Background
The role of carbohydrate antigen 19‐9 (CA 19‐9) in response assessment among patients with intrahepatic cholangiocarcinoma (iCCA) remains unknown. The authors studied the association of ...the CA 19‐9 response (defined as a reduction >50% from baseline) with the radiologic response and the outcome in patients with unresectable iCCA.
Methods
A prospective cohort of 422 patients who were initially diagnosed with unresectable iCCA, had baseline CA 19‐9 levels ≥100 U/mL, and received treatment with systemic therapies at the authors' institution between January 2017 and December 2021 were enrolled in this study. The radiologic response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. A landmark assessment of the CA 19‐9 response and the radiologic response was performed. The associations between CA 19‐9 response and imaging response, progression‐free survival (PFS), and overall survival (OS) were analyzed.
Results
Two hundred sixty‐seven patients (63.3%) had a CA 19‐9 response. A CA 19‐9 response was observed in 123 of 132 (93.2%) radiologic responders and in 144 of 290 (49.7%) radiologic nonresponders (p < .001). CA 19‐9 responders outperformed nonresponders in median PFS (10.6 vs. 3.6 months; hazard ratio HR, 4.8 months; 95% confidence interval CI, 3.8–6.0 months; p < .001) and OS (21.4 vs. 6.3 months; HR, 5.3 months; 95% CI, 4.2–6.7 months; p < .001). The common independent predictors of both OS and PFS included metastasis, CA 19‐9 nonresponder status, and radiologic nonresponder status in multivariable analysis.
Conclusions
CA 19‐9 response is a valuable addition to assess tumor response and is associated with improved outcomes in patients with iCCA. Achieving a CA 19‐9 response should be one of the therapeutic objectives of patients with iCCA after systemic therapies.
Plain language summary
A decline in carbohydrate antigen 19‐9 levels from elevated baseline levels should be one of the therapeutic aims of patients with intrahepatic cholangiocarcinoma who are managed with systemic therapies.
Biomarkers for predicting treatment outcomes are an unmet need for patients with intrahepatic cholangiocarcinoma (iCCA) treated with systemic therapies. This article shows that the carbohydrate antigen 19‐9 response correlates with the radiologic response and outcome of patients with iCCA after treatment.
The prognosis of biliary tract cancer (BTC) remains unsatisfactory. This single-arm, phase II clinical trial (ChiCTR2000036652) investigated the efficacy, safety, and predictive biomarkers of ...sintilimab plus gemcitabine and cisplatin as the first-line treatment for patients with advanced BTCs. The primary endpoint was overall survival (OS). Secondary endpoints included toxicities, progression-free survival (PFS), and objective response rate (ORR); multi-omics biomarkers were assessed as exploratory objective. Thirty patients were enrolled and received treatment, the median OS and PFS were 15.9 months and 5.1 months, the ORR was 36.7%. The most common grade 3 or 4 treatment-related adverse events were thrombocytopenia (33.3%), with no reported deaths nor unexpected safety events. Predefined biomarker analysis indicated that patients with homologous recombination repair pathway gene alterations or loss-of-function mutations in chromatin remodeling genes presented better tumor response and survival outcomes. Furthermore, transcriptome analysis revealed a markedly longer PFS and tumor response were associated with higher expression of a 3-gene effector T cell signature or an 18-gene inflamed T cell signature. Sintilimab plus gemcitabine and cisplatin meets pre-specified endpoints and displays acceptable safety profile, multiomics potential predictive biomarkers are identified and warrant further verification.
To investigate the effect of metronomic chemotherapy of low dose phosphoramide combined with prednisolone (CP metronomic chemotherapy) on proliferation and apoptosis of RPMI 8226 cells, and to ...explore its regulating effect on Notch1/NF-κB signaling pathways.
Experiment was divided into the DMSO control group, and the phosphoramide mustard (PM) group, the prednisolone group, the phosphoramide mustard plus prednisolone group (the CP group). RPMI 8226 cells were treated with different drugs, CCK-8 method was used to detect cell proliferation, flow cytometry was used to detect the cell cycle and apoptosis, reverse transcription PCR was used to detect Notch1 and NF-κB mRNA expression level.
Compared with DMSO control group, RPMI8226 cell proliferation inhibition rate in all the PM, prednisolone and CP groups increased significantly with prolonging of time (r of 0.994,0.996,0.999, respectively, P<0.001). And at the same time, the inhibitory rate of cell proliferation was significantly different; the cell inhibitory
To investigate effects of low-dose cyclophosphamide and prednisone (CP) metronomic chemotherapy on microvessel density of bone marrow, serum vascular endothelial growth factor (VEGF) and platelet ...derived growth factor BB (PDGF-BB)in multiple myeloma (MM) patients.
54 refractory or relapsed MM patients were treated with CP metronomic chemotherapy consisted of oral cyclophosphamide (CTX, 50 mg/d) and prednisone (Pred, 15 mg/d). Bone marrow and peripheral blood of each patient were collected before and 2, 4, 6 months after treatment. Among the 37 assessable patients, 30 cases were responsive with the response rate of 81.08%. Another 17 cases were follow-uped less than 6 months or failure to obtain serum samples or lost to follow-up. Microvessel density of bone marrow was measured by immunohistochemistry and serum VEGF/PDGF-BB expression was analyzed by ELISA in the 37 assessable patients.
2, 4, 6 months following CP metronomic chemotherapy, microvessel densities of bone marrow in the responders were 33.1 ± 4.8/H
Beach wetland, an important part of the river ecosystem, plays an insignificant role on the stability of the river ecosystem as a transition zone between the river and terrestrial ecosystems. Since ...the operation of Three Gorges Reservoir, water discharge, river channel erosion and lowering, the collapse of river bank slope at downstream of the dam and shrinkage of the beach, result in the adverse impact on the waterway conditions and also reduction of beach area in the middle reaches of the Yangtze River. In response to adverse changes in the middle reaches of Yangtze River since the operation of Three Gorges reservoir, Yangtze River Waterway Bureau will implement numerous protection engineering to prevent the collapse of bank and the degeneration of the beach. In the recent years, the protection structure with ecological functions is more and more widely used. The test proved that the colonization of plants in the structure of ecological protection can restore the beach vegetation, species diversity, and to prevent the wetland area to reduce and improve the ecological environment of the local area.
HCAP1 is a novel hepatic cancer related gene located on human chromosome 17p13.3. The loss of heterozygosity occurred at 17p13.3 in various human cancers. In order to investigate the effects of ...exogenous HCAP1 gene products on cell proliferation of T lymphoma Jurkat cell line, HCAP1 gene! was transfected into Jurkat cells mediated by liposome, and the cells stably expressing exogenous HCAP1 were screened with G418. The effects of HCAP1 products on cell proliferation were assessed by viable cell count, cell growth curve and colony formation assay in soft agar. The results showed that the HCAP1 transgenic Jurkat cells displayed slow growth rate, extended doubling time and reduced colony formation capability, as compared with the cells transfected with pBK/CMV empty vector (P < 0.01). It is concluded that exogenous HCAP1 gene products could inhibit the proliferation of Jurkat cells.
