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2.
Zhonghua Bing Li Xue Za Zhi ; 53(7): 672-677, 2024 Jul 08.
Article in Chinese | MEDLINE | ID: mdl-38955697

ABSTRACT

Objective: To assess the capability of seven reference medical laboratories to detect BCR::ABL1 p210 transcription levels and to compare the results among those laboratories. Methods: The interlaboratory comparison was carried out in two stages. The samples were prepared by the reference laboratory. The quantitative values of BCR::ABL1 p210 of the comparison samples covered 0.001%-0.01%, 0.01%-0.1%, 0.1%-1%, 1%-10% and>10% in each stage. Real-time quantitative PCR (RT-PCR) and dPCR (digital PCR) were used to examine the samples. The conversion factor (CF) was calculated and validated for each laboratory. Results: In the RT-PCR comparison, one laboratory was failed to detect BCR::ABL1 p210 in fourteen samples at the first stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.133-0.338) and 95% limits of agreement within ±5 folds (upper limit 0.147-0.785, lower limit -0.770--0.109), and the corresponding CF values were calculated and validated. In the dPCR comparison, one laboratory did not report results at the second stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.026-0.267) and 95% limits of agreement within±5 folds (upper limit 0.084-0.991, lower limit -0.669--0.135), and the corresponding CF values were calculated and validated. The samples with BCR::ABL1 p210 quantitative values of 0.01%-0.1%, 0.1%-1%, 1%-10% and >10% could be detected by both RT-PCR and qPCR. When the quantitative value of BCR::ABL1 p210 was 0.001%-0.01%, the detection rate of dPCR was higher than that of RT-PCR (85.56% vs. 68.00%). Conclusions: A good consistency is present among various laboratories. The quantitative value of BCR::ABL1 p210 is comparable among laboratories as shown by the CF value conversion. For quantitative detection of BCR::ABL1 p210 deep molecular reaction, dPCR has a higher positive detection rate and more advantages than RT-PCR. To ensure the accuracy and reproducibility of the BCR::ABL1 p210 test, it is imperative for every laboratory to enhance their daily quality control practices.


Subject(s)
Fusion Proteins, bcr-abl , Real-Time Polymerase Chain Reaction , Humans , Fusion Proteins, bcr-abl/genetics , Real-Time Polymerase Chain Reaction/methods , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Reproducibility of Results
3.
Zhonghua Nei Ke Za Zhi ; 63(8): 769-775, 2024 Aug 01.
Article in Chinese | MEDLINE | ID: mdl-39069865

ABSTRACT

Objective: To evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and tislelizumab in the treatment of unresectable intrahepatic cholangiocarcinoma (ICC). Methods: The clinical data of 12 patients with unresectable ICC who received HAIC combined with lenvatinib and tislelizumab in the First Affliated Hospital of Soochow University from October 2021 to April 2023 were retrospectively analyzed. HAIC included gemcitabine plus oxaliplatin; this regimen was combined with lenvatinib and tislelizumab within 3-7 days after its initial administration. Relevant laboratory examinations were performed before each cycle of HAIC, and enhanced computed tomography/magnetic resonance imaging examinations were performed every 6-9 weeks. Tumor response to treatment was evaluated using the modified Response Evaluation Criteria in Solid Tumors. The objective response rate, disease control rate, progression-free survival, overall survival, and treatment-related adverse reactions of patients with ICC were statistically analyzed. Results: The objective response rate to HAIC combined with lenvatinib and tislelizumab was 6/12; the disease control rate was 8/12; the median progression-free survival was 11.8 months; and the median overall survival was 14.2 months. Three patients had grade Ⅳ adverse reactions (increased alanine aminotransferase and aspartate aminotransferase thrombocytopenia), while three patients had grade Ⅲ adverse reactions (increased total bilirubin, alanine aminotransferase, and aspartate aminotransferase). The remaining patients had grade Ⅰ-Ⅱ adverse reactions. There were no serious complications related to interventional surgery. Conclusions: Use of HAIC (gemcitabine plus oxaliplatin) combined with lenvatinib and tislelizumab in the treatment of unresectable ICC may be safe and feasible. Preliminary clinical studies have shown that this combination can improve the survival and prognosis of patients with ICC.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Bile Duct Neoplasms , Cholangiocarcinoma , Phenylurea Compounds , Quinolines , Humans , Cholangiocarcinoma/drug therapy , Quinolines/administration & dosage , Quinolines/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Phenylurea Compounds/administration & dosage , Phenylurea Compounds/therapeutic use , Bile Duct Neoplasms/drug therapy , Male , Female , Infusions, Intra-Arterial , Gemcitabine , Deoxycytidine/analogs & derivatives , Deoxycytidine/administration & dosage , Middle Aged , Oxaliplatin/administration & dosage , Oxaliplatin/therapeutic use , Hepatic Artery , Aged , Treatment Outcome
4.
J Endocrinol Invest ; 2024 May 24.
Article in English | MEDLINE | ID: mdl-38787506

ABSTRACT

PURPOSE: Thyroid cancer is one of a set of extrahepatic cancers that closely linked to metabolic dysfunction-associated fatty liver disease (MAFLD). However, the connection between MAFLD and the characteristics of papillary thyroid cancer (PTC) remains unexplored. METHODS: Between Jan 2020 and Oct 2022, surgical cases of PTC patients were examined at the first Affiliated Hospital of Wenzhou Medical University. Clinical data extracted from the electronic medical system underwent a rigorous comparison between two groups, classified based on MAFLD criteria, using logistic regression analysis. RESULTS: In this study of 4,410 PTC patients, 18.3% had MAFLD. MAFLD emerged as a distinct risk factor for lymph node metastasis (OR = 1.230, 95% CI 1.018-1.487) in this cohort, especially in females (OR = 1.321, 95% CI 1.026-1.702) and those with BMI ≥ 23 kg/m2 (OR = 1.232, 95% CI 1.004-1.511). The presence of MAFLD was found to significantly elevate the risk of BRAF V600E mutation in both subgroups characterized by FIB-4 score ≥ 1.3 (OR = 1.968, 95% CI 1.107-3.496) and BMI < 23 kg/m2 (OR = 2.584, 95% CI 1.012-6.601). Moreover, among the subset of individuals without non-alcoholic fatty liver disease (NAFLD), it was noted that MAFLD considerably increased the likelihood of tumor multifocality (OR = 1.697, 95% CI 1.111-2.592). Nevertheless, MAFLD did not exhibit any correlation with increased tumor size, extra-thyroidal extension (ETE), or later TNM stage in PTC. CONCLUSION: In this cross-sectional study, we discovered a significant association between MAFLD and increased occurrences of lymph node metastasis. Furthermore, MAFLD was linked to a higher chance of BRAF V600E mutation and the presence of multiple tumors in certain subgroups.

5.
Article in Chinese | MEDLINE | ID: mdl-38311946

ABSTRACT

Objective: To analyze and summarize the trends and hot spots in the field of neurological damage caused by electric welding operations, and to provide ideas for new researches by searching the domestic and international literature. Methods: In December 2022, using Web of Science Citation Index (Web of Science), China Journal Full-Text Database (CNKI) and Wanfang Database as search databases, literature search was conducted on the Chinese and English search terms related to eletrical welding operations and neurological damage. The bibliometric analysis software VOSviewer 1.6.18 and CiteSpace 6.1.6 were used to visualize the publication year, publication quantity, country, research institution and key words of the literature. Results: A total of 309 articles (112 in Chinese and 197 in English) were included in this study. The first domestic and international papers were published in 1976 and 1994 respectively, and the number of papers reached the peak in 2006 and 2018, and then showed a downward trend to varying degrees. In China, Shandong First Medical University (including Shandong Institute of Occupational Health and Occupational Disease Prevention and Shandong Academy of Medical Sciences) and Wuhan University of Science and Technology had the largest number of publications. The 309 articles were from 52 Chinese journals and 86 English journals. The co-occurrence analysis of key words showed that the domestic research mainly focused on eletrical welding operation, welding workers, neurobehavioral function and manganese, and the nervous system damage caused by manganese in welding smoke was the field of international attention. Long term exposure, risk, and performance were key buzzwords in the field. Conclusion: The research focus in the field of nervous system damage caused by electric welding operation has an obvious trend of time evolution, gradually transiting from clinical manifestations to its toxic mechanism and early biomarkers.


Subject(s)
Manganese , Nervous System Diseases , Occupational Diseases , Smoke , Welding , Humans , Asian People , Bibliometrics , China , Manganese/analysis , Manganese/toxicity , Welding/methods , Nervous System Diseases/etiology , Smoke/adverse effects , Occupational Diseases/etiology , Occupational Exposure/adverse effects , Occupational Exposure/analysis
6.
J Clin Nurs ; 33(5): 1709-1723, 2024 May.
Article in English | MEDLINE | ID: mdl-38156732

ABSTRACT

AIMS: To identify studies and the content of the interventions that have facilitated the implementation of pressure injury (PI) prevention measures in nursing home settings. DESIGN AND METHOD: A scoping review methodology was employed. The author has carried out the following steps successively: Identified this scoping review's questions, retrieved potentially relevant studies, selected relevant studies, charted the data, summarised the results, and consulted with stakeholders from nursing homes in China. DATA SOURCES: Six electronic databases and three resources of grey literature-PubMed, CINAHL, Web of Science Core Collection, Embase, Cochrane Central Register of Controlled Trials, Psych INFO, Open Grey, MedNar, ProQuest Dissertations, and Theses Full Texts were searched from January 2002 through May 2022. RESULTS: Forty articles were included, among which the primary interventions were quality improvement, training and education, evidence-based practice, device-assisted PI prophylaxis, nursing protocols, and clinical decision support systems. Twenty-three outcome indicators were summarised in 40 articles, which included 10 outcome indicators, seven process indicators, and six structural indicators. Furthermore, only five articles reported barriers in the process of implementing interventions. CONCLUSION: The common interventions to promote the implementation of PI prevention measures in nursing homes are quality improvement, training, and education. Relatively limited research has been conducted on evidence-based practice, clinical decision support systems, device-assisted PI prophylaxis, and nursing protocols. In addition, there is a paucity of studies examining the impediments to implementing these measures and devising targeted solutions. Therefore, it is recommended that future studies include analysis and reporting of barriers and facilitators as part of the article to improve the sustainability of the intervention. IMPACT: This article reminds nursing home managers that they should realise the importance of implementation strategies between the best evidence of PI prevention and clinical practice. Also, this review provides the types, contents, and outcome indicators of these strategies for managers of nursing homes to consider what types of interventions to implement in their organisations. TRIAL AND PROTOCOL REGISTRATION: The protocol of this scoping review was published as an open-access article in June 2022 (Yang et al., 2022).

7.
J Nutr Health Aging ; 26(10): 954-961, 2022.
Article in English | MEDLINE | ID: mdl-36259584

ABSTRACT

OBJECTIVES: The study aimed to evaluate the association of dietary iron intake with incident dementia and brain iron deposition. DESIGN/SETTING/PARTICIPANTS: We included dementia-free participants from the UK Biobank who completed at least one 24-hour dietary recall at study baseline (2009-2012) and were followed up to 2021. Incident dementia was determined through linkage to medical records and death registries. Brain MRI was conducted in a subgroup of participants since 2014, with T2* measurements being used as indicators of brain iron deposition. MEASUREMENTS: Cox proportional hazard models were used to assess the associations of high (top quintile) and low (bottom quintile) versus medium (quintile 2 to 4) level of dietary iron intake with incident dementia, respectively. Linear regression was applied to assess the relations between dietary iron intake and brain T2* measurements. RESULTS: During follow-up (mean = 9.5 years), a total of 1,454 participants (650 women and 804 men) developed dementia among 191,694 participants (55.0% female; mean age, 56.2 years). When adjusted for sociodemographic, lifestyle, and other dietary factors, participants with low dietary iron intake (< 10.05 mg/day) had a significantly higher dementia risk (hazard ratio [HR], 1.50, 95% confidence interval [CI], 1.19-1.89), while the relation for high intake (> 16.92 mg/day) was non-significant (HR, 1.16, 95% CI, 0.92-1.46). A significant gender difference (P-interaction < 0.001) was observed, with a U-shaped association in male participants (HR for low vs. medium, 1.56, 95% CI, 1.14-2.13; HR for high vs. medium, 1.39, 95% CI, 1.03 - 1.88; P-nonlinearity < 0.001) and no significant association in females, regardless of their menopause status. In general, dietary iron intake was not related to T2* measurements of iron deposition in most brain regions. CONCLUSION: Our findings suggested a U-shape relationship between dietary iron intake and risk of dementia among males, but not females.


Subject(s)
Iron, Dietary , Iron , Humans , Male , Female , Prospective Studies , Risk Factors , Brain/diagnostic imaging
8.
Nan Fang Yi Ke Da Xue Xue Bao ; 42(3): 448-456, 2022 Mar 20.
Article in Chinese | MEDLINE | ID: mdl-35426812

ABSTRACT

RNA binding protein (RBP) plays a key role in gene regulation and participate in RNA translation, modification, splicing, transport and other important biological processes. Studies have shown that abnormal expression of RBP is associated with a variety of diseases. The Musashi (Msi) family of mammals is an evolutionarily conserved and powerful RBP, whose members Msi1 and Msi2 play important roles in the regulation of stem cell activity and tumor development. The Msi family members regulate a variety of biological processes by binding and regulating mRNA translation, stability and downstream cell signaling pathways, and among them, Msi2 is closely related to embryonic growth and development, maintenance of tumor stem cells and development of hematological tumors. Accumulating evidence has shown that Msi2 also plays a crucial role in the development of solid tumors, mainly by affecting the proliferation, invasion, metastasis and drug resistance of tumors, involving Wnt/ß-catenin, TGF-ß/SMAD3, Akt/mTOR, JAK/STAT, Numb and their related signaling pathways (Notch, p53, and Hedgehog pathway). Preclinical studies of Msi2 gene as a therapeutic target for tumor have achieved preliminary results. This review summarizes the molecular structure, physiological function, role of Msi2 in the development and progression of various solid tumors and the signaling pathways involved.


Subject(s)
Hedgehog Proteins , Neoplasms , Animals , Mammals/metabolism , Neoplasms/genetics , Neoplastic Stem Cells , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Signal Transduction
9.
Fa Yi Xue Za Zhi ; 37(4): 511-515, 2021 Aug.
Article in Chinese | MEDLINE | ID: mdl-34726004

ABSTRACT

ABSTRACT: Objective To detect the uncontrolled new psychoactive tryptamines involved in drug-related cases with high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Methods White and brown powder obtained in actual cases were extracted and analyzed by gas chromatography-quadrupole time-of-flight mass spectrometry (GC-QTOF-MS), ultra-high performance liquid chromatography-linear ion trap quadrupole-orbitrap mass spectrometry (UPLC-LTQ-Orbitrap MS) and 1H-nuclear magnetic resonance spectroscopy (1H-NMR). Results After detection by GC-QTOF-MS, the components of white powder showed main characteristic fragment ion peaks at m/z 218.141 0 (molecular ion peak), 72.080 6 (base peak), etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 219.149 4. The main ions in the secondary mass spectrum under the collision-induced dissociation (CID) mode were m/z 160.076 3 and 72.080 8. After detection by GC-QTOF-MS, the components of brown powder showed main characteristic fragment ion peaks at m/z 246.135 7 (molecular ion peak), 58.065 1 (base peak), etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 247.145 0. The main ions in the secondary mass spectrum under CID mode were m/z 202.087 1, 160.076 3 and 134.060 5. NIST 17 library retrieval and 1H-NMR confirmed that the white powder and brown powder contained new psychoactive tryptamines 4-OH-MET and 4-AcO-DMT, respectively. Conclusion GC-QTOF-MS, UPLC-LTQ-Orbitrap MS and 1H-NMR can be used together to identify unknown new psychoactive substances.


Subject(s)
Tryptamines , Chromatography, High Pressure Liquid , Gas Chromatography-Mass Spectrometry , Magnetic Resonance Spectroscopy , Mass Spectrometry
10.
Fa Yi Xue Za Zhi ; 37(4): 524-526, 2021 Aug.
Article in Chinese | MEDLINE | ID: mdl-34726006

ABSTRACT

ABSTRACT: Abstract.


Subject(s)
N,N-Dimethyltryptamine
12.
Int J Oral Maxillofac Surg ; 50(8): 1012-1018, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33468437

ABSTRACT

This article reports the surgical resection of clinically benign tumours in the maxillomandibular deep lobe of the parotid gland via sternocleidomastoid muscle-parotid space (SPS) approach. The use of maxillary-mandibular planes to subdivide the deep lobe of the parotid gland in order to establish the tumour location and accessibility is introduced. This approach, which does not raise a skin flap, may preserve the superficial lobe. Ten patients with clinically benign tumours in the maxillomandibular deep lobe of the parotid gland were treated via the SPS approach. The patients were followed up for 3-5 years and the surgical outcomes were analysed. All tumours were completely enucleated via the SPS approach with an optimal aesthetic outcome. No permanent facial weakness or tumour recurrence was identified during the 3-5 years of follow-up. The SPS approach to surgical resection is an ideal option for clinically benign tumours in the maxillomandibular deep lobe of the parotid gland and demonstrates good results.


Subject(s)
Parotid Gland , Parotid Neoplasms , Esthetics, Dental , Humans , Neck Muscles/diagnostic imaging , Neck Muscles/surgery , Neoplasm Recurrence, Local , Parotid Neoplasms/diagnostic imaging , Parotid Neoplasms/surgery , Postoperative Complications , Retrospective Studies
13.
Article in Chinese | MEDLINE | ID: mdl-32062900

ABSTRACT

To analyze the difficulty, distinction and result of the first national public health practice skills competition among college students, it showed the general situation of this competition, and discussed the present situation, problems and countermeasures of skills training for students majoring in preventive medicine. Based on such competition, educators can promote teaching reform and post competency training.


Subject(s)
Public Health Practice , Public Health/education , Students , Humans , Universities
14.
Opt Express ; 27(11): 15495-15504, 2019 May 27.
Article in English | MEDLINE | ID: mdl-31163745

ABSTRACT

We demonstrate a top-illuminated high-speed uni-traveling carrier photodiode (UTC-PD) with a novel design in the p-type absorber, which can effectively shorten the photon absorption depth at telecommunication wavelengths (1.31~1.55 µm) and further enhance the bandwidth-efficiency product of UTC-PD. In our proposed new UTC-PD structure, the p-type In0.53Ga0.47As absorption layer is replaced by the type-II GaAs0.5Sb0.5 (p)/In0.53Ga0.47As (i) hybrid absorber. Due to the narrowing of the bandgap and enhancement of the photo-absorption process at the type-II interface between the GaAs0.5Sb0.5 and In0.53Ga0.47As layers, our device shows an over 16.7% improvement in the responsivity compared with that of UTC-PD with the same thickness of pure In0.53Ga0.47As absorber (0.7 µm) and a zero optical coupling loss. Our demonstrated device with a simple top-illuminated structure offers a large active mesa (25 µm), a wide optical-to-electrical (O-E) bandwidth (33 GHz), a high responsivity (0.7 A/W), and a high saturation current (>5 mA) under 1.31 µm optical wavelength. These promising results suggest that our proposed PD structure can fundamentally overcome the trade-off among bandwidth, efficiency, and device active diameter of high-speed PDs.

15.
J Eur Acad Dermatol Venereol ; 33(8): 1569-1576, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30989708

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) is the most common skin disorder in infancy. However, the diagnosis and definite significance of infantile AD remains a debated issue. OBJECTIVE: To analyse the phenotypes of AD in infancy, to establish diagnostic criteria and to estimate the prevalence of this condition in China. METHODS: This is a multicentric study, in which 12 locations were chosen from different metropolitan areas of China. Following careful and complete history-taking and skin examination, the definite diagnosis of AD was made and the severity based on the SCORAD index was determined by local experienced dermatologists. Based on the detailed phenotyping, the major and representative clinical features of infantile AD were selected to establish the diagnostic criteria and evaluate their diagnostic efficacy. RESULTS: A total of 5967 infants were included in this study. The overall point prevalence of AD was 30.48%. The infantile AD developed as early as at the second month of life, and its incidence peaked in the third month of life at 40.81%. The proportion of mild, moderate and severe AD was 67.40%, 30.57% and 2.03%, respectively. The most commonly seen manifestations in the infantile AD were facial dermatitis (72.07%), xerosis (42.72%) and scalp dermatitis (27.93%). We established the novel diagnostic criteria of infants, which included: (i) onset after 2 weeks of birth; (ii) pruritus and/or irritability and sleeplessness comparable with lesions; and (iii) all two items above with one of the following items can reach a diagnosis of AD: (i) eczematous lesions distributed on cheeks and/or scalp and/or extensor limbs, and (ii) eczematous lesions on any other parts of body accompanied by xerosis. CONCLUSIONS: In China, the prevalence of AD in infancy is 30.48% according to clinical diagnosis of dermatologists. The novel Chinese diagnostic criteria for AD in infants show a higher sensitivity and comparable specificity.


Subject(s)
Dermatitis, Atopic/diagnosis , Phenotype , China/epidemiology , Dermatitis, Atopic/epidemiology , Female , Humans , Infant , Male , Prevalence
16.
Dis Esophagus ; 32(12)2019 Dec 31.
Article in English | MEDLINE | ID: mdl-30888392

ABSTRACT

Iodine-125 (125I) seed-loaded stent placement has served as an effective palliation for malignant esophageal strictures in China. We performed a retrospective study to identify the prognostic factors of this irradiation stent placement in advanced esophageal cancer patients. A total of 201 patients who underwent 125I seed-loaded stent placement were included in this study from June 2012 to March 2016 at five hospitals in China. The Cox regression models adjusted for stratification factors were used, and a stepwise multivariate analysis was performed to predict the overall survival and relief of dysphagia on the basis of pretreatment clinical characteristics, respectively. Three independent prognostic factors were identified for overall survival: histopathological subtype (squamous cell carcinoma vs. adenocarcinoma, hazard ratio [HR] 1.45, 95% confidence interval [CI95%]: 1.01-2.09, P = 0.046), serum total protein (≥66 g/L vs. <66 g/L, HR 0.61, CI95%: 0.48-0.59, P = 0.023), and performance status (<2 vs. ≥2, HR 1.57, CI95%: 1.09-2.08, P = 0.013). Four factors were significantly associated with the relief of dysphagia: T stage (T3 vs. T4, P = 0.003), tumor location (superior vs. inferior, P = 0.049), tumor-node-metastasis classification (IV vs. II, P = 0.025), and age (≥71 years vs. <71 years, P = 0.029). Prognostic factors identified from this analysis can be used to aid clinical decision-making and design future clinical trials.


Subject(s)
Adenocarcinoma/mortality , Carcinoma, Squamous Cell/mortality , Deglutition Disorders/mortality , Esophageal Neoplasms/mortality , Iodine Radioisotopes/administration & dosage , Stents , Adenocarcinoma/complications , Adenocarcinoma/radiotherapy , Aged , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/radiotherapy , China , Deglutition Disorders/etiology , Deglutition Disorders/radiotherapy , Esophageal Neoplasms/complications , Esophageal Neoplasms/radiotherapy , Female , Humans , Male , Middle Aged , Neoplasm Staging , Palliative Care , Prognosis , Proportional Hazards Models , Retrospective Studies , Treatment Outcome
17.
Clin. transl. oncol. (Print) ; 20(8): 1080-1086, ago. 2018. ilus, tab
Article in English | IBECS | ID: ibc-173692

ABSTRACT

Purpose: Pulmonary benign metastasizing leiomyoma (PBML), a rare condition of smooth muscle tumor, originates from women with a history of uterine leiomyoma (LM). Numerous genetic studies of uterine LM have been reported; however, there are few cytogenetic and molecular descriptions of PBML. Therefore, molecular subtyping is necessary to understand the pathogenesis of metastasizing sites. Methods: Driver gene exon-capture sequencing was performed on one patient’s peripheral blood, paraffin samples from primary uterine LM, and lung metastasizing leiomyoma 8 years later. Results: The results showed that the same missense mutations of BLMH, LRP2, MED12, SMAD2, and UGT1A8 were concurrently mutated in the primary uterine LM and the PBML. Moreover, a splice mutation of PTEN (c.492+1G>A) was uniquely identified in the lung metastasis of the patient. Conclusion: This study indicates that the metastatic lung lesions were derived from the same malignant cell clone of uterine LMs and later acquired the novel driver mutations in the evolution of the tumor. In addition, driver gene sequencing can discriminate somatic driver mutations as biological indicators of potential malignant leiomyoma and can identify pathogenic variation driver mutations, which could be used for individualized therapy


No disponible


Subject(s)
Humans , Female , Leiomyoma/pathology , Uterine Neoplasms/pathology , Neoplasm Metastasis/pathology , Lung Neoplasms/pathology , Uterine Neoplasms/genetics , Leiomyoma/genetics , Lung Neoplasms/secondary , High-Throughput Nucleotide Sequencing/methods , Genetic Markers
18.
Clin. transl. oncol. (Print) ; 20(7): 912-921, jul. 2018. ilus, tab, graf
Article in English | IBECS | ID: ibc-173643

ABSTRACT

Purpose: Aspirin could reduce the risk of cancer metastasis. Circulating tumor cells (CTCs) are a key factor of cancer metastasis, but no evidence has revealed how aspirin affects CTCs and its epithelial-mesenchymal transition (EMT). Here, we conducted a clinical trial to investigate how aspirin affects CTCs in metastatic colorectal cancer (MCC) and breast cancer patients (MBC). Methods: The trial is retrospective registered at clinicaltrials.gov (NCT02602938). The eligible patients are given 100 mg aspirin q.d. for 8 weeks, and CTCs are evaluated at baseline, 4 and 8 weeks for absolute number, phenotype (epithelial type, E+, mesenchymal type, M+, and biophenotypic type, B+), and vimentin expression. Results: Data on 21 MCC and 19 MBC patients are analyzed, and it revealed that the CTC numbers decreased with aspirin treatment in MCC (p < 0.001) but not MBC (p = 0.0532); besides, ratio of E+ CTCs increased (p = 0.037) and M+ CTCs decreased at 2 months in MCC (p = 0.013), but neither the ratio of E+ or M+ CTCs changes significantly in MBC; vimentin expression of M+ CTCs is higher than E+ and B+ CTCs either in MBC or MCC patients at baseline (p < 0.01); and aspirin suppresses the vimentin expression in M+ (p = 0.002)and B+ (p = 0.006) CTCs of MCC and M+ CTCs of MBC (p = 0.004); besides it find vimentin expression in B+ (p = 0.004) or M+ (p < 0.001), CTCs are markedly decreased in patients with total CTC numbers declined. Conclusion: Aspirin could decrease CTCs numbers and block EMT transition in MCC patients and part of MBC patients


No disponible


Subject(s)
Humans , Male , Female , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Aspirin/pharmacokinetics , Neoplastic Cells, Circulating , Colorectal Neoplasms/pathology , Breast Neoplasms/pathology , Neoplastic Cells, Circulating/pathology , Colorectal Neoplasms/therapy , Breast Neoplasms/therapy , Neoplasm Metastasis/pathology , Retrospective Studies , Biomarkers, Tumor/analysis , Epithelial-Mesenchymal Transition
19.
Clin Transl Oncol ; 20(8): 1080-1086, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29484624

ABSTRACT

PURPOSE: Pulmonary benign metastasizing leiomyoma (PBML), a rare condition of smooth muscle tumor, originates from women with a history of uterine leiomyoma (LM). Numerous genetic studies of uterine LM have been reported; however, there are few cytogenetic and molecular descriptions of PBML. Therefore, molecular subtyping is necessary to understand the pathogenesis of metastasizing sites. METHODS: Driver gene exon-capture sequencing was performed on one patient's peripheral blood, paraffin samples from primary uterine LM, and lung metastasizing leiomyoma 8 years later. RESULTS: The results showed that the same missense mutations of BLMH, LRP2, MED12, SMAD2, and UGT1A8 were concurrently mutated in the primary uterine LM and the PBML. Moreover, a splice mutation of PTEN (c.492+1G>A) was uniquely identified in the lung metastasis of the patient. CONCLUSION: This study indicates that the metastatic lung lesions were derived from the same malignant cell clone of uterine LMs and later acquired the novel driver mutations in the evolution of the tumor. In addition, driver gene sequencing can discriminate somatic driver mutations as biological indicators of potential malignant leiomyoma and can identify pathogenic variation driver mutations, which could be used for individualized therapy.


Subject(s)
Biomarkers, Tumor/genetics , High-Throughput Nucleotide Sequencing/methods , Leiomyoma/pathology , Lung Neoplasms/secondary , Mutation , Uterine Neoplasms/pathology , Female , Genetic Testing , Humans , Leiomyoma/genetics , Lung Neoplasms/genetics , Middle Aged , Prognosis , Uterine Neoplasms/genetics
20.
J Endocrinol Invest ; 41(9): 1097-1102, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29374854

ABSTRACT

OBJECTIVE: A reduction in insulin-stimulated glucose uptake in skeletal muscles is a characteristic of insulin resistance and type 2 diabetes mellitus (T2DM). The glucagon-like peptide (GLP)-1 agonist liraglutide can reduce blood glucose levels in individuals with T2DM. However, its effect on insulin-induced glucose metabolism in the skeletal muscle of insulin resistance is unknown. We investigated the effects and action mechanisms of liraglutide on insulin resistance (IR) in the skeletal muscle cells treatment with palmitic acid (PA). METHODS: The cell-surface GLUT4myc levels were determined by an antibody-coupled colorimetric assay. The phosphorylation levels of Akt, PI3K(p85α), AS160, IRS1, IKK, and JNK were determined by western blotting. The quantifications of mRNA levels of TNFα, IL-1ß, and IL-6 were determined by real-time PCR. Analysis of variance was used for data analysis. RESULTS: PA elevated not only phosphorylation of JNK, IRS1 serines, and IKKα/ß, but also the expression of IL-6, TNFα and IL-1ß in C2C12-GLUT4myc cells. PA can reduce phosphorylation of IRS1 tyrosine. These effects of PA were reversed by liraglutide. In addition, liraglutide can reverse PA-decreased insulin-stimulated cell-surface GLUT4 levels, Akt, PI3K(p85α), and AS160 phosphorylation. CONCLUSIONS: Liraglutide can enhance insulin-induced GLUT4 translocation by inhibiting IRS1 serine phosphorylation in PA-treated muscle cells.


Subject(s)
Hypoglycemic Agents/pharmacology , Insulin Receptor Substrate Proteins/metabolism , Insulin Resistance/physiology , Liraglutide/pharmacology , Muscle Fibers, Skeletal/metabolism , Palmitates/toxicity , Animals , Cell Line , Glucose Transporter Type 4/metabolism , Humans , Insulin Receptor Substrate Proteins/antagonists & inhibitors , Mice , Muscle Fibers, Skeletal/drug effects , Phosphorylation/drug effects , Phosphorylation/physiology
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