composition changes may influence the outcomes of docetaxel therapy. METHODS: We conducted a retrospective review of 333 patients with metastatic prostate cancer treated with docetaxel at a comprehensive cancer center between October 7, 2004 and December 31, 2012. Body composition parameters were measured based on the areas of muscle and adipose tissues in the visceral and subcutaneous compartments on CT images at L3-4 levels. Dose calculations, toxicity and adverse reaction profiles, and overall survival were analyzed. RESULTS: Obese patients were younger at the diagnosis of prostate cancer and had a shorter duration from diagnosis to docetaxel therapy. Analysis of body composition found that a high visceral fat-to-subcutaneous fat area ratio (VSR) was associated with poor prognosis but a high visceral fat-to-muscle area ratio (VMR) and high body mass index were associated with increased duration from starting docetaxel to death, allowing such men to catch up with patients with normal body mass index in overall survival from cancer diagnosis to death. Cox proportional hazard regression showed that age ≥65 years, high VSR, abnormal serum alkaline phosphatase, and >10% reduction of initial dosage were significant predictors of shorter time between starting docetaxel and death, and that high VMR, obesity, and weekly regimens were significant predictors of longer survival after docetaxel. CONCLUSION: Obese and overweight patients may benefit more from weekly docetaxel regimens using the reference dosage of 35 mg/m2 without empirical dosage reduction.
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Antineoplásicos/administração & dosagem , Composição Corporal , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Índice de Massa Corporal , Docetaxel , Relação Dose-Resposta a Droga , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Resultado do TratamentoRESUMO
Genome-wide association studies have identified polymorphisms at chromosome 9q22.23 as a new thyroid cancer (TC) susceptibility locus in populations of European descent. Since then, the relationship between three common variations (rs965513, rs1867277, and rs71369530) of FOXE1 and TC has been reported in various ethnic groups; however, the results have been inconclusive. To derive a more precise estimation of the relationship as well as to quantify the between-study heterogeneity and potential bias, a meta-analysis including 120,258 individuals from 16 studies was performed. An overall random-effect per-allele odds ratio (OR) of 1.74 (95 % confidence interval (95 % CI), 1.62-1.86, P<10(-5)) and 1.62 (95 % CI, 1.50-1.76, P<10(-5)) was found for the rs965513 and rs1867277 polymorphisms, respectively. In addition, we also detected significant association of FOXE1 polyalanine tract (rs71369530) with TC risk (OR=2.01; 95 % CI, 1.66-2.44, P<10(-5)). Significant associations were also detected under dominant and recessive genetic models. In the subgroup analysis by ethnicity, significantly increased risks were found for the rs965513 polymorphism among Caucasians (OR=1.79; 95 % CI, 1.69-1.91, P<10(-5)) and Asians (OR=1.42; 95 % CI, 1.12-1.81, P=0.004). Ethnicity was identified as a potential source of between-study heterogeneity for rs965513. When stratified by sample size, study design, histological types of TC, and radiation exposure status, significantly increased risks were found for the rs965513 polymorphism. This meta-analysis demonstrated that the three common variations on FOXE1 is a risk factor associated with increased TC susceptibility, but these associations vary in different ethnic populations.
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Fatores de Transcrição Forkhead/genética , Predisposição Genética para Doença , Polimorfismo Genético , Neoplasias da Glândula Tireoide/genética , Variação Genética , Humanos , Viés de Publicação , Risco , Neoplasias da Glândula Tireoide/etiologiaRESUMO
Most clinical studies of heparin-induced thrombocytopenia have not included cancer patients who have high risk of thromboembolism, frequent exposure to heparin, and many potential causes of thrombocytopenia other than heparin-induced thrombocytopenia. To estimate the incidence and prevalence of heparin-induced thrombocytopenia in cancer patients, we identified cases based on diagnostic codes, anti-heparin antibody testing, and clinical characteristics (4T score) at a comprehensive cancer center between 1 October 2008 and 31 December 2011. We estimated that the prevalence of heparin-induced thrombocytopenia to be 0.02% among all cancer patients and 0.24% among cancer patients exposed to heparin. The annual incidence of heparin-induced thrombocytopenia was 0.57 cases per 1000 cancer patients exposed to heparin. Of the 40 cancer patients with the International Classification of Diseases (Ninth Revision; ICD-9) code for heparin-induced thrombocytopenia, positive anti-heparin antibody, and 4T score ≥4, 5 (12.5%) died of related thromboembolic or hemorrhagic complications. In a multivariate logistic regression model, male gender was a significant (p = 0.035) factor, and non-hematological malignancy was a significant (p = 0.017) factor associated with anti-heparin antibody positivity. Future studies may further examine the risk factors associated with heparin-induced thrombocytopenia in larger cohorts.
Assuntos
Antibacterianos/uso terapêutico , Ruptura Prematura de Membranas Fetais , Esfregaço Vaginal , Feminino , Ruptura Prematura de Membranas Fetais/diagnóstico , Ruptura Prematura de Membranas Fetais/tratamento farmacológico , Ruptura Prematura de Membranas Fetais/etiologia , Idade Gestacional , Glucocorticoides/uso terapêutico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Gravidez , Fatores de Risco , Tocolíticos/uso terapêuticoRESUMO
OBJECTIVE: To evaluate the effects of different types of nitric oxide synthase (NOS) inhibitors on cerebral mitochondrial structure and function in fetal rats with intrauterine distress. METHODS: Rats were divided into control group, acute ischemia group, treatment group 1 injection of [N omega-nitro-L-arginine (L-NNA) 4 mg/kg into pregnant rats' abdomen before ischemia], reperfusion group, treatment group 2 [injection of L-NNA 4 mg/kg into pregnant rats' abdomen before ischemia followed by injection of aminoguanidine (AG) 500 mg/kg before operation]. Changes of mitochondrial structure were observed by transmission electron microscopy and expression of neuronal nitric oxide synthase (nNOS) mRNA(A) through RT-PCR. Inducible nitric oxide synthase (iNOS) activity and mitochondrial Na(+)K(+)-ATPase and cytochrome oxidase activity were measured. RESULTS: (1) The A of NOS (5 min, 15 min) in acute ischemia group was higher than that of treatment group 1 (P < 0.05). There was no difference between the A of nNOS (30 min) in two groups (P > 0.05). But the A of nNOS in two groups was higher than that in control group (P < 0.05). (2) iNOS activities in reperfusion group were all higher than those in treatment group 2. Both of those in two groups were higher than that in control group (P < 0.05). (3) Mitochondrial Rsv (5 min, 15 min) in acute ischemia group was smaller than those of treatment group 1 (P < 0.05). There was no difference between mitochondrial Rsv (30 min) in two groups (P > 0.05). Mitochondrial Rsv in reperfusion group was all smaller than those in treatment group 2. And mitochondrial Rsv in all the groups was smaller than that in control group (P < 0.05). (4) Na(+)K(+)-ATPase activity in treatment group 2 was higher than those in reperfusion group (P < 0.05). Na(+)K(+)-ATPase activity in two groups was lower than that in control group (P < 0.05). CONCLUSIONS: nNOS and iNOS play a role in cerebral mitochondrial structure and function damage in fetal rats with intrauterine distress. L-NNA has some limited treatment effect on mitochondrial damage when intrauterine distress induces acute fetal hypoxic-ischemic brain damage. AG plays an obvious treatment role in mitochondrial damage during reperfusion following ischemia.
Assuntos
Encéfalo/enzimologia , Sofrimento Fetal/patologia , Guanidinas/farmacologia , Mitocôndrias/enzimologia , Proteínas do Tecido Nervoso/metabolismo , Óxido Nítrico Sintase/metabolismo , Animais , Encéfalo/ultraestrutura , Feminino , Sofrimento Fetal/enzimologia , Mitocôndrias/ultraestrutura , Proteínas do Tecido Nervoso/antagonistas & inibidores , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase Tipo I , Óxido Nítrico Sintase Tipo II , Gravidez , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
OBJECTIVE: To compare the level of interleukin-6 (IL-6), interleukin-8 (IL-8), human chorionic gonadotropin (hCG) with transvaginal ultrasonographic measurement in prediction of the cervix ripening and the time of term labor. METHODS: The 79 cases of primiparous women of term pregnancy were chosen as the research subjects. The maternal level of IL-6, IL-8, hCG in cervicovaginal secretions were measured. The cervical length, internal cervical os wedge width and forebag length were measured by transvaginal ultrasonography. The cervical Bishop score was also determined. RESULTS: (1) The levels of IL-6, IL-8, hCG in cervicovaginal secretions were significantly higher in women they are in labor than that of women at term not in labor (782 +/- 508) ng/L, (10,539 +/- 8 680) ng/L, (114 +/- 86) IU/L, versus (155 +/- 75) ng/L, (7,113 +/- 6 050) ng/L, (35 +/- 21) IU/L, respectively. (2) The levels of cervicovaginal secretions IL-6, IL-8, hCG and the length of cervical, forebag were significant correlation with the cervical Bishop score (P < 0.05, r = 0.42, 0.24, 0.44, -0.56, 0.35) respectively. (3) The levels of cervicovaginal secretions IL-6, IL-8, the length of cervical, forebag measured by transvaginal ultrasonography and the cervical Bishop score were significant correlation to the onset time of term labor (P < 0.01, r = -0.42, -0.46, 0.64, -0.52, -0.41) respectively, and all these markers also could predict the onset of term labor in < or = 7 days, The predictive value on onset labor within < or = 7 days by cervical length < or = 30 mm: the sensitivity, specificity, positive values and negative value are 0.83, 0.89, 0.91 and 0.81 respectively. (4) Among the several markers in predicting cervix ripening and onset of labor, the best one was the transvaginal ultrasonographic measurement of cervical length. CONCLUSIONS: The levels of cervicovaginal secretions IL-6, IL-8, the length of cervical and forebag measured by transvaginal ultrasonography and the Bishop score are valuable in prediction of cervix ripening and onset of labor. The cervical length measured by transvaginal ultrasonography is the best one.