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  • 1
    In: Journal of Oncology, Hindawi Limited, Vol. 2022 ( 2022-1-27), p. 1-11
    Abstract: Background. The morbidity and mortality of gastric cancer are high in China. There are challenges to develop precise and individualized drug regimens for patients with gastric cancer after a standard treatment. Choosing the most appropriate anticancer drug after a patient developing drug resistance is very important to improve the patient’s prognosis. MiniPDX has been widely used as a new and reliable preclinical research model to predict the sensitivity of anticancer drugs. Methods. The OncoVee® MiniPDX system developed by Shanghai LIDE Biotech Co., Ltd. was used to establish the MiniPDX models using specimens of patients with gastric cancer. The cancer tissues were biopsied under endoscopy, and then, the tumor cell suspension was prepared for a drug sensitivity test by subcutaneously implanting into Balb/c-nude mice. The selected optimal regimen obtained from the MiniPDX assay was used to treat patients with drug-resistant gastric cancer. Results. We successfully established an individualized and sensitive drug screening system for four patients from January 2021 to July 2021. MiniPDX models identified potentially effective drugs for these four patients, with partial remission in two of the patients after treatment and disease progression in the remaining of two patients. Severe side effects from chemotherapy or targeted therapy were not observed in all patients. Conclusion. Establishing a personalized drug screening system for patients with drug-resistant gastric cancer can guide the selection of clinical drugs, improve the clinical benefit of patients, and avoid ineffective treatments. It can be an effective supplement for treatment options.
    Type of Medium: Online Resource
    ISSN: 1687-8469 , 1687-8450
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2461349-6
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  • 2
    In: OncoTargets and Therapy, Informa UK Limited, Vol. Volume 13 ( 2020-10), p. 10567-10580
    Type of Medium: Online Resource
    ISSN: 1178-6930
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2495130-4
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 11 ( 2022-1-13)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2022-1-13)
    Abstract: Desmoid tumor is a rare disease, which is histologically characterized by local invasion, monoclonality, and fibroblast proliferation; and clinically characterized by a variable and often unpredictable course. The treatment of desmoid tumor is mainly surgical resection, but the recurrence rate is high. In recent years, a variety of treatment methods, including endocrine therapy, surgery, radiotherapy, chemotherapy, non-steroidal anti-inflammatory drugs, targeted drugs, interferon and more, have been used and achieved certain curative effects. In addition, in view of the inertia characteristics of desmoid tumor, observation is also a first-line scheme recommended by multiple guidelines. In the past, the research progress of targeted therapy for desmoid tumor is relatively slow and the curative effect is limited. Thus, targeted therapy is usually used as a remedial treatment after the failure of other conventional treatment methods. However, in recent years, with the rapid progress in the basic research of targeted therapy, some new targeted drugs are increasingly used for the clinical treatment of desmoid tumor and have achieved good results. Herein, we described a patient with aggressive fibromatosis in the abdominal cavity. Following a combined treatment using anlotinib and celecoxib, the patient achieved a partial response with mild toxicity. Simultaneously, the patient’s pain symptoms completely disappeared. This case indicates that the combination of anlotinib and NSAIDs could be an effective treatment for desmoid tumor.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e16016-e16016
    Abstract: e16016 Background: Advanced gastric cancer has poor prognosis and short survival period. Anti-PD-1 antibodies have shown some efficacy in second-line treatment of advanced or metastatic GC/GEJ cancer, but were not superior to monotherapy. The combination of chemotherapy and anti-PD-1 antibody has been proved to have synergistic effect. Nab-paclitaxel is one of the most commonly used second-line regimens in China. Therefore,we aimed to evaluate the efficacy and safety of sintilimab combined with Nab-paclitaxel in the treatment of advanced GC/GEJ cancer patients. Methods: We retrospectively analyzed patients with advanced GC/GEJ cancer that progressed after first line systemic therapies and treated with sintilimab combined with Nab-paclitaxel from April 1, 2019 to December 31, 2021. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), and safety. Results: Thirty-nine patients were enrolled and eligible for response assessment. Complete response (CR) was not observed, 15 patients achieved partial response (PR), 16 patients had stable disease (SD) and 9 patients had progression disease (PD). The ORR and DCR were 15 (38.5%) and 31 (79.5%), respectively. Median PFS was 5.4 months (95%CI: 3.072-7.728). We further analyzed PFS between different subgroups of chemoimmunotherapy regimens in order to find which patients could benefit more. Firstly, The PFS of HER2 positive and HER2 negative patients was 7.1months (95%CI:3.367-10.833) and 5.3 months (95%CI:4.018-6.582), respectively (p = 0.947). The median PFS of PD-L1 positive, PD-L1 negative and PD-L1 unknown patients was 5.3months (95%CI:3.744-6.856), 8.1months(95%CI:3.371-12.829) and 6.1 months(95%CI:2.649-9.551)(p = 0.918). Finally, we analyzed the effect of chemoimmunotherapy cycles on PFS. The results showed that PFS of 〉 4 cycles was numerically longer than that of ≤ 4 cycles, and PFS were 7.1 months (95%CI:4.378-9.822) and 5.2months (95%CI:3.091-7.309)(p = 0.424), respectively. Most of the adverse events (AEs) were grade 1-2.The most common treatment-related adverse events (TRAEs) of grade 3-4 were anemia 5(12.8%), neutropenia 5(12.8%), leukopenia 4(10.3%). The potential immune-related adverse events (irAEs) were grade 1 pneumonia 1(2.6%). Only one patient developed grade 4 hepatitis (2.6%). Conclusions: These results indicated that sintilimab combined with Nab-paclitaxel exhibited good anti-tumor activity and acceptable safety profile as second-line treatment for advanced or metastatic gastric cancer. These results warrant further accrual and evaluation and explore which patients can benefit more from the combined treatment strategy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2021
    In:  Cell Death & Disease Vol. 12, No. 4 ( 2021-04-01)
    In: Cell Death & Disease, Springer Science and Business Media LLC, Vol. 12, No. 4 ( 2021-04-01)
    Abstract: Utidelone (UTD1), a novel microtubule stabilizing agent, is an epothilone B analogue which was produced by genetic engineering. UTD1 has exhibited broad antitumor activity in multiple solid tumors. However, its activity and mechanism in colorectal cancer (CRC) remain to be studied. In this study, UTD1 dramatically inhibited CRC cell proliferation (with 0.38 µg/ml, 0.77 µg/ml IC50 in RKO and HCT116, respectively) in vitro. Immunofluorescence staining showed that UTD1 induced the formation of microtubule bundling and asters in RKO cells. Flow cytometry analysis demonstrated that UTD1 induced cell cycle to arrest in G2/M phase, subsequent apoptosis. Significantly, UTD1 exhibited stronger effect on inducing apoptosis than paclitaxel and 5-FU, especially in HCT15 cells which is ABCB1 high-expression. UTD1 exposure cleaved caspase-3 and poly ADP-ribose polymerase (PARP), decreased mitochondrial membrane potential, released cytochrome c, increased the production of active oxygen and activated c-Jun N-terminal kinase (JNK), suggesting ROS/JNK pathway was involved in this process. Moreover, UTD1 inhibited tumor growth and was more effective and safer compared with paclitaxel and 5-FU in RKO xenograft in nude mice. Taken together, our findings first indicate that UDT1 inhibits tumor growth in CRC xenograft model and may be a promising agent for CRC treatment.
    Type of Medium: Online Resource
    ISSN: 2041-4889
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2541626-1
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  • 6
    In: Journal of Oncology, Hindawi Limited, Vol. 2022 ( 2022-3-25), p. 1-8
    Abstract: Background. Human epidermal growth factor receptor 2 (HER2) is a member of the large ErbB family and an important oncogene in many solid tumors. Pyrotinib has been approved for the treatment of HER2-positive, recurrent, or metastatic breast cancer. However, there are very few clinical studies on pyrotinib in other HER2-positive solid tumors. Therefore, more evidence of clinical research is impendently needed to shepherd pyrotinib-based therapy in HER2-positive nonbreast advanced solid tumors. Patients and Methods. We performed a retrospective analysis of HER2-positive nonbreast advanced solid tumors patients with HER2 amplification or mutations who were administered with pyrotinib-based therapy in Henan Cancer Hospital between July 1, 2019, and December 2, 2021. In our research, 25 eligible patients were included with 16 patients with lung cancer, 6 patients with gastric cancer, 2 patients with colorectal cancer, and 1 patient with cholangiocarcinoma. Progression-free survival (PFS) is our main research end point. Results. The median PFS was 188 days (95% CI: 83–not reached (NR)), and overall survival (OS) was 250 days (95% CI: 188–NR), respectively. 16 patients with lung cancer had a median PFS of 204 days (95% CI: 55–NR) and 6 patients with gastric cancer had PFS of 142 days (95% CI: 83–NR), respectively. The median OS was 366 days (95% CI: 248–NR) in patients with lung cancer and 179 days (95% CI: 90–NR) in patients with gastric cancer. The median PFS and OS of patients receiving 〉 3 line treatment were lower than those receiving ≤3 line treatment (PFS: 188 days vs 204 days, p = 0.92 ; OS: 188 days vs 366 days, p = 0.43 ). All 25 patients can be evaluated. The objective response rate (ORR) was 24%, and the disease control rate (DCR) was 68%. Lung cancer ORR was 25%, and gastric cancer ORR was 16.7%. In addition, the DCR of lung cancer was 62.5% and that of gastric cancer was 66.7%. In addition, the ORR and DCR of patients receiving treatment ≤3 lines were higher than those receiving treatment 〉 3 lines (ORR: 35.7% vs 9.1%, p = 0.18 ; DCR: 71.4% vs 63.6%, p 〉 0.99 ). The most common treatment-related adverse events (TRAEs) were diarrhea (84%), but only 3 patients (12%) reported grade 3 diarrhea with good control. Conclusion. These results show that in HER2-positive nonbreast advanced solid tumors, the treatment based on pyrotinib regimen has good antitumor activity and acceptable safety. This retrospective study aims to promote larger clinical studies to further clarify the efficacy and safety of pyrotinib in the treatment of nonbreast solid tumors.
    Type of Medium: Online Resource
    ISSN: 1687-8469 , 1687-8450
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2461349-6
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  • 7
    Online Resource
    Online Resource
    Elsevier BV ; 2022
    In:  Drug Discovery Today Vol. 27, No. 11 ( 2022-11), p. 103343-
    In: Drug Discovery Today, Elsevier BV, Vol. 27, No. 11 ( 2022-11), p. 103343-
    Type of Medium: Online Resource
    ISSN: 1359-6446
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 1500337-1
    SSG: 15,3
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e15064-e15064
    Abstract: e15064 Background: Human epidermal growth factor receptor 2 (HER2) is a member of the ErbB family and a key oncogene in solid tumors. Pyrotinib has been approved for the treatment of HER2-positive, recurrent or metastatic breast cancer. However, there are very few clinical studies on pyrotinib in other HER2-positive solid tumors. Therefore, more clinical evidence is urgently needed to guide pyrotinib-based therapy in HER2-positive non-breast advanced solid tumors. Methods: We retrospectively analyzed HER2-positive non-breast advanced solid tumors patients with HER2 amplification or mutations who were treated with pyrotinib-based therapy in Henan Cancer Hospital between July 1, 2019 and December 2, 2021. In this study, 25 eligible patients were included with 16 patients with lung cancer, 6 with gastric cancer, 2 with colorectal cancer and 1 with cholangiocarcinoma. The primary end point was progression-free survival (PFS). Results: The median PFS and overall survival (OS) were 188 days (95% CI: 83–NA days) and 250 days (95% CI: 188–NA days), respectively. 16 patients with lung cancer and 6 patients with gastric cancer had a median PFS of 204 days (95% CI: 55–NA days) and 142 days (95% CI: 83–NA days), respectively. The median OS was 366 days (95% CI: 248–NA days) in patients with lung cancer and 179 days (95% CI: 90–NA days) in patients with gastric cancer. Patients receiving 〉 3 lines of therapies had a numerically lower median PFS and OS than those receiving≤ 3 lines of treatments (PFS:188 vs 204 days, p=0.92; OS:188 vs 366 days, P = 0.43). All 25 patients were available for efficacy evaluation. The objective response rate (ORR) was 24% and disease control rate (DCR) was 68%. The ORR for lung cancer was 25% and for gastric cancer was 16.7%. In addition, the DCR for lung cancer was 62.5% and for gastric cancer was 66.7%. Moreover, patients receiving≤3 lines of treatments had a numerically higher ORR and DCR than those receiving 〉 3 lines of treatment (ORR:35.7% vs 9.1%,p=0.18; DCR:71.4% vs 63.6%, P>0.99). The most common treatment-related adverse events (TRAEs) were diarrhea (84%), but only 3 (12%) patients reported grade 3 diarrhea which could be well controlled. Conclusions: These results indicated that pyrotinib-based therapy exhibited good anti-tumor activity and acceptable safety profile in HER2-positive non-breast advanced solid tumors. This retrospective study is a pilot study aimed at promoting larger-scale studies to further clarify the safety and efficacy of pyrotinib in the treatment of non-breast solid tumors. Keywords: pyrotinib, HER2-positive, solid tumor, retrospective study, advanced solid tumors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-6-18)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-6-18)
    Abstract: The prognosis of patients with advanced urothelial carcinoma is dismal. Platinum-based chemotherapy is still the main first-line treatment for advanced urothelial carcinoma, while immunotherapy can be used as a first-line treatment option for people who cannot tolerate platinum. Immunotherapy is preferred in the second-line treatment of bladder urothelial carcinoma. PD-1 inhibitors (Pembrolizumab, nivolumab and atezolizumab) and PD-L1 inhibitors (Ddurvalumab and avelumab) have not been approved for the treatment of advanced urothelial cancer in China. We describe a patient with advanced urothelial carcinoma experienced disease progression after gemcitabine chemotherapy. Following a treatment of domestic PD-1 inhibitor (sintilimab), the patient achieved a durable complete response with mild toxicity. This case indicates that PD-1 inhibitor sintilimab might be a second-line treatment choice for advanced urothelial carcinoma.
    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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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-3-15)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-3-15)
    Abstract: Cancer-associated fibroblasts (CAFs) has been recognized as one cause of tumor resistance to immune checkpoint blockade therapy, but the underlying mechanisms still remain elusive. In the present study, a bone marrow-derived CAF (BMF) -rich tumor model is successfully established by subcutaneously mixed inoculation of BMFs and tumor cells into mice and the BMF-mixed tumor xenografts are demonstrated to be resistant to anti-PD-L1 antibody immunotherapy compared to the mere tumor xenografts. In vitro assays via the co-culture system of BMFs and tumor cells indicate that the co-cultured BMFs are induced to overexpress PD-L1, while there is no such a phenomenon in the co-cultured cancer cells. The further knock-out of PD-L1 in BMFs rescues the sensitivity of BMF-mixed tumor xenografts to PD-L1 blockade therapy. Mechanistically, via the microarray assay, we identify that the upregulation of PD-L1 in BMFs stimulated by cancer cells is medicated by the activation of the Wnt/β-catenin signaling pathway in BMFs. Moreover, the administration of Wnt/β-catenin signaling inhibitors, including XAV-939 and Wnt-C59, distinctly inhibits the upregulation of PD-L1 expression in the co-cultured BMFs. The further combination administration of XAV-939 significantly potentiates the therapeutic outcome of PD-L1 blockade therapy in BMF-mixed tumors. In summary, our study demonstrates that Wnt inhibition augments PD-L1 blockade efficacy by overcoming BMF-mediated immunotherapy resistance.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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