LWJ-M30, a conjugate of DM1 and B6, for the targeted therapy of colorectal cancer with improved therapeutic effects.

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide as well as a significant cause of mortality. The conventional treatment could cause serious side effects and induce drug resistance, recurrence and metastasis of cancers. Hence, specific targeting of cancer cells without affecting the normal tissues is currently an urgent necessity in cancer therapy. The emerging of peptide-drug conjugates (PDC) is regarded as a promising approach to address malignant tumors. LWJ-M30, a conjugate of DM1 and B6 peptide, targeted transferrin receptors (TfRs) on the surface of the CRC cells, showing a powerful anti-cancer effect. LWJ-M30 significantly inhibited the HCT116 cells proliferation and migration in vitro. LWJ-M30 also dramatically decreased the level of polymeric tubulin, while the disruption of microtubules caused the cell cycle to be arrested in the G2/M phase. LWJ-M30 induced the HCT116 cells apoptosis both in vivo and in vitro. The results in vivo demonstrated that LWJ-M30 could inhibit the HCT116 growth without affecting the mouse body weight. Taking these results together, our data indicated that LWJ-M30 could improve the therapeutic effects of DM1 while reducing the systemic toxicity in normal tissues.

XHL11, a novel selective EGFR inhibitor, overcomes EGFRT790M-mediated resistance in non-small cell lung cancer.

The first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib significantly improved the therapeutic effect in non-small cell lung cancer (NSCLC) patients with EGFR mutation. However, the EGFRT790M mutation occurs and results in acquired resistance. Consequently, mutant selective third-generation EGFR TKIs represented by AZD9291 (Osimertinib) have been developed to offer more effective therapeutic treatment, but the clinical application is limited by the acquired resistance and the high costs. A series of 5-chloropyrimidine-2,4-diamine derivatives were synthesized and screened for in vitro antitumor activity on H1975 and A431 cells. XHL11 showed the strongest antineoplastic activity. Compared to AZD9291, XHL11 suppressed cellular proliferation and colony formation and induced apoptosis in H1975 cells with EGFRL858R/T790M mutation. In addition, XHL11 caused expression changes in EGFR and apoptosis-related pathways. Moreover, oral administration of XHL11 suppressed tumor progression in vivo in a H1975 subcutaneous xenograft model. These data demonstrated that XHL11 might be developed as a promising EGFR TKI for the therapeutic use of NSCLC patients.

[Relationship between perceptions of safety climate at workplace and depressive disorders in manufacturing workers].

OBJECTIVE: To investigate the risk factors for depressive disorders in manufacturing workers and to provide a basis for developing health promotion measures at workplace. METHODS: A questionnaire survey was performed in 8085 front-line production workers from 33 manufacturing enterprises in Nanhai District of Foshan, Guangdong Province, China. The questionnaire contained a survey of demographic characteristics, the Safety Climate Scale, the Center for Epidemiological Studies Depression Scale, etc. The multilevel logistic regression analysis was applied to investigate the risk factors for depressive disorders in workers. RESULTS: A total of 6260 workers completed the survey; their mean age was 31.1 ± 8.6 years, and 53.2% of them were males. The multilevel logistic regression analysis showed that after adjustment for sociodemographic factors such as age, sex, and martial status, more depressive disorders were reported in the enterprises with higher score of "production safety training" than in those with lower score (OR = 1.46, 95%CI = 1.07 ∼ 1.97); fewer depressive disorders were reported in the enterprises with higher score of "colleagues concerned about production safety" than in those with lower score (OR = 0.08, 95%CI = 0.03 ∼ 0.26); the relationships of "safety warnings and precautions" and "managers concerned about production safety" with workers' depressive disorders were not statistically significant (OR = 0.78, 95%CI = 0.48 ∼ 1.28; OR = 1.08, 95%CI = 0.68 ∼ 1.72). CONCLUSION: Depressive disorders in manufacturing workers are related to the safety climate at workplace, which indicates that a good safety climate at workplace should be created to prevent and control depressive disorders in workers.

[Associations of occupational safety atmosphere and behaviors with unintentional injuries].

OBJECTIVE: To evaluate the associations of perception of safety atmosphere at workplace, occupational safety attitude and behaviors with occupational unintentional injury among manufacturing workers. METHODS: A cross-sectional study was performed and a self-administered questionnaire was used to inquire socio-demographic characteristics, perceived safety atmosphere, occupational safety attitudes, occupational safety behaviors and occupational unintentional injuries among 10585 manufacturing workers selected from 46 enterprises in Guangdong. Structural equation modeling was applied to assess the relationship of the perception of safety atmosphere at workplace, occupational safety attitude, and occupational safety behaviors with occupational unintentional injury. RESULTS: Among 24 pathways supposed in structural equation model, 20 pathways (except for the attitude toward occupational safety, the attitude toward managers' support, the work posture and individual protection) were significantly related to the occupational unintentional injuries. The further analysis indicated that the perceived safety atmosphere might impact the occupational unintentional injuries by the attitude toward occupational safety and occupational safety behaviors. CONCLUSION: Workers' perception of safety atmosphere indirectly influenced on occupational unintentional injuries through occupational safety attitudes and occupational safety behaviors.