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Biomedical subjects

Liwei Wang

Publications and source records attributed to Liwei Wang.

At least 19 recordsLinked to original sources
PubMed2026

An RPA-assisted homogeneous electrochemical DNA sensor for on-site eDNA detection toward early warning of crown-of-thorns starfish outbreaks.

Crown-of-thorns starfish (COTS) outbreaks seriously threaten coral reef ecosystems, while conventional monitoring approaches are time-consuming and often lack sufficient sensitivity for early warning. Existing electrochemical DNA sensors usually require complex electrode-surface immobilization procedures, which can lead to uneven probe distribution, significant steric hindrance, and poor stability. Meanwhile, the low concentration of environmental DNA (eDNA) in marine environments further complicates detection. To overcome these challenges, this study developed a homogeneous electrochemical DNA sensor assisted by recombinase polymerase amplification (RPA) for COTS eDNA detection. Target DNA was first amplified by RPA, and the amplification products were then hybridized in solution with capture probe (CP)-modified magnetic beads (MB) and biotin-labeled signal probe (SP) to form sandwich-structured MB complexes. These complexes were subsequently magnetically enriched and immobilized on the electrode surface for electrochemical signal readout. Under optimized conditions, the sensor displayed a linear response to COTS genomic DNA from 3.77 fg/μL to 1 ng/μL, with an LOD of 2.02 fg/μL and an LOQ of 3.77 fg/μL. The sensor was applied to Xisha Islands samples, and the results agreed with droplet digital PCR (ddPCR) (P > 0.05), demonstrating its potential for sensitive and reliable on-site COTS eDNA detection.

Animals↗
PubMed2026

Chinese expert consensus on precision testing and molecular diagnosis of pancreatic cancer (2025).

This consensus by the CSCO Pancreatic Cancer Expert Committee establishes evidence-based guidelines for molecular testing in pancreatic ductal adenocarcinoma. It details recommendations for biomarkers (e.g., KRAS, BRCA, MSI), liquid biopsy, and precision imaging to direct targeted therapies and immunotherapy, aiming to standardize diagnosis and optimize individualized patient care. Pancreatic ductal adenocarcinoma (PDAC) is the most common pathological type of primary pancreatic malignancy, accounting for ~95% of cases and generally referred to as pancreatic cancer [1]. Its prognosis is extremely poor and its incidence continues to rise [2]. According to the most recent global cancer statistics, the incidence of pancreatic cancer ranks 12th among all cancers, and its mortality ranks 6th, making it one of the deadliest malignancies worldwide [3]. Approximately 57% of patients have metastatic disease at diagnosis and require systemic therapy, for which chemotherapy remains the standard first-line option [1]. However, the overall response rate to currently available systemic regimens is low, and the 5-year survival rate for patients with metastatic disease remains below 5% [3]. Although most pancreatic cancers harbor canonical driver mutations, they exhibit marked heterogeneity at the molecular level. Whole-genome sequencing (WGS) and integrative genomic analyses have identified molecular subtypes of PDAC with potential clinical relevance [4-9]. With the increasing implementation of precision oncology, the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Pancreatic Cancer give a level 1 recommendation to perform genetic and other molecular testing on tissue or cytologic specimens as part of the pathological diagnostic work-up, in order to guide individualized treatment, including targeted therapy and immunotherapy [10]. To further promote the use of genetic and molecular testing in the precision treatment of pancreatic cancer, the CSCO Pancreatic Cancer Expert Committee convened a multidisciplinary panel to develop the present Chinese Expert Consensus on Precision Testing and Molecular Diagnosis of Pancreatic Cancer (2025), aiming to provide clinicians with an authoritative reference for precision diagnostics and treatment decision-making.

Humans↗
PubMed2007

The death domain superfamily in intracellular signaling of apoptosis and inflammation.

The death domain (DD) superfamily comprising the death domain (DD) subfamily, the death effector domain (DED) subfamily, the caspase recruitment domain (CARD) subfamily, and the pyrin domain (PYD) subfamily is one of the largest domain superfamilies. By mediating homotypic interactions within each domain subfamily, these proteins play important roles in the assembly and activation of apoptotic and inflammatory complexes. In this chapter, we review the molecular complexes assembled by these proteins, the structural and biochemical features of these domains, and the molecular interactions mediated by them. By analyzing the potential molecular basis for the function of these domains, we hope to provide a comprehensive understanding of the function, structure, interaction, and evolution of this important family of domains.

Animals↗
PubMed2006

Association of elevated GRP78 expression with increased lymph node metastasis and poor prognosis in patients with gastric cancer.

Glucose-regulated protein 78 (GRP78) has been implicated in the protection of tumor cells from cytotoxic damage and apoptosis and thus assists cells in survival under oxygen-deprivation and nutrient-stress conditions. However, its expression and potential role in gastric cancer development and progression have not been reported. In the present study, we determined the level of GRP78 expression in the primary tumor in 86 cases of resected gastric cancer by using immunohistochemistry and analyzed the relationships between GRP78 and clinicopathological characteristics. We found that GRP78 was overexpressed in the tumor specimens when compared with the expression in adjacent tumor-free gastric mucosa. Furthermore, the level of GRP78 expression in both primary tumors and metastatic lymph nodes was inversely correlated with patient survival. Overexpression of GRP78 was directly correlated with Sp1 expression and increased lymph node metastasis. Knocking down GRP78 expression inhibited tumor cell invasion in vitro and growth and metastasis in a xenograft nude mouse model. Therefore, our data imply that dysregulated expression of GRP78 may contribute to the development and progression of gastric cancer.

Adult↗
PubMed2006

Proteolytic stability of insecticidal toxins expressed in recombinant bacilli.

The production of the vegetative mosquitocidal toxin Mtx1 from Bacillus sphaericus was redirected to the sporulation phase by replacement of its weak, native promoter with the strong sporulation promoter of the bin genes. Recombinant bacilli developed toxicity during early sporulation, but this declined rapidly in later stages, indicating the proteolytic instability of the toxin. Inhibition studies indicated the action of a serine proteinase, and similar degradation was also seen with the purified B. sphaericus enzyme sphericase. Following the identification of the initial cleavage site involved in this degradation, mutant Mtx1 proteins were expressed in an attempt to overcome destructive cleavage while remaining capable of proteolytic activation. However, the apparently broad specificity of sphericase seems to make this impossible. The stability of a further vegetative toxin, Mtx2, was also found to be low when it was exposed to sphericase or conditioned medium. Random mutation of the receptor binding loops of the Bacillus thuringiensis Cry1Aa toxin did, in contrast, allow production of significant levels of spore-associated protein in the form of parasporal crystals. The exploitation of vegetative toxins may, therefore, be greatly limited by their susceptibility to proteinases produced by the host bacteria, whereas the sequestration of sporulation-associated toxins into crystals may make them more amenable to use in strain improvement.

Amino Acid Sequence↗
PubMed2006

RUNX3 inhibits the expression of vascular endothelial growth factor and reduces the angiogenesis, growth, and metastasis of human gastric cancer.

PURPOSE: Recent studies indicated that RUNX3 exhibits potent antitumor activity. However, the underlying molecular mechanisms of this activity remain unclear. In the present study, we used a gastric cancer model to determine the effect of RUNX3 expression on tumor angiogenesis. EXPERIMENTAL DESIGN: The effects of increased RUNX3 expression on vascular endothelial growth factor (VEGF) expression in and angiogenic potential of human gastric cancer cells were determined in vitro and in animal models. RUNX3 and VEGF expression was determined in 120 human gastric cancer specimens and their relationship was analyzed. RESULTS: RUNX3 gene transfer suppressed VEGF expression in human gastric cancer cells. Down-regulation of VEGF expression correlated with a significantly impaired angiogenic potential of human gastric cancer cells. Furthermore, RUNX3 restoration inhibited tumor growth and metastasis in animal models, which was consistent with inhibition of angiogenesis as determined by evaluating VEGF expression and tumor microvessel formation. In gastric cancer specimens, loss or decrease in RUNX3 expression inversely associated with increased VEGF expression and elevated microvessel formation. CONCLUSIONS: Our clinical and experimental data provide a novel molecular mechanism for the antitumor activity of RUNX3 and may help design effective therapy targeting RUNX3 pathway to control gastric cancer growth and metastasis.

Adenocarcinoma↗
PubMed2006

A new method for measuring reaction times for odour detection at iso-intensity: Comparison between an unpleasant and pleasant odour.

A psychophysical detection test was developed to measure the reaction time of human subjects to a pleasant and an unpleasant odour. The response latencies to stimulation with a malodour (valeric acid) and pleasant odorant (amyl acetate) were compared over a range of different stimulus strengths. By expressing reaction time as a function of detection rate, the responses to the two odours can be compared at iso-intensity across the concentration range. This is the first study that allows odorants to be compared at the same intensity over a range of concentrations. The malodour valeric acid was detected more rapidly than amyl acetate; at the 50% detection level the reaction time for the detection of amyl acetate was 1.74 s compared 1.36 s for valeric acid (380 ms or 22% faster). Women were significantly faster than men at detecting both the unpleasant (by 18%) and pleasant (by 26%) odour at the 50% detection level and this disparity increased with decreasing stimulus strength. In conclusion, we demonstrate the ability of a new method for the measurement of reaction times to odour detection to discriminate between two different odours - a malodour and a non-malodour.

Adolescent↗
PubMed2006

On image matrix based feature extraction algorithms.

Principal component analysis (PCA) and linear discriminant analysis (LDA) are two important feature extraction methods and have been widely applied in a variety of areas. A limitation of PCA and LDA is that when dealing with image data, the image matrices must be first transformed into vectors, which are usually of very high dimensionality. This causes expensive computational cost and sometimes the singularity problem. Recently two methods called two-dimensional PCA (2DPCA) and two-dimensional LDA (2DLDA) were proposed to overcome this disadvantage by working directly on 2-D image matrices without a vectorization procedure. The 2DPCA and 2DLDA significantly reduce the computational effort and the possibility of singularity in feature extraction. In this paper, we show that these matrices based 2-D algorithms are equivalent to special cases of image block based feature extraction, i.e., partition each image into several blocks and perform standard PCA or LDA on the aggregate of all image blocks. These results thus provide a better understanding of the 2-D feature extraction approaches.

Algorithms↗
PubMed2005

Crystal structure of MC159 reveals molecular mechanism of DISC assembly and FLIP inhibition.

The death-inducing signaling complex (DISC) comprising Fas, Fas-associated death domain (FADD), and caspase-8/10 is assembled via homotypic associations between death domains (DDs) of Fas and FADD and between death effector domains (DEDs) of FADD and caspase-8/10. Caspase-8/10 and FLICE/caspase-8 inhibitory proteins (FLIPs) that inhibit caspase activation at the DISC level contain tandem DEDs. Here, we report the crystal structure of a viral FLIP, MC159, at 1.2 Angstroms resolution. It reveals a noncanonical fold of DED1, a dumbbell-shaped structure with rigidly associated DEDs and a different mode of interaction in the DD superfamily. Whereas the conserved hydrophobic patch of DED1 interacts with DED2, the corresponding region of DED2 mediates caspase-8 recruitment and contributes to DISC assembly. In contrast, MC159 cooperatively assembles with Fas and FADD via an extensive surface that encompasses the conserved charge triad. This interaction apparently competes with FADD self-association and disrupts higher-order oligomerization required for caspase activation in the DISC.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Changes in the odor quality of androstadienone during exposure-induced sensitization.

Androstadienone is a steroid found in human sweat and other secretions. It has been widely proposed as a candidate for a human pheromone. As an odorant it possesses some unique properties. Here we demonstrate that, firstly, there is a very wide range of thresholds in the human population, and they are not normally distributed. Secondly, repetitive exposure causes a decrease in detection threshold of more than four orders of magnitude, and thirdly, accompanying this sensitization process is a change in the perceived odor quality. Those with low to intermediate sensitivities ascribe to it a wide range of odor descriptors across the hedonic scale, but as these individuals become sensitized, their description changes to predominantly putrid. We propose that this change in odor quality reflects the presence of at least two receptor populations for androstadienone; a low-affinity receptor conveying pleasant odor qualities and a high-affinity receptor mediating unpleasant odor qualities. We further propose that repetitive exposure results in the increased expression of the high-affinity receptor thereby shifting the balance of perception to the negative end of the hedonic scale.

Adult↗
PubMed2005

Expression of autocrine motility factor correlates with the angiogenic phenotype of and poor prognosis for human gastric cancer.

Autocrine motility factor (AMF) is a cytokine known to regulate tumor cell motility. Recent studies have extended its role to many other aspects of cancer biology. In the present study, we examined the level of AMF expression and its relationship with vascular endothelial growth factor (VEGF) expression and the angiogenic phenotype in human gastric cancer and their effect on survival. The AMF and VEGF expression level and tumor microvessel density (MVD) status in archived tissue specimens from 86 resected gastric cancer cases were determined. AMF expression was significantly higher in both primary tumors and lymph node metastases than in adjacent normal gastric mucosa and normal gastric mucosa from individuals without gastric cancer. In univariate survival analyses, strong AMF expression was associated with inferior survival (P = 0.028). In a Cox proportional hazards model, strong AMF expression (P = 0.019) was independently prognostic of poor survival. Strong AMF expression in the lymph node metastases was associated with poor survival (P = 0.011). Furthermore, AMF expression in the primary tumors was directly correlated with VEGF expression and MVD status. We found the first clinical evidence that AMF expression is directly correlated with VEGF expression and MVD status and predicts clinical outcome in patients with gastric cancer, supporting the hypothesis that the AMF/AMF receptor pathway plays an important role in multiple aspects of cancer biology.

Antigens, CD34↗
PubMed2005

Polymorphisms of thymidylate synthase in the 5'- and 3'-untranslated regions associated with risk of gastric cancer in South China: a case-control analysis.

Fruits and certain vegetables have a protective effect on gastric cancer (GC) and folate is one of the nutrients in fruits and vegetables. We hypothesized that the polymorphisms of thymidylate synthase (TYMS) gene involved in folate metabolism are associated with GC risk. In a population-based case-control study of 337 GC cases and 326 controls, frequency-matched by age, sex and residential areas in a southern Chinese population, we genotyped the 28 bp tandem repeat in the TYMS 5'-untranslated enhanced region (TSER) and the 6 bp deletion/insertion at bp 1494 in the TYMS 3'-untranslated region (TS3'UTR). We found that although the TSER polymorphism had no main effect on GC risk, the TS3'UTR 6 bp/6 bp genotype was associated with a significantly increased risk of GC [adjusted odds ratio (OR) = 1.96, 95% confidence interval (CI) = 1.18-3.25], especially the non-cardiac gastric cancer (2.16, 1.22-3.82), compared with the 0 bp/0 bp genotype. However, when we evaluated these two polymorphisms together and used the combined genotype with zero variant allele (TSER 2R and TS3'UTR 6 bp variant alleles) as the reference, we found that the combined genotype with three or four variant alleles was associated with a significantly increased risk of GC (2.06, 1.12-3.79), especially the non-cardiac gastric cancer (2.33, 1.19-4.59), and this significant association was more pronounced among older women (>60 years old), non-smokers, and never tea drinkers. In conclusion, the TYMS polymorphisms, especially the TS3'UTR polymorphism, are associated with GC risk, especially the non-cardiac gastric cancer, and the TSER 2R and TS3'UTR 6 bp alleles may jointly play a role in the etiology of GC in the southern Chinese population. Larger studies are warranted to verify these findings.

3' Untranslated Regions↗
PubMed2005

Loss of RUNX3 expression significantly affects the clinical outcome of gastric cancer patients and its restoration causes drastic suppression of tumor growth and metastasis.

Identification of precise prognostic marker and effective therapeutic target is pivotal in the treatment of gastric cancer. In the present study, we determined the level of RUNX3 expression in gastric cancer cells and gastric cancer specimens and the impact of its alteration on cancer biology and clinical outcome. There was a loss or substantial decrease of RUNX3 protein expression in 86 cases of gastric tumors as compared with that in normal gastric mucosa (P < 0.0001), which was significantly associated with inferior survival duration (P = 0.0005). In a Cox proportional hazards model, RUNX3 expression independently predicted better survival (P = 0.036). Moreover, various human gastric cancer cell lines also exhibited loss or drastic decrease of RUNX3 expression. Enforced restoration of RUNX3 expression led to down-regulation of cyclin D1 but to up-regulation of p27, caspase 3, 7, and 8 expression, cell cycle arrest, and apoptosis in vitro, and dramatic attenuation of tumor growth and abrogation of metastasis in animal models. Therefore, we offered both clinical and mechanistic evidence that RUNX3 was an independent prognostic factor and a potential therapeutic target for gastric cancer.

Apoptosis↗
PubMed2005

Drastic down-regulation of Krüppel-like factor 4 expression is critical in human gastric cancer development and progression.

Krüppel-like factor 4 (KLF4) is highly expressed in epithelial tissues such as the gut and skin. However, the role of KLF4 in human gastric cancer development and progression is unknown. Here we show that KLF4 protein expression was decreased or lost in primary tumors and, in particular, lymph node metastases when compared with that in normal gastric mucosa. Moreover, loss of KLF4 expression in the primary tumors was significantly associated with poor survival, and also an independent prognostic marker in a multivariate analysis. Consistently, most human gastric cancer cell lines exhibited loss of or a substantial decrease in KLF4 expression at both RNA and protein levels. Enforced restoration of KLF4 expression resulted in marked cell growth inhibition in vitro and significantly attenuated tumor growth and total abrogation of metastasis in an orthotopic animal model of gastric cancer. Mechanism studies indicated that promoter hypermethylation and hemizygous deletion contributed to the down-regulation of KLF4 expression and the induction of apoptosis contributed to the antitumor activity of KLF4. Collectively, our data provide first clinical and casual evidence and potential mechanism that the alteration of KLF4 expression plays a critical role in gastric cancer development and progression.

Aged↗
PubMed2005

Expression of activated signal transducer and activator of transcription 3 predicts expression of vascular endothelial growth factor in and angiogenic phenotype of human gastric cancer.

PURPOSE: Angiogenic behavior is a critical aspect of cancer biology and subject to regulation by multiple molecular pathways. Because the signal transducer and activator of transcription 3 (Stat3) transcription factor regulates multiple genes important to angiogenesis, we sought to determine whether Stat3 expression is related to vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) in gastric cancer and whether these factors predict survival in gastric cancer patients. EXPERIMENTAL DESIGN: The expression of Stat3 and VEGF was determined by immunohistochemistry using archival tissues from 86 cases of resected human gastric cancer and confirmed by Western blot analysis. Angiogenic phenotype was determined by CD34 staining and microvessel counting. RESULTS: Stat3 expression correlated with VEGF expression and MVD. In univariate survival analyses, Stat3 expression (P = 0.013) and MVD (P = 0.036) were associated with inferior survival. However, when Stat3 expression, VEGF expression, MVD, stage, completeness of resection, Lauren's histologic classification, and age were entered into a Cox proportional hazards model, only strong Stat3 expression (P = 0.049) and advanced stage (P < 0.01) were independently prognostic of poor survival. Furthermore, genetically enforced alterations of activated Stat3 expression led to altered VEGF expression and angiogenic potential in human gastric cancer cells. CONCLUSION: Dysregulated Stat3 activation may play an important role in VEGF overexpression and elevated angiogenic phenotype in gastric cancer and contribute to gastric cancer development and progression.

Antigens, CD34↗
PubMed2005

Structure formation in injectable poly(lactide-co-glycolide) depots. II. Nature of the gel.

The benzyl benzoate solutions of poly(D,L-lactide-co-glycolide), a random oriented synthesized copolymer with L/G ratio of 50:50, have been shown to form gels during aging and upon injection into buffer or water. The gelation properties influence drug release kinetics for these injectable, depot-forming solutions. In this article, we report on the mechanism of gelation. We find that only polymers that have a certain average block length of glycolide units form gels during aging as well as depots upon in vitro. Thus, gel formation is likely due to the formation of ordered solvated aggregates of blocky glycolide units. Rheometry, differential scanning calorimetry, and nuclear magnetic resonance were used to investigate the gelation kinetics and the polymer molecular parameters. Of all the polymers used, poly(lactide-co-glycolide)s with glycolide average block length <2.9 did not show any gelation behavior. The details of the gelation process are also solvent dependent.

Calorimetry, Differential Scanning↗
PubMed2005

Expression of endothelial nitric oxide synthase correlates with the angiogenic phenotype of and predicts poor prognosis in human gastric cancer.

BACKGROUND: Angiogenesis is a critical aspect of cancer biology and is subject to regulation by multiple molecular pathways. We evaluated the expression of nitric oxide synthase (NOS) III and its relationship with the angiogenic phenotype and expression of the transcription factor Sp1, as well as their effect on survival in patients with gastric cancer. METHODS: The NOS III expression level and tumor microvessel density (MVD) status were determined via immunohistochemistry, using archived tissue specimens from 86 resected gastric cancer cases; these findings were then correlated with Sp1 expression and clinicopathological features. RESULTS: NOS III protein expression was significantly higher in both primary tumors and lymph node metastases than in normal gastric mucosa. In primary tumors, NOS III expression correlated highly with Sp1 expression (P = 0.001) and MVD status (P = 0.001). Patients with strong Sp1 expression were more likely to have strong NOS III expression (15 times) and a high MVD (7 times) than were those with negative Sp1 expression. In univariate survival analyses, strong NOS III expression (P = 0.042), strong Sp1 expression (P = 0.007), and a high MVD (P = 0.036) were associated with worse survival. However, when patients' NOS III and Sp1 expression levels, MVD status, disease stage, completeness of resection, Lauren's classification, and age were entered in a Cox proportional hazards model, only strong NOS III (P = 0.019) and Sp1 expression (P = 0.029) and advanced disease stage (P = 0.006) were independently prognostic of poor survival. CONCLUSION: Our results indicated that the expression of NOS III, a potential downstream effector of Sp1, may play an important role in tumor angiogenesis and aggressiveness in gastric cancer.

Age Factors↗