Objective: To systematically evaluate the effects of lead therapies on percutaneous coronary intervention (PCI) after acute myocardial infarction (AMI). Methods: A randomized controlled trial (RCT) in the CNKI, Wanfang, VIP, ProQuest, PubMed, Cochrane Library, Scopus, and Web of Science databases was searched until January 2023. Two researchers strictly screened and checked the included literature, extracted relevant data, and used the Cochrane Manual to assess the risk quality of the literature. Using RevMan 5.3 software, Meta-analysis of 4 main outcome measures [cardiac function-related indicators, 6-minute walking distance (6 MWT), quality of life (SF-36), Seattle angina pectoris scale (SAQ)], and 3 secondary outcome measures [adverse event incidence, death incidence, and readmission rate]. Results: 22 studies were finally included with 1754 subjects, but the overall quality of the included studies was not high. The results of the meta-analysis showed that, in the cardiac function-related indicators compared to controls, improved left ventricular ejection fraction (LVEF) index (MD = 1.42, 95%CI [−0.94, 3.79], P < .00001); however, compared with the Baduanjin group, Tai Chi ball + Baduanjin group and control group, there was no significant difference ( P > .05); compared with the control group, the guidance therapy group improved the left ventricular end-diastolic volume (LVEDV) index (MD = −4.67, 95%CI [−6.8, −2.71], P < .00001). In comparison, the lead group improved the 6 MWT (MD = 69.44, 95%CI [30.12, 108.76], P < .00001); the SF-36 score (MD = 10.05, 95%CI [8.68, 11.42], P < .00001])and the SAQ score (MD = 6.2, 95%CI [3.97, 8.44], P < .00001). Among the secondary outcome measures, the incidence of adverse events was statistically significant (RR = 0.17, 95%CI [0.1, 0.32], P < .00001); statistically significant (RR = 0.29, 95%CI (0.1, 0.87), P < .00001); readmission (RR = 0.39, 95%CI [0.17, 0.87, 0.89], P < .00001). Conclusion: Based on the current study, combining conventional therapy/ exercise or using simple lead therapy after PCI can improve the treatment effect and improve the quality of life.
The prevalence and mortality rates of colorectal cancer (CRC) are increasing worldwide. Radiation resistance hinders radiotherapy, a standard treatment for advanced CRC, leading to local recurrence and metastasis. Elucidating the molecular mechanisms underlying radioresistance in CRC is critical to enhance therapeutic efficacy and patient outcomes. Bioinformatic analysis and tumour tissue examination were conducted to investigate the CPT1A mRNA and protein levels in CRC and their correlation with radiotherapy efficacy. Furthermore, lentiviral overexpression and CRISPR/Cas9 lentiviral vectors, along with in vitro and in vivo radiation experiments, were used to explore the effect of CPT1A on radiosensitivity. Additionally, transcriptomic sequencing, molecular biology experiments, and bioinformatic analyses were employed to elucidate the molecular mechanisms by which CPT1A regulates radiosensitivity. CPT1A was significantly downregulated in CRC and negatively correlated with responsiveness to neoadjuvant radiotherapy. Functional studies suggested that CPT1A mediates radiosensitivity, influencing reactive oxygen species (ROS) scavenging and DNA damage response. Transcriptomic and molecular analyses highlighted the involvement of the peroxisomal pathway. Mechanistic exploration revealed that CPT1A downregulates the FOXM1-SOD1/SOD2/CAT axis, moderating cellular ROS levels after irradiation and enhancing radiosensitivity. CPT1A downregulation contributes to radioresistance in CRC by augmenting the FOXM1-mediated antioxidant response. Thus, CPT1A is a potential biomarker of radiosensitivity and a novel target for overcoming radioresistance, offering a future direction to enhance CRC radiotherapy.
Mutational activation of KRAS is a common oncogenic event in lung cancer, yet effective therapies are still lacking. Here, we identify B cell lymphoma 6 (BCL6) as a lynchpin in KRAS-driven lung cancer. BCL6 expression was increased upon KRAS activation in lung tumor tissue in mice and was positively correlated with the expression of KRAS-GTP, the active form of KRAS, in various human cancer cell lines. Moreover, BCL6 was highly expressed in human KRAS-mutant lung adenocarcinomas and was associated with poor patient survival. Mechanistically, the MAPK/ERK/ELK1 signaling axis downstream of mutant KRAS directly regulated BCL6 expression. BCL6 maintained the global expression of prereplication complex components; therefore, BCL6 inhibition induced stalling of the replication fork, leading to DNA damage and growth arrest in KRAS-mutant lung cancer cells. Importantly, BCL6-specific knockout in lungs significantly reduced the tumor burden and mortality in the LSL-KrasG12D/+ lung cancer mouse model. Likewise, pharmacological inhibition of BCL6 significantly impeded the growth of KRAS-mutant lung cancer cells both in vitro and in vivo. In summary, our findings reveal a crucial role of BCL6 in promoting KRAS-addicted lung cancer and suggest BCL6 as a therapeutic target for the treatment of this intractable disease.
BackgroundBTG3 (B-cell translocation gene 3) has been identified as a tumor suppressor and hypermethylation contributes to its down-regulation in some tumors, but its role in hepatocellular carcinoma (HCC) remain unknown. This study aimed to detect the expression and methylation status of BTG3 in HCC cell lines or tissues, and determine its function in HCC progression. MethodologyThe expression of BTG3 was detected in HCC cell lines and HCC tissue by real-time RT-PCR, Western blot or immunohistochemistry. The promoter methylation status of BTG3 was measured by using methylation-specific PCR in HCC cell lines. A series of assays were performed to evaluate the effect of BTG3 on proliferation, invasion and cell cycle transition in vitro. ResultsBTG3 expression was lower in HCC cell lines than in hepatocyte cell line LO2 (P<0.05). BTG3 was also down-regulated in HCC tissues. Its expression was positively correlated with differentiation and distant metastasis (P<0.05). Patients with lower BTG3 expression had shorter overall survival time (P=0.029). DNA methylation directed repression of BTG3 mRNA expression in HCC cell lines. BTG3 suppressed proliferation, invasion and induces G1/S cycle arrest of HCC cells in vitro. ConclusionDown-regulation of BTG3 due to the promoter hypermethylation is closely associated with proliferation, invasion and cell cycle arrest of HCC cells. It may be a novel prognostic biomarker for HCC patients.
The prevalence and mortality rates of colorectal cancer (CRC) are increasing worldwide. Radiation resistance hinders radiotherapy, a standard treatment for advanced CRC, leading to local recurrence and metastasis. Elucidating the molecular mechanisms underlying radioresistance in CRC is critical to enhance therapeutic efficacy and patient outcomes. Bioinformatic analysis and tumour tissue examination were conducted to investigate the CPT1A mRNA and protein levels in CRC and their correlation with radiotherapy efficacy. Furthermore, lentiviral overexpression and CRISPR/Cas9 lentiviral vectors, along with in vitro and in vivo radiation experiments, were used to explore the effect of CPT1A on radiosensitivity. Additionally, transcriptomic sequencing, molecular biology experiments, and bioinformatic analyses were employed to elucidate the molecular mechanisms by which CPT1A regulates radiosensitivity. CPT1A was significantly downregulated in CRC and negatively correlated with responsiveness to neoadjuvant radiotherapy. Functional studies suggested that CPT1A mediates radiosensitivity, influencing reactive oxygen species (ROS) scavenging and DNA damage response. Transcriptomic and molecular analyses highlighted the involvement of the peroxisomal pathway. Mechanistic exploration revealed that CPT1A downregulates the FOXM1-SOD1/SOD2/CAT axis, moderating cellular ROS levels after irradiation and enhancing radiosensitivity. CPT1A downregulation contributes to radioresistance in CRC by augmenting the FOXM1-mediated antioxidant response. Thus, CPT1A is a potential biomarker of radiosensitivity and a novel target for overcoming radioresistance, offering a future direction to enhance CRC radiotherapy.
Several randomized controlled clinical trials have compared therapy with or without thalidomide in the treatment of advanced non-small cell lung cancer (NSCLC). However, these studies did not produce consistent results. We carried out a meta-analysis to determine the efficacy and safety of thalidomide-based therapy in patients with advanced NSCLC. For this meta-analysis, we selected randomized clinical trials that compared thalidomide in combination with other therapy or other therapy alone in patients with advanced NSCLC. The outcomes included median overall survival (OS), one- and two-year survival, tumor response, and toxicities. Hazard ratios (HRs) or risk ratios (RRs) were reported with 95% confidence intervals (CIs). A total of 5 eligible trials were included for the meta-analysis, with 729 patients in the thalidomide group and 711 patients in the control group. Compared with non-thalidomide-based therapy, patients receiving thalidomide plus other therapy did not differ significantly in terms of one- and two-year survival or tumor response (RR = 1.32, 95% CI: 0.66-2.63, p = 0.43; RR = 1.22, 95% CI: 0.48-3.11, p = 0.68; RR = 1.05, 95% CI: 0.92-1.19, p = 0.51, respectively). However, thalidomide-based therapy induced more grade 3-4 dizziness and constipation (RR = 2.05, 95% CI: 1.10-3.81, p = 0.02; RR = 4.78, 95% CI: 1.84-12.38, p = 0.001, respectively). The addition of thalidomide to other therapy did not improve survival and tumor response in patients with advanced NSCLC, and thalidomide-based therapy was associated with more grade 3/4 dizziness and constipation.
Upregulation of histone methyltransferase SET domain bifurcated 1 (SETDB1) is associated with poor prognosis in cancer patients. However, the mechanism of oncogenicity of SETDB1 in cancer is hitherto unknown. Here, we show that SETDB1 is upregulated in human colorectal cancer (CRC) where its level correlates with poor clinical outcome. Ectopic SETDB1 promotes CRC cell proliferation, whereas SETDB1 attenuation inhibits this process. Flow cytometry reveals that SETDB1 promotes proliferation by driving the CRC cell cycle from G0/G1 phase to S phase. Mechanistically, SETDB1 binds directly to the STAT1 promoter region resulting in increased STAT1 expression. Functional characterization reveals that STAT1-CCND1/CDK6 axis is a downstream effector of SETDB1-mediated CRC cell proliferation. Furthermore, SETDB1 upregulation is sufficient to accelerate in vivo proliferation in xenograft animal model. Taken together, our results provide insight into the upregulation of SETDB1 within CRC and can lead to novel treatment strategies targeting this cell proliferation-promoting gene.
This study was aimed to explore the applicable value of multiplex nested reverse transcription-polymerase chain reaction (multiplex nested RT-PCR)for the detection of platelet-derived growth factor receptor alpha (PDGFRα) fusion gene in myeloproliferative neoplasms (MPN). Bone marrow or peripheral blood samples from 146 patients with MPN were analyzed by using a novel multiplex nested RT-PCR. The result showed that PDGFRα fusion gene was found in 6 out of the 146 bone marrow or peripheral blood samples, the positive rate was 4.11%, 4 from the 6 patients received treatment with imatinib and showed therapeutic effect. It is concluded that the multiplex nested RT-PCR has a series of advantages such as high sensitivity, specificity, and time-saving, and can be applied for determination of the molecular type of MPN, and also for the diagnosis and therapy of MPN.
Objective Checkpoint immunotherapy unleashes T-cell control of tumours but is suppressed by immunosuppressive myeloid cells. The transmembrane protein MS4A4A is selectively highly expressed in tumour-associated macrophages (TAMs). Here, we aimed to reveal the role of MS4A4A + TAMs in regulating the immune escape of tumour cells and to develop novel therapeutic strategies targeting TAMs to enhance the efficacy of immune checkpoint inhibitor (ICI) in colorectal cancer. Design The inhibitory effect of MS4A4A blockade alone or combined with ICI treatment on tumour growth was assessed using murine subcutaneous tumour or orthotopic transplanted models. The effect of MS4A4A blockade on the tumour immune microenvironment was assessed by flow cytometry and mass cytometry. RNA sequencing and western blot analysis were used to further explore the molecular mechanism by which MS4A4A promoted macrophages M2 polarisation. Results MS4A4A is selectively expressed by TAMs in different types of tumours, and was associated with adverse clinical outcome in patients with cancer. In vivo inhibition of MS4A4A and anti-MS4A4A monoclonal antibody treatment both curb tumour growth and improve the effect of ICI therapy. MS4A4A blockade treatment reshaped the tumour immune microenvironment, resulting in reducing the infiltration of M2-TAMs and exhausted T cells, and increasing the infiltration of effector CD8 + T cells. Anti-MS4A4A plus anti-programmed cell death protein 1 (PD-1) therapy remained effective in large, treatment-resistant tumours and could induce complete regression when further combined with radiotherapy. Mechanistically, MS4A4A promoted M2 polarisation of macrophages by activating PI3K/AKT pathway and JAK/STAT6 pathway. Conclusion Targeting MS4A4A could enhance the ICI efficacy and represent a new anticancer immunotherapy.
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