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BACKGROUND: High hepatitis B virus (HBV) DNA level is an independent risk factor for postoperative HBV-associated liver cancer recurrence. We sought to examine whether HBV DNA level and antiviral therapy are associated with survival outcomes in patients with advanced hepatocellular carcinoma (HCC) treated with anti-programmed cell death protein 1 (PD-1)based immunotherapy. METHODS: This single-institution retrospective analysis included 217 patients with advanced HBV-related HCC treated from 1 June 2018, through 30 December 2020. Baseline information was compared between patients with low and high HBV DNA levels. Overall survival (OS) and progression-free survival (PFS) were compared, and univariate and multivariate analyses were applied to identify potential risk factors for oncologic outcomes. RESULTS: The 217 patients included in the analysis had a median survival time of 20.6 months. Of these HBV-associated HCC patients, 165 had known baseline HBV DNA levels. Baseline HBV DNA level was not significantly associated with OS (P = 0.59) or PFS (P = 0.098). Compared to patients who did not receive antiviral therapy, patients who received antiviral therapy had significantly better OS (20.6 vs 11.1 months, P = 0.020), regardless of HBV DNA levels. Moreover, antiviral status (adjusted HR = 0.24, 95% CI 0.094-0.63, P = 0.004) was an independent protective factor for OS in a multivariate analysis of patients with HBV-related HCC. CONCLUSIONS: HBV viral load does not compromise the clinical outcome of patients with HBV-related HCC treated with anti-PD-1-based immunotherapy. The use of antiviral therapy significantly improves survival time of HBV-related HCC patients.
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Carcinoma Hepatocelular , Hepatite B Crônica , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Humanos , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/virologia , DNA Viral , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/virologia , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND: Although the concept of declined immune function associated with cancer has been accepted extensively, real-world clinical studies focusing on analysis of the peripheral blood immune changes underlying ageing, immunity and cancer are scarce. METHODS: In this case-control study, we retrospectively analysed 1375 cancer patients and enrolled 275 age and gender matched healthy individuals. Flow cytometry was conducted to assess the immune changes. Further analysis was examined by SPSS 17.0 and GraphPad Prism 9 software. RESULTS: Cancer patients showed obviously decreased CD3+ T, CD3+CD4+ Th, CD3+CD8+ CTL, CD19+ B, CD16+CD56+ NK cell counts and lower percentage of PD-1 (programmed cell death protein-1, PD-1) positive cells than healthy control (P < 0.0001). For cancer patients, the reference range of circulating percentage of PD-1+CD45+ cells, PD-1+CD3+ T cells, PD-1+CD3+CD4+ Th cells and PD-1+CD3+CD8+ CTL (Cytotoxic T Lymphocyte, CTL) were 11.2% (95% CI 10.8%-11.6%), 15.5% (95% CI 14.7%-16.0%), 15.4% (95% CI 14.9%-16.0%) and 14.5% (95% CI 14.0%-15.5%), respectively. Moreover, the reduction of CD3+ T, CD3+CD4+ Th, CD3+CD8+ CTL, CD19+ B cell counts accompanied with age and stage advancing (P < 0.05). CD16+CD56+ NK cells decreased with stage, but elevated in aged and male cancer patients (P < 0.05). Additionally, the percentage of PD-1 positive cells varied across cancer types, raised with age and stage. Head and neck, pancreatic, gynaecological and lung demonstrated a higher level of the percentage of PD-1 positive cells than melanoma, prostate, and breast cancer (P < 0.05). CONCLUSIONS: This study provides the reference range of the percentage of PD-1 positive cells on peripheral blood, confirms the decreased immune cells and a series of immune changes accompanying with cancer, expands our real world evidence to better understand the interactions of ageing, cancer and immunity. Moreover, the circulating percentage of PD-1 positive cells shows similar tumor type distribution with tumor mutational burden (TMB), supports that it maybe a potential predictive biomarker for immune checkpoint inhibitor therapy.
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INTRODUCTION: Immune-related pneumonitis is an uncommon but potentially life-threatening adverse event associated with anti-programmed cell death protein-1 therapy, and has a higher recurrence rate than that of other pneumonitis. Glucocorticoids are the first treatment of choice for patients with immune-related pneumonitis over grade 1. Given the toxicity associated with glucocorticoids, they should be withdrawn gradually as soon as pneumonitis is controlled. However, low-dose glucocorticoids are maintained in some patients to prevent immune-related pneumonitis. CASE REPORT: We report a rare case of a patient with Hodgkin lymphoma who developed grade 2 immune-related pneumonitis, requiring long-term low-dose glucocorticoid maintenance therapy, during which pneumonitis disappeared, and complete response was achieved. MANAGEMENT AND OUTCOME: Tislelizumab treatment was stopped tentatively, and the patient was given prednisone at an initiating dose of 1â mg/kg/d. The cough symptoms were relieved significantly, and pneumonitis was reduced. The prednisone gradually dwindled, but the immune-related pneumonitis was recurrent, requiring prednisone 10 mg daily maintenance therapy. Subsequently, prednisone and tislelizumab were administered simultaneously, and at present, pneumonitis disappeared and the lesions are in complete remission. DISCUSSION: Low-dose glucocorticoids might play an important role in controlling the recurrence and development of immune-related pneumonitis. The dose and course of glucocorticoid in immune-related pneumonitis patients should be individualized to minimize the toxicity of glucocorticoid.
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Doença de Hodgkin , Pneumonia , Humanos , Prednisona , Glucocorticoides , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Doença de Hodgkin/tratamento farmacológico , Indução de RemissãoRESUMO
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy with a high relapse rate of up to 40%. The prognosis of the disease needs improvement and requires a understanding of its molecular mechanism. We investigated the mechanisms of DLBCL development and its sensitivity to chemotherapy by focusing on circPCBP2/miR-33a/b/PD-L1 axis. Human DLBCL specimens and cultured cancer cell lines were used. Features of circPCBP2 were systematically characterized through Sanger sequencing, Actinomycin D, RNase R treatment, and FISH. The expression levels of circPCBP2, miR-33a/b, PD-L1, stemness-related markers, ERK/AKT and JAK2/STAT3 signaling were measured using qRT-PCR, western blotting, and immunohistochemistry. Stemness of DLBCL cells was assessed through spheroid formation assay and flow cytometry. Cell viability and apoptosis upon cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) treatment were determined using MTT assay and flow cytometry, respectively. Interactions of circPCBP2-miR-33a/b and miR-33a/b-PD-L1 were validated using dual luciferase activity assay and RNA-RIP. Nude mouse xenograft model was used to assess the function of circPCBP2 in DLBCL growth in vivo. circPCBP2 was upregulated in human DLBCL specimens and cultured DLBCL cells while miR-33a/b was reduced. Knockdown of circPCBP2 or miR-33a/b overexpression inhibited the stemness of DLBCL cells and promoted cancer cell apoptosis upon CHOP treatment. circPCBP2 directly bound with miR-33a/b while miR-33a/b targeted PD-L1 3'-UTR. circPCBP2 disinhibited PD-L1 signaling via sponging miR-33a/b. miR-33a/b inhibitor and activating PD-L1 reversed the effects of circPCBP2 knockdown and miR-33a/b mimics, respectively. circPBCP2 knockdown restrained DLBCL growth in vivo and potentiated the anti-tumor effects of CHOP. In conclusion, circPCBP2 enhances DLBCL cell stemness but suppresses its sensitivity to CHOP via sponging miR-33a/b to disinhibit PD-L1 expression. circPCBP2/miR-33a/b/PD-L1 axis could serve as a diagnosis marker or therapeutic target for DLBCL.
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Linfoma Difuso de Grandes Células B , MicroRNAs , RNA Circular , Animais , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Camundongos , MicroRNAs/genética , Recidiva Local de Neoplasia , RNA Circular/genéticaRESUMO
BACKGROUND: The prognosis of patients with metastatic malignant melanoma is very poor and partly due to resistance to conventional chemotherapies. The study's objectives were to assess the activity and tolerability of apatinib, an oral small molecule anti-angiogenesis inhibitor, in patients with recurrent advanced melanoma. METHODS: This was a single-arm, single-center phase II trial. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Eligible patients had received at least one first-line therapy for advanced melanoma and experienced recurrence. Apatinib (500 mg) was orally administered daily. RESULTS: Fifteen patients (V660E BRAF status: 2 mutation, 2 unknown, 11 wild type) were included in the analysis. The median PFS was 4.0 months. There were two major objective responses, for a 13.3% response rate. Eleven patients had stable disease, with a DCR of 86.7%. The median OS was 12.0 months. The most common treatment-related adverse events of any grade were hypertension (80.0%), mucositis oral (33.3%), hand-foot skin reaction (26.7%), and liver function abnormalities, hemorrhage, diarrhea (each 20%). The only grade ≥3 treatment-related adverse effects that occurred in 2 patients was hypertension (6.7%) and mucositis (6.7%). No treatment-related deaths occurred. CONCLUSION: Apatinib showed antitumor activity as a second- or above-line therapy in patients with malignant melanoma. The toxicity was manageable. CLINICALTRIALS.GOV IDENTIFIER: NCT03383237.
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Melanoma , Recidiva Local de Neoplasia , Piridinas , Antineoplásicos/uso terapêutico , Humanos , Hipertensão/induzido quimicamente , Melanoma/tratamento farmacológico , Mucosite/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Piridinas/efeitos adversosRESUMO
BACKGROUND: Colorectal cancer (CRC) is the third most prevalent cancer worldwide and poses a serious challenge for clinicians. Previous studies have shown promising results in patients with Microsatellite Stable microsatellite-stable CRC refractory to chemotherapy upon treating with (Programmed Cell Death Protein 1) PD-1 inhibitor combined with regorafenib. Herein, we report a unique case of a patient for whom the conventional chemotherapy and radiotherapy were ineffective, but showed a prolonged stable disease with third-line treatment with regorafenib and PD-1 inhibitor, sintilimab. CASE PRESENTATION: A 64-year-old East Asian female patient was admitted to a regional cancer hospital presenting with abdominal unease due to increased stool frequency and bloody stool. Digital anal examination revealed adenocarcinoma, while genetic profiling of the tumor resections detected wild-type KRAS mutations in codon 12 and 13. Microsatellite instability (MSI) analysis for detecting germline mutations of (Mismatch-repair) MMR genes showed stable phenotype. In December 2016, Miles' resection for intestinal adhesion release and iliac vessel exploration in the rectum was performed (Tumor, Node, Metastasis [TNM]: T3N0M0; stage IIA). The adjuvant chemotherapeutic regimen consisted of a combination of capecitabine at 1.5 g (twice daily) and oxaliplatin therapy at 200 mg for three cycles from February 2016; followed by administering capecitabine tablets orally (1.5 g bid) for five cycles as post-operative palliative care. The patient tested positive for hepatic C virus, which was managed by oral antiviral agents. Following recurrence of rectal adenocarcinoma after 4 years and disease progression with a previous chemotherapeutic regimen, regorafenib was administered at 120 mg once daily combined with sintilimab 200 mg, and the patient's progress was monitored. A follow-up computerized tomography imaging in March 2020 showed disease progression, additionally presented nodule formation (TNM: T3NxM1b; stage IVB). According to Response Evaluation Criteria in Solid Tumors criteria (RECIST), the patient showed a complete response (CR) after treatment with regorafenib and sintilimab immunotherapy. CONCLUSION: Data from this clinical case report support future exploration of combination treatment of the oral multi-kinase inhibitor regorafenib with PD-1 targeted monoclonal antibodies in patients with metastatic microsatellite-stable CRC.
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Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Feminino , Humanos , Repetições de Microssatélites , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Compostos de Fenilureia , PiridinasRESUMO
Global change caused by carbon emissions alone has become a common challenge for all countries. However, current debates about urbanization and carbon emissions generally do not take into account the heterogeneities in urbanization and economic development levels. The goal of this study is to revisit the urbanization-emissions nexus by considering such heterogeneities in the Chinese context. The results reveal that there is significant heterogeneity in the total factor carbon emission performance index across provinces. Specifically, the relationship between carbon emission performance and urbanization reflects a U-shaped curve. Urbanization is found to have a stronger inhibiting effect on carbon emission performance when economic development levels improve. The results suggest that tailoring policies to each region's conditions, promoting investments in energy-saving and emissions-reducing technologies, and improving the use of public transportation could be mitigation strategies for global change that lead to low-carbon urbanization.
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Blocking the PD-L1/PD-1 interaction with an antibody produces a durable response in patients with diverse advanced cancers. However, it remains elusive on whether the engagement of PD-L1 to PD-1 leads to tumor-intrinsic signaling. In this study, we aim to explore novel protein substrates participating in transducing this tumor-intrinsic PD-L1 signaling. To this end, we performed a BioID (proximity-dependent biotin identification) assay, in which we fused PD-L1 to BirA* (a promiscuous mutant of bacterial biotin ligase BirA) and overexpressed it in the lung adenocarcinoma A549 cell line. Through streptavidin affinity capture and mass spectrometry analysis, we identified 57 candidate proteins including 18 PD-L1/PD-1-interaction-dependent neighbors. In addition to this, 9 out of 57 candidates were involved in the EGFR signaling pathway, which is known to play a critical role in tumorigenesis and multiple therapeutic resistances of lung cancer. This study will provide a new insight in understanding tumor-intrinsic PD-L1-signaling effectors of lung cancer.
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Adenocarcinoma/metabolismo , Antígeno B7-H1/metabolismo , Biotina/metabolismo , Neoplasias Pulmonares/metabolismo , Transdução de Sinais , Células A549 , Adenocarcinoma/patologia , Carbono-Nitrogênio Ligases/genética , Carbono-Nitrogênio Ligases/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Espectrometria de Massas , Mutação , Receptor de Morte Celular Programada 1/metabolismo , Ligação Proteica , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismoRESUMO
Angiotensin-(1-7) [Ang-(1-7)] has been shown to play a significant role in the pathogenesis of lung inflammation via Mas receptor; however, its effect in chronic obstructive pulmonary disease (COPD) remains unknown. To explore the effect of Ang-(1-7) on a cigarette smoke (CS) exposure-induced COPD model, 40 C57BL/6J mice were divided into four groups (n = 10) and exposed to air or CS for 8 weeks. After that, they were treated with saline or Ang-(1-7) at 0.3 mg/kg for 2 weeks by subcutaneous infusion using osmotic pump. The day following drug/vehicle challenge, lung function was examined and bronchoalveolar lavage (BAL) was performed. Chemokine (C-X-C motif) ligand 1, interleukin-6, and tumor necrosis factor-α protein levels in BAL fluid were determined using ELISA; the corresponding mRNA levels in lung tissues were measured using RT-PCR. Mas1 receptor, pIκBα, IκBα, nuclear NF-κB-p65 protein, pERK1/2, ERK2, pp38, and p38 proteins expression in lung tissues were examined by immunohistochemical staining and western blotting. Ang-(1-7) challenge had no effect on the decreased lung function and emphysema induced by CS exposure. However, Ang-(1-7) treatment blocked CS exposure-induced lung inflammatory responses and lung fibrosis, as determined by Masson's Trichrome staining. Exposure to CS for 8 weeks caused irreversible loss of lung function and emphysema, which could not be reversed by Ang-(1-7) treatment. Thus, the beneficial effect of Ang-(1-7) may be confined to pulmonary inflammation and fibrosis.
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Angiotensina I/farmacologia , Fragmentos de Peptídeos/farmacologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Transdução de Sinais/efeitos dos fármacos , Fumaça/efeitos adversos , Fator de Transcrição RelA/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/química , Quimiocina CXCL1/análise , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Injeções Subcutâneas , Interleucina-6/análise , Interleucina-6/genética , Interleucina-6/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/metabolismo , Fosforilação/efeitos dos fármacos , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Fibrose Pulmonar/induzido quimicamente , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Nicotiana/metabolismo , Fator de Transcrição RelA/genética , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Patients suffering from locally advanced gastric or gastroesophageal junction adenocarcinoma often face a high postoperative recurrence rate. Despite aggressive treatment, less than 50% survive beyond five years. Ongoing clinical studies are exploring ways to prolong patient survival, revealing that perioperative chemotherapy can extend both the period of recurrence-free survival and overall survival for this group of patients. Currently, combining chemotherapy and immune checkpoint inhibitors has become a critical treatment approach for advanced gastric or gastroesophageal junction adenocarcinoma. However, the effectiveness of this approach in locally advanced patients remains unverified. This article delves into the latest research concerning the use of perioperative chemotherapy coupled with immune checkpoint inhibitors in locally advanced gastric or gastroesophageal junction adenocarcinoma treatment, and highlights prospective challenges and discusses how to best identify patients who may benefit from combined chemotherapy and immune checkpoint inhibitor therapy.
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Global capital markets are sensitive to extreme and physical events. This research explores the influence of COVID-19 on cross-border arbitrage strategies in emerging markets. Specifically, this study develops a novel cross-market pairs trading strategy centered on healthcare stocks, tailored for the unique dynamics of the emerging market environment. The feasibility of cross-border arbitrage strategies in emerging markets is demonstrated by comparing the performance of the strategy before and after the outbreak. Additionally, sensitivity analysis of the risk preference factors before and after the COVID-19 outbreak further supports this argument. These findings offer valuable insights for international investors seeking arbitrage between emerging and other markets and, effectively responding to global shocks.
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Background: The optional regimens of subsequent therapy after failure of anti-programmed cell death protein-1 (PD-1) antibody in metastatic renal cell carcinoma (mRCC) remain to be explored. There are reports of the efficacy of single-agent vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) in patients with mRCC after failure of anti-PD-1 antibody therapy. However, it is not clear whether it is beneficial for patients to receive anti-PD-1 antibody as post-progression treatment. It has great significance to explore whether continuous application of anti-PD-1 antibody is beneficial for patients with mRCC whose diseases progressed to the state of pre-anti-PD-1 therapy. The purposes of this study are to explore the efficacy and safety of subsequent treatment on whether to continue using anti-PD-1 antibody therapy for patients who have progressive mRCC after prior treatment with anti-PD-1 antibody. Methods: The clinical data of patients with mRCC from the Department of Immunotherapy in the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital from February 1, 2019 to December 31, 2021 were analyzed retrospectively. The primary endpoints were the objective response rate (ORR) and progression-free survival (PFS). The ORR and disease control rate (DCR) were estimated with Fisher's exact test. PFS and overall survival (OS) were assessed using the Kaplan-Meier method and log-rank tests. The associations between potential prognostic variables and PFS were evaluated with univariate and multivariate Cox regression analyses. A P value of less than or equal to 0.05 was deemed as statistically significant. Results: A total of 35 patients were included in this study, during which 19 received VEGFR-TKI monotherapy and 16 received the VEGFR-TKI plus anti-PD-1 antibody therapy. Until the last follow-up on June 30, 2022, 19 patients experienced progressive disease (PD), five were in remission, and 11 kept stable disease (SD). After a median follow-up of 28.7 [95% confidence interval (CI): 17.0-35.6] months, the median PFS (mPFS) was 11.6 months for the VEGFR-TKI group and 9.1 months for the VEGFR-TKI plus anti-PD-1 antibody group [hazard ratio (HR) =0.81, 95% CI: 0.32-1.03, P=0.44]. Median OS (mOS) were 16.9 and 11.2 months respectively (HR =0.99, 95% CI: 0.44-2.27, P=0.90). The ORRs were 26.3% and 0% (P=0.049), and the DCRs were 47.4% and 43.8% (P=0.55) respectively. Treatment-related adverse events (TRAEs) occurred in 14 patients (73.7%) in the VEGFR-TKI group and 14 patients (87.5%) in the VEGFR-TKI plus anti-PD-1 antibody group (P=0.42); grade 3/4 TRAEs occurred in two patients (10.5%) and six patients (37.5%) respectively (P=0.11). Conclusions: VEGFR-TKI monotherapy is an efficacious regimen for patients with mRCC whose diseases progressed on previous anti-PD-1 antibody therapy, and continuous anti-PD-1 therapy after failure of anti-PD-1 antibody could not provide additional clinical benefit but increased the incidence of TRAEs.
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BACKGROUND: Postoperative recurrence of tongue squamous cell carcinoma (TSCC) has always been a clinical problem for patients and doctors. Surgery and radiotherapy are the main treatment methods for TSCC, but reoperation often leads to functional impairment. Side effects of radiotherapy include mucosal gland damage, dry mouth, weakened or lost taste. Improved treatment is needed. OBJECTIVE: To evaluate the clinical outcome of a patient with TSCC treated with Microdrop aminolevulinic acid (ALA) photodynamic treatment (PDT) twice. METHODS: ALA was dissolved in 5 % lidocaine and the concentration of ALA was 20 % by Microdrop method. Then, the tumor tissue was expanded 1 cm outward, and the injection points were evenly distributed with an upper and lower left and right interval of 2-3 mm. The 1 ml syringe was used to perform the injection in the skin of the tumor area, and there was a small cuticle at each injection point. A pathologically confirmed patient with TSCC received twice Microdrop ALA-PDT treatments, which were evaluated at 1 month and 4 months later. RESULTS: After 3 h of Microdrop ALA injection, the wavelength of semiconductor laser was set to 630 nm, and the energy of 300 mW /cm2 was irradiated for 30 min. After two treatments, the lesions were not visible, and no recurrence occurred after 4 months of follow-up. The patient's tongue function was well preserved and the cosmetic effect was good. CONCLUSION: Microdrop ALA-PDT may be effective in the salvage treatment of select tongue squamous cell carcinoma.
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Environmental regulation has played an essential function in reducing pollution and it also influences the flow of labor. Although studies on employment and environmental regulation have gained prominence, most researches ignore the heterogeneity of regulatory tools and its discrepant impacts on different skilled labor; moreover, few literatures have explored how environmental regulations affect employment. Therefore, this study creatively incorporates environmental regulation, industrial green transformation and employment skill structure into a unified analytical framework, categorizing environmental regulations into command-and-control type, market-incentive type and voluntary type and analyzing the heterogeneous influences of environmental regulations on employment skill structure. Meanwhile, we explore the indirect impact of environmental regulations on the employment skill structure from the mediating role of industrial green transformation. The following are the research findings: (1) From a national perspective, both command-and-control and market-incentive types present a U-shaped association with employment skill structure, and their intensity has not surpassed the turning point yet; while the voluntary type is positively connected with the employment skill structure. (2) From the regional analysis, the findings in central and western areas are consistent with the national results; while the market-incentive and voluntary types show a reciprocal U-shaped connection with employment skill structure in eastern, and their regulatory intensity is in the rising stage of the curve. (3) Industrial green transformation acts as a partly mediator between market-incentive type and employment skill structure, but presents a suppression effect between command-and-control type, voluntary type, and employment skill structure. This paper takes industrial green transformation as the mediating variable, which emphasizes the importance of industrial green transformation and enhances the understanding on the mechanism of environmental regulation influencing employment skill structure. The research results provide theoretical support and significant reference for China in formulating policies to facilitate industrial green transformation, mitigate pollution, and optimize employment skill structure.
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Emprego , Trabalho de Parto , Gravidez , Feminino , Humanos , China , Poluição Ambiental , IndústriasRESUMO
BACKGROUND: Factors affecting progenitor cell mobilization in patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) are incompletely understood. The aim of this retrospective study was to determine which factors are crucial for effective mobilization and collection of autologous peripheral blood stem cells (PBSC) prior to transplantation in Chinese patients. PATIENTS AND METHODS: A total of 239 patients with lymphoma (198 NHL and 41 HL patients) underwent PBSC collection after mobilization with granulocyte-colony-stimulating factor (G-CSF) or G-CSF plus chemotherapy priming. RESULTS: Patient characteristics at diagnosis and transplant, including low Eastern Cooperative Oncology Group score (P = 0.013), lack of extranodal invasion (P = 0.034), previously administered radiotherapy regimens (P = 0.040), treatment with platinum prior to mobilization (P = 0.042), previous chemotherapy regimens (P = 0.001) and cycles (P < 0.001), and chemotherapy regimens (P < 0.001) were statistically significant for successful mobilization in multivariate analysis. Premobilization factors, including previous radiotherapy (P = 0.009), previous chemotherapy regimens (P = 0.043) and cycles (P = 0.039), low platelet count prior to mobilization (P = 0.042), and lower CD34+ cells in peripheral blood (PB) (P = 0.050) or bone marrow (BM) (P = 0.007) were considered possibly predictive of poor mobilization. We found the patients who had chemosensitive lymphoma had worse progress-free survival (PFS) than the patients with initial treatment and high risks (P = 0.017). CONCLUSION: Our analysis showed that high amounts of chemotherapy, radiotherapy, low platelet count, chemosensitive recurrent patients, combination chemotherapy plus G-CSF and low CD34+ cells in BM prior to mobilization could emerged as important predictive factors for mobilization failure in Chinese patients with NHL and HL.
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Mobilização de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Adolescente , Adulto , Antígenos CD34/biossíntese , Antineoplásicos/farmacologia , China , Intervalo Livre de Doença , Feminino , Fator Estimulador de Colônias de Granulócitos/metabolismo , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/etnologia , Doença de Hodgkin/radioterapia , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/etnologia , Linfoma não Hodgkin/radioterapia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos RetrospectivosRESUMO
OBJECTIVE: To compare the chemotherapeutic efficacies of third-generation plus platinum doublets in advanced non-small cell lung cancer (NSCLC) patients. METHODS: A total of 1112 patients were diagnosed as advanced NSCLC at Chinese Academy of Medical Science and Cancer Hospital from January 2005 to August 2009. Their clinical efficacies and regimen compositions were retrospectively analyzed. All calculations were performed by SPSS 17.0. RESULTS: Differences in objective response rate (ORR) existed among four third-generation agents (paclitaxel, gemcitabine, vinorelbine and docetaxel) plus platinum doublets. Their ORRs were 35.6%, 35.4%, 25.9% and 37.4% respectively (χ(2) = 16.331, P = 0.001). And vinorelbine doublets had the lowest ORR (all P < 0.01). The ORRs of cisplatin and carboplatin doublets were 35.2% and 33.5% respectively. There was no difference in ORR among them (χ(2) = 0.352, P = 0.569). Subgroup analysis showed that the ORRs of four third generation plus platinum doublets were 34.8%, 35.3%, 23.2% and 37.1% in non-agers. And the vinorelbine doublets performed the worst. In the patients with squamous-cell lung cancer, the ORRs of paclitaxel and gemcitabine doublets were 45.5% and 28.4% respectively. And the paclitaxel doublets had the better performance (χ(2) = 5.250, P = 0.026). When combined with carboplatin, the ORRs of four doublets were 36.2%, 16.7%, 15.4% and 32.0% respectively. And the paclitaxel regimen was more effective than the gemcitabine and vinorelbine regimens (P = 0.018 and P = 0.034). The influences of subsequent therapy were nullified when the progression-free survival (PFS) was analyzed. The PFSs of these doublets were (3.67 ± 0.19), (2.95 ± 0.18), (3.05 ± 0.36) and (3.40 ± 0.37) months respectively. There was no difference among them. Pairwise comparisons showed that the mean PFS of patients on paclitaxel doublets was longer than those on gemcitabine doublets. And their PFSs were (3.67 ± 0.19) and (2.95 ± 0.18) months respectively (χ(2) = 7.037, P = 0.008). The PFSs of cisplatin and carboplatin doublets were (3.05 ± 0.14) and (3.65 ± 0.20) months respectively. The patients on carboplatin doublets had a longer PFS than that of those on cisplatin doublets (χ(2) = 6.012, P = 0.014). CONCLUSIONS: No difference exist in ORRs among different third-generation plus platinum doublets. But as the first-line treatment of advanced NSCLC, carboplatin doublets is superior to cisplatin doublets in terms of PFS.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Platina/administração & dosagem , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the mutations of epidermal growth factor receptor (EGFR) in tumor tissue and pleural effusion in advanced non-small cell lung cancer (NSCLC) patients, and to analyze the relationship between EGFR mutations and the clinicopathologic characteristics. METHODS: Two-hundred and forty-one cases of formalin-fixed, paraffin-embedded tumor tissues and 14 paired pleural effusions from advanced NSCLC patients were collected. Twenty-nine different EGFR mutations in exons 18-21 were assessed by scorpions and amplification refractory mutation system (scorpions ARMS) using real time PCR. The relationship between the EGFR mutations and clinical parameters was analyzed using statistical methods. EGFR mutation of 37 cases were detected with direct sequencing, and assessed the sensitivity, the specificity and the accuracy of scorpions ARMS. RESULTS: EGFR somatic mutations were detected in 114 of 234 advanced NSCLC patients, with the mutation rate of 48.7%, including deletions in exon 19 in 65 patients and point mutation of L858R in exon 21 in 39 patients; both accounting for 91.2% (104/114) of all types of EGFR mutations. The test results of 14 paired pleural effusion specimens were entirely the same to the tissues. The concordance rate of 2 different detection methods was 94.6%. Mutation rate was higher in women (55.9%) than in men (42.2%), and there was no difference in mutation rates between smokers and non-smokers; patients in stage IIIB and stage IV; adenocarcinoma and non-adenocarcinoma. CONCLUSIONS: EGFR somatic mutations appear to occur frequently in Chinese. Scorpions ARMS technology is a sensitive method to detect EGFR mutations and is suitable for screening patients who would likely respond to EGFR inhibitors therapy.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Deleção de Genes , Neoplasias Pulmonares/genética , Mutação Puntual , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/metabolismo , Éxons , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Adulto JovemRESUMO
Background: Ovarian clear cell carcinoma (OCCC), which is resistant to traditional treatment, has a poor prognosis. Immune checkpoint inhibitors (ICIs) have been emerged in the past decade and are now widely used in clinics. However, OCCC reportedly responds poorly to ICIs, and ICI monotherapy is rarely used for patients with OCCC. Methodology & Results: We report the case of a patient with refractory OCCC who received an ICI (nivolumab) monotherapy treatment and achieved a complete response despite the occurrence of pseudoprogression. Nivolumab was discontinued after 2 years, and the patient remained in complete remission more than a year after treatment withdrawal. Conclusion: This is the first report of complete remission being achieved in a case of refractory OCCC after pseudoprogression during nivolumab monotherapy.
Assuntos
Adenocarcinoma de Células Claras , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Nivolumabe/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológicoRESUMO
Despite recent progress in treating advanced non-small cell lung cancer, clinical intervention in extensive-stage small-cell lung cancer (ES-SCLC) remains stagnant. The purpose of this study was to evaluate the clinical efficacy of cytokine-induced killer (CIK) cells combined with cytotoxic chemotherapy, followed by anti-programmed death 1 antibody (sintilimab) maintenance, in ES-SCLC patients. To explore a new method for safe treatment of ES-SCLC patients, thirteen ES-SCLC patients were enrolled between June 2019 and December 2021. All patients received first-line chemotherapy (etoposide plus platinum) combined with CIK cell therapy. Patients who reached a stable disease state or responded well to treatment received sintilimab maintenance treatment. The primary objective of this study was to determine the median overall survival (OS); the secondary objective was to assess the objective response rate (ORR), progression-free survival 1 and 2 (PFS1 was defined as the duration from the signing of informed consent to the date of tumor progression, or death, or the last follow-up. PFS2 was defined as the duration from the first day of sintilimab treatment to the date of tumor progression, death, or the last follow-up.), and adverse reactions. At a 24.1-month follow-up, the median OS was 11.8 (95% confidence interval [CI]: 10.6-13.0) months, median PFS1 was 5.5 (95% CI: 5.0-6.0) months, and the median PFS2 was 2.3 (95% CI: 0.5-4.1) months. The ORR was 76.9% (10/13), the disease control rate was 100% (13/13), and the 20-month survival rate was 41.7%. Eight participants exhibited grade 3 or 4 adverse events after combination therapy. During maintenance treatment with sintilimab, level 3 adverse events occurred in 1 patient (1/9). In conclusion, adding CIK cells to standard chemotherapy regimens, followed by maintenance therapy with sintilimab, may represent a new safe and effective treatment strategy. Clinical trial registration: ClinicalTrials.gov (NCT03983759).
RESUMO
Purpose: This study determined the efficacy of low-dose gemcitabine combined with programmed death-1 (PD-1) inhibitors for treating multiple malignancies, providing a cost-effective and safe treatment option. Study Design: This study included 61 patients with advanced solid tumors treated with low-dose gemcitabine combined with PD-1 inhibitors at the Henan Cancer Hospital between January 2018 and February 2022. We retrospectively reviewed medical records to evaluate several clinical factors, including progression-free survival (PFS), overall survival (OS), adverse effects (AEs), and objective response to treatment. Results: Sixty-one patients received treatment with low-dose gemcitabine combined with PD-1 inhibitors. The objective response rate (ORR) was 29.5% and the disease control rate (DCR) was 62.3%. The median PFS was 4.3 months (95% confidence interval, 2.3 to 6.3 months) and the median OS was 15.0 months (95% confidence interval, 8.8 to 21.2 months). Hematological toxicity, mainly leukopenia or thrombocytopenia, was the most common AE, with any-grade and grade 3/4 hematological toxicity reported in 60.7 and 13.1% of patients, respectively. Conclusions: Low-dose gemcitabine combined with PD-1 inhibitors may offer a novel treatment option for patients with advanced malignancies.