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1.
J Appl Clin Med Phys ; 25(6): e14271, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38273673

RESUMO

PURPOSE: The use of volumetric modulated arc therapy (VMAT), simultaneous integrated boost (SIB), and hypofractionated regimen requires adequate patient setup accuracy to achieve an optimal outcome. The purpose of this study was to assess the setup accuracy of patients receiving left-sided breast cancer radiotherapy using deep inspiration breath-hold technique (DIBH) and surface guided radiotherapy (SGRT) and to calculate the corresponding setup margins. METHODS: The patient setup accuracy between and within radiotherapy fractions was measured by comparing the 6DOF shifts made by the SGRT system AlignRT with the shifts made by kV-CBCT. Three hundred and three radiotherapy fractions of 23 left-sided breast cancer patients using DIBH and SGRT were used for the analysis. All patients received pre-treatment DIBH training and visual feedback during DIBH. An analysis of variance (ANOVA) was used to test patient setup differences for statistical significance. The corresponding setup margins were calculated using the van Herk's formula. RESULTS: The intrafractional patient setup accuracy was significantly better than the interfractional setup accuracy (p < 0.001). The setup margin for the combined inter- and intrafractional setup error was 4, 6, and 4 mm in the lateral, longitudinal, and vertical directions if based on SGRT alone. The intrafractional error contributed ≤1 mm to the calculated setup margins. CONCLUSION: With SGRT, excellent intrafractional and acceptable interfractional patient setup accuracy can be achieved for the radiotherapy of left-sided breast cancer using DIBH and modern radiation techniques. This allows for reducing the frequency of kV-CBCTs, thereby saving treatment time and radiation exposure.


Assuntos
Suspensão da Respiração , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Erros de Configuração em Radioterapia , Radioterapia Guiada por Imagem , Radioterapia de Intensidade Modulada , Neoplasias Unilaterais da Mama , Humanos , Feminino , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Neoplasias Unilaterais da Mama/radioterapia , Erros de Configuração em Radioterapia/prevenção & controle , Radioterapia Guiada por Imagem/métodos , Órgãos em Risco/efeitos da radiação , Pessoa de Meia-Idade , Neoplasias da Mama/radioterapia , Prognóstico
2.
Drug Dev Res ; 83(2): 512-524, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34541682

RESUMO

Circular RNAs (circRNAs) play vital regulatory roles in the development of ovarian cancer (OC). However, the functions of circRNA Atlastin GTPase 2 (circATL2) in paclitaxel (PTX) resistance of OC are still unclear. As a result, circATL2 was upregulated in PTX-resistant OC tissues and cells. CircATL2 knockdown reduced IC50 of PTX, inhibited colony formation ability and promoted cell cycle arrest and apoptosis in PTX-resistant OC cells. Silencing of circATL2 restrained PTX resistance in vivo. Furthermore, miR-506-3p could be targeted by circATL2 and miR-506-3p inhibition reversed the impacts of circATL2 knockdown on PTX resistance and cell progression in PTX-resistant OC cells. NFIB was identified as the target of miR-506-3p. MiR-506-3p overexpression suppressed PTX resistance and malignant behaviors of PTX-resistant OC cells, with NFIB elevation rescued the impacts. To summarize, circATL2 promoted the resistance of OC to PTX by sponging miR-506-3p to upregulate NFIB expression, providing a new sight in chemoresistance of OC.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Fatores de Transcrição NFI/genética , Fatores de Transcrição NFI/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Paclitaxel/farmacologia
3.
Jpn J Clin Oncol ; 48(9): 799-805, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30060202

RESUMO

BACKGROUND: We hypothesized that survival varied significantly between retroperitoneal soft tissue sarcoma (STS) and extremity/trunk STS. This study explored the reasons for the different outcomes and identified patient characteristics for survival. METHODS: This retrospective study identified 213 consecutive patients with localized primary STS from January 2002 to July 2013, including 47 retroperitoneal STS (22.1%) and 166 extremity/trunk STS (77.9%). Local failure-free survival (LFFS), distant metastasis-free survival (DMFS) and overall survival (OS) were constructed by the Kaplan-Meier method. Univariate Cox proportional hazards regression models were fit to assess the ability of patient characteristics to predict survival. RESULTS: At presentation, patients with retroperitoneal STS had larger tumor size (median size 18 cm vs. 6 cm; P < 0.001) and positive margin (21.3% vs. 8.4%; P = 0.014), and less often received radiotherapy (2.1% vs. 45.8%; P < 0.001). The median follow-up time for the entire population was 68 months (range, 5-127 months). Local recurrence was more frequent in patients with retroperitoneal STS compared with patients with extremity/trunk STS (53.2% vs. 28.3%; P = 0.001). LFFS and OS were lower in patients with retroperitoneal STS than extremity/trunk STS, with 5-year LFFS (50% vs. 74.3%; P < 0.001) and 5-year OS (65.4% vs. 77.5%; P = 0.017), respectively. CONCLUSION: Retroperitoneal STS was associated with significantly worse survival compared with extremity/trunk STS. Larger tumor size, more patients with positive margin and fewer patients received radiotherapy in retroperitoneal group may result in worse survival compared with extremity/trunk disease.


Assuntos
Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Demografia , Extremidades/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Retroperitoneais/patologia , Estudos Retrospectivos , Tronco/patologia , Resultado do Tratamento
4.
Jpn J Clin Oncol ; 44(3): 241-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24453273

RESUMO

OBJECTIVE: The incidence of radiation-induced late xerostomia varies greatly in nasopharyngeal carcinoma patients treated with radiotherapy. The single-nucleotide polymorphisms in genes involved in DNA repair and fibroblast proliferation may be correlated with such variability. The purpose of this paper was to evaluate the association between the risk of developing radiation-induced late xerostomia and four genetic polymorphisms: TGFß1 C-509T, TGFß1 T869C, XRCC3 722C>T and ATM 5557G>A in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. METHODS: The severity of late xerostomia was assessed using a patient self-reported validated xerostomia questionnaire. Polymerase chain reaction-ligation detection reaction methods were performed to determine individual genetic polymorphism. The development of radiation-induced xerostomia associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for equivalent uniform dose. RESULTS: A total of 43 (41.7%) patients experienced radiation-induced late xerostomia. Univariate Cox proportional hazard analyses showed a higher risk of late xerostomia for patients with XRCC3 722 TT/CT alleles. In multivariate analysis adjusted for clinical and dosimetric factors, XRCC3 722C>T polymorphisms remained a significant factor for higher risk of late xerostomia. CONCLUSIONS: To our knowledge, this is the first study that demonstrated an association between genetic polymorphisms and the risk of radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. Our findings suggest that the polymorphisms in XRCC3 are significantly associated with the risk of developing radiation-induced late xerostomia.


Assuntos
Proteínas de Ligação a DNA/genética , Neoplasias Nasofaríngeas/radioterapia , Polimorfismo de Nucleotídeo Único , Radioterapia de Intensidade Modulada/efeitos adversos , Fator de Crescimento Transformador beta1/genética , Xerostomia/etiologia , Adulto , Idoso , Carcinoma , Fatores de Confusão Epidemiológicos , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Reação em Cadeia da Polimerase , Fatores de Risco , Autorrelato , Índice de Gravidade de Doença , Inquéritos e Questionários , Xerostomia/genética
5.
Artigo em Inglês | MEDLINE | ID: mdl-38918234

RESUMO

Radiation pneumonia is a common adverse reaction during radiotherapy in lung cancer patients, which negatively impacts the quality of life and survival of patients. Recent studies have shown that compound Kushen injection (CKI), a traditional Chinese medicine (TCM), has great anti-inflammatory and anticancer potential, but the mechanism is still unclear. We used CiteSpace, the R package "bibliometrix," and VOSviewers to perform a bibliometrics analysis of 162 articles included from the Web of Science core collection. A network pharmacology-based approach was used to screen effective compounds, screen and predict target genes, analyze biological functions and pathways, and construct regulatory networks and protein interaction networks. Molecular docking experiments were used to identify the affinity of key compounds and core target. The literature metrology analysis revealed that over 90% of the CKI-related studies were conducted by Chinese scholars and institutions, with a predominant focus on tumors, while research on radiation pneumonia remained limited. Our investigation identified 60 active ingredients of CKI, 292 genes associated with radiation pneumonia, 533 genes linked to lung cancer, and 37 common targets of CKI in the treatment of both radiation pneumonia and lung cancer. These core potential targets were found to be significantly associated with the OS of lung cancer patients, and the key compounds exhibited a good docking affinity with these targets. Additionally, GO and KEGG enrichment analysis highlighted that the bioinformatics annotation of these common genes mainly involved ubiquitin protein ligase binding, cytokine receptor binding, and the PI3K/Akt signaling pathway. Our study revealed that the main active components of CKI, primarily quercetin, luteolin, and naringin, might act on major core targets, including AKT1, PTGS2, and PPARG, and further regulated key signaling pathways such as the PI3K/Akt pathway, thereby playing a crucial role in the treatment of radiation pneumonia and lung cancer. Moreover, this study had a certain promotional effect on further clinical application and provided a theoretical basis for subsequent experimental research.

6.
Bioresour Technol ; 394: 130232, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38141881

RESUMO

Microalgae, known for rapid growth and lipid richness, hold potential in biofuels and high-value biomolecules. The symbiotic link with bacteria is crucial in large-scale open cultures. This study explores algal-bacterial interactions using a symbiotic model, evaluating acid-resistant Lactic acid bacteria (LAB), stress-resilient Bacillus subtilis and Bacillus licheniformis, and various Escherichia coli strains in the Aurantiochytrium sp. SW1 system. It was observed that E. coli SUC significantly enhanced the growth and lipid production of Aurantiochytrium sp. SW1 by increasing enzyme activity (NAD-IDH, NAD-ME, G6PDH) while maintaining sustained succinic acid release. Optimal co-culture conditions included temperature 28 °C, a 1:10 algae-to-bacteria ratio, and pH 8. Under these conditions, Aurantiochytrium sp. SW1 biomass increased 3.17-fold to 27.83 g/L, and total lipid content increased 2.63-fold to 4.87 g/L. These findings have implications for more efficient microalgal lipid production and large-scale cultivation.


Assuntos
Microalgas , Escherichia coli , Ácido Succínico , Biomassa , Simbiose , NAD , Lipídeos , Biocombustíveis
7.
J Clin Oncol ; : JCO2302261, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950321

RESUMO

PURPOSE: To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). PATIENTS AND METHODS: We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT. RESULTS: Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment. CONCLUSION: The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.

8.
Sci Rep ; 13(1): 17018, 2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-37813917

RESUMO

The goal of the study was to evaluate the inter- and intrafractional patient setup accuracy of target volumes located in the head, thoracic, abdominal, and pelvic regions when using SGRT, by comparing it with that of laser alignment using patient skin marks, and to calculate the corresponding setup margins. A total of 2303 radiotherapy fractions of 183 patients were analyzed. All patients received daily kilovoltage cone-beam computed tomography scans (kV-CBCT) for online verification. From November 2019 until September 2020, patient setup was performed using laser alignment with patient skin marks, and since October 2020, using SGRT. The setup accuracy was measured by the six degrees of freedom (6DOF) corrections based on the kV-CBCT. The corresponding setup margins were calculated using the van Herk formula. Analysis of variance (ANOVA) was used to evaluate the impact of multiple factors on the setup accuracy. The inter-fractional patient setup accuracy was significantly better using SGRT compared to laser alignment with skin marks. The mean three-dimensional vector of the translational setup deviation of tumors located in the thorax, abdomen, and pelvis using SGRT was 3.6 mm (95% confidence interval (CI) 3.3 mm to 3.9 mm) and 4.5 mm using laser alignment with skin marks (95% CI 3.9 mm to 5.2 mm; p = 0.001). Calculation of setup margins for the combined inter- and intra-fractional setup error revealed similar setup margins using SGRT and kV-CBCT once a week compared to laser alignment with skin marks and kV-CBCT every other day. Furthermore, comparable setup margins were found for open-face thermoplastic masks with AlignRT compared to closed-face thermoplastic masks with laser alignment and mask marks. SGRT opens the possibility to reduce the number of CBCTs while maintaining sufficient setup accuracy. The advantage is a reduction of imaging dose and overall treatment time. Open-face thermoplastic masks may be used instead of closed-face thermoplastic masks to increase the patient's comfort.


Assuntos
Radioterapia Guiada por Imagem , Humanos , Radioterapia Guiada por Imagem/métodos , Posicionamento do Paciente/métodos , Erros de Configuração em Radioterapia/prevenção & controle , Planejamento da Radioterapia Assistida por Computador/métodos , Tórax/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico/métodos , Abdome/diagnóstico por imagem , Pelve/diagnóstico por imagem
9.
Neuro Oncol ; 25(12): 2207-2220, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-37379245

RESUMO

BACKGROUND: Brain metastasis (BM) are a devastating consequence of lung cancer. This study was aimed to screen risk factors for predicting BM. METHODS: Using an in vivo BM preclinical model, we established a series of lung adenocarcinoma (LUAD) cell subpopulations with different metastatic ability. Quantitative proteomics analysis was used to screen and identify the differential protein expressing map among subpopulation cells. Q-PCR and Western-blot were used to validate the differential proteins in vitro. The candidate proteins were measured in LUAD tissue samples (n = 81) and validated in an independent TMA cohort (n = 64). A nomogram establishment was undertaken by performing multivariate logistic regression analysis. RESULTS: The quantitative proteomics analysis, qPCR and Western blot assay implied a five-gene signature that might be key proteins associated with BM. In multivariate analysis, the occurrence of BM was associated with age ≤ 65 years, high expressions of NES and ALDH6A1. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.934 (95% CI, 0.881-0.988) in the training set. The validation set showed a good discrimination with an AUC of 0.719 (95% CI, 0.595-0.843). CONCLUSIONS: We have established a tool that is able to predict occurrence of BM in LUAD patients. Our model based on both clinical information and protein biomarkers will help to screen patient in high-risk population of BM, so as to facilitate preventive intervention in this part of the population.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Encefálicas , Neoplasias Pulmonares , Humanos , Idoso , Neoplasias Pulmonares/genética , Neoplasias Encefálicas/genética , Análise Multivariada , Nomogramas
10.
Toxicol Res (Camb) ; 12(2): 201-215, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37125330

RESUMO

Introduction: Qishenbuqi capsule (QSBQC), a listed Chinese patent prescription, comprises of 4 herbs. Clinically, it has been shown to improve immune functions. Methods: Subjects with Qi deficiency and non-Qi deficiency were recruited, who then took QSBQC for 4 weeks. Traditional Chinese medicine (TCM) syndrome scores and the levels of white blood cells, CD3+ T cells (CD3+), CD4+ T cells (CD3+CD4+), CD8+ T cells (CD3+CD8+), and CD4+/CD8+ were determined. Serum metabolomics was used to explore the metabolic mechanisms of QSBQC on improving immunity. Meanwhile, the potential active ingredients, targets, and pathways of QSBQC on enhancing immunity were screened by network pharmacology. Results: QSBQC significantly improved TCM syndrome scores and increased the number of CD8+ T cells of both Qi deficiency and non-Qi deficiency subjects. Serum metabolomics revealed that QSBQC regulated 18 differential metabolites and 8 metabolic pathways of Qi deficiency, and 12 differential metabolites and 7 metabolic pathways of non-Qi deficiency subjects. The "herbs-compounds-pathways" diagram showed that PQ-2, cimifugin, and divaricatol were the main active components. Pathways in cancer and arginine and proline metabolism could be the most important pathways. Conclusion: Our research revealed the immunoenhancing mechanisms of QSBQC and improved the combination of TCM theory and modern western medicine theory.

11.
Int J Clin Oncol ; 17(2): 160-4, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21638025

RESUMO

We present a rare case of duodenal metastasis from invasive breast lobular carcinoma, which first presented clinically as elevated serum tumor marker levels, followed by jaundice but with no other clinical evidence of recurrence and metastasis. A 53-year-old woman underwent modified radical mastectomy of the left breast (pT2 N3 M0 stage III c) followed by postoperative chemo-radiotherapy and hormonal therapy. After about 3 years, the patient presented with elevated serum tumor marker levels and mild jaundice. She was subsequently admitted to the hospital for nausea and severe vomiting. A duodenoscopy revealed the thickening of duodenal papilla on the lateral wall and stenosis. A duodenal tissue biopsy revealed poorly differentiated adenocarcinoma, and immunohistochemical staining suggested that the carcinoma was of breast origin. The patient received further radiation and chemotherapy. Although duodenal metastases of breast cancer are rare, physicans should be alert and vigilant when a patient with a history of breast cancer presents with new gastrointestinal symptoms.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Lobular , Neoplasias Duodenais , Invasividade Neoplásica , Neoplasias da Mama/cirurgia , Carcinoma Lobular/patologia , Carcinoma Lobular/secundário , Carcinoma Lobular/terapia , Neoplasias Duodenais/patologia , Neoplasias Duodenais/secundário , Neoplasias Duodenais/terapia , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade
12.
Digit Health ; 8: 20552076221138313, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406155

RESUMO

Objective: This study aimed to explore the practical application and effect of Kolb's experiential learning theory in the clinical nursing training of traditional Chinese medicine (TCM). Methods: This study is a quasi-experimental study. Eighty clinical nurses from a class-III grade-A general hospital were enrolled in 2020 and 2021, respectively, as research subjects. The subjects in the control group were trained in "theory explanation, clinical practice, summary and Q&A, [and] centralized examination." The subjects in the experimental group were first grouped according to Kolb's experiential learning style. The training followed a "problem-exploration-practice-exploration-theory-explanation-summary-centralized examination" structure based on Kolb's experiential learning cycle, the training place is Conference Room 1 of the hospital. The training time is from February to August 2020 and 2021. The application effect of the experiential learning theory was evaluated by analyzing course evaluation questionnaires and the final examination results. Results: The total score of the course evaluation questionnaire of the experimental group was 112.23 ± 5.88. The difference compared with the control group was statistically significant (P < .01). In the experimental group, the theoretical score was 85.27 ± 3.29, and the operational score was 85.36 ± 3.01. The differences compared with the control group were statistically significant (P < .01). Conclusion: The application of Kolb's experiential learning theory to the training of TCM clinical nursing can make the clinical practice of TCM nursing more "scientific" and the training more effective, and it can improve the subjective initiative of students.

13.
Chin Herb Med ; 14(1): 111-116, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36120123

RESUMO

Objective: To investigate the potential effect of Lysimachia capillipes capilliposide (LCC) on the chemo sensitivity and the stemness of human ovarian cancer cells. Methods: Cell Counting Kit-8 (CCK8) was used to measure the IC50 values. The apoptosis of cells was measured through flow cytometry. Evaluation of the stemness and differentiation markers was performed by the immunoblotting and the immunostaining assays. RNA-seq was performed through the Illumina HiSeq PE150 platform and differentially expressed genes (DEGs) were screened out through the bioinformation analysis. Overexpression or knockdown of Fos gene was achieved by shRNA transfection. Results: Pre-exposure of A2780T cells with 10 µg/mL LCC sensitized them to paclitaxel, of which the IC50 value reduced from 8.644 µmol/L (95%CI: 7.315-10.082 µmol/L) to 2.5 µmol/L (95%CI: 2.233-2.7882 µmol/L). Exposure with LCC enhanced the paclitaxel-induced apoptosis and inhibited the colony formation of A2780T cells. LCC exposure reduced the expression of cancer stemness markers, ALDH1, Myd88 and CD44, while promoting that of terminal differentiation markers, NFATc1, Cathepsin K and MMP9. RNA-seq analysis revealed that the expressions of FOS and JUN were upregulated in LCC-treated A2780T cells. A2780T cells overexpressing Fos gene displayed increased paclitaxel-sensitivity and reduced cell stemness, and shared common phenotypes with LCC-treated A2780T cells. Conclusion: These findings suggested that LCC promoted terminal differentiations of ovarian cancer cells and sensitized them to paclitaxel through activating the Fos/Jun pathway. LCC might become a novel therapy that targets at cancer stem cells and enhances the chemotherapeutic effect of ovarian cancer treatments.

14.
Cytokine ; 56(2): 477-80, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21741269

RESUMO

The association between present/null polymorphism of glutathione S-transferase T1 (GSTT1) and breast cancer risk are still inconclusive. We performed a meta-analysis to derive a more precise estimation of the relationship. A total of 48 studies including 17,254 cases and 21,163 controls were involved in this meta-analysis. When all studies were pooled into the meta-analysis, significantly elevated breast cancer risk was associated with null genotype (OR=1.138, 95% CI=1.051-1.232). When stratified by ethnicity, significantly increased risks were found for Caucasians (OR=1.185, 95% CI=1.075-1.306), but no statistically significantly increased risks were found in Asians (OR=1.017, 95% CI=0.846-1.223) and Africans (OR=1.160, 95% CI=0.815-1.650). In the subgroup analysis by controls source, statistically significantly elevated risks were both found in population-based studies (OR=1.123, 95% CI=1.014-1.243) and hospital-based studies (OR=1.181, 95% CI=1.056-1.321). When stratified by menopausal status, no statistically significantly increased risks were found in premenopausal women (OR=1.115, 95% CI=0.925-1.345) and postmenopausal women (OR=1.077, 95% CI=0.992-1.169). In summary, this meta-analysis suggests that the GSTT1 null genotype is a risk allele for breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Glutationa Transferase/genética , Polimorfismo Genético , Neoplasias da Mama/enzimologia , Feminino , Humanos
15.
Bioengineered ; 12(1): 8679-8689, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34635007

RESUMO

Glioma is an intracranial malignant tumor with high morbidity in China. Limited efficacy has been achieved in the treatment of glioma through the application of epidermal growth factor receptor (EGFR) inhibitors, which is reported to be related to the poor permeability of the brain-blood barrier (BBB) to EGFR inhibitors. AZD3759 and osimertinib are both BBB-penetrating EGFR inhibitors. The present study aimed to investigate the inhibitory effects of AZD3759 and osimertinib on glioma and compare their efficacy and the underlying mechanisms. C6 and U87 cells were incubated with different concentrations of AZD3759 (1, 2, and 4 µM) and 4 µM osimertinib, respectively. C6-LUC xenograft animals were administered different doses of AZD3759 (15, 30, and 60 mg/kg) and 60 mg/kg osimertinib. We found that proliferation was significantly suppressed and that apoptosis and cell cycle arrest were dramatically induced in both C6 and U87 cells by AZD3759 in a dose-dependent manner. Compared to AZD3759, osimertinib had inferior effects on proliferation, apoptosis, and cell cycle. In vivo experiments verified that the anti-tumor efficacy of AZD3759 against C6 xenograft tumors was dose dependent and superior to that of osimertinib. The inhibitory effects of AZD3759 on the Janus kinase (JAK)/STAT pathway were observed in both glioma cells and tumor tissues, which were more significant than those of osimertinib. In conclusion, AZD3759 may inhibit the progression of glioma via a synergistic blockade of the EGFR and JAK/STAT signaling pathways.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/tratamento farmacológico , Janus Quinases/antagonistas & inibidores , Piperazinas/farmacologia , Quinazolinas/farmacologia , Animais , Apoptose , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Proliferação de Células , Receptores ErbB/antagonistas & inibidores , Glioma/metabolismo , Glioma/patologia , Humanos , Masculino , Camundongos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Am J Cancer Res ; 11(4): 1051-1068, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33948345

RESUMO

Cancer stem cells (CSCs) are a cellular subpopulation accelerating cancer cell growth, invasion and metastasis and survival. After chemoradiotherapy, CSCs are enriched because of their survival advantages and lead to tumor relapse and metastasis. Elimination of CSCs is critically important for the radical treatment of human cancers. Long non-coding RNAs (lncRNAs) are a group of RNAs longer than 200 nucleotides and have no protein-coding potential. Aberrant expressions of lncRNAs are associated with human diseases including cancer. LncRNAs function as cancer biomarkers, prognostic factors and therapeutic targets. They induce cancer stemness by chromatin modification, transcriptional regulation or post-transcriptional regulation of target genes as a sponge or through assembling a scaffold complex. Several factors caused aberrant expressions of lncRNAs in CSCs such as genes mutations, epigenetic alteration and environmental stimuli. Targeting of lncRNAs has been demonstrated to significantly reverse the chemoradioresistance of CSCs. In this review, we have summarized the progress of studies regarding lncRNAs-mediated therapy resistance of CSCs and clarified the molecular mechanisms. Furthermore, we have for the first time analyzed the influences of lncRNAs on cell metabolism and emphasized the effect of tumor microenvironment on lncRNAs functions in CSCs. Overall, the thorough understanding of the association of lncRNAs and CSCs would contribute to the reversal of therapy resistance.

17.
Asia Pac J Clin Oncol ; 16(4): 266-272, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32285607

RESUMO

AIM: To evaluate the role of radiotherapy (RT) in the treatment of localized primary adult rhabdomyosarcoma (RMS). METHODS: This retrospective study identified 62 consecutive adult patients with localized primary RMS from January 2000 and July 2016. Local failure-free survival (LFFS), distant metastasis-free survival (DMFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. Multivariate Cox proportional hazards regression models were fit to assess the ability of patient characteristics to predict survival. RESULTS: With a median follow-up of 33 months (range, 6-195 months), the 5-year LFFS, DMFS and OS of all patients were 64.0%, 50.0% and 45.0%, respectively. RT was administered to 28 patients (45.2%). Patients who received RT had a higher 5-year LFFS (81.7% vs 47.2%), 5-year DMFS (59.4% vs 43.1%) and 5-year OS (57.1% vs 34.8%) compared with patients who did not received RT. In mulitvariate analysis, RT retained significance as an independent predictor of improved LFFS [hazard ratio (HR) = 0.282; 95% confidence interval (CI), 0.095-0.838; P = 0.023], DMFS (HR = 0.289; 95% CI, 0.125-0.991; P = 0.004) and OS (HR = 0.334; 95% CI, 0.153-0.727; P = 0.006). CONCLUSIONS: RT significantly reduced local recurrence, distant metastasis and tumor mortality compared with no radiotherapy for localized primary adult RMS.


Assuntos
Rabdomiossarcoma/radioterapia , Adulto , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Rabdomiossarcoma/mortalidade , Rabdomiossarcoma/patologia , Análise de Sobrevida
18.
Asia Pac J Clin Oncol ; 14(2): e109-e115, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29071781

RESUMO

AIM: The aim of this study was to determine the effect of local recurrence on overall survival in patients with intermediate high-grade localized primary soft tissue sarcoma (STS) of extremity and abdominothoracic wall. METHODS: This retrospective study identified 133 consecutive patients with intermediate high-grade localized primary STS of extremity and abdominothoracic wall from January 2000 to July 2010. Survival curves were constructed by the Kaplan-Meier method and log-rank test was used to assess statistical significance. Hazard ratios (HRs) were calculated based on multivariable Cox logistic regression method. RESULTS: The 5-year cumulative incidence of local recurrence was 26.0% with a median follow-up of 68 months (range, 5-127 months). The univariate analysis showed that local recurrence was associated with decreased overall survival, with 5-year overall survival of 80.5% and 53.6% in the no local recurrence patients and local recurrence patients, respectively (P = 0.001). The multivariate analysis demonstrated that local recurrence was a negative prognostic factor for overall survival (HR = 2.115, 95% confidence interval [CI] 1.036-4.319, P = 0.040). Radiotherapy significantly reduced local recurrence compared with surgery alone (HR = 0.387, 95% CI 0.180-0.877, P = 0.019), while larger tumor size (HR = 3.184, 95% CI 1.351-7.506 P = 0.008) was correlated with higher rate of local recurrence. CONCLUSION: Local recurrence in patients with intermediate high-grade localized primary STS is associated with decreased overall survival.


Assuntos
Extremidades/patologia , Recidiva Local de Neoplasia/mortalidade , Sarcoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
19.
J Int Med Res ; 44(2): 231-40, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26880795

RESUMO

OBJECTIVE: To examine the role of microRNA (miR)-205 in proliferation, migration and invasion of nasopharyngeal carcinoma (NPC). METHODS: The human NPC cell line CNE2 was transfected with miR-205 mimic, anti-miR-205 inhibitor or scrambled oligonucleotide (control). Cell proliferation was assessed via MTT assay. Cell migration and invasion were evaluated by transwell migration and Matrigel® invasion assay, respectively. Radiation induced apoptosis was quantified via Caspase-Glo3/7 assay. Apoptotic proteins and epithelial-mesenchymal transition (EMT) proteins were semiquantified by Western blot analysis. RESULTS: Overexpression of miR-205 increased the proliferation, migration and invasion of CNE2 cells, and decreased radiation-induced apoptosis compared with control cells. MiR-205 overexpression downregulated E-cadherin and upregulated Snail expression via downregulation of PTEN and upregulation of AKT. CONCLUSION: MiR-205 plays vital roles in tumourigenesis and tumour progression in NPC, and may be a potential treatment target.


Assuntos
Células Epiteliais/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética , Antagomirs/genética , Antagomirs/metabolismo , Apoptose/efeitos da radiação , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Células Epiteliais/patologia , Células Epiteliais/efeitos da radiação , Raios gama , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Nasofaringe/metabolismo , Nasofaringe/patologia , Nasofaringe/efeitos da radiação , Invasividade Neoplásica , PTEN Fosfo-Hidrolase/antagonistas & inibidores , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/agonistas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo
20.
Cancer Med ; 5(12): 3371-3377, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27925455

RESUMO

This prospective study aimed at assessing the efficiency and safety of concurrent chemoradiotherapy (CCRT) using paclitaxel (PTX) plus oxaliplatin (OHP) in unresectable locally advanced esophageal cancer patients. Between January 2006 and December 2010, 34 patients with unresectable locally advanced esophageal cancer were enrolled in this study. Radiotherapy was delivered with a daily fraction of 2.0 Gy to a total dose of 60 Gy over 6 weeks. Concurrent PTX (135 mg/m², d1 ) and OHP (130 mg/m², d1 ) were administered on Day 1 and Day 29 of radiotherapy. Of these patients, 76.5% completed the treatment course with a response rate of 73.5%, including eight (23.5%) patients with complete response and 17 (50.0%) patients with partial response. The median overall survival (OS) time was 23.7 months (range: 4.0-65.5 months) with 1-, 3- and 5-year OS rates were 64.3%, 36.6% and 25.8%, respectively. The median progression-free survival (PFS) time was 21.2 months with 1-, 3- and 5-year PFS rates were 63.8%, 30.9% and 20.4%, respectively, During the CCRT course, the main grade 3 or greater acute toxicities were leukopenia (38.2%), esophagitis (14.7%), and dysphagia (11.8%), with late toxicity being infrequent. Although this study did not meet its primary endpoint, the application of CCRT with PTX and OHP in unresectable locally advanced esophageal carcinoma yielded satisfactory clinical outcomes and manageable toxicities.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Terapia Combinada , Neoplasias Esofágicas/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Paclitaxel/administração & dosagem , Falha de Tratamento , Resultado do Tratamento
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