Biomedical subjects

Qian Guo

Publications and source records attributed to Qian Guo.

At least 19 recordsLinked to original sources

PubMed2026

RHAMM drives formation of polyploid cancer cells and confers resistance to ER-targeted therapy in breast cancer.

Endocrine resistance in ER+ breast cancer remains a major clinical challenge. Here, we identify RHAMM as a key driver of resistance by orchestrating polyploid cancer cell (PCC) formation. Single-cell transcriptomics uncovered a G2/M-enriched, RHAMM+ subpopulation in endocrine-resistant tumors. Mechanistically, RHAMM binds Septin9/10 to promote aberrant cytoskeleton polymerization, activating YAP independent of Hippo signaling, which induces cytokinesis failure and facilitates PCC generation. Concurrently, RHAMM destabilizes p21 mRNA, enabling cell cycle progression despite genomic instability. The RHAMM-p21 axis serves as a bypass mechanism supporting polyploidization. Upon endocrine treatment, RHAMM is transcriptionally up-regulated by Slug. Clinically, RHAMMhigh signatures are enriched in metastatic and recurrent ER+ tumors and correlate with poor prognosis, highlighting its therapeutic relevance. Importantly, targeting RHAMM or YAP abrogates PCC formation and restores fulvestrant sensitivity. These findings reveal RHAMM-mediated polyploidization as an adaptive mechanism underlying endocrine resistance, suggesting the therapeutic potential of targeting the RHAMM-YAP axis.

Humans↗

PubMed2026

Decoding tumor immune microenvironment heterogeneity by single-cell and spatial multi-omics: From immunotherapy resistance to translational biomarkers.

Immune checkpoint blockade has transformed cancer therapy, yet primary and acquired resistance remain major clinical challenges. Increasing evidence indicates that immunotherapy resistance cannot be fully explained by tumor-intrinsic alterations or conventional biomarkers such as PD-L1 expression, tumor mutational burden, or microsatellite instability. Instead, therapeutic response is shaped by the tumor immune microenvironment (TIME) as a heterogeneous, spatially organized, and dynamically evolving ecosystem. Single-cell omics has revealed diverse immune and stromal cell states, including progenitor and terminally exhausted T cells, suppressive myeloid programs, B-cell/TLS-associated immune-reactive states, and CAF-mediated exclusion phenotypes. Spatial transcriptomics, spatial proteomics, and imaging-based approaches further demonstrate that these cell states assemble into distinct immune niches, including immune-inflamed, T-cell-excluded, myeloid-suppressive, metabolic/hypoxic, and TLS-associated niches. These spatial ecosystems determine whether antitumor immune cells can access malignant cells, receive antigen-presenting support, or become restrained by stromal, vascular, metabolic, and myeloid barriers. In this review, we summarize how single-cell and spatial multi-omics redefine TIME heterogeneity in immunotherapy resistance, highlight ligand-receptor communication networks linking cell states to spatial immune dysfunction, and discuss emerging translational biomarkers for patient stratification. We further propose that future immunotherapy biomarkers should evolve from static single-marker assays toward longitudinal, spatially resolved, and interpretable multi-omics models that guide precision combination immunotherapy.

Humans↗

PubMed2026

One Plasmid Is All You Need: Genome Editing in Escherichia coli Using Endogenous TnpB and Endogenous Recombination System.

Escherichia coli (E. coli) is a key workhorse of biotechnology. Commonly used CRISPR-Cas9 systems for E. coli genome editing are complex and impose metabolic stress on the host, creating demand for more streamlined strategies. Recent studies identified the IS605 transposon-associated TnpB as a programmable RNA-guided (ωRNA) DNA endonuclease, prompting us to explore whether endogenous TnpB in E. coli (EcoTnpB) could be harnessed for genome editing. Biochemical and cellular analyses demonstrated that EcoTnpB efficiently cleaves both chromosomal and plasmid DNA at custom-specified sites in a TAM-dependent manner. Interestingly, E. coli possesses an endogenous recombination machinery capable of repairing EcoTnpB-induced DNA double-strand breaks (DSBs), challenging the long-held view that bacteria lack efficient homologous recombination systems. Based on these findings, we established a single-plasmid editing system (SPEED) in which genome editing is achieved by simply providing ωRNA and a homologous recombination template. By utilizing endogenous EcoTnpB together with the host HR pathway, this system enabled inducible and seamless genome editing at multiple genomic loci in BL21 (DE3), with editing efficiencies ranging from approximately 29% to 56%. Our results demonstrate for the first time that endogenous TnpB can be harnessed for genome editing and may hold potential for broader applications, such as species-specific antimicrobial development.

Escherichia coli↗

PubMed2006

Socio-demographic and cultural comparison of overweight and obesity risk and prevalence in adolescents in Southern California and Wuhan, China.

PURPOSE: This study performed parallel analyses on two large samples of seventh graders living in Los Angeles, California and in Wuhan, China to make direct comparisons of overweight and obesity risks in Western and Eastern cultural environments. METHODS: Two representative samples of 1772 and 1896 seventh grade students were randomly selected from the public or parochial middle schools in the greater Los Angeles area of Southern California in the United States, and public schools in Wuhan city of China. Two body mass index (BMI) references recently established by the U.S. National Center for Health Statistics (NCHS) and the International Obesity Task Force (IOTF), respectively, were used to define overweight (85th < or = BMI < 95th percentile) and obesity (BMI > or = 95th percentile). Logistic regressions were conducted to examine relationships between socioeconomic status (SES) and obesity risk. RESULTS: The prevalence rates of combined overweight and obesity in Los Angeles and in Wuhan were 43.1% and 12.1%, respectively, by the US-NCHS reference, and 45.8% and 11.9%, respectively, by the IOTF reference. Chinese-American adolescents had higher prevalence rates for overweight and obesity than those from China. SES was positively related to the risk of overweight and obesity in the Chinese sample, whereas a negative association was found in Southern California adolescents. Urbanicity was significantly positively related to higher overweight and obesity prevalence. CONCLUSION: Different overweight and obesity prevalence estimates and SES effects were observed for American and Chinese adolescent samples. Research on the underlying mechanisms is needed to help us to set up a tailored program for obesity prevention in Eastern and Western cultural environments.

Adolescent↗

PubMed2006

Tobacco use among youth and adults in Mainland China: the China Seven Cities Study.

OBJECTIVE: The China Seven Cities Study (CSCS) monitors geographic and temporal trends in tobacco use among adolescents and adults in seven cities throughout Mainland China: Harbin, Shenyang, Wuhan, Chengdu, Kunming, Hangzhou, and Qingdao. This article presents the methodology and prevalence data from the baseline survey of the CSCS, conducted in 2002. METHODS: Stratified random samples of middle schools, high schools, and colleges were selected within each city. Students and their parents completed self-report surveys of their tobacco use. Data were obtained from 6138 middle school students, 5848 academic high school students, 2448 vocational high school students, 2556 college students, and 25 697 parents. RESULTS: Smoking prevalence varied across age groups, school types, genders, and cities. Past-month smoking prevalence was 9% among middle school students, 8% among academic high school students, 26% among vocational high school students, 21% among college students, and 40% among parents. Smoking prevalence was higher among males than among females, with larger gender disparities among adults than among youth. Smoking also varied across cities, with higher smoking prevalence in southwestern cities and lower prevalence in coastal cities. Intraclass correlations of students within schools are presented to inform statistical power estimates for further research in China. CONCLUSIONS: These results provide a baseline for future longitudinal studies of smoking in these cities and identify demographic groups at risk for tobacco-related disease. Effective smoking prevention programmes for youth and smoking cessation programmes for adults are needed in China, especially in the lower-income southwestern cities and in vocational high schools throughout the country.

Adolescent↗

PubMed2006

Utility of the theory of reasoned action and theory of planned behavior for predicting Chinese adolescent smoking.

One third of smokers worldwide live in China. Identifying predictors of smoking is important for prevention program development. This study explored whether the Theory of Reasoned Action (TRA) and Theory of Planned Behavior (TPB) predict adolescent smoking in China. Data were obtained from 14,434 middle and high school students (48.6% boys, 51.4% girls) in seven geographically varied cities in China. TRA and TPB were tested by multilevel mediation modeling, and compared by multilevel analyses and likelihood ratio tests. Perceived behavioral control was tested as a main effect in TPB and a moderation effect in TRA. The mediation effects of smoking intention were supported in both models (p<0.001). TPB accounted for significantly more variance than TRA (p<0.001). Perceived behavioral control significantly interacted with attitudes and social norms in TRA (p<0.001). Therefore, TRA and TPB are applicable to China to predict adolescent smoking. TPB is superior to TRA for the prediction and TRA can better predict smoking among students with lower than higher perceived behavioral control.

Adolescent↗

PubMed2006

Heritability of cigarette smoking and alcohol use in Chinese male twins: the Qingdao twin registry.

BACKGROUND: China has the world's largest concentration of smokers (350 million) and rising alcohol consumption, yet little is known about tobacco and alcohol use aetiology. In 2000, the Chinese National Twin Registry was established to provide a genetically informative resource for investigation of health behaviour including tobacco and alcohol use. METHODS: Using standard twin methodology, this study aimed to examine the relative contribution of genetic and environmental influences on cigarette smoking and alcohol drinking in a sample of adult Chinese twins (n = 1010 individual twins). More than half of the male twins were smokers (58%), and 32.5% reported alcohol consumption. Among male smokers, 46.4% smoked 20 or more cigarettes per day (heavy smokers) and among drinkers, 32.8% consumed one or more drinks per day. Nearly all female twins were non-smokers (99.2%) and non-drinkers (98.7%); therefore, genetic analysis was limited to male data. RESULTS: In men, current smoking was significantly heritable [75.1%, 95% confidence interval (CI) 56.7-87.5] with no evidence for a significant contribution of shared environmental effects. Heavy smoking was more strongly influenced by genes (66.2%, 95% CI 0-88.4) than shared environment (8.7%, 95% CI 0-71.0). Similarly, current drinking was more strongly influenced by genetic effects (59.5%, 95% CI 0-87.8) than by shared environmental effects (15.3%, 95% CI 0-72.1). Amount of alcohol consumed was influenced to a similar degree by genetic (42.4%, 95% CI 0-91.8) and shared environmental factors (39.2%, 95% CI 0-82.7). CONCLUSIONS: These results support findings from twins of Western origin on the aetiology of tobacco and alcohol use and encourage further work in Chinese twins.

Adult↗

PubMed2006

A randomized intervention of smoking for adolescents in urban Wuhan, China.

BACKGROUND: Tobacco use is a significant public health problem in China. Culturally specific smoking prevention programs are needed for Chinese adolescents. This study evaluated a school-based smoking prevention curriculum with a social normative approach developed in the United States for adolescents in urban Wuhan, China. METHODS: As a randomized trial, the intervention was implemented in 1998 with 7th grade students in seven schools with seven matched control schools. Multilevel logistic regression models were used to compare ever and recent (past-month) smoking behaviors for the control and program conditions. RESULTS: At the 1-year follow-up, smoking had increased more rapidly in the control schools than in the program schools. The odds of baseline nonsmokers initiating smoking did not differ between the program and control groups (OR=1.08 with 95% CI=0.71, 1.64). The program prevented progression to recent smoking among boys who were baseline ever smokers. Among boys who were recent smokers at baseline, the prevention program significantly reduced risk of remaining recent smokers at follow-up (OR=0.45 with 95% CI=0.23, 0.88). CONCLUSIONS: This social normative smoking prevention curriculum did not demonstrate a significant primary prevention effect but showed potential for secondary prevention. Culturally specific smoking prevention programs are needed for Chinese adolescents.

Adolescent↗

PubMed2006

Weight perception and weight-related sociocultural and behavioral factors in Chinese adolescents.

BACKGROUND: Rapid economic development accompanied by imported Western media, advertising, fashion, and lifestyle in mainland China has resulted in shifts in cultural beliefs and beauty ideals in adolescents. The present study focused on understanding relationships among weight perception and weight-related sociocultural and behavioral factors in Chinese adolescents. METHODS: Data collected in 2002 from 6863 middle and high school students and their parents from four large cities in mainland China were used. Weight status was determined by measured weight and height. Weight perception, media exposure, attitudes, and health behaviors were assessed by a structured questionnaire survey. RESULTS: Boys were more likely to describe themselves as either too thin or relatively thin than girls (37.32% vs. 18.79%), while girls more often considered themselves either relatively heavy or too heavy than boys (50.83% vs. 26.54%). Girls who were actually normal or underweight were more likely than boys to describe themselves as either relatively heavy or very heavy (41.6% vs. 11.6%), while boys who were actually normal or overweight were more likely than girls to believe themselves as underweight (30.9% vs. 15.7%). Girls who were frequently exposed to media from Japan, Korea, Hong Kong, and Taiwan, and placed high value on their physical appearance, were more likely to be dissatisfied with their body weight, which in turn were more likely to restrict consumption of certain foods, smoke cigarettes, and drink alcohol. Similar results were not observed in boys. CONCLUSIONS: Weight dissatisfaction was prevalent in Chinese adolescents and was significantly related to media exposure, attitudes towards physical appearance, and adoption of certain health-risk behaviors in girls. Our findings underscore the importance of sociocultural influences in shaping realistic body image and have implications for prevention and early intervention for establishing health behavioral practices during adolescence.

Adolescent↗

PubMed2006

Clinical significance of subcellular localization of KL-6 mucin in primary colorectal adenocarcinoma and metastatic tissues.

AIM: To assess subcellular localization of KL-6 mucin and its clinicopathological significance in colorectal carcinoma as well as metastatic lymph node and liver tissues. METHODS: Colorectal carcinoma tissues as well as metastatic lymph node and liver tissues were collected from 82 patients who underwent colorectomy or hepatectomy. Tissues were subjected to immunohistochemical analysis using KL-6 antibody. RESULTS: Of the 82 colorectal carcinoma patients, 6 showed no staining, 29 showed positive staining only in the apical membrane, and 47 showed positive staining in the circumferential membrane and/or cytoplasm. Positive staining was not observed in non-cancerous colorectal epithelial cells surrounding the tumor tissues. The five-year survival rate was significantly lower in cases showing positive staining in the circumferential membrane and/or cytoplasm (63.0%) than those showing positive staining only in the apical membrane (85.7%) and those showing no staining (100%). Statistical analysis between clinicopathological factors and subcellular localization of KL-6 mucin showed that KL-6 localization in the circumferential membrane and/or cytoplasm was significantly associated with the presence of venous invasion (P = 0.0003), lymphatic invasion (P<0.0001), lymph node metastasis (P<0.0001), liver metastasis (P = 0.058), and advanced histological stage (P<0.0001). Positive staining was observed in all metastatic lesions tested as well as in the primary colorectal carcinoma tissues. CONCLUSION: The subcellular staining pattern of KL-6 in colorectal adenocarcinoma may be an important indicator for unfavorable behaviors such as lymph node and liver metastasis, as well as for the prognosis of patients.

Adenocarcinoma↗

PubMed2006

Human homologue of SETA binding protein 1 interacts with cathepsin B and participates in TNF-Induced apoptosis in ovarian cancer cells.

Lysosomal cysteine protease cathepsin B has been reported to play an important role in apoptosis of many different cancer cells, but the regulation of cathepsin B in apoptosis is poorly understood. Human homologue of SETA binding protein 1 (hSB1) was identified to interact with cathepsin B by yeast-two hybrid method, and the interaction was confirmed in vitro GST pull-down assay and in vivo coimmunoprecipitation experiment. hSB1 was co-localized with cathepsin B in cellular lysosomes. Our previous study has shown that TNF can induce ovarian cancer cells OV-90 apoptosis and the apoptosis process is cathepsin B-depended. Here we provide evidence that overexpression of cathepsin B-interacting protein hSB1 could suppress TNF-triggered apoptosis in OV-90 cells, but has no effect on cellular cathepsin B activity. hSB1 may function as a regulator of cathepsin B-mediated apoptosis.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Influences affecting adolescent smoking behavior in China.

This study examined multiple influences on the use of tobacco by adolescents in China. Using the theory of triadic influences as a guide, we selected interpersonal, attitudinal/cultural, and intrapersonal constructs from baseline data to predict adolescent smoking 1 year later. We used prospective data from middle and high school students (N = 11,583) and their parents from the China Seven Cities Study, a longitudinal study that is evaluating the effects of changing economic and social factors on health behaviors including tobacco use. A multilevel regression analysis provided some support that each of the influences in the theory of triadic influences affects adolescent smoking in China. After adjusting for important confounders including age, gender, socioeconomic status, and smoking behaviors (lifetime and past 30-day) at baseline, we found significant risk factors within each of the three categories, including interpersonal influences (parental monitoring, good friend smoking, and peer smoking), attitudinal/cultural influences (school academic ranking, initial liking of smoking, and the meaning of smoking), and intrapersonal influences (susceptibility to smoking, and low self-confidence to quit smoking). Results suggest that the etiology of smoking among adolescents in China might be similar to that observed in western countries and that some of the techniques used successfully in prevention programs in those countries might be useful guides when developing prevention programs in China.

Adolescent↗

PubMed2006

Using caffeoyl pyrrolidine derivative LY52, a potential inhibitor of matrix metalloproteinase-2, to suppress tumor invasion and metastasis.

LY52 is a caffeoyl pyrrolidine derivative designed to fit the S'1 active pocket of gelatinases that act in tumor invasion and metastasis. Herein, we examined the effects of LY52 on expression of matrix metalloproteinase (MMP)-2 expression in human breast cancer MDA-MB-231 cells and on in vitro invasion and in vivo metastasis. LY52 significantly blocked MMP-2 activity as evidenced by a decrease in the degradation of succinylated gelatin. Gelatin zymography analysis showed that LY52 (0.1-200 microg/ml) inhibited expression of active MMP-2 in concanavalin A-stimulated MDA-MB-231 cells. Inhibition of MMP-2 expression was also observed in tissue of tumor xenografts in mice that were orally administered LY52 (25 or 100 mg/kg). Furthermore, LY52 displayed an inhibitory effect on in vitro invasion of MDA-MB-231 cells and pulmonary metastasis of B16F10 murine melanoma cells in mice without significant toxic effects. These results suggest that LY52 is a potential MMP-2 inhibitor that may effectively suppress tumor invasion and metastasis.

Animals↗

PubMed2005

Cathepsin B and its interacting proteins, bikunin and TSRC1, correlate with TNF-induced apoptosis of ovarian cancer cells OV-90.

Increasing evidence suggests that lysosomal cysteine proteases cathepsins contribute to the progression of cell apoptosis. Here we found that apoptosis of ovarian cancer cells OV-90 triggered by TNF was cathepsin B-depended. Two cathepsin B binding proteins, bikunin and TSRC1, were identified by yeast two-hybrid method and the interactions were confirmed in vitro and in vivo. Overexpression of bikunin could suppress TNF-induced apoptosis of OV-90 cells, and TSRC1 overexpression had an opposite effect on apoptosis. The presented results suggest that cathepsin B and its interacting proteins, bikunin and TSRC1, are involved in the apoptotic pathway of ovarian cancer cells.

ADAMTS Proteins↗

PubMed2005

KL-6 mucin expression in carcinoma of the ampulla of Vater: association with cancer progression.

AIM: To assess histochemical expression of KL-6 and its clinicopathological significance in carcinoma of the ampulla of Vater. METHODS: Ampullary carcinoma tissues were collected from 38 patients who underwent pancreatoduodenectomy or local resection. Tissues were subjected to immunohistochemical analysis using KL-6 antibody. RESULTS: Positive staining of ampullary carcinoma cells was observed in 26 (68.4%) cases. Staining was not found in the surrounding non-cancer regions of the ampullary tissues. Remarkable KL-6 expression was observed in invasive carcinoma cells in pancreatic and duodenal tissues and in metastatic carcinoma cells in lymph nodes. Positive KL-6 expression was related to lymph node metastasis (P = 0.020), pancreatic invasion (P = 0.016), duodenal invasion (P = 0.034), and advanced stage of TNM clinical classification (P = 0.010). Survival analysis showed that positive expression of KL-6 was related to a poorer prognosis (P = 0.029). CONCLUSION: The aberrant expression of KL-6 mucin is significantly related to unfavorable behaviors of carcinoma of the ampulla of Vater.

Aged↗

PubMed2005

The competitive dynamics between tumor cells, a replication-competent virus and an immune response.

Replication-competent viruses have been used as an alternative therapeutic approach for cancer treatment. However, new clinical data revealed an innate immune response to virus that may mitigate the effects of treatment. Recently, Wein, Wu and Kirn have established a model which describes the interaction between tumor cells, a replication-competent virus and an immune response (Cancer Research 63 (2003):1317-1324). The purpose of this paper is to extend their model from the viewpoints of mathematics and biology and then prove global existence and uniqueness of solution to this new model, to study the dynamics of this novel therapy for cancers, and to explore a explicit threshold of the intensity of the immune response for controlling the tumor. We also study a time-delayed version of the model. We analytically prove that there exists a critical value tau0 of the time-delay tau such that the system has a periodic solution if tau > tau0. Numerical simulations are given to verify the analytical results. Furthermore, we numerically study the spatio-temporal dynamics of the model. The effects of the diffusivity of the immune response on the tumor growth are also discussed.

Adenoviridae↗

PubMed2005

Des-gamma-carboxyprothrombin expression in cancer and/or non-cancer liver tissues: association with survival of patients with resectable hepatocellular carcinoma.

Des-gamma-carboxyprothrombin (DCP), also known as a protein induced by vitamin K absence or antagonist II, is an abnormal prothrombin. The level of serum DCP is used in clinical diagnosis and prognosis of patients with hepatocellular carcinoma (HCC). Our previous immunohistochemical study showed that DCP is expressed not only in cancer tissues but also in the surrounding non-cancer tissues of HCC patients. However, clinical significance of DCP expression in non-cancer tissues of HCC patients remains unclear. In this study, we examined the relationship between histochemical expression of DCP in cancer and/or non-cancer tissues and the clinical outcome of the HCC patients. A retrospective study was performed of 132 patients each with a single primary HCC nodule. Expression of DCP in tissues was evaluated with immunohistochemical staining using anti-DCP antibody (MU-3). Serum DCP levels were determined using enzyme immunoassay with a double antibody sandwich system. Experimental and clinical data were processed by univariate and multivariate statistical analyses. DCP expression, even if it was observed only in non-cancer tissues, was related to poorer prognosis. Univariate and multivariate analyses showed that DCP expression in cancer and/or non-cancer tissues was a significant prognostic factor. Furthermore, the combined evaluation of tissue DCP expression and serum DCP levels showed that prognosis was poorest for patients showing positive tissue DCP expression and high levels of serum DCP. These results suggest that immunohistochemical evaluation of DCP expression not only in cancer but also in non-cancer tissues serves as a valuable factor in the prognosis of HCC patients and that the combined evaluation of tissue DCP expression and serum DCP level will be more valuable than either factor alone in the effective treatment and prognosis.

Adolescent↗

PubMed2005

Epidermal growth factor-mediated growth control of confluent mammary epithelial cells cultured on artificial basement membrane.

Local epithelial cell growth is involved in physiological and pathological processes such as development, morphogenesis and carcinogenesis. Cell growth is triggered by the binding of growth factors, such as epidermal growth factor (EGF) to their own receptors (i.e. EGFR). In confluent states, EGFRs are distributed on the basal-lateral side of polarized cells. Therefore, the delivery of EGF to EGFR is thought to be regulated by both tight junctions between the cells, as well as by the basement membrane to which the cells are attached. This research constructed a new culture device with which EGF can be delivered to either the basal-lateral or apical side of confluent epithelial cells that are cultured on an artificial Matrigel basement membrane. Cells in a confluent state started to regrow as a result of incubation with basal medium containing EGF, but not as a result of incubation with apical medium containing EGF. The rate of confluent epithelial cell regrowth depended on EGF concentrations supplied via the basement membrane. In contrast, cells in which tight junctions were disrupted by pre-treatment with EGTA displayed regrowth as a result of incubation with apical medium containing EGF. These results suggest that EGF signaling from the basal-lateral side is regulated by the basement membrane, while that from the apical side is blocked by the tight junctions. Thus, this culture model can be readily used to study the control of local growth of epithelial cells in physiological and pathological processes.

Blotting, Western↗