Inhibition of Prostaglandin-Degrading Enzyme 15-PGDH Mitigates Acute Murine Lung Allograft Rejection.

PURPOSE: Acute rejection is a frequent complication among lung transplant recipients and poses substantial therapeutic challenges. 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme responsible for the inactivation of prostaglandin E2 (PGE2), has recently been implicated in inflammatory lung diseases. However, the role of 15-PGDH in lung transplantation rejection remains elusive. The present study was undertaken to examine the expression of 15-PGDH in rejected lung allografts and whether inhibition of 15-PGDH ameliorates acute lung allograft rejection. METHODS: Orthotopic mouse lung transplantations were performed between donor and recipient mice of the same strain or allogeneic mismatched pairs. The expression of 15-PGDH in mouse lung grafts was measured. The efficacy of a selective 15-PGDH inhibitor (SW033291) in ameliorating acute rejection was assessed through histopathological examination, micro-CT imaging, and pulmonary function tests. Additionally, the mechanism underlying the effects of SW033291 treatment was explored using CD8+ T cells isolated from mouse lung allografts. RESULTS: Increased 15-PGDH expression was observed in rejected allografts and allogeneic CD8+ T cells. Treatment with SW033291 led to an accumulation of PGE2, modulation of CD8+ T-cell responses and mitochondrial activity, and improved allograft function and survival. CONCLUSION: Our study provides new insights into the role of 15-PGDH in acute lung rejection and highlights the therapeutic potential of inhibiting 15-PGDH for enhancing graft survival. The accumulation of PGE2 and modulation of CD8+ T-cell responses represent potential mechanisms underlying the benefits of 15-PGDH inhibition in this model. Our findings provide impetus for further exploring 15-PGDH as a target for improving lung transplantation outcomes.

Disruption of extracellular redox balance drives persistent lung fibrosis and impairs fibrosis resolution.

Lung fibrosis is a devastating outcome of various diffuse parenchymal lung diseases. Despite rigorous research efforts, the mechanisms that propagate its progressive and nonresolving nature remain enigmatic. Oxidative stress has been implicated in the pathogenesis of lung fibrosis. However, the role of extracellular redox state in disease progression and resolution remains largely unexplored. Here, we show that compartmentalized control over extracellular reactive oxygen species (ROS) by aerosolized delivery of recombinant extracellular superoxide dismutase (ECSOD) suppresses an established bleomycin-induced fibrotic process in mice. Further analysis of publicly available microarray, RNA-seq and single-cell RNAseq datasets reveals a significant decrease in ECSOD expression in fibrotic lung tissues that can be spontaneously restored during fibrosis resolution. Therefore, we investigate the effect of siRNA-mediated ECSOD depletion during the established fibrotic phase on the self-limiting nature of the bleomycin mouse model. Our results demonstrate that in vivo knockdown of ECSOD in mouse fibrotic lungs impairs fibrosis resolution. Mechanistically, we demonstrate that transforming growth factor (TGF)-ß1 downregulates endogenous ECSOD expression, leading to the accumulation of extracellular superoxide via Smad-mediated signaling and the activation of additional stores of latent TGF-ß1. In addition, depletion of endogenous ECSOD during the fibrotic phase in the bleomycin model induces an apoptosis-resistant phenotype in lung fibroblasts through unrestricted Akt signaling. Taken together, our data strongly support the critical role of extracellular redox state in fibrosis persistence and resolution. Based on these findings, we propose that compartment-specific control over extracellular ROS may be a potential therapeutic strategy for managing fibrotic lung disorders.

Preoperational diagnosis and management of breast ductal carcinoma in situ arising within fibroadenoma: Two case reports.

BACKGROUND: Ductal carcinoma in situ (DCIS) arising within fibroadenoma is a type of tumor that is rarely encountered in clinic, with only about 100 cases of carcinoma arising within a fibroadenoma reported in the literature. Here, we present two cases of breast DCIS arising within a fibroadenoma and discuss their clinical and imaging findings as well as treatment. CASE SUMMARY: The patients did not have cancer-related personal and family histories. Case 1 (a 49-year-old woman) was diagnosed with a bilateral breast nodule in May 2018 and was followed (preoperative imaging data including ultrasound and mammography) for 3 years; she underwent an excisional biopsy to address an enlargement in nodule size. Case 2 (a 37-year-old woman) was diagnosed with a left breast nodule in June 2021 and consequently received vacuum-assisted biopsy of the tumor which appeared as "irregularly shaped" and "unevenly textured" tissue on ultrasound. The pathological diagnosis was clear in both cases. Both patients underwent breast-conserving surgery and sentinel lymph node biopsy. The two cases received or planned to receive radiotherapy as well as endocrine therapy (tamoxifen). CONCLUSION: Breast DCIS arising within a fibroadenoma is rare, but patients treated with radiotherapy and endocrine therapy can have good prognosis.

A convergent synthetic platform for dual anticancer drugs functionalized by reduced graphene nanocomposite delivery for hepatocellular cancer.

Hepatocellular carcinoma (HCC) is widespread cancer with a high degree of morbidity and mortality in individuals worldwide and a serious concern for its resistance to present chemotherapy drugs. In this investigation, the combination of cisplatin (CPT) and metformin (MET) to kill the HepG2 and caco-2 cells was developed into a new pH-responding magnetic nanocomposite based on reduced graphene oxide. Polyhydroxyethyl methacrylic (PHEA) was then linked employing grafting from approach to the reduced graphene oxide by ATRP polymerization (Fe3O4@rGO-G-PSEA). FT-IR, SEM, XRD, DLS, and TGA analyses evaluated physicochemical characteristics of the nanocomposite. In addition, the cellular uptake property of the nanocomposites was examined by the HepG2 cells. The outcomes of cell viability results indicate that the nanoparticles loaded with MET&CPT showed the lowest concentration rate of HepG2 and Caco-2 cells compared to the drug-loaded single nanocomposite groups and free drugs. The histological analysis has demonstrated relatively safe and does not produce different stress such as swelling and inflammation of the mice organs. Our results show the enhancement in cytotoxicity in HepG2 and Cocoa-2 cells by MET and CPT graphene oxide-based nanocomposite by promoting apoptotic response. Moreover, Fe3O4@rGO-G-PSEA showed potent in vivo antitumor efficacy but showed no adverse toxicity to normal tissues. Together, this study can provide insight into how surface embellishment may tune these nanocomposites' tumor specificity and provide the basis for developing anticancer efficacy.

Type 2 Diabetes Associated with Abnormal p53 Immunohistochemical Patterns in Colorectal Cancer.

Abnormal p53 immunohistochemical pattern (p53-AP) including overexpression, complete absence and heterogeneity is surrogate of TP53 mutation. Using 742 cases of colorectal cancer (CRC), we show p53-AP is more common among type 2 diabetes (T2DM) patients than non-T2DM. Univariately, T2DM was significantly associated with p53-AP in overall patients, patients with microsatellite instability (MSI) stable/MSI-low phenotype or distal colorectal location. Furthermore, p53-AP was positively associated with lymph node metastasis and high TNM stage. Metformin treatment was negatively associated with p53-AP in T2DM patients. The results suggested T2DM might influence carcinogenesis, progression and prognosis via inducing TP53 mutation and abnormal p53 expression in CRC.

Mitochondrial superoxide mediates PM2.5-induced cytotoxicity in human pulmonary lymphatic endothelial cells.

Exposure to airborne fine particulate matter (PM2.5) is associated with a variety of respiratory health effects and contributes to premature mortality. Lymphatic vessels are instrumental in facilitating the transport of toxic materials away from the lung to maintain alveolar clearance and have been shown to play important roles in lung injury and repair. Despite intense research efforts in delineating the effects of PM2.5 on blood vascular endothelial cells, the impacts of PM2.5 on lymphatic endothelial cells (LECs), a specialized subset of endothelial cells that comprise lymphatic vessels, remain enigmatic. Here, we conducted MTT assay and show that treatment of human pulmonary LECs with PM2.5 suppresses cell viability in a time- and dose-dependent manner. We subsequently performed Annexin V/propidium iodide labeling and demonstrate that PM2.5 induces LECs apoptosis and necrosis. Furthermore, we found that manganese superoxide dismutase (SOD2) expression and mitochondrial SOD activity were profoundly reduced following PM2.5 exposure. Mechanistically, we provide compelling evidence that PM2.5 reduces SOD2 expression through activation of Akt pathway, which leads to a disruption of mitochondrial redox homeostasis characterized by increased accumulation of mitochondrial superoxide. Conversely, mitochondria-targeted SOD mimetic (MitoTEMPO) corrects the disturbed oxidative milieu in PM2.5-treated LECs. Additionally, MitoTEMPO ameliorates the deleterious impacts of PM2.5 on mitochondrial DNA integrity and preserves the viability of LECs. Taken together, these novel data support a critical role for mitochondrial superoxide in the pathogenesis of PM2.5-induced LECs injury and identity mitochondrial-targeted antioxidants as promising therapeutic options to treat environmental lung diseases. Our findings are limited to experimental studies with primary LECs, and future investigations in animal models are warranted to shed light on the precise pathophysiology of lymphatic system in response to PM exposure.

[Expression of tumor-associated vascular insulin receptor in colorectal cancer and its relationship with tumor pathological features].

OBJECTIVE: To study the expression of tumor associated vascular insulin receptor (TVIR) in colorectal cancer with or without metabolic syndrome (MS) and its relationship with the pathological features of colorectal cancer. METHODS: The expression of TVIR in 220 colorectal cancer specimens was detected by tissue microarray and immunohistochemistry. The relationships between the expression of TVIR and the pathological features (pathological subtypes, histological grade, invasion depth, lymph node metastasis and TNM stage) of colorectal cancer with/without MS were analyzed. RESULTS: The insulin receptor expression was observed in colorectal cancer tissue or border area between cancer and normal tissue, but not in normal intestinal tissue. The high-expression rates of TVIR in MS group was remarkably lower than that of non-MS group (21.6%vs. 41.0%, P< 0.05). TVIR high expression was significantly associated with tumor deep invasion, lymph node metastasis and high TNM stage (P<0.05 or P<0.01). Univariate logistic regression analysis showed high-expression of TVIR to be significantly associated with risk of deep invasion (OR=2.21, 95% CI: 1.10-4.44, P<0.05), lymph node metastasis (OR=2.21, 95% CI: 1.26-3.86, P<0.01) and high TNM stage (OR=2.08, 95% CI: 1.19-3.63, P<0.05). Such associations can be observed in patients without MS, but not in patients with MS. CONCLUSIONS: s: High-expression of TVIR is associated with aggressive pathological features such as invasion, lymph node metastasis and high TNM stage of colorectal cancer, especially for those patients without MS. TVIR could be a useful biological marker for prognosis of colorectal cancer.

Iodine-125 seed implantation combined with arterial chemoembolization therapy for pain palliation in metastatic bone cancer: a retrospective study.

Bone metastases are the most common sites for malignant tumors. Patients who failed to respond to initial first-line treatment with bisphosphonates usually suffer from extreme pain. The aim of this study was to observe the efficacy of arterial chemoembolization combined with Iodine-125 seed implantation in the treatment of bone metastatic cancer pain. All 14 patients with metastatic bone tumor wo failed first-line treatment underwent arterial chemoembolization the day before the implantation of the particles. A computer stereoscopic TPS was used to design the treatment plans, the number and dose of particles required for implantation. Pain relief was evaluated using several parameters such as Visual Analog Scale (VAS) and Verbal Rating Scales (VRS). Pain intensity was measured pre-operation and 1-week, 1-month, 3-month after the treatment. Meanwhile, we also assessed tumor size using computer tomography (CT). Pain palliation was observed in 35.7% (5/14), 57.1% (8/14), and 78.6% (11/14) of all patients at 1-week, 1-month and 3-month post treatment. Likewise, our analysis showed that the combination therapy resulted in a significant decrease of VAS score (6.71 ± 0.49 before treatment vs 3.36 ± 0.40 at 3 month post treatment) and overall responding rate of 92.0% using VRS pain assessment. Consistently, tumor size was reduced from 42.16 ± 10.32 before treatment to 29.11 ± 8.73 at 3 months post treatment. No serious complications were detected. Our study demonstrate that the combination of arterial chemoembolization and 125I particles resulted in evident pain relief and reduction of tumor burden, suggesting that the combination treatment could be a feasible and promising therapy for bone tumor management.

The safety and efficacy of TACE combined with apatinib on patients with advanced hepatocellular carcinoma: a retrospective study.

As a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor (VEGFR2-TKI), apatinib has a certain anti-tumor effect for a variety of solid tumors. The present study evaluates its efficacy and safety in advanced hepatocellular carcinoma (HCC). In this study, 47 patients with advanced HCC were included. TACE monotherapy group included 22 patients that responded to TACE, while the group that received TACE and apatinib included 25 patients that progressed on TACE and were able to receive apatinib off label. Median overall survival (OS) was significantly improved in the apatinib plus TACE group compared with the TACE group. Similarly, apatinib in combination with TACE significantly prolonged median progression-free survival (PFS) compared with TACE monotherapy. Furthermore, there was a significant difference between combination therapy and monotherapy in both Barcelona clinic liver cancer (BCLC) B and BCLC C group. The combination therapy had a dramatic effect on OS and PFS for patients at both BCLC B and BCLC C level. The most common clinically adverse events of apatinib plus TACE group were fatigue, weight loss, hypertension, hand-foot syndrome and anorexia, which were manageable and tolerable. The efficacy analysis showed that there was no significant association of survival benefit with age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, hypertension and hand-foot syndrome. Patients with macrovascular invasion and extrahepatic invasion showed worse survival benefits. In conclusion, apatinib combined with TACE revealed certain survival benefits for HCC patients who experienced progression following TACE, which can provide a promising strategy for HCC treatment.

Computational Fluid Dynamics Simulation of Hemodynamic Alterations in Sigmoid Sinus Diverticulum and Ipsilateral Upstream Sinus Stenosis After Stent Implantation in Patients with Pulsatile Tinnitus.

OBJECTIVE: To investigate the relationships between upstream venous sinus stenosis and pulsatile tinnitus (PT), and to assess the correlation with diverticulum growth and the effectiveness of stent implantation. METHODS: Patient-specific geometric models were constructed using computed tomography venography images from a patient with PT, with sigmoid sinus diverticulum, and with upstream transverse sinus stenosis, in whom stenting of the upstream sinus stenosis alone achieved complete remission of PT. Computational fluid dynamics simulation based on this patient-specific geometry was performed using commercially available finite element software (ANSYS-14) to qualitatively and quantitatively compare the flow velocity, flow rate, velocity vector, pressure, vorticity, and wall shear stress on the affected side transverse and sigmoid sinuses, before and after stent implantation. RESULTS: Stenting improved the flow direction and magnitude. After stenting, the flow pattern became smoother and more regular. High-speed blood flow at the level of the diverticulum neck was confined to a smaller area, and its direction changed from approximately perpendicular to the diverticular dome to the distal side of the diverticular neck. The diverticulum showed obvious flow reduction, with decreases of 80.7%, 68.7%, 96.1%, and 91.3% in peak velocity, inflow rate, pressure gradient, and peak vorticity, respectively. The abnormally low wall shear stress at the dome of diverticulum was eliminated. CONCLUSIONS: Our findings strongly support a major role of diverticulum stenosis before in PT development and suggest that such stenosis is a causative factor of diverticulum growth. They also confirm the effectiveness of stent implantation for the treatment of PT.

Therapeutic effect of transarterial chemoembolization combined with apatinib on patients with advanced hepatocellular carcinoma / 中国肿瘤临床

Objective: To evaluate the therapeutic effect of transarterial chemoembolization (TACE) combined with apatinib on pa-tients with advanced hepatocellular carcinoma (HCC). Methods:Twenty-one patients were treated with TACE combined with 250 mg of apatinib once a day. Disease classification was assessed by investigators using the modified Response Evaluation Criteria in Solid Tu-mors (mRECIST). The evaluation period was 28 days. Results:The therapeutic effects were classified as follows:3 patients (14.3%) had complete response, 6 patients (28.6%) had partial response, 5 patients (23.8%) had stable disease, and 2 patients (9.5%) had progres-sive disease. The disease control rate was 61.9%, and the objective response rate was 38.1%. In patients, the most frequent adverse events were fatigue (94.4%), anorexia (23.8%), diarrhea (19.0%), hypertension (19.0%), and hand-foot syndrome (19.0%). Conclusion:The short-term therapeutic effect revealed that the combination of TACE and apatinib could be a promising treatment for patients with advanced HCC. Adverse events should be closely monitored and provided with active management.

Therapeutic effect of transarterial chemoembolization combined with apatinib on patients with advanced hepatocellular carcinoma / 中国肿瘤临床

Objective: To evaluate the therapeutic effect of transarterial chemoembolization (TACE) combined with apatinib on pa-tients with advanced hepatocellular carcinoma (HCC). Methods:Twenty-one patients were treated with TACE combined with 250 mg of apatinib once a day. Disease classification was assessed by investigators using the modified Response Evaluation Criteria in Solid Tu-mors (mRECIST). The evaluation period was 28 days. Results:The therapeutic effects were classified as follows:3 patients (14.3%) had complete response, 6 patients (28.6%) had partial response, 5 patients (23.8%) had stable disease, and 2 patients (9.5%) had progres-sive disease. The disease control rate was 61.9%, and the objective response rate was 38.1%. In patients, the most frequent adverse events were fatigue (94.4%), anorexia (23.8%), diarrhea (19.0%), hypertension (19.0%), and hand-foot syndrome (19.0%). Conclusion:The short-term therapeutic effect revealed that the combination of TACE and apatinib could be a promising treatment for patients with advanced HCC. Adverse events should be closely monitored and provided with active management.

Salidroside alleviates oxidative stress in the liver with non- alcoholic steatohepatitis in rats.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is characterized by fat accumulation in the hepatocyte, inflammation, liver cell injury, and varying degrees of fibrosis, and can lead to oxidative stress in liver. Here, we investigated whether Salidroside, a natural phenolic antioxidant product, can protect rat from liver injury during NASH. METHODS: NASH model was established by feeding the male SD rats with high-fat and high-cholesterol diet for 14 weeks. Four groups of male SD rats including, normal diet control group, NASH model group, and Salidroside treatment group with150mg/kg and 300 mg/kg respectively, were studied. Salidroside was given by oral administration to NASH in rats from 9 weeks to 14 weeks. At the end of 14 weeks, liver and serum were harvested, and the liver injury, oxidative stress and histological features were evaluated. RESULTS: NASH rats exhibited significant increases in the following parameters as compared to normal diet control rats: fat droplets with foci of inflammatory cell infiltration in the liver. ALT, AST in serum and TG, TC in hepatocyte elevated. Oxidative responsive genes including CYP2E1 and Nox2 increased. Additionally, NASH model decreased antioxidant enzymes SOD, GSH, GPX, and CAT in the liver due to their rapid depletion after battling against oxidative stress. Compared to NASH model group, treatment rats with Salidroside effectively reduced lipid accumulation, inhibited liver injury in a does-dependent manner. Salidroside treatment restored antioxidant enzyme levels, inhibited expression of CYP2E1 and Nox2 mRNA in liver, which prevented the initial step of generating free radicals from NASH. CONCLUSION: The data presented here show that oral administration of Salidroside prevented liver injury in the NASH model, likely through exerting antioxidant actions to suppress oxidative stress and the free radical-generating CYP2E1 enzyme, Nox2 in liver.

MiR-29a modulates the angiogenic properties of human endothelial cells.

Although extensive investigation has been made on miR-29a in relation to malignancies, only a little information has been provided about the angiogenic property of this miRNA so far. Herein, we sought to investigate the role of miR-29a in regulating cell cycle and angiogenic phenotype of endothelial cells. The results showed that miR-29a is highly expressed and upregulated by hypoxia-mimicking reagents in human umbilical vein endothelial cells (HUVEC). Consistent with this preliminary finding, introduction of exogenous agomiR-29a, or Antagomir-29a altered cell cycle progression and promoted, or repressed the proliferation and tube formation of HUVEC, respectively. Furthermore, by using luciferase reporter assay, the expression of HBP1, a suppressor transcription factor was directly regulated by miR-29a through 3'-UTR. Increased or decreased HBP1 protein level was associated with the inhibition or overexpression of miR-29a, respectively. We conclude that miR-29a has a significant role in regulating cell cycle, proliferation and angiogenic properties of HUVEC, and this function is likely mediated through HBP1 protein at the post-transcriptional level. As a novel molecular target, miR-29a may have a potential value for the treatment of angiogenesis-associated diseases such as cardiovascular diseases and cancers.

MicroRNA-122 suppresses cell proliferation and induces cell apoptosis in hepatocellular carcinoma by directly targeting Wnt/ß-catenin pathway.

AIMS: To validate whether the anti-cancer effect of microRNA-122 (miR-122) on hepatocellular carcinoma (HCC) is mediated through regulating Wnt/ß-catenin signalling pathways. METHODS: The expression levels of miR-122 in HCC tissues and varied hepatoma cells were quantified by real-time PCR. MiR-122 agomir was transfected into HepG2, Hep3B cells to over-express miR-122. The effect of over-expression miR-122 on proliferation and apoptosis of HepG2 and Hep3B cells was evaluated using CCK-8 kit and flow cytometer respectively. The 3'-UTR segments of Wnt1 containing the miR-122 binding sites were amplified by PCR and the luciferase activity in the transfected cells was assayed. Wnt1 mRNA level was quantified using RT-PCR. Protein levels of Wnt1, ß-catenin and TCF-4 were detected using Western blotting. RESULTS: In comparison with the expression level of miR-122 in para-cancerous tissues or Chang liver cell, the expression level in HCC tissues or varied hepatoma cells was significantly decreased (P < 0.05). Over-expression of miR-122 significantly inhibited the proliferation (P < 0.05), and promoted the apoptosis of HepG2 and Hep3B cells. Over-expressed miR-122 down-regulated the protein levels of Wnt1, ß-catenin and TCF-4 (P < 0.05). MiR-122 suppressed the luciferase activity of the pmiR-Wnt1-wt by approximately 50% compared with the negative control, while mutation or removal of the miR-122 binding site using siRNA or mir-122 inhibitor blocked the suppressive effect (P < 0.05). CONCLUSIONS: MiR-122 expression is down-regulated in human HCC. Over-expression of miR-122 inhibits HCC cell growth and promotes the cell apoptosis by affecting Wnt/ß-catenin-TCF signalling pathway.

Role of specific microRNAs for endothelial function and angiogenesis.

Accumulating evidence indicates that various aspects of angiogenesis, such as proliferation, migration, and morphogenesis of endothelial cells, can be regulated by specific miRNAs in an endothelial-specific manner. As novel molecular targets, miRNAs have a potential value for treatment of angiogenesis-associated diseases such as cancers, inflammation, and vascular diseases. In this article, we review the latest advances in the identification and validation of angiogenesis-regulatory miRNAs and their targets, and discuss their roles and mechanisms in regulating endothelial cell function and angiogenesis.

Stimulation of endothelin-1 gene expression by insulin via phosphoinositide-3 kinase-glycogen synthase kinase-3beta signaling in endothelial cells.

Insulin stimulates secretion of the potent vasoactive and mitogenic peptide endothelin-1 (ET-1) from endothelial cells. We sought to investigate whether phosphoinositide-3 kinase (PI3K)-dependent inactivation of glycogen synthase kinase-3beta (GSK3beta) by insulin leads to elevation of ET-1 gene expression in endothelial cells. Inhibition of GSK3beta activity by LiCl or siRNA technique mimicked insulin action to stimulate ET-1 gene expression. Luciferase reporter assay showed insulin stimulated-elevation of ET-1 promoter activity can be abolished by the PI3K inhibitor Wortmannin, but not by the mitogen activated protein kinase (MAPK) inhibitor PD-98059. To further investigate whether the transcription factor vascular endothelial zinc finger-1 (Vezf1) is involved in ET-1 regulation, site-mutated reporter plasmid was used in luciferase reporter assay. A 2-bp mutation in Vezf1 binding element abolished insulin-stimulated elevation of ET-1 promoter activity. Furthermore, siRNA inhibition of Vezf1 led to decline in the levels of ET-1 mRNA and ET-1 peptides. These observations indicate that PI3K-dependent inactivation of GSK3beta by insulin leads to upregulation of ET-1 gene expression and Vezf1 may be a target for ET-1 regulation by insulin. PI3K-GSK3beta signaling may be responsible for insulin stimulation of ET-1 production associated with insulin resistance and hyperinsulinemia.

[Loss of heterozygosity on chromosome 3p in breast cancer and precancerous lesion].

OBJECTIVE: To study the loss of heterozygosity (LOH) on chromosome 3p in breast cancers and precancerous lesion. METHODS: LOH at 11 microsatellite loci was detected in 41 cases of breast cancers and 12 cases of precancerous lesion by polymerase chain reaction and silver stain. The expressions of ER, PR, FHIT and hMLH1 were detected in breast cancer by immunohistochemistry. RESULTS: LOH on 3p was detected in 97% of breast cancers. D3S1295, D3S1029 and D3S1038 located at 3p14, 3p21-p22 and 3p25 were identified as the loci with most frequent LOH (53.1%, 43.6% and 52.5%). LOH of D3S1038 and expression of hMLH1 protein correlated with several clinicopathological features. LOH of D3S1295 had significant negative correlation with the expression of FHIT. In breast precancerous lesions, LOH on 3p was detected in 41.7% lesions. D3S1295 and D3S1029 were also identified as the most frequent LOH locus (27.3% and 16.7%). The smallest common LOH region seems likely lie between 3p14 and 3p25. CONCLUSIONS: The smallest LOH region indicates the existence of breast tumor related genes and some of them affect gene expression.

[The intervention effects of Angelica sinensis, Salvia miltiorrhiza and ligustrazine on peritoneal macrophages during peritoneal dialysis].

OBJECTIVE: To study the effect of Angelica sinensis, Salvia miltiorrhiza and Ligustrazine on function of peritoneal macrophages during peritoneal dialysis. METHODS: Peritoneal macrophages of mice were cultured in culture medium (control), peritoneal dialysate (PD), drugs contained PD containing Angelica, Salvia and Ligustrazine combined (PD-ASL) or separated (PD-A, PD-S, PD-L) with concentration of 2 micrograms/ml, 10 micrograms/ml and 100 micrograms/ml, separately for 24 hrs. The nitric oxide (NO) content, methyl thiazolyl tetrazolium (MTT) reducing capacity (MTT-RC) and phagocytosis capacity of macrophages were determined and compared. RESULTS: NO content and MTT-RC of macrophages cultured in PD group were significantly lower than those of the control (P < 0.01), as compared with those in drug contained PD groups, the NO content in the PD-L group and the MTT-RC in the PD-ASL group were higher significantly (P < 0.01). The phagocytosis capacity and NO content in the PD-ASL group were raised along with the increased concentration of drug in PD. CONCLUSION: Administering Chinese herbal medicine during peritoneal dialysis has important significance in improving the defense function of peritoneal macrophages, reducing the incidence of peritonitis and enhancing the therapeutic effect of peritoneal dialysis.

[Influence of peritoneal dialysate on nitric oxide production and viability of macrophage]

OBJECTIVE: To investigate the influence of commercial peritoneal dialysate (CDS) on function of macrophage. METHODS: Cultured peritoneal macrophages were divided into two experimental groups and their controls.(1) Macrophages were cultured in conditioned culture medium containing 50%CDS (0.139 mol/L glucose) for 24 h. (2)Macrophage were exposed to CDS containing 0.139mol/L glucose for 10, 30 and 60 min respectively, and then cultured in CDS-free medium for 24 h. The nitric oxide (NO) production and MTT in two groups were measured. In each control group, CDS was replaced by same amount of culture medium. RESULTS: NO production and MTT reduction ability (related to cell viability) of experimental groups were remarkably lower than those of controls and the NO production and MTT reduction in 60min CDS-exposed group were lower than that of 10 min and 30 min CDS-exposed group. CONCLUSION: Dialysate may have detrimental effects on viability and other function of macrophage and these effects may related to time length of CDS exposure.