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  • Frontiers Media SA  (7)
  • 1
    Online Resource
    Online Resource
    Current status and challenges of immunotherapy in ALK rearranged NSCLC
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-12-14)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-12-14)
    Abstract: Rearrangements of the anaplastic lymphoma kinase (ALK) gene account for 5-6% in non-small cell lung cancer (NSCLC). ALK rearranged NSCLC is sensitive to ALK tyrosine kinase inhibitors (TKIs) but prone to drug resistance. Meanwhile, ALK rearranged NSCLC has poor response to single immunotherapy. Here we mainly describe the immune escape mechanisms of ALK mutated NSCLC and the role of related biomarkers. Additionally, we collate and evaluate preclinical and clinical studies of novel immune combination regimens, and describe the prospects and perspectives for the in vivo application of novel immune technologies in patients with ALK rearranged NSCLC.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2022.1016869
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 2
    Online Resource
    Online Resource
    Image1.tif
    Frontiers Media SA ; 2022
    In:  Frontiers in Surgery Vol. 9 ( 2022-11-7)
    Details
    In: Frontiers in Surgery, Frontiers Media SA, Vol. 9 ( 2022-11-7)
    Abstract: This study aims to compare the safety and efficacy of extracorporeal shock wave lithotripsy (SWL) and flexible ureteroscopy lithotripsy (f-URS) in treating urinary tract stones. Methods We systematically searched PubMed, Embase, and Cochrane for literature comparing SWL with f-URS. The primary outcomes we focused on were stone-free rate (SFR) and complications; the secondary outcomes were operation time, hospital stay, retreatment rate, number of sessions, and auxiliary procedures rate. We used ReviewManager version 5.4.1 and STATA version 14.2 for meta-analysis. Results Seventeen studies with a total of 2,265 patients were included in the meta-analysis, including 1,038 patients in the SWL group and 1,227 patients in the f-URS group. The meta-analysis indicated that patients in the f-URS group had higher SFR than those in the SWL group [odds ratio (OR): 2.00, 95% confidence interval (CI): 1.29–3.12, p  = 0.002]. In addition, we found no significant difference in complications (OR: 1.08, 95% CI: 0.85–1.37) between the two treatments. Also, we found that the retreatment rate and the auxiliary procedure rate in the f-URS group were significantly lower than those in the SWL group (OR: 0.08, 95% CI: 0.02–0.24, p   & lt; 0.00001; OR: 0.30, 95% CI: 0.11–0.83, p  = 0.02). Moreover, the number of sessions in the f-URS group was significantly lower than that in the SWL group [mean difference (MD): −1.96, 95% CI: −1.55 to −0.33, p  = 0.003]. However, the operation time and hospital stay in the f-URS group were significantly longer than those in the SWL group (MD: 11.24, 95% CI: 3.51–18.56, p  = 0.004; MD: 1.14, 95% CI: 0.85–1.42, p   & lt; 0.00001). Conclusion For 1–2-cm urinary stones, f-URS can achieve a higher SFR than SWL while having a lower retreatment rate, number of sessions, and auxiliary procedure rate. For urinary stones & lt;1 cm, there was no significant difference in SFR between SWL and f-URS groups. The SWL group has a shorter operative time and hospital stay than the f-URS group.
    Type of Medium: Online Resource
    ISSN: 2296-875X
    URL: Article
    URL: Article
    DOI: 10.3389/fsurg.2022.925481
    DOI: 10.3389/fsurg.2022.925481.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2773823-1
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  • 3
    Online Resource
    Online Resource
    Table_3.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-5-7)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-5-7)
    Abstract: Non-small cell lung cancer (NSCLC) patients with HER2 mutations and amplification may benefit from HER2-targeted therapy, including afatinib. However, the data regarding the clinical activity of afatinib in Chinese patients with NSCLC harboring HER2 alterations are limited. Patients and methods We retrospectively included metastatic NSCLC patients harboring HER2 alterations who treated with afatinib. The clinical outcomes included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). The genomic profiling data after progression on afatinib were analyzed. Results We included 54 patients harboring HER2 mutations and 12 patients harboring HER2 amplification. The ORR was 24% (95% CI, 16–36%), the median PFS was 3.3 months (95% CI, 2.2–4.4), and the median OS was 13.9 months (95% CI, 11.4–16.5). Patients with HER2 exon 20 mutations had numerically worse ORR (17% vs 42%), shorter PFS (2.6 vs 5.8 months, HR, 2.5; 95% CI, 1.2–5.5; P = 0.015) and OS (12.9 vs 33.3 months, HR, 4.4; 95% CI, 1.3–14.8; P = 0.009) than patients with other mutations. For HER2-amplified patients, the ORR was 33% (95% CI, 14–61%), the median PFS was 3.3 months (95% CI, 2.6–4.0), and the median OS was 13.4 months (95% CI, 0–27.6). The most frequently mutated genes in afatinib-resistant patients were TP53 (44%) and EGFR (33%). Three afatinib-resistant patients harbored secondary HER2 alterations. Conclusions Our results suggest that afatinib has a promising anti-tumor activity in patients with NSCLC harboring HER2 alterations. To our knowledge, this is the largest retrospective study about the clinical activity of afatinib in NSCLC patients with HER2 alterations.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.657283
    DOI: 10.3389/fonc.2021.657283.s001
    DOI: 10.3389/fonc.2021.657283.s002
    DOI: 10.3389/fonc.2021.657283.s003
    DOI: 10.3389/fonc.2021.657283.s004
    DOI: 10.3389/fonc.2021.657283.s005
    DOI: 10.3389/fonc.2021.657283.s006
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 4
    Online Resource
    Online Resource
    Reduced PHLPP Expression Leads to EGFR-TKI Resistance in Lung Cancer by Activating PI3K-AKT and MAPK-ERK Dual Signaling
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-6-8)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-6-8)
    Abstract: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective in advanced EGFR-mutation non-small cell lung cancer (NSCLC) but the magnitude of tumor regression varies, and drug resistance is unavoidable. The pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) levels are reduced or lost and acts as a tumor suppressor in many cancers. Here, we hypothesized that PHLPP is a key regulator of EGFR-TKI sensitivity and a potential treatment target for overcoming resistance to EGFR-TKI in lung cancer. Methods Cell proliferation and growth inhibition were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assay. PHLPP- knockdown stable cell lines were generated by lentivirus-mediated delivery of PHLPP shRNAs. The expression of PHLPP mRNA and protein levels was detected by real-time quantitative polymerase chain reaction (qPCR) and Western blotting. Immunohistochemical (IHC) staining was performed to detect the PHLPP expression in clinical patient tissue samples. A transcriptomic assay of genome-wide RNA expressions of PHLPP in NSCLC cell lines according to gefitinib sensitivity was obtained from Gene Expression Omnibus (GEO) database. Murine xenograft model was established to verify the function of PHLPP in gefitinib resistance in vivo . Results PHLPP highly expressed in gefitinib-sensitive NSCLC cell lines than gefitinib-resistant NSCLC cell lines. In gefitinib-acquired resistance cell line HCC827-GR, PHLPP expression even dramatically reduced. Knockdown of PHLPP in NSCLC cells decreased cell death induced by the EGFR-TKI, while overexpression PHLPP in gefitinib-resistance NSCLC cells can enhance or restore EGFR-TKIs sensitivity. Mechanism study indicated that PHLPP downregulation attenuates the effect of EGFR-TKI on the both AKT and ERK pathway, thereby decreasing the cell death sensitivity to EGFR inhibitors. In xenograft mice, knockdown of PHLPP decreased tumor response to gefitinib and advanced tumor cells re-growth after gefitinib treatment. In clinical, PHLPP expression were reduced in the post-relapse tumor compared to that of pre-treatment, and lower pre-treatment PHLPP levels were significantly correlated with shorter progression-free survival (PFS) in patients with EGFR-mutant lung adenocarcinoma whom treated with EGFR-TKI. Conclusions Our data strongly demonstrated that loss of PHLPP function was a key factor of EGFR-TKI resistance in NSCLC. Downregulated PHLPP expression activated PI3K-AKT and MAPK-ERK pathway which strengthened cell survival to EGFR-TKI. Therefore, PHLPP expression level was not only a potential biomarker to predict EGFR-TKIs sensitivity but also as a therapeutic target in EGFR-TKIs therapy, enhancing PHLPP expression may be a valuable strategy for delaying or overcoming EGFR-TKIs drug resistance.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2021.665045
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 5
    Online Resource
    Online Resource
    Characterization With KRAS Mutant Is a Critical Determinant in Immunotherapy and Other Multiple Therapies for Non-Small Cell Lung Cancer
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 11 ( 2022-1-5)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2022-1-5)
    Abstract: Non-small cell lung cancer (NSCLC) is a frequent type of cancer, which is mainly characterized clinically by high aggressiveness and high mortality. KRAS oncoprotein is the most common molecular protein detected in NSCLC, accounting for 25% of all oncogenic mutations. Constitutive activation of the KRAS oncoprotein triggers an intracellular cascade in cancer cells, leading to uncontrolled cell proliferation of cancer cells and aberrant cell survival states. The results of multiple clinical trials have shown that different KRAS mutation subtypes exhibit different sensitivities to different chemotherapy regimens. Meanwhile, anti-angiogenic drugs have shown differential efficacy for different subtypes of KRAS mutated lung cancer. It was explored to find if the specificity of the KRAS mutation subtype would affect PD-L1 expression, so immunotherapy would be of potential clinical value for the treatment of some types of KRAS mutations. It was discovered that the specificity of the KRAS mutation affected PD-L1, which opened up immunotherapy as a potential clinical treatment option. After several breakthrough studies, the preliminary test data of many early clinical trials showed that it is possible to directly inhibit KRAS G12C mutation, which has been proved to be a targeted treatment that is suitable for about 10%–12% of patients with advanced NSCLC, having a significant impact on the prolongation of their survival and the improvement of their quality of life. This article reviews the latest progress of treatments for NSCLC with KRAS mutation, in order to gain insight into the biological diversity of lung cancer cells and their potential clinical implications, thereby enabling individualized treatment for patients with KRAS-mutant NSCLC.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2021.780655
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 6
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    Online Resource
    Case Report: Keratoacanthoma and type I diabetes secondary to treatment with PM8001, a bifunctional fusion protein targeting TGF-β and PD-L1
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-8-1)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-8-1)
    Abstract: Immune-related adverse reactions primarily involve the skin and the endocrine, digestive, and respiratory systems. In the endocrine system, these adverse effects mainly include hypophysitis, thyroiditis, hypoadrenalism, and rarely, diabetes mellitus. The most common symptoms in the skin are pruritus, rash, and infrequently, eruptive keratoacanthoma. Here, we report a case of a 67-year-old woman who developed eruptive keratoacanthoma of the skin 6 weeks after beginning treatment with a bispecific antibody (PM8001), targeting both programmed cell death receptor 1 and transforming growth factor β, as well as type I diabetes mellitus–induced ketoacidosis after 13 weeks. The type I diabetes appeared to stabilize after insulin treatment, and the keratoacanthoma gradually resolved after drug discontinuation. This case report describes a case of the effects of PM8001 immunotherapy on the endocrine glands and skin, together with a review of the relevant literature, and summarizes the different clinical characteristics of rare immune-related adverse events resulting from PM8001 immunotherapy to provide a reference for their early detection, diagnosis, and treatment.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2023.1046266
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 7
    Online Resource
    Online Resource
    Comparison of flexible ureteroscopy and mini-percutaneous nephrolithotomy in the treatment for multiple nephrolithiasis
    Frontiers Media SA ; 2022
    In:  Frontiers in Surgery Vol. 9 ( 2022-9-9)
    Details
    In: Frontiers in Surgery, Frontiers Media SA, Vol. 9 ( 2022-9-9)
    Abstract: To compare the outcomes of flexible ureteroscopy and mini-percutaneous nephrolithotomy in the treatment for multiple nephrolithiasis in 1–2 cm size. Methods The clinical data of patients with multiple renal calculi in the range of 1–2 CM who underwent flexible ureteroscopy lithotripsy and percutaneous nephrolithotomy in Qilu Hospital of Shandong University from January 2016 to March 2021 were retrospectively collected and matched using propensity score matching. Then a subgrouping of the number of stones was performed. Patients were divided into Group A and Group B according to their stone numbers. Patients with no statistically significant differences in baseline data were matched to compare the safety and efficacy of the two procedures. Results A total of 210 patients with clinical data were collected, and the patients’ baseline data were not comparable, and 142 patients were finally included in the study after propensity score matching. There was no statistical difference in baseline data between the two groups of patients. The postoperative hospital days (3.00, 2.00 vs. 7.00, 3.00, P   & lt; 0.001), operation time (90.00, 50.00 vs. 110.00, 53.00, P  = 0.018), complications (6, 6.8% vs. 14, 25.9%, P  = 0.001) of patients in flexible ureteroscopy group %, P  = 0.001) was significantly lower than that in the percutaneous nephrolithotomy group. There was no significant difference in stone clearance rate between the two groups (76, 86.4% vs. 42, 77.8%, P  = 0.185). When the number of stones was no more than 3, the operation time (85.00, 49.00 vs. 110.00, 53.00, P  = 0.005) and complications (2, 4.2% vs. 11, 29.7%, P  = 0.001) of f -URS were significantly less than those of mPCNL, but when the number of stones was more than 3, there was no significant difference between the two operations. Conclusion For multiple nephrolithiasis within 1–2 CM, when the number of stones does not exceed 3, flexible ureteroscopy can achieve the same stone clearance rate as percutaneous nephrolithotomy, while having shorter post-operation days, operative time and fewer complications. When the number of stones is more than 3, there are no significant difference between two operations.
    Type of Medium: Online Resource
    ISSN: 2296-875X
    URL: Article
    DOI: 10.3389/fsurg.2022.1004432
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2773823-1
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