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1.
Org Lett ; 26(17): 3481-3486, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38240748

RESUMO

A photocatalytic radical cascade with an unusual endo-trig cyclization was developed, which enables the efficient assembly of divergent tricyclic diterpenoid frameworks. The first total synthesis of abietane 10-epi-epoxyhinoliol was thus achieved in six steps by a subsequent reductive coupling of i-PrBr under photoredox/nickel dual catalysis. Inhibitory tests of chiral 10-epi-epoxyhinoliol and its analogues in 4T1 cancer cells demonstrated the critical role of the C12 hydroxyl group, leading to a discovery of the simplified analogue with better activity.


Assuntos
Antineoplásicos , Ciclização , Catálise , Estrutura Molecular , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Abietanos/química , Abietanos/farmacologia , Abietanos/síntese química , Humanos , Estereoisomerismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos
2.
J Cell Mol Med ; 28(1): e18022, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37929660

RESUMO

Long noncoding RNAs (lncRNAs) play critical roles in the carcinogenesis and progression of cancers. However, the role and mechanism of the pseudogene lncRNA PIN1P1 in gastric carcinoma remain unclear. The expression and effects of lncRNA PIN1P1 in gastric cancer were investigated. The transcriptional regulation of CREB1 on PIN1P1 was determined by ChIP and luciferase assays. The mechanistic model of PIN1P1 in gastric cancer was further explored by RNA pull-down, RIP and western blot analysis. PIN1P1 was overexpressed in gastric cancer tissues, and upregulated PIN1P1 predicted poor prognosis in patients. CREB1 was directly combined with the promoter region of PIN1P1 to promote the transcription of PIN1P1. CREB1-mediated enhanced proliferation, migration and invasion could be partially reversed by downregulation of PIN1P1. Overexpressed PIN1P1 promoted the proliferation, migration and invasion of gastric cancer cells, whereas decreased PIN1P1 showed the opposite effects. PIN1P1 directly interacted with YBX1 and promoted YBX1 protein expression, leading to upregulation of PIN1, in which E2F1 may be involved. Silencing of YBX1 during PIN1P1 overexpression could partially rescue PIN1 upregulation. PIN1, the parental gene of PIN1P1, was elevated in gastric cancer tissues, and its upregulation was correlated with poor patient outcomes. PIN1 facilitated gastric cancer cell proliferation, migration and invasion. To sum up, CREB1-activated PIN1P1 could promote gastric cancer progression through YBX1 and upregulating PIN1, suggesting that it is a potential target for gastric cancer.


Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Proteína 1 de Ligação a Y-Box/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Peptidilprolil Isomerase de Interação com NIMA/genética , Peptidilprolil Isomerase de Interação com NIMA/metabolismo
3.
Gene ; 895: 148019, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-37984538

RESUMO

Circular RNA (circRNA) is a newly discovered endogenous non-coding RNA that plays important roles in the occurrence and development of various cancers. Current research indicates that circRNA can inhibit the function of miRNA by acting as an miRNA sponge, interacting with proteins, and being translated into proteins. Most current research focuses on the circRNA-miRNA interaction; however, few studies have investigated the interaction between circRNAs and RNA binding proteins (RBPs) in breast cancer. In this review, we systematically summarize the potential molecular mechanism of the circRNA-protein interaction in breast cancer. Specifically, we elaborate on the direct interaction between circRNAs and proteins in breast cancer, including the functions of circRNA as protein sponges, decoys, and scaffolds, thereby affecting the progression of breast cancer. We also discuss the indirect interaction between circRNAs and proteins in breast cancer in which RBPs, transcription factors and m6A modifying enzymes could in turn regulate the expression and formation of circRNA. Finally, we discuss the potential application of circRNA-protein interaction for treating breast cancer, providing a reference for further research in this field.


Assuntos
Neoplasias da Mama , MicroRNAs , Humanos , Feminino , RNA Circular/genética , Neoplasias da Mama/genética , MicroRNAs/genética , MicroRNAs/metabolismo
4.
Sci Rep ; 13(1): 18424, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891423

RESUMO

Prostate cancer (PCa) patients with lymph node involvement (LNI) constitute a single-risk group with varied prognoses. Existing studies on this group have focused solely on those who underwent prostatectomy (RP), using statistical models to predict prognosis. This study aimed to develop an easily accessible individual survival prediction tool based on multiple machine learning (ML) algorithms to predict survival probability for PCa patients with LNI. A total of 3280 PCa patients with LNI were identified from the Surveillance, Epidemiology, and End Results (SEER) database, covering the years 2000-2019. The primary endpoint was overall survival (OS). Gradient Boosting Survival Analysis (GBSA), Random Survival Forest (RSF), and Extra Survival Trees (EST) were used to develop prognosis models, which were compared to Cox regression. Discrimination was evaluated using the time-dependent areas under the receiver operating characteristic curve (time-dependent AUC) and the concordance index (c-index). Calibration was assessed using the time-dependent Brier score (time-dependent BS) and the integrated Brier score (IBS). Moreover, the beeswarm summary plot in SHAP (SHapley Additive exPlanations) was used to display the contribution of variables to the results. The 3280 patients were randomly split into a training cohort (n = 2624) and a validation cohort (n = 656). Nine variables including age at diagnosis, race, marital status, clinical T stage, prostate-specific antigen (PSA) level at diagnosis, Gleason Score (GS), number of positive lymph nodes, radical prostatectomy (RP), and radiotherapy (RT) were used to develop models. The mean time-dependent AUC for GBSA, RSF, and EST was 0.782 (95% confidence interval [CI] 0.779-0.783), 0.779 (95% CI 0.776-0.780), and 0.781 (95% CI 0.778-0.782), respectively, which were higher than the Cox regression model of 0.770 (95% CI 0.769-0.773). Additionally, all models demonstrated almost similar calibration, with low IBS. A web-based prediction tool was developed using the best-performing GBSA, which is accessible at https://pengzihexjtu-pca-n1.streamlit.app/ . ML algorithms showed better performance compared with Cox regression and we developed a web-based tool, which may help to guide patient treatment and follow-up.


Assuntos
Excisão de Linfonodo , Neoplasias da Próstata , Masculino , Humanos , Prognóstico , Excisão de Linfonodo/métodos , Linfonodos/patologia , Neoplasias da Próstata/patologia , Antígeno Prostático Específico
5.
Aging (Albany NY) ; 15(15): 7616-7636, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37543427

RESUMO

Both angiogenesis and lncRNAs play crucial roles in the development and progression of breast cancer. Considering the unknown association of angiogenesis and lncRNAs in breast cancer, we aim to identify angiogenesis-related lncRNAs (ARLs) and explore their prognostic value. Here, based on analysis of The Cancer Genome Atlas database, the correlation between ARL and the prognosis and immune infiltration landscape of breast cancer were investigated. Eight ARLs (MAFG-DT, AC097478.1, AL357054.4, AL118556.1, SNHG10, MED14OS, OTUD6B-AS1, and CYTOR) were selected to construct the risk model as a prognostic signature. The survival rate of the patients in the high-risk group was lower than that in the low-risk group. The ARL signature was an independent prognostic predictor, and areas under the curve of 1-, 3-, and 5-year survival were 0.745, 0.695, and 0.699, respectively. The prognostic ARLs were associated with the immune infiltration landscape and could indicate the immune status, immune response, tumor mutational burden, and drug sensitivity of patients with breast cancer. Furthermore, qRT-PCR of clinical samples revealed that OTUD6B-AS1 was correlated with prognostic pathological parameters. OTUD6B-AS1 promoted breast cancer cell proliferation, wound healing, migration, invasion, and human umbilical vein endothelial cells tube formation. Mechanistically, OTUD6B-AS1 regulated EMT- and angiogenesis-related molecules. Taken together, we constructed and verified a robust signature of eight ARLs for the prediction of survival in patients with breast cancer, and the characterization of the immune infiltration landscape. Our findings suggest that OTUD6B-AS1 could be a therapeutic target for patients with breast cancer.


Assuntos
Neoplasias da Mama , RNA Longo não Codificante , Humanos , Feminino , Neoplasias da Mama/genética , RNA Longo não Codificante/genética , Prognóstico , Fenômenos Fisiológicos Cardiovasculares , Células Endoteliais da Veia Umbilical Humana , Microambiente Tumoral/genética
6.
Org Biomol Chem ; 21(31): 6405-6409, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37503699

RESUMO

Inspired by the synthetic method of benzoxazine derivatives and our previous research, a fluorescent probe (SWJT-6) was designed for formaldehyde (FA) detection based on the cyclization reaction. The synthetic SWJT-6 showed excellent colorimetric and ratiometric response to formaldehyde, and could be perfectly used as test strips to detect formaldehyde. It also showed a fast detection time (3 min), low detection limit (5.65 µM) and high selectivity for formaldehyde within various interfering analytes. In addition, SWJT-6 has been successfully applied in bioimaging of intracellular and lysosomal formaldehyde in both HeLa cells and zebrafish.


Assuntos
Corantes Fluorescentes , Peixe-Zebra , Humanos , Animais , Células HeLa , Lisossomos , Formaldeído
7.
Chin J Physiol ; 66(3): 181-187, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37322628

RESUMO

We have previously shown that microRNAs (miRNAs) in nipple discharge are potential diagnostic biomarkers. In particular, exosomes are present in nipple discharge. Herein, we sought to elucidate the protective role of exosomes on miRNAs in nipple discharge and investigate the stability of miRNAs encapsulated in exosomes under degradative conditions. A novel TTMAAlPc-RNA complex method was used to measure the RNase concentration in colostrum and nipple discharge. Quantitative real-time polymerase chain reaction was performed to test the stability of exogenous synthetic miRNAs (cel-lin-4-5p and cel-miR-2-3p) and endogenous miRNAs (hsa-miR-4732-5p, hsa-miR-3646, hsa-miR-4484, and kshv-miR-K12-5-5p). RNase was present and functional in colostrum and nipple discharge. Endogenous miRNAs were more stably expressed compared to exogenous miRNAs at room temperature and 4°C. Triton X-100 (1%, 30 min) destroyed the exosomal membrane, causing RNA degradation in colostrum but not in nipple discharge. Therefore, we confirmed that exosomes in colostrum and nipple discharge could protect miRNAs from degradation by RNase. Exosomes in nipple discharge may be more resistant to Triton X-100 lysis compared to those in the colostrum. Exosomal miRNAs in nipple discharge in breast cancer are stable under degradative conditions. Differential Triton X-100 sensitivity of exosomes of nipple discharge and colostrum warrants further investigation.


Assuntos
Neoplasias da Mama , MicroRNAs , Derrame Papilar , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Octoxinol , MicroRNAs/genética , Derrame Papilar/metabolismo , Ribonucleases
8.
Front Oncol ; 13: 1153076, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124526

RESUMO

Background: Aberrant expression of fatty acid synthase (FASN) was demonstrated in various tumors including breast cancer. A meta-analysis was conducted to investigate the role of FASN in breast cancer development and its potential prognostic significance. Methods: The Web of Science, PubMed, Embase, and Cochrane Library databases were searched to identify studies that evaluated the relationship between FASN expression and overall survival (OS), relapse-free survival (RFS), and disease-free survival (DFS) of breast cancer patients. To analyze the clinicopathological and prognostic values of FASN expression in breast cancer, pooled hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were clustered based on random-effects models. To confirm whether the findings were stable and impartial, a sensitivity analysis was performed, and publication bias was estimated. Data were analyzed using Engauge Digitizer version 5.4 and Stata version 15.0. Results: Five studies involving 855 participants were included. Patients with higher FASN expression did not have a shorter survival period compared to those with lower FASN expression (summary HR: OS, 0.73 [95% CI, 0.41-1.32; P=0.300]; DFS/RFS, 1.65 [95% CI, 0.61-4.43; P=0.323]). However, increased FASN expression was correlated with large tumor size (OR, 2.04; 95% CI, 1.04-4.00; P=0.038), higher human epidermal growth factor receptor 2 (HER2) positivity (OR, 1.53; 95% CI, 1.05-2.23; P=0.028). No significant associations were observed between FASN expression and histological grade (OR, 0.92; 95% CI, 0.41-2.04; P=0.832), Tumor Node Metastasis (TNM) stage (OR, 1.11; 95% CI, 0.49-2.53; P=0.795), nodal metastasis (OR, 1.42; 95% CI, 0.84-2.38; P=0.183), Ki-67 labelling index (OR, 0.64; 95% CI, 0.15-2.63; P=0.533), estrogen receptor (ER) status (OR, 0.90; 95% CI, 0.61-1.32; P=0.586), or progesterone receptor (PR) status (OR, 0.67; 95% CI, 0.29-1.56; P=0.354). Conclusion: FASN is associated with HER2 expression and may contribute to tumor growth, but it has no significant impact on the overall prognosis of breast cancer.

9.
Biosensors (Basel) ; 13(4)2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37185522

RESUMO

In this work, a coumarin derivative, SWJT-14, was synthesized as a fluorescence probe to distinguish cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) in aqueous solutions. The detection limit of Cys, Hcy and GSH for the probe was 0.02 µM, 0.42 µM and 0.92 µM, respectively, which was lower than biothiols in cells. The probe reacted with biothiols to generate different products with different conjugated structures. Additionally, it could distinguish Cys, Hcy and GSH using fluorescence and UV-Vis spectra. The detection mechanism was confirmed by MS. SWJT-14 was successfully used in cellular experiments and detected both endogenous and exogenous biothiols.


Assuntos
Cisteína , Corantes Fluorescentes , Corantes Fluorescentes/química , Diferenciação Celular , Cumarínicos/química , Glutationa , Espectrometria de Fluorescência
10.
Org Biomol Chem ; 21(10): 2167-2171, 2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36799709

RESUMO

A novel ratiometric probe (SWJT-10) based on isophorone derivatives has been designed and synthesized for the detection of formaldehyde (FA). This probe displayed an obvious ratiometric fluorescence response to FA with a blue shift from the NIR (680 nm) to the yellow light region (600 nm) in aqueous solution. And it showed good selectivity, high sensitivity and a fast response to FA (less than 5 s) due to a new recognition mechanism. Moreover, SWJT-10 has been applied to monitor FA in living cells and zebrafish.


Assuntos
Corantes Fluorescentes , Peixe-Zebra , Humanos , Animais , Células HeLa , Fluorescência , Formaldeído
11.
Clin Breast Cancer ; 23(2): 189-198, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36564279

RESUMO

BACKGROUND: Increasing studies have shown that microRNAs (miRNAs) have great diagnostic value in cancer. Axillary lymph node metastasis (ALNM) is closely related to the prognosis of breast cancer. However, it remains unknown whether miRNAs in whole blood could be promising biomarkers in breast cancer ALNM. METHODS: An miRNA microarray was used to screen potential differentially expressed miRNA candidates in whole blood of three breast cancer patients with ALNM and three without ALNM. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect candidate differentially expressed miRNAs in the whole blood of 109 breast cancer patients. Furthermore, bioinformatics analysis was carried to predict the potential targets and enriched pathway of miRNAs. RESULTS: QRT-PCR validated the fact that miR-367-3p, miR-548aq-5p and miR-4710 are downregulated in breast cancer with ALNM compared to it without ALNM. Receiver operating characteristic (ROC) curve analysis revealed that miR-367-3p, miR-548aq-5p and miR-4710 have good diagnostic values. Notably, the three-miRNA signature showed better predictive value, with an area under ROC curve (AUC) of 0.7414. Bioinformatics analysis revealed that the miRNAs could participate in a complex network and thus be involved in cancer-related pathways. CONCLUSIONS: Our findings support the potential of miR-367-3p, miR-548aq-5p and miR-4710 and the three-miRNA signature as biomarkers for breast cancer with ALNM.


Assuntos
Neoplasias da Mama , MicroRNAs , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Metástase Linfática , Biomarcadores Tumorais/genética , MicroRNAs/metabolismo , Biomarcadores , Prognóstico , Curva ROC , Perfilação da Expressão Gênica
12.
Clin Chim Acta ; 537: 118-126, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36330944

RESUMO

BACKGROUND AND AIMS: Methylated Septin9 (mSEPT9) has been suggested for CRC detection. To assess the performance of mSEPT9 in Western China, we compared its diagnostic and recurrence monitoring values with fecal occult blood test (FOBT), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9). MATERIAL AND METHODS: Overall 300 subjects including 209 CRC patients and 91 healthy subjects, who have performed mSEPT9, FOBT, CEA and CA19-9 tests, were involved. Sensitivity, specificity, and area under the ROC curve (AUC) were used to evaluate the efficacy of each method. RESULTS: Plasma mSEPT9 demonstrated an AUC of 0.860, and a sensitivity of 76.4 % for CRC detection. The sensitivity of mSEPT9 was higher than FOBT, CEA and CA 19-9. Though mSEPT9 presented a larger or equal sensitivity for stage Ⅱ-IV CRCs, FOBT showed a better sensitivity for stage I CRCs. Logistical analysis showed the ones with positive mSEPT9, FOBT and CEA were more likely to have CRC (all P < 0.01). Then, the three biomarkers built the nomogram predicting the probability of having CRC. The sensitivity of mSEPT9 was also much higher than CEA for CRC recurrence monitoring. CONCLUSION: The mSEPT9 test performed better than traditional tests for CRC detection, and should be recommended for FOBT-positive ones or individuals who refuse FOBT.


Assuntos
Ácidos Nucleicos Livres , Neoplasias Colorretais , Humanos , Biomarcadores Tumorais/genética , Antígeno Carcinoembrionário , Ácidos Nucleicos Livres/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , DNA , Septinas/genética , Septinas/metabolismo
13.
Polymers (Basel) ; 14(19)2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36236108

RESUMO

Plant polysaccharides are widely found in nature and have a variety of biological activities, including immunomodulatory, antioxidative, and antitumoral. Due to their low toxicity and easy absorption, they are widely used in the health food and pharmaceutical industries. However, low activity hinders the wide application. Chemical modification is an important method to improve plant polysaccharides' physical and chemical properties. Through chemical modification, the antioxidant and immunomodulatory abilities of polysaccharides were significantly improved. Some polysaccharides with poor water solubility also significantly improved their water solubility after modification. Chemical modification of plant polysaccharides has become an important research direction. Research on the modification of plant polysaccharides is currently increasing, but a review of the various modification studies is absent. This paper reviews the research progress of chemical modification (sulfation, phosphorylation, acetylation, selenization, and carboxymethylation modification) of land plant polysaccharides (excluding marine plant polysaccharides and fungi plant polysaccharides) during the period of January 2012-June 2022, including the preparation, characterization, and biological activity of modified polysaccharides. This study will provide a basis for the deep application of land plant polysaccharides in food, nutraceuticals, and pharmaceuticals.

14.
J Fluoresc ; 32(5): 1661-1667, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35618873

RESUMO

A novel near-infrared fluorescent probe SWJT-5 based on dicyanoisophorone was synthesized. It achieved the rapid (within 40 s) and discriminative detection of Cys over Hcy and GSH with a large Stokes shift (205 nm). It showed high selectivity and sensitivity for Cys, and had an obvious enhancement of fluorescence emission. The detection limit was 0.43 µM. This probe also had low background interference and little damage to biological samples. Therefore, SWJT-5 had been applied to bioimaging in living cells successfully.


Assuntos
Cicloexanonas , Cisteína , Corantes Fluorescentes , Animais , Glutationa , Homocisteína , Camundongos , Imagem Óptica/métodos
15.
J Cancer Res Ther ; 18(1): 257-259, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35381794

RESUMO

Oral and maxillofacial anatomy and function are important and complex. They are involved in facial expressions, chewing, language, breathing, and other functions. It is therefore important to choose the optimal treatment plan for oral and maxillofacial tumors. For patients with who cannot tolerate surgery or who refuse surgery or radiotherapy can be treated with cryoablation. Cryoablation can maintain local tissue integrity and organ function and protect facial integrity. It is a repeatable treatment that, if necessary, can be followed by traditional antineoplastic therapies. This study introduces five cases with severe basic diseases who cannot tolerate or have refused surgery or radiotherapy. The patients were diagnosed as having oral and maxillofacial tumors. These patients experienced painful local swelling or breaking of the tumor. All patients received cryoablation combined with other treatments. Local control of the tumors and improved function and quality of life were achieved. In clinical work, for patients with severe basic diseases who cannot tolerate or refuse surgery or radiotherapy, cryoablation has unique advantages, and this approach is expected to become a widely used treatment for oral and maxillofacial tumors.


Assuntos
Ablação por Cateter , Criocirurgia , Neoplasias , Humanos , Neoplasias/etiologia , Qualidade de Vida , Resultado do Tratamento
16.
Support Care Cancer ; 30(6): 4927-4934, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35175418

RESUMO

OBJECTIVE: This study is designed to investigate the status of kinesiophobia and related factors in cancer patients with totally implantable venous access ports (TIAPs). METHODS: This is a cross-sectional study; all the participants were recruited from the Oncology Department and the Daytime Chemotherapy Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, from April 1 to May 31, 2021. The participants were interviewed by researchers using the self-made general information questionnaire and the Tampa Scale of Kinesiophobia-11 (TSK-11) scale, which allows the fear of movement to be quantified. Eligible patients were aged ≥ 18 years, confirmed with cancer, and implanted with a port. The logistic regression model was used to evaluate clinical factors and the risk of kinesiophobia. RESULTS: A total of 282 patients were recruited (aged 58.0 ± 11.5 years), of which gastrointestinal cancer accounted for 54.6%, breast cancer accounted for 22.7%, lung cancer accounted for 11.3%, and other types accounted for 11.3%. The TSK-11 score of the 282 patients was 17.84 ± 6.06 points, 45.7% of the patients reported mild kinesiophobia (TSK-11 ≥ 18), 18.4% of the patients reported moderate to severe kinesiophobia (TSK-11 ≥ 25), and the highest score reached 34 points. Results of logistic regression analysis showed that exercise habits (P = 0.025), pain (P = 0.023), and foreign body sensation (P = 0.003) were the risk factors of kinesiophobia. CONCLUSION: Kinesiophobia is common in cancer patients with TIAPs, and it is closely related to the subjective experience of daily activities, which requires more attention and early intervention to reduce the potential adverse effects.


Assuntos
Medo , Neoplasias , China/epidemiologia , Estudos Transversais , Humanos , Neoplasias/epidemiologia , Inquéritos e Questionários
17.
BMC Cancer ; 22(1): 45, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996395

RESUMO

BACKGROUND: Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. METHODS: We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan-Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm. RESULTS AND CONCLUSIONS: Univariate and multivariate analyses revealed that platelets< 254 × 109/L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell's concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.


Assuntos
Biomarcadores Tumorais/sangue , Linfoma de Burkitt , Adulto , Idoso , Linfoma de Burkitt/sangue , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/epidemiologia , Linfoma de Burkitt/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
18.
Oncogene ; 41(3): 361-371, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34754080

RESUMO

Breast cancer (BC) is the most common cancer in women worldwide, and the exploration of aberrantly expressed genes might clarify tumorigenesis and help uncover new therapeutic strategies for BC. Although RGMA was recently recognized as a tumor suppressor gene, its detailed biological function and regulation in BC remain unclear. Herein, we found that RGMA was downregulated in BC tissues compared with non-tumorous breast tissues, particularly in metastatic BC samples, and that patients with low RGMA expression manifested a poorer prognosis. Furthermore, DNMT1 and DNMT3A were found to be recruited to the RGMA promoter and induced aberrant hypermethylation, resulting in downregulation of RGMA expression in BC. In contrast, RGMA overexpression suppressed BC cell proliferation and colony-formation capabilities and increased BC cell apoptosis. Furthermore, RGMA knockdown accelerated BC cell proliferation and suppressed cellular apoptosis in vitro and in vivo. Reversal of RGMA promoter methylation with 5-Aza-CdR restored RGMA expression and blocked tumor growth. Overall, DNMT1- and DNMT3A-mediated RGMA promoter hypermethylation led to downregulation of RGMA expression, and low RGMA expression contributed to BC growth via activation of the FAK/Src/PI3K/AKT-signaling pathway. Our data thus suggested that RGMA might be a promising therapeutic target in BC.


Assuntos
Neoplasias da Mama/genética , Metilação de DNA/genética , Proteínas Ligadas por GPI/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Humanos , Prognóstico
19.
Chin J Physiol ; 64(5): 251-256, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34708717

RESUMO

Heat shock protein 90α (HSP90α) has been confirmed to be upregulated in the blood in various types of tumors and may therefore serve as a potential tumor marker. However, whether HSP90α exists in nipple discharge remains unknown, and its expression and diagnostic value in nipple discharge remain unclear. In this study, the expression of HSP90α, carcinoembryonic antigen (CEA), and cancer antigen 153 in nipple discharge and blood from 128 patients was measured. Receiver operating characteristic curve was used to assess the diagnostic value of HSP90α. Further, its relationship with clinicopathological parameters of patients with breast cancer was analyzed. The results showed that the expression of HSP90α in nipple discharge was significantly higher in patients with breast cancer than in those with benign disease, and its diagnostic value was better than that of CEA. Combination of HSP90α and CEA showed better diagnostic efficacy than HSP90α or CEA alone. Moreover, the expression of HSP90α displayed a stepwise increase from benign lesions, followed by carcinoma in situ to invasive ductal carcinoma. HSP90α was positively correlated with Ki67 expression. However, there was no significant difference in the expression of HSP90α in blood between patients with breast cancer and benign disease. Further, the expression of HSP90α was higher in nipple discharge than in blood. In summary, HSP90α was upregulated in the nipple discharge of patients with breast cancer, and it may be related to the occurrence and progression of breast cancer. HSP90α in nipple discharge may serve as a potential diagnostic marker for breast cancer.


Assuntos
Neoplasias da Mama , Proteínas de Choque Térmico HSP90/genética , Derrame Papilar , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Feminino , Humanos
20.
J Comput Assist Tomogr ; 45(6): 888-893, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34469908

RESUMO

OBJECTIVE: To compare image quality and radiation dose of split-filter TwinBeam dual-energy (SF-TBDE) with those of single-energy images (SECT) in the contrast-enhanced chest computed tomography (CT). METHODS: Two hundred patients who underwent SF-TBDE (n = 100) and SECT (n = 100) contrast-enhanced chest scanning were retrospectively analyzed. The contrast-to-noise ratio (CNR) and figure of merit (FOM)-CNR of 5 structures (lung, aorta, pulmonary artery, thyroid, and erector spinae) were calculated and subjectively evaluated by 2 independent radiologists. Radiation dose was compared using volume CT dose index and size-specific dose estimate. RESULTS: The CNR and FOM-CNR of lung and erector spinae in SF-TBDE were higher than those of SECT (P < 0.001). The differences in the subjective image quality between the 2 groups were not significant (P = 0.244). Volume CT dose index and size-specific dose estimate of SF-TBDE were lower than those of SECT (6.60 ± 1.56 vs 7.81 ± 3.02 mGy, P = 0.001; 9.25 ± 1.60 vs. 10.55 ± 3.54; P = 0.001). CONCLUSIONS: The SF-TBDE CT can provide similar image quality at a lower radiation dose compared with SECT.


Assuntos
Meios de Contraste , Doses de Radiação , Intensificação de Imagem Radiográfica/métodos , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Radiografia Torácica/métodos , Doenças Torácicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos
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