Simultaneous inhibition of FAK and ROS1 synergistically repressed triple-negative breast cancer by upregulating p53 signalling.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype lacking effective targeted therapies, necessitating innovative treatment approaches. While targeting ROS proto-oncogene 1 (ROS1) with crizotinib has shown promise, resistance remains a limitation. Recent evidence links focal adhesion kinase (FAK) to drug resistance, prompting our study to assess the combined impact of FAK inhibitor IN10018 and crizotinib in TNBC and elucidate the underlying mechanisms. METHODS: We employed the Timer database to analyze FAK and ROS1 mRNA levels in TNBC and adjacent normal tissues. Furthermore, we investigated the correlation between FAK, ROS1, and TNBC clinical prognosis using the GSE database. We conducted various in vitro assays, including cell viability, colony formation, flow cytometry, EdU assays, and western blotting. Additionally, TNBC xenograft and human TNBC organoid models were established to assess the combined therapy's efficacy. To comprehensively understand the synergistic anti-tumor mechanisms, we utilized multiple techniques, such as RNA sequencing, immunofluorescence, cell flow cytometry, C11-BODIPY staining, MDA assay, and GSH assay. RESULTS: The Timer database revealed higher levels of FAK and ROS1 in TNBC tissues compared to normal tissues. Analysis of GEO databases indicated that patients with high FAK and ROS1 expression had the poorest prognosis. Western blotting confirmed increased p-FAK expression in crizotinib-resistant TNBC cells. In vitro experiments showed that the combination therapy down-regulated cyclin B1, p-Cdc2, and Bcl2 while up-regulating BAX, cleaved-Caspase-3, cleaved-Caspase-9, and cleaved PARP. In TNBC xenograft models, the tumor volume in the combination therapy group was 73% smaller compared to the control group (p < 0.0001). Additionally, the combination therapy resulted in a 70% reduction in cell viability in human TNBC organoid models (p < 0.0001). RNA sequencing analysis of TNBC cells and xenograft tumor tissues highlighted enrichment in oxidative stress, glutathione metabolism, and p53 pathways. The combined group displayed a fivefold rise in the reactive oxygen species level, a 69% decrease in the GSH/GSSG ratio, and a sixfold increase in the lipid peroxidation in comparison to the control group. Western blotting demonstrated p53 upregulation and SCL7A11 and GPX4 downregulation in the combination group. The addition of a p53 inhibitor reversed these effects. CONCLUSION: Our study demonstrates that the combination of IN10018 and crizotinib shows synergistic antitumor effects in TNBC. Mechanistically, this combination inhibits cell proliferation, enhances apoptosis, and induces ferroptosis, which is associated with increased p53 levels.

106 Cases of homicide poisoning in China-A retrospective study.

Homicidal poisoning has received limited scholarly attention, despite having recently increased in frequency in China, especially in rural areas, where it causes numerous deaths and disabilities. In this study, the author collected data on 106 cases of homicidal poisoning from 1995 to 2000. Of these cases 105 were found through website established by the Supreme Court of China, and one case was as an exception identified from the internet. There were 46 male perpetrators and 59 female perpetrators. The most common reason male perpetrators poisoned someone was conflict among neighbours (include residents in the same village) (ten cases), and the most common reason female perpetrators did so was an affair (13 cases). Compared with the perpetrators of general homicide, those who poisoned people included a high proportion of female, elderly, and well-educated individuals. This is related to the nonviolent nature of the poisoning, which requires no physical strength. Residents living in rural and urban areas chose poisoning based on convenience. People living in rural areas used pesticides most often, and people in urban areas have greater access to drugs or medications obtained at work or online. In this study, a total of 9.4% of the perpetrators were diagnosed with psychiatric disorders or psychosis. In all, the 106 cases resulted in 58 human deaths. Tetramine and paraquat caused many of the deaths, and this suggests a need for the government to manage and monitor these highly toxic pesticides. These cases are representative of issues in contemporary Chinese society, for example, population mobility, fierce competition.

The relationship between high residential density in student dormitories and anxiety, binge eating and Internet addiction: a study of Chinese college students.

CONTEXT: Although various studies have indicated that high residential density may affect health and psychological outcomes, to our knowledge, there have been no studies regarding the predictive nature of crowded living conditions on binge eating and the use of the Internet as coping strategies. METHODS: A total of 1048 Chinese college students (540 males and 508 females) were randomly selected and asked to complete a battery of questionnaires that included the Zung's Self-Rating Anxiety Scale, the Internet Addiction Test, and Rosenbaum's Self-Control Scale. Binge eating behaviors and compensatory behaviors were also reported, and variables about residential density were measured. RESULTS: Among female participants, binge eating scores were significantly predicted by anxiety caused by high-density living conditions (P = 0.008), and similarly, the frequency of compensatory behaviors was significantly predicted by anxiety caused by high-density living conditions (P = 0.000) and self-control (P = 0.003). Furthermore, the Internet Addiction Test scores were significantly predicted by the anxiety caused by high -density living conditions (P = 0.000) and self-control (P = 0.000). Among male participants, not only were the binge eating scores significantly predicted by the anxiety caused by high-density living conditions (P = 0.000) and self-control (P = 0.000), but the frequency of compensatory behaviors was also significantly predicted by the anxiety caused by high-density living conditions (P = 0.000) and self-control (P = 0.01). Furthermore, Internet Addiction Test scores were significantly predicted by anxiety caused by high-density living conditions (P = 0.000) and self-control (P = 0.000). It was further found that for both genders, subjective factors such as self-control, and the anxiety caused by high-density living conditions had a stronger impact on Internet addiction than objective factors, such as the size of the student's dormitory room. Moreover, self-control was found to act as a moderator in the relationship between anxiety and Internet addiction among male participants. CONCLUSION: Binge eating and Internet use could be considered coping strategies for Chinese college students facing high residential density in their dormitories.

Eating attitudes, weight control behaviors and risk factors for eating disorders among Chinese female dance students

Background and Objectives: Along with the economic development, eating disorders begin to appear in China. In this context, we study potential risks for eating disorders. Methods: 1,199 Chinese students, aged 12-25 years, were randomly selected in spring 2006 from a survey with a series of scales (EAT-26, EDI) that were used as a screening examination for eating attitudes, weight control behaviors and risk factors. Among them were 31 female Chinese dance students. The dancer students were compared with the female high risk group of eating disorders (EAT ≥ 20) and the female low risk group (EAT 0-9) according to their scores on EAT-26 and EDI. Results: There were just 3 dancers (10%) with scores on the EAT-26 who were over the cut-off point of 20 for high risk of an eating disorder. The dance group also showed significantly higher scores than the low risk group (EAT 0-9) not only on the subscales Dieting, and EAT-26 total scores on the EAT-26, but also on the subscales Perfectionism and Maturity Fears on the EDI. Conclusions: Among the group of female Chinese dance students, most participants did not show a high risk for eating disorders and their high scores on some subscales on the EAT-26 and EDI could be caused by their occupation (AU)

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The relationship between Internet addiction and bulimia in a sample of Chinese college students: depression as partial mediator between Internet addiction and bulimia.

BACKGROUND: It has been reported that Internet addiction is associated with substance dependence. Eating disorders have high rates of co-morbidity with substance use disorders. The relationship between Internet addiction and eating disorders was reported in a previous study. AIMS: To examine the hypothesis that Internet addiction is closely associated with bulimia. The hypothesis that depression mediates the relationship between Internet addiction and bulimia symptoms was also tested. METHODS: 2,036 Chinese college students were assessed on Internet addiction, eating behaviors and depression. Binge eating, compensatory behaviors, weight concern, menarche and weight change were also reported. Multiple regression analysis was used to test the mediating effect of depression. RESULTS: Internet addicts showed significantly higher scores on most subscales on EDI-1 than the controls. They reported significantly more binge eating, weight concern and weight change than the controls. Among all of the participants, depression was found to be a partial mediator in the relationship between Internet addiction and bulimia. CONCLUSION: This survey provides evidence of the co-morbidity of Internet addiction and bulimia.

Eating attitudes and weight concern among Chinese middle-age women: A comparison between different age and BMI groups

Background and Objectives: Few studies have been conducted to explore eating behavior and weight concern among middle-aged women. Methods: Participants were a sample of 236 Chinese women aged 30-52. Outcome measures were various symptoms related to eating disorders, the weight concern and psychological characteristics subscales of the Eating Disorder Inventory-2 questionnaire(EDI-2). Independent variables were age, education level and BMI. ANOVA-Test and Linear Regression were performed. Results: A group of women (N = 132, 78%) with normal weight (19 ¡Ü BMI ¡Ü 24) showed dissatisfaction with their weight and wanted to reduce it. Overweight and obese women scored significantly higher on the subscale Body Dissatisfaction on the EDI-2 than women with lower BMI. In comparison to the older group (50-59), the younger group (30-39) and middle-aged group (40-49) expressed the desire to lose weight with a lower BMI. Conclusions: In comparison to age, the BMI had a stronger impact on the psychological and behavioral traits related to the eating disorders among a group of middle-aged Chinese women (AU)