Termansentranberg3537
TSPO was highly expressed in human and murine pancreatic cancer. Notably, TSPO expression was associated with high-grade, premalignant intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanIN) lesions. In GEM models, [
F]V-1008 exhibited robust uptake in early pancreatic cancer, detectable by PET. Furthermore, V-1520 localized to premalignant pancreatic lesions and advanced tumors enabling real-time IGS.
We anticipate that combined TSPO PET/IGS represents a translational approach for precision pancreatic cancer care through discrimination of high-risk indeterminate lesions and actionable surgery.
We anticipate that combined TSPO PET/IGS represents a translational approach for precision pancreatic cancer care through discrimination of high-risk indeterminate lesions and actionable surgery.
Emerging evidence indicates that gut microbiota dysbiosis can reduce the effectiveness of immune checkpoint inhibitors (ICI). Proton pump inhibitors (PPI) are known to induce gut microbiota changes. However, little is known on the effects of PPIs on outcomes with ICI therapy, and it has not been explored in urothelial cancer treatment.
Individual-participant data from the advanced urothelial cancer trials, IMvigor210 (single-arm atezolizumab trial,
= 429) and IMvigor211 (phase III randomized trial of atezolizumab vs. chemotherapy,
= 931) were pooled in a Cox proportional hazard analysis assessing the association between PPI use and overall survival (OS) and progression-free survival (PFS). PPI use was defined as any PPI administration between 30 days prior and 30 days after treatment initiation.
Of the 1,360 participants, 471 (35%) received a PPI within the 60-day window. PPI use was associated with significantly worse OS [HR (95% confidence interval (CI)) = 1.52 (1.27-1.83),
< 0.001] and PFS [1.38 (1.18-1.62),
< 0.001] with atezolizumab, but not chemotherapy (
> 0.05). In the randomized cohort of IMvigor211, the OS treatment effect [HR (95% CI)] of atezolizumab versus chemotherapy was 1.04 (0.81-1.34) for PPI users, compared with 0.69 (0.56-0.84) for PPI nonusers (
= 0.013). Similar associations were noted in the PD-L1 IC2/3 population.
This study indicates PPI use is a negative prognostic marker in advanced urothelial carcinoma treated with ICI therapy, but not chemotherapy. Furthermore, the analysis suggests PPIs influence the magnitude of ICI efficacy, and this warrants further investigation.
This study indicates PPI use is a negative prognostic marker in advanced urothelial carcinoma treated with ICI therapy, but not chemotherapy. Furthermore, the analysis suggests PPIs influence the magnitude of ICI efficacy, and this warrants further investigation.
Biliary tract cancer (BTC) is a heterogeneous group of rare gastrointestinal malignancies with dismal prognosis often associated with inflammation. We assessed the prognostic value of IL6 and YKL-40 compared with CA19-9 before and during palliative chemotherapy. Lificiguat We also investigated in mice whether IL6R inhibition in combination with gemcitabine could prolong chemosensitivity.
A total of 452 Danish participants with advanced (locally advanced and metastatic) BTC were included from six clinical trials (February 2004 to March 2017). Serum CA19-9, IL6, and YKL-40 were measured before and during palliative treatment. Associations between candidate biomarkers and progression-free survival (PFS) and overall survival (OS) were analyzed by univariate and multivariate Cox regression. Effects of inhibiting IL6R and YKL-40 were assessed
, and of IL6R inhibition
.
High pretreatment levels of CA19-9, IL6, and YKL-40, and increasing levels during treatment, were associated with short PFS and OS in patients with advanced BTC. IL6 provided independent prognostic information, independent of tumor location and in patients with normal serum CA19-9. ROC analyses showed that IL6 and YKL-40 were predictive of very short OS (OS < 6 months), whereas CA19-9 was best to predict OS > 1.5 years. Treatment with anti-IL6R and gemcitabine significantly diminished tumor growth when compared with gemcitabine monotherapy in an
transplant model of BTC.
Serum IL6 and YKL-40 are potential new prognostic biomarkers in BTC. IL6 provides independent prognostic information and may be superior to CA19-9 in certain contexts. Moreover, anti-IL6R should be considered as a new treatment option to sustain gemcitabine response in patients with BTC.
Serum IL6 and YKL-40 are potential new prognostic biomarkers in BTC. IL6 provides independent prognostic information and may be superior to CA19-9 in certain contexts. Moreover, anti-IL6R should be considered as a new treatment option to sustain gemcitabine response in patients with BTC.
The Continuing Professional Development (CPD) department of the College of Family Physicians of Canada evaluated the Mainpro+
and CERT+
programs from June 2016 to May 2018 to determine users' awareness of the changes made to each program and to determine user engagement and satisfaction.
To assess changes in CPD program quality, the effects of changes on member understanding of credit reporting and engagement, data accuracy of credit reporting, and the perceptions of the CPD program certification process among providers.
Surveys and interviews were conducted with stakeholders from both groups, and consultations occurred with a third-party consultant. Administrative data and program files were also analyzed. More than 33 000 users (about 95% of all Mainpro+ participants) have accessed Mainpro+ since its launch. Satisfaction varies, with 31% of members and 39% of non-member Mainpro+ participants expressing difficulty entering activities. Most users (79%) understand the changes implemented. Among CERT+ users, half (50%) find the platform easy to use, whereas 23% find it difficult; 86% find the CPD program submission requirements somewhat or very clear. Project limitations include difficulty comparing data between phases and a lack of qualitative data.
The College of Family Physicians of Canada anticipates these program enhancements will lead to higher-quality CPD programs and greater clarity and efficiency for members and CPD providers. All collected data will be used to inform ongoing improvements to both platforms to improve the experience of all users.
The College of Family Physicians of Canada anticipates these program enhancements will lead to higher-quality CPD programs and greater clarity and efficiency for members and CPD providers. All collected data will be used to inform ongoing improvements to both platforms to improve the experience of all users.