B7-H3 is eligible for predicting clinical outcomes in lung adenocarcinoma patients treated with EGFR tyrosine kinase inhibitors.

BACKGROUND: Not all lung adenocarcinoma (LUAD) patients with activating epidermal growth factor receptor (EGFR) mutations respond to tyrosine kinase inhibitors (TKIs) as intended. Thus, biomarkers are needed to identify patients who benefit most from EGFR-targeted therapy. Our previous in vitro data has shown that the co-signal molecule B7-H3 determines EGFR-TKI gefitinib susceptibility of EGFR-mutated LUAD cell lines, based on the potential crosslinking between B7-H3-induced signaling and EGFR signaling. METHODS: We detected tumoral B7-H3 expression in the original biopsy from 56 treatment-naïve LUAD patients and analyzed the association between high/low B7-H3 expression with the clinical outcomes of first-line anti-EGFR therapy. The main criteria for the analysis of response were overall response rate (ORR), disease control rate (DCR), and progression-free survival (PFS), and the secondary criterion was overall survival (OS). RESULTS: In the subgroups of B7-H3 high and low expression, the ORR were 16.0% (4/25) and 74.2% (23/31) (p<0.001), and the DCR were 36.0% (9/25) and 87.1% (27/31) (p<0.001), respectively. The PFS of B7-H3 high [median 8.7, 95% confidence interval (CI) 4.0-13.4] was significantly worse than that of B7-H3 low (median not reached) [HR 6.54 (95% CI 2.18-19.60), p=0.001]. The median OS was 15.9 (95% CI 10.0-21.8) months in the B7-H3 high cohort and 25.7 (95% CI 9.0-42.4) months in the B7-H3 low subjects [HR 2.08 (95% CI 1.07-4.02), p=0.03], respectively. Both the univariate and multivariate analyses identified B7-H3 as an independent factor associated with poor PFS (p=0.001, p=0.000) and OS (p=0.03, p=0.015). CONCLUSION: B7-H3 may serve as a potential biomarker to predict clinical outcomes in EGFR-mutated LUAD patients treated with first-line EGFR-TKIs.

Thalidomide for prevention of camrelizumab-induced reactive cutaneous capillary endothelial proliferation.

OBJECTIVES: The study evaluated the efficacy of thalidomide in prevention of camrelizumab-induced reactive cutaneous capillary endothelial proliferation (RCCEP). METHODS: In this study, patients treated with camrelizumab plus thalidomide or camrelizumab alone were included. The occurrences, onset time, severity of RCCEP and the adverse effect of thalidomide were analysed. RESULTS: A total of 19 patients were enrolled. The incidence of RCCEP in thalidomide group (2/9, 22.2%) was significantly lower than that in camrelizumab group (8/10, 80%). The median onset time of RCCEP was 5 weeks and 4 weeks respectively. The adverse events of thalidomide were mild, and no treatment-associated interruption was observed. CONCLUSIONS: Thalidomide showed a promising in prevention of the RCCEP in patients receiving camrelizumab therapy with an acceptable safety profile.

Investigations of Memory Monitoring in Individuals With Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment.

BACKGROUND: Subjective cognitive decline (SCD) has been called the prodromal stage of amnestic mild cognitive impairment (aMCI); however, further investigation is needed to confirm this observation. OBJECTIVE: To define the relationship between SCD and aMCI. METHOD: In this case-control study, we used the feeling-of-knowing in episodic memory (FOK-EM) test to measure the memory-monitoring function of 40 adults with aMCI, 60 with SCD, and 55 healthy controls. RESULTS: The recognition rates of FOK-EM (53.53% ± 7.82%; 55.12% ± 6.08%) and judgment accuracy of the aMCI and SCD groups (γ values 0.21 ± 0.11; 0.30 ± 0.16) were significantly lower than those of the control group (72.32% ± 5.14%; 0.57 ± 0.16) (F = 116.24, P < 0.01; F = 128.57, P < 0.01; F = 73.33, P < 0.01). The scores for correct decision/correct recognition (RR; 27.2 ± 6.43; 29.36 ± 5.16) and correct decision/false recognition (RF; 30.41 ± 5.06; 27.26 ± 4.37) of the aMCI and SCD groups were also significantly lower than those of the control group (49.35 ± 7.13; 11.16 ± 4.35) (FRR = 132.67, P < 0.01; FRF = 131.8, P < 0.01). CONCLUSION: Mild clinical impairments in memory-monitoring function may precede clinically confirmed objective memory impairment in individuals with SCD.

Prospective memory impairment in patients with white matter lesions.

OBJECTIVE: A vast majority of the episodic memory literature in white matter lesions (WML) had focused on "retrospective memory (RM)", little was known about prospective memory (PM) in WML patients. The aim of our study was to investigate the effect of WML patients on event-based prospective memory (EBPM) and time-based prospective memory (TBPM). In addition, our study attempted to understand the possible mechanisms of PM damage in WML patients. METHODS: A total of 42 WML patients and 40 age and education level matched healthy controls were included. EBPM (an action whenever particular words were presented) and TBPM (an action at certain times) were performed to test the involvement of PM in WML. The extent of WML within cholinergic pathways were assessed using the cholinergic pathways hyperintensities scale (CHIPS). RESULTS: A significant difference was found in the performance of Montreal Cognitive Assessment (MOCA) (21.8 ± 3.9 vs. 26.6 ± 1.7, p < 0.05) and TBPM (2.88 ± 1.21 vs. 4.27 ± 0.78, p < 0.05), but not Mini-Mental State Examination (MMSE) (26.9 ± 2.8 vs. 27.3 ± 1.2, p > 0.05) and EBPM (3.62 ± 1.25 vs.4.47 ± 1.11, p > 0.05) in WML patients compared with the healthy controls. Moreover, TBPM and MOCA scores were negatively correlated with CHIPS scores. CONCLUSIONS: WML patients were impaired in TBPM but not in EBPM, supporting that EBPM and TBPM have different neural mechanisms. Our results demonstrated that WML are involved in the TBPM probably by affecting the central cholinergic pathway.

A Large-Scale, Exome-Wide Association Study of Han Chinese Women Identifies Three Novel Loci Predisposing to Breast Cancer.

Genome-wide association studies have identified more than 90 susceptibility loci for breast cancer. However, the missing heritability is evident, and the contributions of coding variants to breast cancer susceptibility have not yet been systematically evaluated. Here, we present a large-scale whole-exome association study for breast cancer consisting of 24,162 individuals (10,055 cases and 14,107 controls). In addition to replicating known susceptibility loci (e.g., ESR1, FGFR2, and TOX3), we identify two novel missense variants in C21orf58 (rs13047478, Pmeta = 4.52 × 10-8) and ZNF526 (rs3810151, Pmeta = 7.60 × 10-9) and one new noncoding variant at 7q21.11 (P < 5 × 10-8). C21orf58 and ZNF526 possessed functional roles in the control of breast cancer cell growth, and the two coding variants were found to be the eQTL for several nearby genes. rs13047478 was significantly (P < 5.00 × 10-8) associated with the expression of genes MCM3AP and YBEY in breast mammary tissues. rs3810151 was found to be significantly associated with the expression of genes PAFAH1B3 (P = 8.39 × 10-8) and CNFN (P = 3.77 × 10-4) in human blood samples. C21orf58 and ZNF526, together with these eQTL genes, were differentially expressed in breast tumors versus normal breast. Our study reveals additional loci and novel genes for genetic predisposition to breast cancer and highlights a polygenic basis of disease development.Significance: Large-scale genetic screening identifies novel missense variants and a noncoding variant as predisposing factors for breast cancer. Cancer Res; 78(11); 3087-97. ©2018 AACR.

[Neuropsychological study of false memory in patients with amnesia mild cognitive impairment].

OBJECTIVE: To explore the profile of false memory in aMCI (amnesia mild cognitive impairment) and to elucidate the neuropsychological mechanism of false memory. METHODS: False memory provoked by pictures and feeling-of-knowing (FOK) test in episodic memory (EM) were conducted in 25 aMCI patients at our hospital from October 2009 to May 2010. And 25 age and education level-matched healthy patients were recruited into the healthy control (HC) group. RESULTS: As compared with HC group, the rate of false memory was higher in the aMCI group. The rate of false memory in recall stage was 26% ± 7% and that of questionnaire stage 28% ± 12%. And the difference between two group was significant (t = 14.437, 7.597, P < 0.05). The FOK-EM of correct judgment and false recognition in the aMCI group (41% ± 10%) was higher than the HC group. And the difference was significant (t = 4.207, P < 0.05). The rates of false memory in recall and questionnaire stages were positively correlated with FOK-EM in aMCI group (r = 0.563, 0.705, P < 0.01). CONCLUSION: The aMCI patients tend to have more false memory provoked by pictures. The deficit of memory monitoring in aMCI may be the foundation of false memory.

[Memory monitoring in mild cognitive impairment].

OBJECTIVE: To explore the profile of changes of memory monitoring in patients with mild cognitive impairment (MCI). METHODS: Rey- auditory verbal learning test (AVLT) and feeling-of-knowing (FOK) test in episodic memory (EM) and semantic memory (SM) were conducted on 30 MCI patients, 17 males and 13 females, aged (66 +/- 9), and 30 age, education level, word fluency test, and digit span-matched healthy persons as healthy control (HC) group. RESULTS: The EM impairment of the MCI group was (13.7 +/- 2.8), significantly higher than that of the HC group [(8.1 +/- 2.0), P < 0.01], but the SM impairment of the MCI group was (5.4 +/- 1.4), not significantly different from that of the HC group [(5.0 +/- 1.4), P > 0.05]. The EM-FOK of the MCI patients with correct judgment and false recognition was (41.8 +/- 13.2)%, significantly higher than that of the HC group [(28.1 +/- 11.6)%, P < 0.01], however, the SM-FOK levels of the MCI patients with different judgment and recognition were all not significantly different from those of the HC group (all P > 0.05). CONCLUSION: The MCI patients overestimate their memory performance on episodic FOK, but their SM monitoring is not impaired. The deficit of memory monitoring in MCI may be the foundation of subjective memory complaints and is useful for diagnosis of MCI. EM and SM monitoring may depend on different neural mechanisms.

Prefrontal cortex involvement in the event-based prospective memory: evidence from patients with lesions in the prefrontal cortex.

PRIMARY OBJECTIVE: The aim of the present study was to investigate the event-based prospective memory (EBPM) and time-based prospective memory (TBPM) in patients with lesion in prefrontal cortex (PFC) and test the hypothesis that the prefrontal cortex is involved in the prospective memory (PM) network. RESEARCH DESIGN: The performance of patients with lesion in PFC (n = 30) was compared with that of a demographically matched control group (n = 30). METHODS AND PROCEDURES: A neuropsychological battery of tests including EBPM and TBPM tasks were administered to both groups. MAIN OUTCOME AND RESULTS: The group with lesion in PFC were significantly impaired in EBPM, but insignificantly impaired in TBPM tasks. There was no difference in performance of EBPM and TBPM tasks between the patients with lesion in the left and the right PFC. CONCLUSIONS: These results suggest that the patients with lesion in PFC were impaired in EBPM, but not in TBPM, implying that EBPM and TBPM may have different neural substrates. It is possible that PFC is more selectively involved in EBPM, but less in TBPM.