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  • Sheng, Xinan  (28)
  • Si, Lu  (28)
  • 2020-2024  (28)
  • 1
    In: Theranostics, Ivyspring International Publisher, Vol. 12, No. 7 ( 2022), p. 3578-3579
    Type of Medium: Online Resource
    ISSN: 1838-7640
    Language: English
    Publisher: Ivyspring International Publisher
    Publication Date: 2022
    detail.hit.zdb_id: 2592097-2
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  • 2
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 11, No. 1 ( 2023-01), p. e005937-
    Abstract: Accumulating data suggest that mucosal melanoma, well known for its poor response to immune checkpoint blockade (ICB) and abysmal prognosis, is a heterogeneous subtype of melanoma with distinct genomic and clinical characteristics between different anatomic locations of the primary lesions. Primary malignant melanoma of the esophagus (PMME) is a rare, highly aggressive disease with a poorer prognosis compared with that of non-esophageal mucosal melanoma (NEMM). In this study, we retrospectively analyzed the efficacy of anti-programmed death (PD)-1 in patients with PMME and explored its molecular basis. Methods The response and survival of patients with PMME and NEMM under anti-PD-1 monotherapy were retrospectively analyzed. To explore the molecular mechanisms of the difference in therapeutic efficacy between PMME and NEMM, we performed genomic analysis, bulk RNA sequencing, and multiplex immunohistochemistry staining. Results We found that PMME (n=28) responded better to anti-PD-1 treatment than NEMM (n=64), with a significantly higher objective response rate (33.3% (95% CI 14.3% to 52.3%) vs 6.6% (95% CI 0.2% to 12.9%)) and disease control rate (74.1% (95% CI 56.4% to 91.7%) vs 37.7% (95% CI 25.2% to 50.2%)). Genomic sequencing analysis revealed that the genomic aberration landscape of PMME predominated in classical cancer driver genes, with approximately half of PMME cases harboring mutations in BRAF , N/KRAS , and NF1 . In contrast, most NEMM cases were triple wild-type. Transcriptome analysis revealed that, compared with NEMM, PMME displayed more significant proliferation and inflammatory features with higher expression of genes related to antigen presentation and differentiation, and a less immunosuppressive signature with lower expression of inhibitory immune checkpoints and dedifferentiation-related genes. The multiplex immunohistochemical analysis also demonstrated higher CD8 + T-cell infiltration in PMME than in NEMM. Conclusions PMME is an outlier of mucosal melanoma showing a malicious phenotype but a particularly high response rate to ICB because of its distinct molecular characteristics. Patient stratification based on anatomic origin can facilitate clinical decision-making in patients with mucosal melanoma following the verification of our results in future prospective studies.
    Type of Medium: Online Resource
    ISSN: 2051-1426
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2719863-7
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  • 3
    In: Translational Oncology, Elsevier BV, Vol. 14, No. 1 ( 2021-01), p. 100949-
    Type of Medium: Online Resource
    ISSN: 1936-5233
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2443840-6
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  • 4
    In: npj Genomic Medicine, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2021-02-04)
    Abstract: Immune checkpoint inhibitor (ICI) treatments produce clinical benefit in many patients. However, better pretreatment predictive biomarkers for ICI are still needed to help match individual patients to the treatment most likely to be of benefit. Existing gene expression profiling (GEP)-based biomarkers for ICI are primarily focused on measuring a T cell-inflamed tumor microenvironment that contributes positively to the response to ICI. Here, we identified an immunosuppression signature (IMS) through analyzing RNA sequencing data from a combined discovery cohort ( n  = 120) consisting of three publicly available melanoma datasets. Using the ratio of an established IFN- γ signature and IMS led to consistently better prediction of the ICI therapy outcome compared to a collection of nine published GEP signatures from the literature on a newly generated internal validation cohort ( n  = 55) and three published datasets of metastatic melanoma treated with anti-PD-1 ( n  = 54) and anti-CTLA-4 ( n  = 42), as well as in patients with gastric cancer treated with anti-PD - 1 ( n  = 45), demonstrating the potential utility of IMS as a predictive biomarker that complements existing GEP signatures for immunotherapy.
    Type of Medium: Online Resource
    ISSN: 2056-7944
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2813848-X
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  • 5
    In: Urologic Oncology: Seminars and Original Investigations, Elsevier BV, Vol. 40, No. 8 ( 2022-08), p. 385.e1-385.e8
    Type of Medium: Online Resource
    ISSN: 1078-1439
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2011021-2
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  • 6
    Online Resource
    Online Resource
    Elsevier BV ; 2022
    In:  Journal of Investigative Dermatology Vol. 142, No. 4 ( 2022-04), p. 1158-1170.e8
    In: Journal of Investigative Dermatology, Elsevier BV, Vol. 142, No. 4 ( 2022-04), p. 1158-1170.e8
    Type of Medium: Online Resource
    ISSN: 0022-202X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2006902-9
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e21588-e21588
    Abstract: e21588 Background: Primary mucosal melanoma arising in the urinary tract is rare and poorly characterized. Methods: The records of patients with urological mucosal melanoma who presented to the department of Renal Cancer and Melanoma of Peking University Cancer Hospital between September, 2004 and April, 2019 were reviewed. Available clinicopathological and molecular characteristics were summarized, including pathological parameters, gene mutation, primary surgical intervention, systemic treatment and clinical course. The rates of local recurrence rate, loco-regional lymph node metastasis and distant metastasis were assessed. American Joint Committee on Cancer (AJCC) TNM Staging System for bladder cancer/renal pelvis and ureter cancer/urethral carcinoma (8th ed., 2017) were adopted for staging. Results: Fifty-eight patients were involved in the study with a median age of 62.5 years (range: 32-82). The anatomic sites of the primary urological mucosal melanomas were from the urethra (89.7%), bladder (6.9%), ureter (0%) and kidney (0%), and the left (4.4%) were from multiple loci. At initial diagnosis, 75.9% (n=44) were stage I/II disease, 1.7% (n=1) stage III, and 22.4% (n=13) stage IV. There was 3.4% incidence of CKIT mutation and 1.7% of BRAF mutation. After median follow-up of 22.6 mo, 31.4% (16/51) relapsed locally after organ-preserved surgery. 21.6% (11/51) and 39.2% (20/51) developed metastases to reginal lymph nodes and distance, respectively. The median relapse free survival and median overall survival were 12.2 (95%CI: 7.9-16.4) mo and 33.9 (95%CI: 19.2-48.6) mo, respectively. Univariate Cox analysis showed that TNM stage and systemic adjuvant therapy were the prognostic factors of OS, while no association was found with Breslow thickness, miotic rate, ulceration and gender. Conclusions: Urological mucosal melanoma predominantly arises from lower urinary tract with rare BRAF and CKIT mutation. AJCC TNM Staging System for urothelial carcinoma is proved practical for urothelial melanoma, which should be validated in larger population. Future research is required to identify adjuvant treatment approaches to improve disease outcomes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-02-06)
    Abstract: Pucotenlimab is a novel recombinant humanized anti-PD-1 (Programmed death-1) monoclonal antibody, which belongs to the human IgG4/kappa subtype, and can selectively block the binding of PD-1 with its ligands PD-L1 and PD-L2. Methods In this phase 2 trial, patients with locally advanced or metastatic melanoma who had failed conventional treatment (chemotherapy, targeted therapy, interferon, IL-2, et al.) were recruited. The patients were administrated with Pucotenlimab of 3 mg/kg every 3 weeks until disease progression, intolerable toxicity, or treatment discontinuation for any other reasons. The primary endpoint was the overall response rate (ORR). The secondary endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and toxicity. Results One-hundred and nineteen patients were enrolled and followed up for 19.32 (ranging from 15.901 to 24.608) months by the cutoff date of July 30 th , 2021. The ORR was 20.17% (24/119, 95% CI, 13.370%-28.506%) based on both independent review committee (IRC) and the investigator’s assessment per RECIST v1.1. The median PFS were 2.89 (95% CI, 2.037–4.074) months and 2.46 (95% CI, 2.004–4.008) months based on IRC and investigator’s assessment, respectively, per RECIST v1.1. The median OS was 16.59 (95% CI, 13.963–26.973) months. Treatment-related adverse events (TRAEs) occurred in 77.3% (92/119) of the patients. The incidence of Grade ≥ 3 TRAEs was 15.1% (18/119). In addition, none of the patients died because of TRAEs. As for biomarker analysis, Eotaxin (CCL11) and MCP-1 (CCL2) were related to treatment response, while TNF-α and VEGF were related to treatment failure. Conclusions Pucotenlimab as a ≥ 2 nd line therapy showed promising efficacy and tolerable toxicity for patients with locally advanced or metastatic melanoma. Trial registration Clinicaltrials.gov Identifier: NCT04749485 (registered retrospectively on 11/02/2021).
    Type of Medium: Online Resource
    ISSN: 1471-2407
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2041352-X
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 4566-4566
    Abstract: 4566 Background: Disitamab vedotin has shown promising data across a spectrum of HER2 expression in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who progressed on chemotherapy. This study was conducted to evaluate the safety and efficacy of disitamab vedotin plus anti-PD-1 antibody in advanced urothelial carcinoma. Methods: This is an open-label, multicenter, phase 1b/2 trial to evaluate the safety and activity of RC48-ADC combined with toripalimab, a humanized immunoglobin G 4 monoclonal antibody against PD-1 in mUC. Patients received RC48-ADC at 1.5 or 2 mg/kg, in combination with 3mg/kg toripalimab every two weeks in a dose-escalation and expansion cohort until confirmed disease progression assessed by the investigators, unacceptable toxicity, or voluntary withdrawal. The primary endpoint was safety; secondary endpoints included efficacy and tumor tissue biomarkers. Results: Forty-one la/mUC patients were enrolled (22 males; median age 66 y [42-76]; 61% treatment-naïve). 54% of patients had visceral metastases (mets), including 24% with liver mets. The primary site was in upper tract UC in 54%. HER2 expression IHC 2+ or 3+ was in 59% patients, and PD-L1 positive in 32%. No dose-limiting toxicity was observed and the recommended dose was RC48-ADC 2mg/kg plus toripalimab 3mg/kg every two weeks. By the cutoff date of 18 November 2022, the confirmed ORR was 73.2% (95%CI: 57.1, 85.8), including 9.8% CR. The ORR was 76.0% for treatment-naïve patients. In HER2 IHC 3+/2+, IHC 1+, and IHC 0 subgroups, the ORR was 83.3%, 64.3%, and 33.3%, respectively. The ORR was 61.5% and 78.6% in PD-L1 positive and negative subgroups. DCR was 90.2% (95% CI, 76.9–97.3), with a median progression-free survival (PFS) of 9.2 months (95%CI: 5.7-10.3) and 2-year overall survival (OS) rate of 63.2%. All patients experienced treatment-related adverse events (TRAEs). The most common TRAEs were AST/ALT increase (68.3%), peripheral sensory neuropathy (61.0%), asthenia (61.0%), γ-glutamyl transferase increase (56.1%), hypertriglyceridemia (53.7%), and appetite decrease (51.2%). Grade 3 or greater TRAEs occurred in 43.9% of patients. Twenty-three patients (56.1%) had immune-related AEs (14.6% ≥ G3), including immune-related skin reactions, hyperglycemia, pneumonitis, hepatitis, and myositis. Conclusions: RC48-ADC in combination with toripalimab demonstrated promising efficacy in patients with la/mUC and a manageable safety profile. A phase 3 study is currently ongoing to compare the safety and efficacy of this regimen with standard of care. Clinical trial information: NCT04264936 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-5-20)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-5-20)
    Abstract: Background: The best response and survival outcomes between advanced melanoma patients treated with the anti-PD-1 monotherapy vary greatly, rendering a risk model in need to optimally stratify patients based on their likelihood to benefit from the said treatment. Methods: We performed an ad hoc analysis of 89 advanced melanoma patients treated with the anti-PD-1 monotherapy from two prospective clinical trials at the Peking University Cancer Hospital from April 2016 to May 2018. Clinicodemographical characteristics, baseline and early-on-treatment (median 0.6 months after anti-PD-1 monotherapy initiation) routine laboratory variables, including complete blood count and general chemistry, and best response/survival data were extracted and analyzed in both univariate and multivariate logistic and Cox proportional hazard models. Results: After three rounds of screening, risk factors associated with a poorer PFS included a high pre-treatment neutrophil, derived neutrophil-lymphocyte ratio (dNLR), low pre-treatment hemoglobin, and low early-on-/pre-treatment fold change of eosinophil; those with a poorer OS included a high pre-treatment neutrophil, eosinophil, PLT, early-on/pre-treatment fold change of LDH and neutrophil; and those with a poorer best response included a high pre-treatment NLR and early-on-/pre-treatment LDH fold change. Risk models (scale: low, median-low, median high, and high risk) were established based on these risk factors as dichotomous variables and M stage (with vs. without distant metastasis) for PFS (HR 1.976, 95% CI, 1.507–2.592, P & lt; 0.001), OS (HR 2.348, 95% CI, 1.688–3.266), and non-responder (OR 3.586, 95% CI, 1.668–7.713, P = 0.001), respectively. For patients with low, median-low, median-high, and high risks of developing disease progression (PD), six-month PFS rates were 64.3% (95% CI, 43.5–95.0%), 37.5% (95% CI, 22.4–62.9%), 9.1% (95% CI, 3.1–26.7%), and 0%, respectively. For patients with OS risks of low, median-low, median-high, and high, OS rates at 12 months were 82.5% (95% CI, 63.1–100%), 76.6% (95% CI, 58.4–100%), 42.1% (95% CI, 26.3–67.3%), and 23.9% (95% CI, 11.1–51.3%), respectively. For patients with risks of low, median-low, median-high, and high of being a non-responder, objective response rates were 50.0% (95% CI, 15.7–84.3%), 27.8% (95% CI, 9.7–53.5%), 10.3% (95% CI, 2.9–24.2%), and 0%, respectively. Conclusion: A risk scoring model based on the clinicodemographical characteristics and easily obtainable routinely tested laboratory biomarkers may facilitate the best response and survival outcome prediction and personalized therapeutic decision making for the anti-PD-1 monotherapy treated advanced melanoma patients in Asia.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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