inhibitor treatment
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2022 ◽  
Author(s):  
Rizka Tamania Saptari ◽  
Rizkita Rachmi Esyanti ◽  
Riza Arief Putranto

Abstract Stevia (Stevia rebaudiana Bertoni) contains sweet compound widely used as natural sweetener, steviol glycoside (SG). SG is a diterpenoid secondary metabolite synthesized from ent-kaurenoic acid, the same precursor of Gibberellin (GA). Therefore, in this study, a GA inhibitor, Daminozide (0, 10, 20 ppm) was used to block ent-kaurenoic acid conversion towards GA synthesis in attempt to increase SG content of stevia propagated in Temporary Immersion Bioreactor (TIB). Daminozide in 10 mg/L was observed to be the optimum concentration which increased biomass weight and SG content (stevioside and rebaudioside A) up to 40%. The treatment also increased transcripts accumulation of genes enrolled in SG biosynthesis, such as SrKA13H, SrUGT85C2, and SrUGT76G1, indicating SG pathway become more active due to the inhibition of GA pathway. Furthermore, the inhibition of GA was also indicated by the upregulated expression of GA biosynthesis gene (GA3ox) as the result of feedback regulation, and the downregulated expression of GA catabolism gene (GA2ox2) as the result of feed-forward regulation caused by inhibitor treatment.


2022 ◽  
Vol 29 (1) ◽  
pp. 267-282
Author(s):  
Yi-Xiu Long ◽  
Yue Sun ◽  
Rui-Zhi Liu ◽  
Ming-Yi Zhang ◽  
Jing Zhao ◽  
...  

Purpose: Immune-related pneumonitis (IRP) has attracted extensive attention, owing to its increased mortality rate. Conventional chemotherapy (C) has been considered as an immunosuppressive agent and may thus reduce IRP’s risk when used in combination with PD-1/L1 inhibitors. This study aimed to assess the risk of IRP with PD-1/L1 inhibitors plus chemotherapy (I+C) versus PD-1/L1 inhibitors alone (I) in solid cancer treatment. Method: Multiple databases were searched for RCTs before January 2021. This NMA was performed among I+C, I, and C to investigate IRP’s risk. Subgroup analysis was carried out on the basis of different PD-1/L1 inhibitors and cancer types. Results: Thirty-one RCTs (19,624 patients) were included. The I+C group exhibited a lower risk of IRP in any grade (RR, 0.60; 95% CI, 0.38–0.95) and in grade 3–5 (RR, 0.42; 95% CI, 0.21–0.92) as opposed to the I group. The risk of any grade IRP with PD-1 plus chemotherapy was lower than that with PD-1 monotherapy (RR, 0.50; 95% CI, 0.28–0.89), although grade 3–5 IRP was similar. There was no statistically meaningful difference in the risk of any grade IRP between PD-L1 plus chemotherapy and PD-L1 inhibitors monotherapy (RR, 0.95; 95% CI, 0.43–2.09) or grade 3–5 IRP (RR, 0.71;95% CI, 0.24–2.07). In addition, compared with the I group, the I+C group was correlated with a decreased risk in IRP regardless of cancer type, while a substantial difference was only observed in NSCLC patients for grade 3–5 IRP (RR, 0.39; 95% CI, 0.15–0.98). Conclusion: In comparison to PD-1/L1 inhibitor treatment alone, combining chemotherapy with PD-1/L1 inhibitors might reduce the risk of IRP in the general population. Furthermore, PD-1 inhibitors in combination with chemotherapy were correlated with a decreased risk of IRP compared to PD-1 inhibitor treatment alone. In contrast to the I group, the I+C group exhibited a lower risk of IRP, especially for NSCLC patients.


2022 ◽  
Vol 12 ◽  
Author(s):  
Atsuro Murai ◽  
Kaoru Tada ◽  
Tadahiro Nakajima ◽  
Mika Akahane ◽  
Masashi Matsuta ◽  
...  

Patients with bone metastases are treated with long-term bone resorption inhibitors such as bisphosphonates and denosumab. However, resorption inhibitors have been known to cause fractures, such as atypical femoral fractures (AFFs). In recent years, there have been an increasing number of reports of atypical ulna fractures (AUFs) caused by bone resorption inhibitor usage. Treatment of AUFs is complicated, especially when they occur in patients with bone metastases, because it is difficult to discontinue bone resorption inhibitor treatment without the risk of aggravating metastatic lesions. Prophylactic surgery is recommended in AFFs when fractures are predicted, but there are few reports of prophylactic surgery for AUFs. Here, we report a case of incomplete AUF in a 74-year-old woman which was surgically treated with prophylactic plate fixation. The patient had been using denosumab for 6 years to treat bone metastases due to thyroid cancer. After surgery, no fractures were observed for 2 years without discontinuing denosumab, and her forearm function was adequate. AUFs are rare and difficult to treat, so oncologists who treat bone metastases need to pay special attention to diagnose this incomplete AUF before the fracture worsens. We believe that detection of a possible fracture and prophylactic surgery can improve prognosis.


BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Xi Chen ◽  
Haiying Kong ◽  
Linxiang Luo ◽  
Shuiyun Han ◽  
Tao Lei ◽  
...  

Abstract Purpose We sought to understand the clinical course and molecular phenotype of patients who showed disease progression after programmed cell death ligand 1 (PD-L1) inhibitor treatment but subsequently responded to PD-1 inhibitor treatment. We also explored the response to PD-1-axis targeted therapy of classical Hodgkin lymphoma (cHL) according to genetically driven PD-L1 and programmed cell death ligand 2 (PD-L2) expression. Methods Five patients in a phase II clinical trial of CS1001 (PD-L1 inhibitor) for relapsed or refractory (R/R) cHL were retrospectively reviewed. Formalin-fixed, paraffin-embedded whole tissues from the five patients were evaluated for 9p24.1 genetic alterations based on FISH and the expression of PD-L1, PD-L2, PD-1, major histocompatibility complex (MHC) class I–II, and the tumor microenvironment factorsCD163 and FOXP3 in the microenvironmental niche, as revealed by multiplex immunofluorescence. Results All five patients showed primary refractory disease during first-line treatment. Four patients received PD-1 inhibitor after dropping out of the clinical trial, and all demonstrated at least a partial response. The progression-free survival ranged from 7 to 28 months (median = 18 months), and 9p24.1 amplification was observed in all five patients at the PD-L1/PD-L2 locus. PD-L1 and PD-L2 were colocalized on Hodgkin Reed-Sternberg (HRS) cells in four of the five (80%) patients. There was differential expression of PD-L1 and PD-L2 in cells in the tumor microenvironment in cHL, especially in HRS cells, background cells and tumor-associated macrophages. Conclusions PD-L1 monotherapy may not be sufficient to block the PD-1 pathway; PD-L2 was expressed in HRS and background cells in cHL. The immunologic function of the PD-L2 pathway in anti-tumor activity may be underestimated in R/R cHL. Further study is needed to elucidate the anti-tumor mechanism of PD-1 inhibitor and PD-L1 inhibitor treatment.


Author(s):  
Akiyoshi Senda ◽  
Takaya Komori ◽  
Yoshihiro Ishida ◽  
Teruasa Murata ◽  
Atsushi Otsuka ◽  
...  

Though a variety of immune-related adverse events of immune checkpoint inhibitors (ICIs) including bullous pemphigoid have been reported, non-bullous pemphigoid (NBP) associated with ICI therapy was scarcely reported. We present a case of NBP with a long latent disease course without diagnosis during nivolumab, an ICI therapy.


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