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1.
Nat Commun ; 14(1): 2053, 2023 04 12.
Article En | MEDLINE | ID: mdl-37045824

Antimicrobial exposure during curative-intent treatment of triple-negative breast cancer (TNBC) may lead to gut microbiome dysbiosis, decreased circulating and tumor-infiltrating lymphocytes, and inferior outcomes. Here, we investigate the association of antimicrobial exposure and peripheral lymphocyte count during TNBC treatment with survival, using integrated electronic medical record and California Cancer Registry data in the Oncoshare database. Of 772 women with stage I-III TNBC treated with and without standard cytotoxic chemotherapy - prior to the immune checkpoint inhibitor era - most (654, 85%) used antimicrobials. Applying multivariate analyses, we show that each additional total or unique monthly antimicrobial prescription is associated with inferior overall and breast cancer-specific survival. This antimicrobial-mortality association is independent of changes in neutrophil count, is unrelated to disease severity, and is sustained through year three following diagnosis, suggesting antimicrobial exposure negatively impacts TNBC survival. These results may inform mechanistic studies and antimicrobial prescribing decisions in TNBC and other hormone receptor-independent cancers.


Anti-Infective Agents , Triple Negative Breast Neoplasms , Female , Humans , Biomarkers, Tumor , Breast , Lymphocytes , Lymphocytes, Tumor-Infiltrating
2.
Chemosphere ; 326: 138406, 2023 Jun.
Article En | MEDLINE | ID: mdl-36925006

Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic and ubiquitous pollutants that need to be solved. The low-molecular-weight organic acid (LMWOA) holds the promise to accelerate the capacity of microbes to degrade PAHs. However, the degradation mechanism(s) with multi-LMWOAs has not been understood yet, which is closer to the complex environmental biodegradation in nature. Here, we demonstrated a comprehensive cellular and proteomic response pattern by investigating the relationship between a model PAH degrading strain, B. subtilis ZL09-26, and the mixture LMWOAs (citric acid, glutaric acid, and oxalic acid). As a result, multi-LMWOAs introduced a highly enhanced phenanthrene (PHE) degradation efficiency with up to 3.1-fold improvement at 72 h, which is accompanied by the enhancement of strain growth and activity, but the releasement of membrane damages and oxidative stresses. Moreover, a detailed proteomic analysis revealed that the synergistic perturbation of various metabolic pathways jointly governed the change of cellular behaviors and improved PHE degradation in a network manner. The obtained knowledge provides a foundation for designing the artificial LMWOAs mixtures and guides the rational remediation of contaminated soils using bio-stimulation techniques.


Phenanthrenes , Polycyclic Aromatic Hydrocarbons , Soil Pollutants , Biodegradation, Environmental , Molecular Weight , Proteomics , Phenanthrenes/toxicity , Phenanthrenes/analysis , Polycyclic Aromatic Hydrocarbons/analysis , Organic Chemicals , Acids , Soil Pollutants/analysis
3.
JAMA Oncol ; 9(4): 473-480, 2023 04 01.
Article En | MEDLINE | ID: mdl-36729432

Importance: Sexual orientation and gender identity data are not collected by most hospitals or cancer registries; thus, little is known about the quality of breast cancer treatment for patients from sex and gender minority (SGM) groups. Objective: To evaluate the quality of breast cancer treatment and recurrence outcomes for patients from SGM groups compared with cisgender heterosexual patients. Design, Setting, and Participants: Exposure-matched retrospective case-control study of 92 patients from SGM groups treated at an academic medical center from January 1, 2008, to January 1, 2022, matched to cisgender heterosexual patients with breast cancer by year of diagnosis, age, tumor stage, estrogen receptor status, and ERBB2 (HER2) status. Main Outcomes and Measures: Patient demographic and clinical characteristics, as well as treatment quality, as measured by missed guideline-based breast cancer screening, appropriate referral for genetic counseling and testing, mastectomy vs lumpectomy, receipt of chest reconstruction, adjuvant radiation therapy after lumpectomy, neoadjuvant chemotherapy for stage III disease, antiestrogen therapy for at least 5 years for estrogen receptor-positive disease, ERBB2-directed therapy for ERBB2-positive disease, patient refusal of an oncologist-recommended treatment, time from symptom onset to tissue diagnosis, time from diagnosis to first treatment, and time from breast cancer diagnosis to first recurrence. Results were adjusted for multiple hypothesis testing. Compared with cisgender heterosexual patients, those from SGM groups were hypothesized to have disparities in 1 or more of these quality metrics. Results: Ninety-two patients from SGM groups were matched to 92 cisgender heterosexual patients (n = 184). The median age at diagnosis for all patients was 49 years (IQR, 43-56 years); 74 were lesbian (80%), 12 were bisexual (13%), and 6 were transgender (6%). Compared with cisgender heterosexual patients, those from SGM groups experienced a delay in time from symptom onset to diagnosis (median time to diagnosis, 34 vs 64 days; multivariable adjusted hazard ratio, 0.65; 95% CI, 0.42-0.99; P = .04), were more likely to decline an oncologist-recommended treatment modality (35 [38%] vs 18 [20%]; multivariable adjusted odds ratio, 2.27; 95% CI, 1.09-4.74; P = .03), and were more likely to experience a breast cancer recurrence (multivariable adjusted hazard ratio, 3.07; 95% CI, 1.56-6.03; P = .001). Conclusions and Relevance: This study found that among patients with breast cancer, those from SGM groups experienced delayed diagnosis, with faster recurrence at a 3-fold higher rate compared with cisgender heterosexual patients. These results suggest disparities in the care of patients from SGM groups and warrant further study to inform interventions.


Breast Neoplasms , Sexual and Gender Minorities , Humans , Female , Male , Adult , Middle Aged , Gender Identity , Breast Neoplasms/therapy , Breast Neoplasms/radiotherapy , Retrospective Studies , Case-Control Studies , Receptors, Estrogen , Mastectomy , Neoplasm Recurrence, Local/surgery , Sexual Behavior/psychology
4.
Breast Cancer Res Treat ; 196(1): 175-183, 2022 Nov.
Article En | MEDLINE | ID: mdl-36030472

PURPOSE: As survival with early-stage, hormone receptor (HR)-positive breast has improved, it is essential to understand the long-term risks of incident comorbidities with different adjuvant endocrine therapy (ET) options. METHODS: Women treated with tamoxifen and/or an aromatase inhibitor (AI) for stages 1-3, HR-positive/HER2-negative breast cancer from 2000 to 2016 in either of two healthcare systems in the San Francisco Bay Area were included. We considered the following comorbidities: cerebrovascular accidents, congestive heart failure, dementia, depression/anxiety, diabetes mellitus, hyperlipidemia, myocardial infarction, non-alcoholic steatohepatitis, osteoporosis/fracture, peripheral vascular disease, and venous thromboembolism. Cause-specific Cox proportional hazards models were fit to time-to-new-diagnosis for each comorbidity, accounting for death as a competing risk. Hazard ratios (HR) and 95% confidence intervals (CI) for tamoxifen versus AI were reported. RESULTS: Among 2,902 analyzed patients, the median age at diagnosis was 58.3 years; 67.6% were non-Hispanic white, 22.3% Asian, 7.5% Hispanic, and 1.7% non-Hispanic Black. Half (54.7%) used AIs only, 27.6% used tamoxifen only and 17.7% used both tamoxifen and AIs sequentially. Tamoxifen was associated with a lower risk of osteoporosis than AI (multivariable HR 0.45, 95% CI 0.32-0.62). No other incident comorbidity risk varied between users of tamoxifen versus AIs. CONCLUSION: In a diverse, multi-institutional, contemporary breast cancer cohort, the only incident comorbidity that differed between ET options was osteoporosis, a known side effect of AIs. These results may inform clinical decision-making about ET, and reassure patients who have bothersome symptoms on AIs that they are unlikely to develop worse comorbidities if they switch to tamoxifen.


Breast Neoplasms , Osteoporosis , Antineoplastic Agents, Hormonal/adverse effects , Aromatase Inhibitors/adverse effects , Breast Neoplasms/drug therapy , Breast Neoplasms/epidemiology , Comorbidity , Female , Hormones , Humans , Middle Aged , Osteoporosis/chemically induced , Tamoxifen/adverse effects
5.
Breast Cancer Res Treat ; 194(2): 475-482, 2022 Jul.
Article En | MEDLINE | ID: mdl-35624175

PURPOSE: The early months of the COVID-19 pandemic led to reduced cancer screenings and delayed cancer surgeries. We used insurance claims data to understand how breast cancer incidence and treatment after diagnosis changed nationwide over the course of the pandemic. METHODS: Using the Optum Research Database from January 2017 to March 2021, including approximately 19 million US adults with commercial health insurance, we identified new breast cancer diagnoses and first treatment after diagnosis. We compared breast cancer incidence and proportion of newly diagnosed patients receiving pre-operative systemic therapy pre-COVID, in the first 2 months of the COVID pandemic and in the later part of the COVID pandemic. RESULTS: Average monthly breast cancer incidence was 19.3 (95% CI 19.1-19.5) cases per 100,000 women and men pre-COVID, 11.6 (95% CI 10.8-12.4) per 100,000 in April-May 2020, and 19.7 (95% CI 19.3-20.1) per 100,000 in June 2020-February 2021. Use of pre-operative systemic therapy was 12.0% (11.7-12.4) pre-COVID, 37.7% (34.9-40.7) for patients diagnosed March-April 2020, and 14.8% (14.0-15.7) for patients diagnosed May 2020-January 2021. The changes in breast cancer incidence across the pandemic did not vary by demographic factors. Use of pre-operative systemic therapy across the pandemic varied by geographic region, but not by area socioeconomic deprivation or race/ethnicity. CONCLUSION: In this US-insured population, the dramatic changes in breast cancer incidence and the use of pre-operative systemic therapy experienced in the first 2 months of the pandemic did not persist, although a modest change in the initial management of breast cancer continued.


Breast Neoplasms , COVID-19 , Adult , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Breast Neoplasms/therapy , COVID-19/epidemiology , Early Detection of Cancer , Female , Humans , Insurance, Health , Male , Pandemics
6.
J Clin Epidemiol ; 141: 151-156, 2022 01.
Article En | MEDLINE | ID: mdl-34670111

OBJECTIVES: To present the history and potential for development of evidence-based (EB) social work in China. STUDY DESIGN AND SETTING: The conception and methodology of EB social work is a potential strategy to support high quality development of social work in China. This article documents and analyzes the progress of EB social work in China. We focus on current research, reasons, challenges, and strategies. RESULTS: EB social work started late in China. The number of EB social work literature and systematic reviews has increased since 2004. The development of EB social work has been uneven nationally with few practitioners and decision makers involved. However, more and more social work researchers received training in evidence-based practice through national workshops and conferences. CONCLUSION: EB social work faced various challenges, but there are now more opportunities for EB social work development in China. Researchers, practitioners, managers and decision makers are encouraged to work together to establish a thorough methodological system and use existing evidence as much as possible when carrying out social work programs and services.


Evidence-Based Practice , Social Work , China , Humans
7.
Lung ; 199(4): 389-394, 2021 08.
Article En | MEDLINE | ID: mdl-34415400

PURPOSE: Vitronectin (VTN), a multifunctional glycoprotein, is involved in various biological and pathological processes. The purpose of this study was to explore the effect of VTN on mesenchymal-epithelial transition (MET) of pulmonary fibroblast cells. METHODS: Lentivirus encoding for VTN-specific shRNA was constructed and infected into the cultured fibroblast WI-38 cells. Real-time PCR and Western blot were applied to examine the expression of VTN in WI-38 cells. MTT assay was used to assess cell proliferation. Western blot was conducted to examine the expression of MET-related and apoptosis-related proteins. RESULTS: The knockdown of VTN significantly inhibited the growth of WI-38 cells compared to the control group. Meanwhile, knockdown of VTN remarkably increased the expression of Bax and Caspase 3 compared with the control group. Furthermore, knockdown of VTN significantly promoted the expression of E-cadherin in comparison to control group. CONCLUSIONS: Knockdown of VTN promoted the expression of apoptosis-related factors, meanwhile, facilitated the MET process of fibroblast cells by regulating the expression of relevant factors. In sum, VTN performed a potential regulator in cell growth and MET of pulmonary fibroblast cells, which can be considered as a potential target for diagnose and therapy of relevant diseases.


Fibroblasts , Vitronectin , Cell Differentiation , Cell Line, Tumor , Cell Proliferation , Epithelial-Mesenchymal Transition , Lung
8.
Interact Cardiovasc Thorac Surg ; 33(4): 550-556, 2021 10 04.
Article En | MEDLINE | ID: mdl-34148094

OBJECTIVES: The aim of this study was to evaluate the efficacy of adjuvant chemotherapy (ACT) for thymic squamous cell carcinoma after completely resection. METHODS: Patients with thymic squamous cell carcinoma treated with complete resection between January 2009 and December 2016 were retrospectively identified. Kaplan-Meier analysis was used to summarize the time-to-event variables. Univariable and multivariable Cox proportional hazards regression analyses were performed. RESULTS: A total of 116 patients were analysed with 44 patients in the non-ACT group and 72 patients in the ACT group. No significant difference was found in the 5-year recurrence-free survival (RFS) rate (58.1% vs 51%, P = 0.33) or the 5-year overall survival (OS) rate (77.7% vs 67.1%, P = 0.26) between the ACT group and the non-ACT group. Masaoka stage was the only independent prognostic factor for both RFS and OS. Subgroup analysis showed significant improvement in 5-year RFS for Masaoka stage II patients (P = 0.035) and 5-year OS (P = 0.036) for Masaoka stage III patients when comparing ACT with non-ACT. No chemotherapy-related death occurred. The most frequent adverse effect higher than grade 3 was neutropenia. CONCLUSIONS: For completely resected thymic squamous cell carcinoma, ACT significantly improved the 5-year RFS in Masaoka stage II patients and the 5-year OS in Masaoka stage III patients.


Carcinoma, Squamous Cell , Thymus Neoplasms , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Chemotherapy, Adjuvant , Humans , Neoplasm Staging , Prognosis , Retrospective Studies , Thymus Neoplasms/pathology , Thymus Neoplasms/surgery
9.
JCO Oncol Pract ; 17(12): e1837-e1845, 2021 12.
Article En | MEDLINE | ID: mdl-33844591

PURPOSE: Race and ethnicity have been shown to affect quality of cancer care, and patients with low English proficiency (LEP) have increased risk for serious adverse events. We sought to assess the impact of primary language on health care engagement as indicated by clinical trial screening and engagement, use of genetic counseling, and communication via an electronic patient portal. METHODS: Clinical and demographic data on patients with breast cancer diagnosed and treated from 2013 to 2018 within the Stanford University Health Care system were compiled via linkage of electronic health records, an internal clinical trial database, and the California Cancer Registry. Logistic and linear regression models were used to evaluate for association of clinical trial engagement and patient portal message rates with primary language group. RESULTS: Patients with LEP had significantly lower rates of clinical trial engagement compared with their English-speaking counterparts (adjusted odds ratio [OR], 0.29; 95% CI, 0.16 to 0.51). Use of genetic counseling was similar between language groups. Rates of patient portal messaging did not differ between English-speaking and LEP groups on multivariable analysis; however, patients with LEP were less likely to have a portal account (adjusted OR, 0.89; 95% CI, 0.83 to 0.96). Among LEP subgroups, Spanish speakers were significantly less likely to engage with the patient portal compared with English speakers (estimated difference in monthly rate: OR, 0.43; 95% CI, 0.24 to 0.77). CONCLUSION: We found that patients with LEP had lower rates of clinical trial engagement and odds of electronic patient portal enrollment. Interventions designed to overcome language and cultural barriers are essential to optimize the experience of patients with LEP.


Breast Neoplasms , Limited English Proficiency , Breast Neoplasms/therapy , Communication Barriers , Delivery of Health Care , Female , Hispanic or Latino , Humans
10.
Ann Thorac Surg ; 112(5): 1585-1592, 2021 11.
Article En | MEDLINE | ID: mdl-33347849

BACKGROUND: The study aimed to evaluate the role of postoperative radiotherapy (PORT) in the treatment of trachea and main bronchus adenoid cystic carcinoma (ACC) with a positive surgical margin. METHODS: Patients with pathologically confirmed trachea or main bronchus ACC operated on at Shanghai Chest Hospital were enrolled. Survival, univariate, and multivariate analyses were performed. The χ2 test was applied to analyze the failure patterns among different groups (R0/0: negative margin resection without PORT; R1/0: positive margin resection without PORT; R1/1: positive margin resection with PORT). RESULTS: From January 2001 to December 2014, 77 patients were deemed eligible for the study. Pairwise comparisons showed that the overall survival rate of group R1/1 was comparable to that of group R0/0 (P = .438), and significantly longer than the rate of group R1/0 (P = .032). Additionally, the local disease-free survival rate of group R1/1 was much higher than that of group R0/0 (P = .023) and R1/0 (P = .001). Cox multivariate analysis identified the radiologic feature (P = .012) and PORT (P = .006) as significantly favorable prognostic factors for locoregional disease-free survival. By contrast, for overall survival, PORT (P = .032) was the only corresponding variable identified by univariate analysis. Furthermore, PORT significantly decreased the locoregional recurrence rate (P = .002) but not distant metastases (P > .999). CONCLUSIONS: PORT helped patients with tracheobronchial ACC and microscopic positive surgical margins to achieve a similar outcome as patients with complete resection. R0 resection may not be necessary for tracheobronchial ACC if it is difficult to be completely resected.


Bronchial Neoplasms/pathology , Bronchial Neoplasms/radiotherapy , Carcinoma, Adenoid Cystic/pathology , Carcinoma, Adenoid Cystic/radiotherapy , Margins of Excision , Tracheal Neoplasms/pathology , Tracheal Neoplasms/radiotherapy , Adult , Aged , Bronchial Neoplasms/mortality , Bronchial Neoplasms/surgery , Carcinoma, Adenoid Cystic/mortality , Carcinoma, Adenoid Cystic/surgery , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Retrospective Studies , Survival Rate , Tracheal Neoplasms/mortality , Tracheal Neoplasms/surgery , Treatment Outcome , Young Adult
11.
Transl Lung Cancer Res ; 9(5): 2059-2073, 2020 Oct.
Article En | MEDLINE | ID: mdl-33209626

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. The expected 5-year survival of stage III NSCLC ranges from 13% to 36% for stage III. Due to the heterogeneity and poor efficacy of stage III patients, there is great controversy on how to optimize the therapy strategy. Immunotherapy is providing better clinical efficacy to more NSCLC patients, and is rapidly extending its range of care from advanced stage to locally advanced stage and early stage NSCLC. Due to the patient's strong treatment intention, drug availability, and a few encouraging results from clinical trials (NADIM, NCT02716038, etc.), the authors observed a case of stage III NSCLC that achieved complete remission after receiving neoadjuvant chemotherapy combined with immunotherapy. In view of such a satisfactory result in neoadjuvant therapy, this article discusses how comprehensive treatment for stage III NSCLC patients may be conducted and the manner in which various therapeutic techniques can be mastered in the era of immunotherapy. Immunotherapy has opened the exploratory space for finding resolutions to numerous challenges of treating stage III NSCLC. Further clinical studies and exploration of personalized treatment, guided by imaging data, and clinical and pathological biomarkers are imperative for the benefit of these patients.

12.
Aging (Albany NY) ; 12(6): 4815-4821, 2020 03 30.
Article En | MEDLINE | ID: mdl-32224505

BACKGROUND: To investigate the clinicopathologic characteristics and survival outcomes of patients with thymic epithelial tumors (TET) according to age at diagnosis. RESULTS: A total of 4431 patients were analyzed. Gender, race, tumor histology and surgery were similar between different age groups. The 0-18 group was associated with a higher risk of distant metastasis. Compared to patients aged above 80, the hazard ratios (HR) for patients aged 0-18, 19-30, 31-40, 41-50, 51-60, 61-70, 71-80 were 1.079, 0.739, 0.614, 0.621, 0.633, 0.673, 0.861, respectively. From the subgroup analysis for the adult patients who were above 19 years old, we found that the 19-70 group had significant better cancer specific survival (CSS) and overall survival (OS) than the above 70 group. CONCLUSIONS: Age is a strong independent prognostic factor for survival in TET. Pediatric TET has a higher risk of distant metastasis and an inferior CSS. For the adults who were above 19, patients older than 70-year-old were associated with a shorter CSS. METHODS: Information of 4431 TET patients was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Demographic features, clinicopathologic characteristics and survival outcomes were compared between patients diagnosed at different age groups (0-18, 19-30, 31-40, 41-50, 51-60, 61-70, 71-80, above 80).


Neoplasms, Glandular and Epithelial/diagnosis , Neoplasms, Glandular and Epithelial/epidemiology , Thymus Neoplasms/diagnosis , Thymus Neoplasms/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Prognosis , Young Adult
13.
J Cancer ; 9(21): 3986-3990, 2018.
Article En | MEDLINE | ID: mdl-30410603

Objective: To evaluate the clinicopathologic characteristics of the long-time survivals and construct a clinical nomogram using the Surveilance, Epidemiology, and End Results (SEER) database. Materials and Methods: Information of patients diagnosed with M1 stage esophageal cancer from 2010-2014 was retrieved from SEER database. Patients with unknown information of AJCC TNM stage or metastatic sites or marital status or surgery or survival were excluded. Demographic and clinicopathologic characteristics were compared between LTS (long time survivals: patients who have survived for no less than 2 years) and STS (shorter time survivals: patients who have survived for less than 2 years). Cox regression analysis was performed to evaluate prognostic factors. A nomogram comprising demographic and clinicopathologic factors was established to predict 1-year survival and 2-year survival for patients with M1 diseases. Results: A total of 2981 patients from the SEER database were included for analysis. Compared with the STS, married people and patients with well differentiated tumors or oligometastatic site were more likely to be LTS. Also, LTS were associated with significantly less bone metastasis and more surgery. The OS nomogram, which had a c-index of 0.633, was based on the eleven variables: gender, age, marital status, T stage, N stage, histology, grade, number of important metastatic organs and primary surgery. Conclusions: Married patients, patients with well differentiated tumors, patients with oligometastatic site, patients without bone metastasis or liver metastasis and those who underwent surgery are associated with long time survivals. We developed a nomogram predicting 1- and 2-year OS and CSS for M1 stage esophageal cancer. The prognostic model may improve clinicians' abilities to predict individualized survival and to make treatment recommendations.

14.
J Transl Med ; 16(1): 100, 2018 04 16.
Article En | MEDLINE | ID: mdl-29661186

BACKGROUND: Radiation-induced lung toxicity (RILT) is a severe complication of radiotherapy in patients with thoracic tumors. Through proteomics, we have previously identified vitronectin (VTN) as a potential biomarker for patients with lung toxicity of grade ≥ 2 radiation. Herein, we explored the molecular mechanism of VTN in the process of RILT. METHODS: In this study, lentivirus encoding for VTN and VTN-specific siRNA were constructed and transfected into the cultured fibroblasts and C57BL mice. Real-time PCR, western blot and ELISA were used to examine expression of collagens and several potential proteins involved in lung fibrosis. Hematoxylin-eosin and immunohistochemical staining were used to assess the fibrosis scores of lung tissue from mice received irradiation. RESULTS: The expression of VTN was up-regulated by irradiation. The change trend of collagens, TGF-ß expression and p-ERK, p-AKT, and p-JNK expression levels were positively related with VTN mRNA level. Furthermore, overexpression of VTN significantly increased the expression level of α-SMA, as well as the degree of lung fibrosis in mice at 8 and 12 weeks post-irradiation. By contrast, siRNA VTN induced opposite results both in vitro and in vivo. CONCLUSIONS: VTN played a positive role in the lung fibrosis of RILT, possibly through modulation of fibrosis regulatory pathways and up-regulating the expression levels of fibrosis-related genes. Taken together, all the results suggested that VTN had a novel therapeutic potential for the treatment of RILT.


Lung/metabolism , Lung/pathology , Radiation Injuries/metabolism , Vitronectin/metabolism , Animals , Cell Line , Collagen Type I/metabolism , Collagen Type III/metabolism , Fibroblasts/metabolism , Fibroblasts/radiation effects , Gene Expression Regulation , Humans , Male , Mice, Inbred C57BL , Pulmonary Fibrosis/genetics , Pulmonary Fibrosis/pathology
15.
Cancer Med ; 7(6): 2504-2517, 2018 06.
Article En | MEDLINE | ID: mdl-29683265

Esophageal squamous cell carcinoma (ESCC) is the eighth cause of cancer-related deaths worldwide. To screen potential biomarkers associated with early recurrence/metastasis (R/M) of ESCC patients after radical resection, ESCC patients were analyzed by a comparative proteomics analysis using iTRAQ with RPLC-MS to screen differential proteins among R/M groups and adjacent normal tissues. The proteins were identified by qRT-PCR, Western blotting, and tissue microarray. The protein and mRNA expression difference of PHB2 between tumor tissues of ESCC patients and adjacent normal tissues, ESCC patients with and without metastasis, four ESCC cell lines and normal esophageal epithelial cells were inspected using immunohistochemical staining, qRT-PCR, and Western blotting. The EC109 and TE1 cells were used to establish PHB2 knockdown cell models, and their cell proliferation and invasion ability were determined by cell counting method, Transwell® assay. Thirteen proteins were selected by cutoff value of 0.67 fold for underexpression and 1.5-fold for overexpression. Seven proteins were confirmed to be associated with R/M among the 13 proteins. The potential biomarker PHB2 for early recurrence/metastasis of ESCC was identified. PHB2 expression was related to the OS of ESCC patients (P = 0.032) and had high levels in the tumor tissues and human cell lines of ESCC (P = 0.0002). Also, the high PHB2 expression promoted the metastasis of ESCC (P = 0.0075), suggesting high PHB2 expression was a potential prognostic biomarker. Experiments showed that PHB2 could significantly promote the proliferation and cell invasion ability of human ESCC cell lines and the knockdown of PHB2 suppressed the phosphorylation level of AKT, as well as the expression of MMP9 and RAC1. PHB2 could predict the early metastasis of ESCC patients.


Biomarkers, Tumor , Esophageal Squamous Cell Carcinoma/metabolism , Esophageal Squamous Cell Carcinoma/pathology , Proteomics , Tissue Array Analysis , Cell Line, Tumor , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/mortality , Gene Expression Profiling , Humans , Immunohistochemistry , Neoplasm Metastasis , Neoplasm Staging , Prohibitins , Proteomics/methods , Recurrence , Tissue Array Analysis/methods
16.
Oncotarget ; 6(42): 44963-70, 2015 Dec 29.
Article En | MEDLINE | ID: mdl-26517681

BACKGROUND: Young non-small cell lung cancer (NSCLC) patients under the age of 40 can further be categorized into different age subgroups. Whether they have homogeneous clinical features and survival outcomes remains unexplored. METHODS: Information of 4623 NSCLC patients up to 40 years old from 1988 to 2012 was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Clinicopathologic characteristics and survival outcomes were compared between patients diagnosed at 18-30 years old (younger group) and those at 31-40 years old (older group). RESULTS: The proportion of patients in the younger group among all lung cancer patients was stable between 1988 and 2012. However, the proportion of patients in the older group decreased from 1.2% to 0.5%. The younger patients had a higher proportion of adenocarcinoma (P = 0.016), a lower proportion of large cell carcinoma (P = 0.008), a higher proportion of stage I disease (P = 0.002) and a lower proportion of stage III disease (P < 0.001). The younger patients had significantly better lung cancer-specific survival (LCSS) in the whole cohort (P < 0.001) and in the subgroup of patients with stage I (P = 0.038) or stage IV (P < 0.001) disease. Multivariate survival analysis showed that patients under 30 years old was an independent predictor of both better LCSS (P = 0.010) and overall survival (OS) (P = 0.018). CONCLUSIONS: Adult NSCLC patients under 30 years old had distinctive clinicopathologic characteristics and survival outcomes compared to patients diagnosed at 31-40 years old.


Carcinoma, Large Cell/diagnosis , Carcinoma, Non-Small-Cell Lung/diagnosis , Lung Neoplasms/diagnosis , Adenocarcinoma , Adenocarcinoma of Lung , Adolescent , Adult , Age Factors , Carcinoma, Large Cell/mortality , Carcinoma, Large Cell/pathology , Carcinoma, Large Cell/therapy , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Chi-Square Distribution , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Male , Multivariate Analysis , Neoplasm Staging , Proportional Hazards Models , Retrospective Studies , Risk Factors , SEER Program , Time Factors , United States/epidemiology , Young Adult
17.
Radiat Oncol ; 9: 232, 2014 Oct 25.
Article En | MEDLINE | ID: mdl-25344056

BACKGROUND: A retrospective study to compare the failure patterns and effects of elective nodal irradiation (ENI) or involved field irradiation (IFI) for cervical and upper thoracic esophageal squamous cell carcinoma (SCC) patients. METHODS: One hundred and sixty nine patients with the cervical and upper thoracic esophageal SCC were analyzed retrospectively; 99 patients (59%) underwent IFI and 70 patients (41%) received ENI. We defined "Out-PTVifi in-PTVeni metastasis" as lymph node metastasis occurring in the cervical prophylactic field of PTVeni thus out of PTVifi. RESULTS: Out-PTVifi in-PTVeni cervical node metastasis occurred in 8% of patients in the IFI group, all within 2 years after treatment. However, it occurred in 10% of patients in the ENI group, and these failures happened gradually since one year after treatments. No difference was found in OS and the incidences of Grade ≥ 3 treatment-related esophageal and lung toxicities between the two groups. CONCLUSIONS: ENI for cervical and upper thoracic esophageal SCC patients did not bring longer OS and better long-term control of cervical lymph nodes. Although ENI might delay cervical nodes progression in elective field; it could not decrease the incidence of these failures.


Carcinoma, Squamous Cell/radiotherapy , Esophageal Neoplasms/radiotherapy , Lymph Nodes/radiation effects , Lymphatic Irradiation/mortality , Thoracic Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Retrospective Studies , Risk Factors , Survival Rate , Thoracic Neoplasms/mortality , Thoracic Neoplasms/pathology
18.
Radiother Oncol ; 113(2): 175-81, 2014 Nov.
Article En | MEDLINE | ID: mdl-25613396

BACKGROUND AND PURPOSE: To propose revisions of CT-based cervical and thoracic lymph node levels for esophageal cancer in UICC 7th version. MATERIAL AND METHODS: One hundred and forty-nine patients who underwent surgery were analyzed retrospectively for hypothesis validation, 338 patients who underwent definitive radiotherapy to evaluate the feasibility in clinical work, and 121 patients from another independent cohort for external evaluation. We redefined Level VI in the RTOG consensus guideline of CT-based cervical lymph node levels, and established a new Level 1 in the IASLC guideline of CT-based thoracic lymph node levels. We also shrunk Level 3p. Lymph nodes were assigned into different levels by three criteria. RESULTS: We encountered stratification problems in 63 patients by JSED criteria and in 24 patients by RTOG criteria. Multivariate analysis showed that nodal status was independently associated with OS in the three cohorts (p<0.001). No significant difference was found between the Level 1 only group and the mediastinal nodes only group (p>0.05). CONCLUSIONS: The proposed hypothesis clearly defined the boundary area between the cervical and thoracic parts, brought more convenience for stratification, better predicted patients' OS and provided information for both pre-treatment evaluation and multidisciplinary treatment planning.


Esophageal Neoplasms/pathology , Lymph Nodes/pathology , Esophageal Neoplasms/therapy , Female , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Neck , Neoplasm Staging , Prognosis , Retrospective Studies , Survival Rate , Thorax , Tomography, X-Ray Computed
19.
Radiat Oncol ; 7: 142, 2012 Aug 22.
Article En | MEDLINE | ID: mdl-22913676

PURPOSE: To investigate the long-term outcome of esophageal squamous cell carcinoma (SCC) treated by irradiation with or without concurrent chemotherapy. METHODS AND MATERIALS: A prospective clinical trial was carried out from 1998 to 2000. One hundred and eleven patients were randomly enrolled to receive either late course accelerated hyperfractionated irradiation (LCAF) or LCAF with concurrent chemotherapy (LCAF + CT). For LCAF, 41.4 Gy in 23 fractions was first delivered at five fractions per week, followed by 27 Gy in 18 fractions at two 1.5 Gy fractions a day. Concurrent chemotherapy of cis-platinum and 5-fluorouracil was administered for four cycles. Overall survival (OS), locoregional recurrence and distant metastasis were observed. Late toxicity was scored by RTOG criteria, and quality of life (QOL) was also evaluated. RESULTS: The median follow-up time was 24 months for all patients and 138 months for 17 living patients. Median survival time was 25 months and 32 months in LCAF and LCAF + CT (p = 0.653), respectively. For an entire group of patients, overall survivals were 34%, 27% and 22%; locoregional recurrence rates were 30%, 36% and 41%; and distant metastasis rates were 26%, 28% and 29% at 5-yr, 8-yr and 10-yr, respectively. Incidences of ≥ Grade 3 late toxicity were 29% at 10-yr. There were no statistically significant differences between LCAF and LCAF + CT with respect to the parameters mentioned above. Cumulative incidence of late toxicities of ≥ Grade 3 increased sharply after the attained age of 70 years. Eighty-eight percent of patients lived with good KPS (≥ 90) and 94% could eat regular or soft diet. CONCLUSION: The long-term outcome of esophageal SCC patients who received LCAF or LCAF + CT was good. The locoregional and distant failures occurred more often in the first three years after treatment, but could continuously occur up to 10 years. The late toxicity was acceptable. Late toxicities ≥ Grade 3 were more likely to occur in elderly patients. QOL was good in living patients.


Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Dose Fractionation, Radiation , Esophageal Neoplasms/therapy , Neoplasm Recurrence, Local/therapy , Adult , Aged , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Cisplatin/administration & dosage , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Prognosis , Prospective Studies , Quality of Life , Survival Rate
20.
Zhong Yao Cai ; 32(10): 1560-3, 2009 Oct.
Article Zh | MEDLINE | ID: mdl-20112721

OBJECTIVE: To study the effects of Qing-Xuan tablets (QXT) on behavior pattern and striatal TNF-alpha in mice model of Parkinson's disease (PD). METHODS: The PD models were established by intraperitoneal injection of MPTP (30 mg/kg). 30 C57BL/6J mice were randomly divided into six groups: control group, PD model group, QXT high dosage group, QXT middle dosage group, QXT low dosage group and trihexyphenidyl hydrochloride group. After 7 days of treatment, the behavior pattern of mice were observed, and striatum were seperated to detect the content of TNF-alpha by ELISA. RESULTS: QXT increased the behavior of mice in behavioral tests (open field, pole test, grid test) (P<0.05 or P<0.01) but depressed TNF-alpha activity in striatum (P<0.05). CONCLUSION: QXT can significantly enhance the behavioral activity of mice,and depress TNF-alpha content in striatum,which suggest QXT can effectively relieve the symptom of PD.


Behavior, Animal/drug effects , Corpus Striatum/drug effects , Drugs, Chinese Herbal/pharmacology , Neuroprotective Agents/pharmacology , Parkinson Disease, Secondary/prevention & control , Tumor Necrosis Factor-alpha/biosynthesis , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects , Animals , Corpus Striatum/metabolism , Disease Models, Animal , Drugs, Chinese Herbal/administration & dosage , Male , Mice , Mice, Inbred C57BL , Motor Activity/drug effects , Neuroprotective Agents/administration & dosage , Parkinson Disease, Secondary/chemically induced , Parkinson Disease, Secondary/metabolism , Parkinson Disease, Secondary/physiopathology , Plants, Medicinal/chemistry , Random Allocation
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