Proteomics study of primary and recurrent adamantinomatous craniopharyngiomas.

BACKGROUND: Adamantinomatous craniopharyngiomas (ACPs) are rare benign epithelial tumours with high recurrence and poor prognosis. Biological differences between recurrent and primary ACPs that may be associated with disease recurrence and treatment have yet to be evaluated at the proteomic level. In this study, we aimed to determine the proteomic profiles of paired recurrent and primary ACP, gain biological insight into ACP recurrence, and identify potential targets for ACP treatment. METHOD: Patients with ACP (n = 15) or Rathke's cleft cyst (RCC; n = 7) who underwent surgery at Sanbo Brain Hospital, Capital Medical University, Beijing, China and received pathological confirmation of ACP or RCC were enrolled in this study. We conducted a proteomic analysis to investigate the characteristics of primary ACP, paired recurrent ACP, and RCC. Western blotting was used to validate our proteomic results and assess the expression of key tumour-associated proteins in recurrent and primary ACPs. Flow cytometry was performed to evaluate the exhaustion of tumour-infiltrating lymphocytes (TILs) in primary and recurrent ACP tissue samples. Immunohistochemical staining for CD3 and PD-L1 was conducted to determine differences in T-cell infiltration and the expression of immunosuppressive molecules between paired primary and recurrent ACP samples. RESULTS: The bioinformatics analysis showed that proteins differentially expressed between recurrent and primary ACPs were significantly associated with extracellular matrix organisation and interleukin signalling. Cathepsin K, which was upregulated in recurrent ACP compared with that in primary ACP, may play a role in ACP recurrence. High infiltration of T cells and exhaustion of TILs were revealed by the flow cytometry analysis of ACP. CONCLUSIONS: This study provides a preliminary description of the proteomic differences between primary ACP, recurrent ACP, and RCC. Our findings serve as a resource for craniopharyngioma researchers and may ultimately expand existing knowledge of recurrent ACP and benefit clinical practice.

Long-term and short-term cardiovascular disease mortality among patients of 21 non-metastatic cancers.

INTRODUCTION: Previous studies on cardiovascular disease (CVD) death risk in cancer patients mostly focused on overall cancer, age subgroups and single cancers. OBJECTIVES: To assess the CVD death risk in non-metastatic cancer patients at 21 cancer sites. METHODS: A total of 1,672,561 non-metastatic cancer patients from Surveillance, Epidemiology, and End Results (SEER) datebase (1975-2018) were included in this population-based study, with a median follow-up of 12·7 years. The risk of CVD deaths was assessed using proportions, competing-risk regression, absolute excess risks (AERs), and standardized mortality ratios (SMRs). RESULTS: In patients with localized cancers, the proportion of CVD death and cumulative mortality from CVD in the high-competing risk group (14 of 21 unique cancers) surpassed that of primary neoplasm after cancer diagnosis. The SMRs and AERs of CVD were found higher in patients with non-metastatic cancer than the general US population (SMR 1·96 [95 %CI, 1·95-1·97]-19·85[95 %CI, 16·69-23·44]; AER 5·77-210·48), heart disease (SMR 1·94[95 %CI, 1·93-1·95]-19·25[95 %CI, 15·76-23·29]; AER 4·36-159·10) and cerebrovascular disease (SMR 2·05[95 %CI, 2·02-2·08]-24·71[95 %CI, 16·28-35·96]; AER 1·01-37·44) deaths. In the high-competing risk group, CVD-related SMR in patients with localized stage cancer increased with survival time but followed a reverse-dipper pattern in the low-competing risk group (7 of 21 cancers). The high-competing risk group had higher CVD-related death risks than the low-competing risk group. CONCLUSION: The CVD death risk in patients with non-metastatic cancer varied by cancer stage, site and survival time. The risk of CVD mortality is higher in 14 out of 21 localized cancers (high-competing cancers). Targeted strategies for CVD management in non-metastatic cancer patients are needed.

Non-cancer-specific survival in patients with primary central nervous system lymphoma: A multi-center cohort study.

Objective: The study aimed to evaluate the non-cancer-specific death risk and identify the risk factors affecting the non-cancer-specific survival (NCSS) in patients with primary central nervous system lymphoma (PCNSL). Methods: This multi-center cohort study included 2497 patients with PCNSL in the Surveillance, Epidemiology and End Results (SEER) database from 2007 to 2016, with a mean follow-up of 4.54 years. The non-cancer-specific death risk in patients with PCNSL and primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) was evaluated using the proportion of deaths, standardized mortality ratio (SMR), and absolute excess risk (AER). Univariate and multivariate competing risk regression models were utilized to identify the risk factors of NCSS. Results: PCNSL was the most frequent cause of death in PCNSL patients (75.03%). Non-cancer-specific causes constituted a non-negligible portion of death (20.61%). Compared with the general population, PCNSL patients had higher risks of death from cardiovascular disease (CVD) (SMR, 2.55; AER, 77.29), Alzheimer's disease (SMR, 2.71; AER, 8.79), respiratory disease (SMR, 2.12; AER, 15.63), and other non-cancer-specific diseases (SMR, 4.12; AER, 83.12). Male sex, Black race, earlier year of diagnosis (2007-2011), being unmarried, and a lack of chemotherapy were risk factors for NCSS in patients with PCNSL and PCNS-DLBCL (all P < 0.05). Conclusion: Non-cancer-specific causes were important competing causes of death in PCNSL patients. More attention is recommended to non-cancer-specific causes of death in the management of PCNSL patients.

Association of marital status with cardiovascular outcome in patients with breast cancer.

Background: The influences of marital status on cardiovascular death risk in patients with breast cancer remained unclear. This study aimed to evaluate the associations of different marital status with cardiovascular death risk in patients with breast cancer. Methods: A total of 182,666 female breast cancer patients were enrolled in this study from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2014, and was divided into two groups: married (N=107,043) and unmarried (N=75,623). A 1:1 propensity score matching (PSM) was applied to reduce inter-group bias between the two groups. Competing-risks model was used to assess the associations between different marital status and cardiovascular death risk in patients with breast cancer. Results: After PSM, marital status was an independent predictor for cardiovascular death in patients with breast cancer. Unmarried condition was associated with increased cardiovascular death risk than married condition among breast cancer patients [unadjusted model: hazard ratio (HR) =2.012, 95% confidence interval (CI): 1.835-2.208, P<0.001; Model 1: HR =1.958, 95% CI: 1.785-2.148, P<0.001; Model 2: HR =1.954, 95% CI: 1.781-2.144, P<0.001; Model 3: HR =1.920, 95% CI: 1.748-2.107, P<0.001]. With the exception of separated condition (adjusted HR =0.886, 95% CI: 0.474-1.658, P=0.705), further unmarried subgroups analysis showed that the other three unmarried status were associated with increased cardiovascular death risk as follows: single (adjusted HR =1.623, 95% CI: 1.421-1.853, P<0.001), divorced (adjusted HR =1.394, 95% CI: 1.209-1.608, P<0.001), and widowed (adjusted HR =2.460, 95% CI: 2.227-2.717, P<0.001). In particularly, widowed condition showed the highest cardiovascular death risk in all 4 unmarried subgroups. Conclusions: Unmarried condition (e.g., single, divorced and widowed) was associated with elevated cardiovascular death risk compared with their married counterparts in patients with breast cancer, suggesting that more attention and humanistic care should be paid to unmarried breast cancer patients (especially the widowed patients) in the management of female breast cancer patients.

Cardiovascular and Other Competing Causes of Death in Male Breast Cancer Patients: A Population-Based Epidemiologic Study.

PURPOSE: Male breast cancer (MBC) is a rare disease that tends to occur in elderly men. Little is known about the causes of death in MBC because of the small sample size of most studies. This study aimed to investigate the causes of death in MBC patients. PATIENTS AND METHODS: MBC patient data were obtained from the Surveillance, Epidemiology, and End Results database (1975-2016). Time trends of MBC mortality in the US population were analyzed using Joinpoint software. We calculated the proportion of each cause of death in the overall cohort and in different patient subgroups. Competing risk models were used to calculate cumulative mortality at different follow-up times. The risk of cardiovascular death (CVD) in MBC patients was compared to that of the age-matched general population by calculating standardized mortality ratio (SMR). RESULTS: In total, 6426 patients were included in the analysis. MBC mortality rate increased between 2004 and 2019 (annual percentage change=1.16, 95% confidence interval [CI]: 0.50, 1.80). There were 1757 patients (27.3%) who died of non-breast cancer causes. CVD was the leading cause of death in patients who were elderly or had localized disease. MBC patients had a 6.58-fold higher risk of CVD than the general population (SMR=6.58, 95% CI: 6.14, 7.05). CONCLUSION: Non-breast cancer death accounts for the majority of deaths in MBC patients who are elderly or have localized cancer. Compared to the general population, MBC patients have an increased risk of CVD. These results highlight the importance of monitoring cardiovascular comorbidities in MBC patients.

[Protective effects of penehyclidine hydrochloride against acute renal injury induced by hemorrhagic shock and lipopolysaccharides in rats].

OBJECTIVE: To investigate the effect of penehyclidine hydrochloride (PHC) in a rat model of renal injury induced by hemorrhagic shock and lipopolysaccharides (LPS). METHODS: Forty-five healthy Wistar rats were randomized into sham operated group, model group, and 3 penehyclidine hydrochloride (PHC) dose (1, 2 and 3 mg/kg) groups (PHC1, PHC2, and PHC3 groups, respectively). The arterial blood samples were collected to determine the concentrations of serum tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-1 (IL-1), urine creatinine (Cr) and blood urine nitrogen (BUN), and the renal tissues were collected to measure the expressions of ICAM-1 and nuclear factor-κB (NF-κB) and observe the pathological changes. RESULTS: TNF-α, IL-8, IL-1, Cr, BUN, ICAM-1 and NF-κB in the 3 PHC groups were significantly lower than those in the model group (P<0.05). TNF-α, IL-8, IL-1, Cr and BUN were significantly lower in PHC1 (P<0.05) than in the PHC2 and PHC3 groups, and ICAM-1 and NF-κB were similar between 3 PHC groups (P>0.05). Compared with the model group, the 3 PHC groups showed lessened pathological changes in the renal tubules. CONCLUSION: PHC has protective effects against renal injury induced by hemorrhagic-endotoxin shock in rats, and treatment with 1 mg/kg PHC produces the most significant protective effect.