Bacteria/Nanozyme Composites: New Therapeutics for Disease Treatment.

Bacterial therapy is recognized as a cost-effective treatment for several diseases. However, its development is hindered by limited functionality, weak inherent therapeutic effects, and vulnerability to harsh microenvironmental conditions, leading to suboptimal treatment activity. Enhancing bacterial activity and therapeutic outcomes emerges as a pivotal challenge. Nanozymes have garnered significant attention due to their enzyme-mimic activities and high stability. They enable bacteria to mimic the functions of gene-edited bacteria expressing the same functional enzymes, thereby improving bacterial activity and therapeutic efficacy. This review delineates the therapeutic mechanisms of bacteria and nanozymes, followed by a summary of strategies for preparing bacteria/nanozyme composites. Additionally, the synergistic effects of such composites in biomedical applications such as gastrointestinal diseases and tumors are highlighted. Finally, the challenges of bacteria/nanozyme composites are discussed and propose potential solutions. This study aims to provide valuable insights to offer theoretical guidance for the advancement of nanomaterial-assisted bacterial therapy.

Supramolecular Lipid Nanoparticles Based on Host-Guest Recognition: A New Generation Delivery System of mRNA Vaccines For Cancer Immunotherapy.

Dendritic cell (DC) maturation is a crucial process for antigen presentation and the initiation of T cell-mediated immune responses. Toll-like receptors play pivotal roles in stimulating DC maturation and promoting antigen presentation. Here, a novel message RNA (mRNA) cancer vaccine is reported that boosts antitumor efficacy by codelivering an mRNA encoding tumor antigen and a TLR7/8 agonist (R848) to DC using supramolecular lipid nanoparticles (SMLNP) as a delivery platform, in which a new ionizable lipid (N2-3L) remarkably enhances the translation efficiency of mRNA and a ß-cyclodextrin (ß-CD)-modified ionizable lipid (Lip-CD) encapsulates R848. The incorporation of R848 adjuvant into the mRNA vaccine through noncovalent host-guest complexation significantly promotes DC maturation and antigen presentation after vaccination, thus resulting in superior antitumor efficacy in vivo. Moreover, the antitumor efficacy is further boosted synergized with immune checkpoint blockade by potentiating the anticancer capability of cytotoxic T lymphocytes infiltrated in tumor sites. This work indicates that SMLNP shows brilliant potential as next-generation delivery system in the development of mRNA vaccines with high efficacy.

Engineering Clinically Relevant Probiotics with Switchable "Nano-Promoter" and "Nano-Effector" for Precision Tumor Therapy.

Probiotics have the potential as biotherapeutic agents for cancer management in preclinical models and human trials by secreting antineoplastic or immunoregulatory agents in the tumor microenvironment (TME). However, current probiotics lack the ability to dynamically respond to unique TME characteristics, leading to limited therapeutic accuracy and efficacy. Although progress has been made in customizing controllable probiotics through synthetic biology, the engineering process is complex and the predictability of production is relatively low. To address this, here, for the first time, this work adopts pH-dependent peroxidase-like (POD-like) artificial enzymes as both an inducible "nano-promoter" and "nano-effector" to engineer clinically relevant probiotics to achieve switchable control of probiotic therapy. The nanozyme initially serves as an inducible "nano-promoter," generating trace amounts of nonlethal reactive oxygen species (ROS) stress to upregulate acidic metabolites in probiotics. Once metabolites acidify the TME to a threshold, the nanozyme switches to a "nano-effector," producing a great deal of lethal ROS to fight cancer. This approach shows promise in subcutaneous, orthotopic, and colitis-associated colorectal cancer tumors, offering a new methodology for modulating probiotic metabolism in a pathological environment.

Relevance and mechanism of STAT3/miR-221-3p/Fascin-1 axis in EGFR TKI resistance of triple-negative breast cancer.

The epidermal growth factor receptor 1 (EGFR) plays a crucial role in the progression of various malignant tumors and is considered a potential target for treating triple-negative breast cancer (TNBC). However, the effectiveness of representative tyrosine kinase inhibitors (TKIs) used in EGFR-targeted therapy is limited in TNBC patients. In our study, we observed that the TNBC cell lines MDA-MB-231 and MDA-MB-468 exhibited resistance to Gefitinib. Treatment with Gefitinib caused an upregulation of Fascin-1 (FSCN1) protein expression and a downregulation of miR-221-3p in these cell lines. However, sensitivity to Gefitinib was significantly improved in both cell lines with either inhibition of FSCN1 expression or overexpression of miR-221-3p. Our luciferase reporter assay confirmed that FSCN1 is a target of miR-221-3p. Moreover, Gefitinib treatment resulted in an upregulation of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in MDA-MB-231 cells. Using Stattic, a small-molecule inhibitor of STAT3, we observed a significant enhancement in the inhibitory effect of Gefitinib on the growth, migration, and invasion of MDA-MB-231 cells. Additionally, Stattic treatment upregulated miR-221-3p expression and downregulated FSCN1 mRNA and protein expression. A strong positive correlation was noted between the expression of STAT3 and FSCN1 in breast cancer tissues. Furthermore, patients with high expression levels of both STAT3 and FSCN1 had a worse prognosis. Our findings suggest that elevated FSCN1 expression is linked to primary resistance to EGFR TKIs in TNBC. Moreover, we propose that STAT3 regulates the expression of miR-221-3p/FSCN1 and therefore modulates resistance to EGFR TKI therapy in TNBC. Combining EGFR TKI therapy with inhibition of FSCN1 or STAT3 may offer a promising new therapeutic option for TNBC.

Experience of high polymer gel pad assisted ultrasound monitoring in the treatment of infant urolithiasis during extracorporeal shock wave lithotripsy.

In the extracorporeal shock wave lithotripsy for infants, we used a medical polymer gel pad to assist ultrasonic positioning, so that the ultrasonic probe could be far away from the shock wave energy field. Although not affecting the ultrasonic positioning and monitoring effect, we discussed the protective effect of this method on the ultrasonic probe. A retrospective analysis was made on 21 infants (0-3 years old) who received ESWL in our hospital from June 2021 to February 2023. After the stones were accurately located by B-ultrasound before surgery, a 4 * 5 * 10 cm medical polymer gel pad was placed between the skin and the ultrasonic probe to keep the ultrasonic probe away from the shock wave energy field. The B-ultrasonic wave source locked the target stone through the gel pad, and the lithotripter Dornier Compact Delta II was used for lithotripsy. The extracorporeal shock wave lithotripsy was completed under the whole process of B-ultrasonic monitoring. All patients completed the surgery under ultrasound monitoring, and there were no abnormalities in the ultrasound probe during the surgery. The average stone size was 0.60 ± 0.21 cm, the surgical time was 39.8 ± 13.8 min, and the total energy of lithotripsy was 7.41 ± 4.35 J. There were no obvious complications in all patients after the surgery. After 2 weeks of ultrasound examination, the success rate of lithotripsy in 21 patients reached 85.7%. We believe that the use of the gel pad increases the distance between the ultrasonic probe and the skin, leaving the probe away from the shock wave energy field, avoiding the damage of the shock wave source to the ultrasonic probe, and does not affect the monitoring effect of ultrasound on stones and the success rate of lithotripsy, which is worthy of further promotion in the field of children's urinary stones.

The impact of Angiopoietin-2 genetic polymorphisms on susceptibility for malignant breast neoplasms.

Breast cancer causes morbidity and mortality among women worldwide, despite much research illuminating the genetic basis of this disease. Anti-angiogenesis therapies have been widely studied, although the association between angiopoietin-2 (ANGPT2) single nucleotide polymorphisms (SNPs) and breast cancer subtypes remains unclear. This case-control study included 464 patients with malignant breast neoplasms and 539 cancer-free females. We explored the effects of ANGPT2 SNPs on the susceptibility for a malignant breast neoplasm in a Chinese Han population. Five ANGPT2 SNPs (rs2442598, rs734701, rs1823375, 11,137,037, and rs12674822) were analyzed using TaqMan SNP genotyping. Carriers of the variant GG allele of rs1823375 were less likely than wild-type carriers to be diagnosed with clinically staged breast cancer, while females with human epidermal growth factor receptor 2 (HER2)-enriched disease carrying the CG or the CG+GG genotype at rs1823375 were significantly less likely than CC genotype carriers to be of lymph node status N1-N3. We also found that the T-T-C-A-T ANGPT2 haplotype significantly increased the risk for developing a malignant breast neoplasm by 1.385-fold (95% CI: 1.025-1.871; p < 0.05). Our study is the first to document a correlation between ANGPT2 polymorphisms and the development and progression of a malignant breast neoplasm in females of Chinese Han ethnicity.

Development and Validation of a Homemade and Low-Cost Three-Dimensional Laparoscopic Simulator for Novices.

Background: The aim of this study was to design a low-cost three-dimensional (3D) laparoscopic simulator and validate its training effectiveness. Materials and Methods: We designed a low-cost 3D laparoscopic simulator using magnifying glass and cardboard box. Thirty-two laparoscopic novices were randomly divided into 3D group and two-dimensional (2D) group. The 3D group was trained on 3D simulator four times with 24 hours interval, and the 2D group was trained on 2D simulator. Five standardized laparoscopic tasks were performed by novices in each training. In the second part, subjects were transferred to the opposite simulator for one test after 24 hours of the fourth training. The completing time and errors for each task were recorded to assess the construct validity of simulator. Finally, the face validity and the content validity were evaluated through a closed-ended questionnaire. Results: There was no significant difference between the two groups in demographic or psychometric variables (P > .05). Compared with the 2D group, novices using 3D simulator had a better performance in five laparoscopic tasks, including a faster completing time (P < .001) and lower errors during training (P < .05). Additionally, the increased laparoscopic skill involved with our 3D simulator could be transferred to subsequent performance in 2D simulator (P < .05). Meanwhile, the score of face validity and content validity in our 3D simulator was significantly higher than that in 2D simulator (P < .05). Conclusion: Our 3D laparoscopic simulator effectively improved laparoscopic skills of novice surgeons, suggesting that the low-cost 3D simulator had satisfactory performance to satisfy requirement for novice training.

Evodiamine suppresses the progression of non-small cell lung carcinoma via endoplasmic reticulum stress-mediated apoptosis pathway in vivo and in vitro.

BACKGROUND: Evodiamine (EVO) is one of the major components isolated from Evodia rutaecarpa (Juss.). Recent studies have shown that EVO has an anti-cancer effect. However, the pharmacological mechanism by which EVO impacts cancer is still poorly understood. OBJECTIVES: This study focused on asking the anti-cancer effect of EVO in human non-small cell lung carcinoma (NSCLC), and in particular to investigate whether EVO acts via modulating the endoplasmic reticulum stress (ERS)-mediated apoptosis pathway. MATERIALS AND METHODS: A Lewis lung carcinoma (LLC) tumor-bearing mouse model was treated with low-dose EVO (5 mg/kg) and high-dose EVO (10 mg/kg) intraperitoneally for 14 d. The effects of EVO on tumor growth, apoptosis, and ERS were assessed. In addition, NSCLC A549 and LLC cells were treated with EVO in vitro. The effects of EVO on cell proliferation, apoptosis, and ERS were investigated. Finally, 4-phenylbutyric acid (4-PBA), an ERS inhibitor, was used to validate whether EVO induced apoptosis of NSCLC cells by modulating ERS. RESULTS: EVO treatment significantly inhibited tumor growth in LLC tumor-bearing mice. H&E staining indicated that EVO treatment reduced the number of tumor cells and the nucleo-plasmic ratio. Immunostaining showed that EVO treatment significantly decreased the expression of Ki-67. TUNEL staining revealed that EVO induced apoptosis in the tumor. Likewise, EVO treatment up-regulated the expression of apoptosis-related genes and proteins and increased activation of the ERS pathway in the tumor. Additionally, EVO inhibited cell proliferation and increased cell apoptotic rates in A549 and LLC cells. EVO also increased the expression levels of genes and proteins associated with ERS-mediated apoptosis pathway in vitro. The effects of EVO on apoptosis were abolished by 4-PBA treatment. CONCLUSIONS: Our study demonstrated that EVO suppresses the progression of NSCLC by modulating the ERS-mediated apoptosis pathway.

An NIR Discrete Metallacycle Constructed from Perylene Bisimide and Tetraphenylethylene Fluorophores for Imaging-Guided Cancer Radio-Chemotherapy.

To promote the clinical theranostic performances of platinum-based anticancer drugs, imaging capability is urgently desired, and their chemotherapeutic efficacy needs to be upgraded. Herein, a theranostic metallacycle (M) is developed for imaging-guided cancer radio-chemotherapy using perylene bisimide fluorophore (PPy) and tetraphenylethylene-based di-Pt(II) organometallic precursor (TPE-Pt) as building blocks. The formation of this discrete supramolecular coordination complex facilitates the encapsulation of M by a glutathione (GSH)-responsive amphiphilic block copolymer to prepare M-loaded nanoparticles (MNPs). TPE-Pt acts as a chemotherapeutic drug and also an excellent radiosensitizer, thus incorporating radiotherapy into the nanomedicine to accelerate the therapeutic efficacy and overcome drug resistance. The NIR-emission of PPy is employed to detect the intracellular delivery and tissue distribution of MNPs in real time. In vitro and in vivo investigations demonstrate the excellent anticancer efficacy combining chemotherapy and radiotherapy; the administration of this nanomedicine effectively inhibits the tumor growth and greatly extends the survival rate of cisplatin-resistant A2780CIS-tumor-bearing mice. Guided by in vivo fluorescence imaging, radio-chemotherapy is precisely carried out, which facilitates boosting of the therapeutic outcomes and minimizing undesired side effects. The success of this theranostic system brings new hope to supramolecular nanomedicines for their potential clinical translations.

Geniposide Ameliorates Liver Fibrosis Through Reducing Oxidative Stress and Inflammatory Respose, Inhibiting Apoptosis and Modulating Overall Metabolism.

Liver fibrosis is a progressive liver damage condition caused by various factors and may progress toward liver cirrhosis, and even hepatocellular carcinoma. Many studies have found that the disfunction in metabolism could contribute to the development of liver fibrosis. Geniposide, derived from Gardenia jasminoides J. Ellis, has been demonstrated with therapeutic effects on liver fibrosis. However, the exact molecular mechanisms of such liver-protection remain largely unknown. The aim of this study was to explored the effect of geniposide on metabolic regulations in liver fibrosis. We used carbon tetrachloride (CCl4) to construct a mouse model of liver fibrosis and subsequently administered geniposide treatment. Therapeutic effects of geniposide on liver fibrosis were accessed through measuring the levels of hepatic enzymes in serum and the pathological changes in liver. We also investigated the effects of geniposide on inflammatory response, oxidative stress and apoptosis in liver. Furthermore, serum untargeted metabolomics were used to explore the metabolic regulatory mechanisms behind geniposide on liver fibrosis. Our results demonstrated that geniposide could reduce the levels of hepatic enzymes in serum and ameliorate the pathological changes in liver fibrosis mice. Geniposide enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased methane dicarboxylic aldehyde (MDA) levels in liver. Geniposide treatment also decreased the levels of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-alpha (TNF-a) in liver tissue homogenate. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining demonstrated that geniposide could reduce the apoptosis of hepatocytes. Geniposide increased the protein expression of B-cell lymphoma-2 (Bcl-2) and downregulated the protein expression of Bcl-2 Associated X (Bax), cleaved-Caspase 3, and cleaved-Caspase 9. Serum untargeted metabolomics analysis demonstrated that geniposide treatment improved the metabolic disorders including glycerophospholipid metabolism, arginine and proline metabolism, and arachidonic acid (AA) metabolism. In conclusion, our study demonstrated the protective effects of geniposide on liver fibrosis. We found that geniposide could treat liver fibrosis by inhibiting oxidative stress, reducing inflammatory response and apoptosis in the liver, and modulating glycerophospholipid, and arginine, proline, and AA metabolism processes.

Plasmon-Driven Catalytic Chemotherapy Augments Cancer Immunotherapy through Induction of Immunogenic Cell Death and Blockage of IDO Pathway.

Clinical trials confirm the combination of indoleamine 2,3-dioxygenase (IDO) blockade and immunogenic chemotherapy represents a brilliant future in cancer therapy. However, it remains challenging to precisely activate chemo-immunotherapy in situ to avoid side effects from the systemic administrations and reverse the poor immunogenicity and immunosuppressive microenvironment in tumor sites. Herein, a hybrid nanomedicine ("RPMANB NPs") to co-deliver an IDO inhibitor (NLG919) and a chemotherapeutic prodrug to amplify the therapeutic benefits are designed. Attributed to the delicate surface engineering, the RPMANB NPs possess excellent pharmacokinetics and tumor accumulation. The loaded NLG919 are released inside cancer tissues/cells due to the collapse of the metal-organic framework platform triggered by the highly concentrated phosphate, reversing the immunosuppressive tumor microenvironment by suppressing IDO activity. The potent chemotherapeutic drug is precisely activated through a highly efficient plasmon-driven catalysis in the presence of near-infrared light, eliciting antitumor immunity by triggering immunogenic cell death and avoiding side effects through in situ activation of chemotherapy. In vivo studies demonstrate that the chemo-immunotherapy greatly suppresses the tumor growth by promoting intratumoral accumulation of cytotoxic T lymphocytes and downregulating regulatory T cells. This work establishes a robust delivery platform to overcome the current obstacles of tumor treatments by combining precisely activatable chemotherapy with immunotherapy.

p-STAT3 expression in breast cancer correlates negatively with tumor size and HER2 status.

ABSTRACT: Although some studies have reported the expression and clinical significance of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in breast cancer tissues, it is still controversial whether p-STAT3 play a role in promoting or suppressing cancer. Here, we used immunohistochemistry analysis to explore expression of p-STAT3 in 407 cases of breast cancer, and analyzed the relationship between p-STAT3 expression and the clinicopathological characteristics and prognosis of breast cancer patients. Positive p-STAT3 expression was seen in 112 cases (27.5%) of breast cancer. p-STAT3 expression was negatively correlated with tumor size, tumor stage and human epidermal growth factor receptor 2 (HER2) status, and the positive rate of p-STAT3 was lowest in HER2-enriched subtype breast cancer (15.3%), while other subtypes were luminal B (23.0%), luminal A (30.2%), and triple-negative breast cancer (TNBC) (37.5%). Logistic regression model multivariate analysis showed that the independent correlation factor of p-STAT3 expression in breast cancer was tumor size (OR = 0.187, 95% CI = 0.042-0.839, P = .029) and HER2 status (OR = 0.392, 95% CI = 0.216-0.710, P = .002). In this study, no clear relationship was observed between patients' prognosis and expression of p-STAT3. Therefore, we suggest that p-STAT3 expression in breast cancer is negatively correlated with tumor size and HER2 status, but appears to have no effect on survival.

Combined High Resistin and EGFR Expression Predicts a Poor Prognosis in Breast Cancer.

Elevated levels of resistin and epidermal growth factor receptor (EGFR) facilitate the development of breast cancer, although there are no reports of any correlation between these proteins. This study analyzed 392 human breast cancer tissue specimens and 42 samples of adjacent normal tissue. Rates of positive and strongly positive resistin expression were significantly higher in breast cancer tissue than in the adjacent nontumor tissue (83.2% vs. 23.8% and 20.9% vs. 0.0%, respectively; P < 0.001 for both comparisons). Positive resistin expression was significantly associated with tumor size, grade, stage, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, and molecular classification; strongly positive resistin expression was associated with tumor grade, ER, PR, HER2 status, and molecular classification. Significantly positive correlations were observed between positive and strongly positive resistin expression and corresponding levels of EGFR expression. Relapse-free and overall survival was worse for patients with high levels of both proteins than for those with high levels of only one protein or normal levels of both proteins. Our evidence suggests that combined high levels of resistin and EGFR expression correlate with survival in patients with breast cancer.

Cancer cell membrane-coated gold nanorods for photothermal therapy and radiotherapy on oral squamous cancer.

The combination of different modalities greatly enhances the anticancer efficacy of each treatment by combining their merits, showing promising potential in clinical translation. Herein, we fabricated cancer cell membrane-coated gold nanorods (GNR@Mem) possessing excellent photothermal transfer ability in the second near-infrared window and radiosensitizing ability under X-ray irradiation. The cancer cell membrane coating endowed the nanomedicine with stability in the physiological environment and selective homotypic targeting to specific cancer cells in vitro. Under NIR light and X-ray irradiation, the gold nanorods induced a temperature increase, reactive oxygen generation, and subsequent damage to the DNA helix structure, leading to enhanced cell apoptosis. Benefitting from its relative long circulation time in the blood and homotypic targeting effect, the tumor accumulation of GNR@Mem significantly increased. The in vivo results demonstrate that the combination of photothermal therapy and radiotherapy effectively suppresses tumor growth without noticeable systemic toxicity.

High Expression of Both Resistin and Fascin-1 Predicts a Poor Prognosis in Patients with Colorectal Cancer.

Emerging evidence indicates that resistin and fascin-1 may possess a causal role in the development of several types of cancers. However, the clinical significance of resistin expression in colorectal cancer (CRC) tissues is unclear, and there are no reports of any correlation between resistin and fascin-1. Our analyses explored the expression of resistin in CRC tissue and analyzed the clinical and prognostic significance of the observed positive correlation between resistin and fascin-1. The rate of strongly positive resistin expression (27.5%) was significantly higher in CRC tissues than in normal colorectal tissues (5.2%). Strongly positive resistin expression is related to multiple poor prognostic factors in CRC, including depth of tumor invasion, lymph node metastasis, and tumor stage. In this study, survival was worse in CRC patients with high levels of both resistin and fascin-1 expression than in those with high levels of only one protein or normal levels of both proteins. We suggest that a combined high level of resistin and fascin-1 expression correlates reliably with survival in CRC, so it may serve as a potential therapeutic target.

Impacts of RETN genetic polymorphism on breast cancer development.

The adipokine resistin is linked with obesity, inflammation and various cancers, including breast cancer. This study sought to determine whether certain polymorphisms in the gene encoding resistin, RETN, increase the risk of breast cancer susceptibility. We analyzed levels of resistin expression in breast cancer tissue and samples from The Cancer Genome Atlas database. We also examined associations between four RETN single nucleotide polymorphisms (SNPs; rs3745367, rs7408174, rs1862513 and rs3219175) and breast cancer susceptibility in 515 patients with breast cancer and 541 healthy women without cancer. Compared with wild-type (GG) carriers, those carrying the AG genotype of the RETN SNP rs3219175 and those carrying at least one A allele in the SNP rs3219175 had a higher chance of developing breast cancer (adjusted odds ratio, AOR: 1.295, 95% confidence intervals, CI: 1.065-1.575 and 2.202, 1.701-2.243, respectively). When clinical aspects and the RETN SNP rs7408174 were examined in the breast cancer cohort, the CT genotype was linked to late-stage disease, while women with luminal A disease and at least one C allele were likely to progress to stage III/IV disease and to develop highly pathological grade III disease. Moreover, resistin-positive individuals were at greater risk than resistin-negative individuals for developing pathological grade III disease (OR: 5.020; 95% CI: 1.380-18.259). This study details risk associations between resistin and RETN SNPs in breast cancer susceptibility in Chinese Han women.

Angiopoietin-2 gene polymorphisms are biomarkers for the development and progression of colorectal cancer in Han Chinese.

Colorectal cancer (CRC) is one of the most common cancers in Han Chinese and is characterized by low rates of early diagnosis and poor survival rates. Angiopoietin-2 (Ang2), an endothelial tyrosine kinase, is involved in CRC progression, but little is known about the association between single nucleotide polymorphisms (SNPs) and diagnosis or prognosis of CRC. This study reports on the association between 5 SNPs of the Angpt2 gene (rs2442598, rs734701, rs1823375, 11137037, and rs12674822) and CRC susceptibility as well as clinical outcomes in 379 patients with CRC and in 1,043 cancer-free healthy controls. Carriers of the CG allele at rs1823375 and those with the GT+TT allele of the variant rs12674822 were at greater risk of CRC than their respective wild-type counterparts. Moreover, carriers of the GT or GT+TT allele in rs12674822 were significantly more likely to have tumor involvement in both the colon and rectum compared with wild-type (GG) carriers, while 5-year progression-free survival was also significantly worse in those carrying the GT+TT allele in rs12674822 compared with wild-type carriers. Our study is the first to describe correlations between Angpt2 polymorphisms and CRC development and progression in people of Chinese Han ethnicity.

Correlations between angiopoietin-2 gene polymorphisms and lung cancer progression in a Chinese Han population.

Lung cancer is the most common malignancy in China and is associated with a poor survival rate amongst Han Chinese. The high mortality is largely attributed to late-stage diagnosis, when treatment is largely ineffective. Identification of genetic variants could potentially assist with earlier diagnosis and thus more effective treatment. The development and progression of lung cancer is stimulated by angiopoietin-2 (Ang2), a ligand for Tie2, an endothelial tyrosine kinase. Patients with lung cancer with higher serum Ang2 levels have significantly poorer survival than patients with lower serum Ang2 levels. We explored the effects of Ang2 single nucleotide polymorphisms (SNPs) on lung cancer susceptibility. We used lung cancer tissue and serum samples to measure Ang2 expression in a Chinese Han population. Five Ang2 SNPs (rs2442598, rs734701, rs1823375, 11137037, and rs12674822) were analyzed using TaqMan SNP genotyping in 695 patients with lung cancer and 900 cancer-free controls. Carriers of the variant GT allele of rs12674822 had a higher risk of lung cancer than wild-type (GG) carriers, while the presence of the CC genotype at rs11137037 was associated with higher clinical stage disease compared with having the AA genotype. Our study is the first to document a correlation between Ang2 polymorphisms and lung cancer development and progression in people of Chinese Han ethnicity.

FSCN1 gene polymorphisms: biomarkers for the development and progression of breast cancer.

Breast cancer is a major cause of cancer mortality worldwide. Fascin-1 (FSCN1) is an actin-binding protein found in mammalian cells, including endothelial, neuronal and mesenchymal cells. FSCN1 overexpression has been indicated in breast cancer patients. However, scant information is available regarding the association between FSCN1 single nucleotide polymorphisms (SNPs) and the risk or prognosis of breast cancer. We report on the association between 6 SNPs of the FSCN1 gene (rs56156320, rs8772, rs3801004, rs2966447, rs852479 and rs1640233) and breast cancer susceptibility as well as clinical outcomes in 316 patients with breast cancer and in 222 healthy controls. Carriers of the AC or AC + CC allele of the variant rs56156320 were at greater risk of breast cancer compared with wild-type (AA) carriers. Moreover, carriers of at least one G allele in rs3801004 were likely to progress to stage III/IV disease and lymph node metastasis. Individuals with at least one T allele at FSCN1 SNP rs2966447 were at higher risk of developing pathologic grade G3 disease. Furthermore, individuals bearing the C/C haplotype at SNPs rs56156320 and rs3801004 had nearly twice the risk of breast cancer. Our results indicate that genetic variations in the FSCN1 gene may serve as an important predictor of early-stage breast cancer.

Hypoxia induced mitogenic factor (HIMF) triggers angiogenesis by increasing interleukin-18 production in myoblasts.

Inflammatory myopathy is a rare autoimmune muscle disorder. Treatment typically focuses on skeletal muscle weakness or inflammation within muscle, as well as complications of respiratory failure secondary to respiratory muscle weakness. Impaired respiratory muscle function contributes to increased dyspnea and reduced exercise capacity in pulmonary hypertension (PH), a debilitating condition that has few treatment options. The initiation and progression of PH is associated with inflammation and inflammatory cell recruitment and it is established that hypoxia-induced mitogenic factor (HIMF, also known as resistin-like molecule α), activates macrophages in PH. However, the relationship between HIMF and inflammatory myoblasts remains unclear. This study investigated the signaling pathway involved in interleukin-18 (IL-18) expression and its relationship with HIMF in cultured myoblasts. We found that HIMF increased IL-18 production in myoblasts and that secreted IL-18 promoted tube formation of the endothelial progenitor cells. We used the mouse xenograft model and the chick chorioallantoic membrane assay to further explore the role of HIMF in inflammatory myoblasts and angiogenesis in vivo. Thus, our study focused on the mechanism by which HIMF mediates IL-18 expression in myoblasts through angiogenesis in vitro and in vivo. Our findings provide an insight into HIMF functioning in inflammatory myoblasts.