[Expression and clinical significance of MTDH and VEGF in triple-negative breast cancer].

OBJECTIVE: To study the expression and clinical significance of MTDH and VEGF in triple-negative breast cancer (TNBC). METHODS: Tissue samples of 168 breast cancers (including 112 TNBC tissue and 56 non-TNBC tissue), 10 breast fibroadenomas and 15 normal breast tissues were collected. Postoperative specimens were examined by immunohistochemistry for MTDH and VEGF expression. The correlation between the expression of MTDH and VEGF and clinicopathological features was analyzed. RESULTS: MTDH and VEGF were expressed in 57.1% and 49.4% of breast cancer patients, 64.3% and 56.3% in TNBC patients, respectively, significantly higher than that in the non-TNBC tissues, breast fibroadenomas and normal breast tissues (P<0.05 for all). Statistically significant correlation was found between the MTDH and VEGF expressions (r=0.356, P<0.001). Moreover, MTDH expression was correlated with tumor size, BMI index, lymph node metastasis, pathological stage, recurrence and metastasis, and the expression of p53 and Ki-67 proteins (P<0.05 for all). The VEGF protein expression was correlated with lymph node metastasis, pathological staging, recurrence and metastasis, and the expression of Ki-67 protein (P<0.05 for all). The patients with high expression of MTDH and VEGF showed a lower DFS and OS (P<0.05 for both). CONCLUSIONS: MTDH and VEGF expression may be correlated with tumor angiogenesis and progression and has the potential to be valuable prognostic factors in patients with TNBC.

Interleukin-35 pretreatment attenuates lipopolysaccharide-induced heart injury by inhibition of inflammation, apoptosis and fibrotic reactions.

Previous studies have demonstrated that targeting inflammation is a promising strategy for treating lipopolysaccharide (LPS)-induced sepsis and related heart injury. Interleukin-35 (IL-35), which consists of two subunits, Epstein-Barr virus-induced gene 3 (EBI3) and p35, is an immunosuppressive cytokine of the IL-12 family and exhibits strong anti-inflammatory activity. However, the role of IL-35 in LPS-induced heart injury reains obscure. In this study, we explored the role of IL-35 in heart injury induced by LPS and its potential mechanisms. Mice were treated with a plasmid encoding IL-35 (pIL-35) and then injected intraperitoneally (ip) with LPS (10 mg/kg). Cardiac function was assessed by echocardiography 12 h later. LPS apparently decreased the expression of EBI3 and p35 and caused cardiac dysfunction and pathological changes, which were significantly improved by pIL-35 pretreatment. Moreover, pIL-35 pretreatment significantly decreased the levels of cardiac proinflammatory cytokines including TNF-α, IL-6, and IL-1ß, and the NLRP3 inflammasome. Furthermore, decreased number of apoptotic myocardial cells, increased BCL-2 levels and decreased BAX levels inhibited apoptosis, and LPS-induced upregulation of the expression of cardiac pro-fibrotic genes (MMP2 and MMP9) and fibrotic factor (Collagen type I) was inhibited. Further investigation indicated that pIL-35 pretreatment might suppressed the activation of the cardiac NF-κBp65 and TGF-ß1/Smad2/3 signaling pathways in LPS-treated mice. Similar cardioprotective effects of IL-35 pretreatment were observed in mouse myocardial fibroblasts challenged with LPS in vitro. In summary, IL-35 pretreatment can attenuate cardiac inflammation, apoptosis, and fibrotic reactions induced by LPS, implicating IL-35 as a promising therapeutic target in sepsis-related cardiac injury.

[Relation of lymphatic microvessel density detected by monoclonal antibody D2-40 with VEGF-C expression in breast cancer].

OBJECTIVE: To investigate the relationship of lymphatic micovessel density (LMVD) detected by monoclonal antibody D2-40) with the VEGF-C expression in human breast cancer. METHODS: Tissue samples of 102 breast cancers, 25 breast fibroadenomas and 10 normal breasts were collected. Immunohistochemical staining was used to detected the lymphatic micovessels with monoclonal antibody D2-40. The expression of VEGF-C was detect by SP immunohistochemistry, and VEGF-C mRNA by hybridization in situ. RESULTS: In 102 breast cancers, the positive rate of D2-40 was 76.5% (78/102), higher than that in the breast fibroadenomas. LMVD in the periphery of breast cancer was 30.1 lymphatic microvessels per x 100 field of vision, which was significantly higher than that in the central area of the tumors (P = 0.000). The LMVD in the periphery of the breast cancers was correlated with the number of metastatic lymph nodes (r = 0.964, P < 0.01). The positive rates of VEGF-C protein and mRNA were 55.9% (57/102) and 59.8% (61/102), respectively, significantly higher than that in the breast fiberoadenomas and normal breast tissues (chi2 = 11.653, P = 0.003; chi2 = 10.345, P = 0.006), and were significantly correlated with the status of lymph node metastasis, clinical stage and the expressions of c-erbB-2 and p53 protein (P < 0.05). Both of VEGF-C protein and mRNA were significantly correlated with LMVD detected by D2-40 (P < 0.05), especially with the LMVD in the periphery of breast cancers (P < 0.05). CONCLUSION: The monoclonal antibody D240 can be used to detect the lymphatic endothelium in human breast cancer. The lymphatic microvessel density in the periphery of breast cancer is correlated with the lymph node metastasis and expression of VEGF-C. Therefore, VEGF-C may play a significant role in the lymphangiogenesis leading to metastasis of breast cancer.

[Viability of corneal epithelial cells and cleavage of corneal basement after ethanol effect].

OBJECTIVE: To evaluate the viability of corneal epithelial cells and to determine the anatomic cleavage on the epithelial basement membrane after various exposure times to 20% ethanol during epithelial flap preparation in laser-assisted subepithelial keratectomy (LASEK) in cadaver eyes. METHODS: Six human cadaver eyes were exposed to 20% ethanol for 20, 30 and 40 seconds (2 eyes for each group), and another one eye was used as the control. PCNA staining was performed to determine the viability of corneal epithelial cells. Immunofluorescence staining using monoclonal antibodies against collagen VII, and immunohistological staining using monoclonal antibodies against laminin were performed to detect the anatomic location of the cleavage plane on the corneal epithelial flaps created by 20 seconds exposure to 20% ethanol in cadaver eyes. RESULTS: Hematoxylin and eosin staining of epithelial flaps revealed a coherent stratified epithelium. The PCNA positive rates of the epithelial cells in the flap decreased in the 20-second group, 30-second group and 40-second group successively. Immunohistological staining to laminin was patchy in the lifted flap and the remaining corneal basement membrane. Immunofluorescence to collagen VII, the main component of anchoring fibrils remained exclusively in the corneal bed. CONCLUSIONS: Viability of the epithelial flap decreased with longer time exposure to ethanol. The cleavage plane of the ethanol-treated corneal epithelial flap is located between the lamina lucida and the lamina densa of the basement membrane where laminin forms hemidesmosome.

Intravenous leiomyomatosis with right atrium extension in two patients: A case report.

Intravenous leiomyomatosis (IVL) is a rare benign tumor of the uterus mesoderm, which can spread via the vein, from the micro-vein to the inferior vena cava, and even to the right atrium. IVL was first described this disease in 1896 and the first presented case of IVL with right atrium extension in the autopsy was described in 1907. On rare occasions, the tumors may extend into the regional and systemic veins, thus reaching the heart. This may subsequently cause intracardiac leiomyomatosis (ICL), which may lead to congestive heart failure and on occasion, sudden fatalities. Due to its rarity and diffuse symptoms, the misdiagnosis of ICL is common and as a result, the condition may be under-reported. The present study reported two cases of IVL resected at the General Hospital of Shenyang Military Command. A hysteromyomectomy for uterine fibroids was performed on each patient (Case 1, 41 years ago; Case 2, 3 years ago). One patient presented with chest pain following a period of activity and the other presented with heart neoplasm during a routine health examination.

Expression of p57kip2, Rb protein and PCNA and their relationships with clinicopathology in human pancreatic cancer.

AIM: To investigate the effects of inhibiting factor of cell cycle regulation p57(kip2), retinoblastinoma protein (Rb protein) and proliferating cell nuclear antigen (PCNA) in the genesis and progression of human pancreatic cancer. METHODS: The expression of p57(kip2), Rb protein and PCNA in tumor tissues and adjacent tissues of 32 patients with pancreatic cancer was detected with SP immunohistochemical technique. RESULTS: p57(kip2) protein positive-expression rate in tumor tissues of pancreatic cancer was 46.9 %, which was lower than that in adjacent pancreatic tissues (75.0 %) (chi(2)=5.317, P<0.05), p57(kip2) protein positive-expression correlated significantly with tumor cell differentiation (well-differentiation versus moderate or low-differentiation, P<0.05) but did not correlate significantly with lymph node metastasis (lymph node metastasis versus non-lymph node metastasis, P>0.05); Rb gene protein positive-expression rate in tumor tissues was 50.0 %, which was also lower than that in adjacent pancreatic tissues (78.1 %) (chi(2)=5.497, P<0.05); PCNA positive-expression rate was 71.9 %, being higher than that in adjacent pancreatic tissues (43.8 %) (chi(2)=5.189, P<0.05), PCNA positive-expression also correlated significantly with tumor cell differentiation and lymph node metastasis (well-differentiation versus moderate or low- differentiation, lymph node metastasis versus non-lymph node metastasis, P<0.05). Rb protein positive-expression rate in the tumor tissues of p57(kip2) protein positive-expression group was 53.3 %; and Rb protein positive-expression rate in the tumor tissues of p57(kip2) protein negative-expression group was 47.1 %. There was no significant relationship between the two groups (r=0.16507, P>0.05). CONCLUSION: The decreased expression of p57(kip2), Rb protein or over-expression of PCNA protein might contribute to the genesis or progression of pancreatic cancer, p57(kip2), Rb protein and PCNA may play an important role in genesis and progression of pancreatic cancer.

Expression of P57(kip2) and cyslinE proteins in human pancreatic cancer.

OBJECTIVE: To investigate the effects of p57(kip2) and cyclinE proteins on the genesis and progression of human pancreatic cancer. METHODS: The expression of p57(kip2) and cyclinE proteins in tumor tissues and adjacent tissues of pancreatic cancer in 32 patients was detected by SP immunohistochemical technique. RESULTS: The p57(kip2) protein positive-expression rate in tumor tissues of pancreatic cancer was 46.9%, which was lower than that in adjacent pancreatic tissue (P < 0.05). The p57(kip2) protein positive-expression correlated significantly with tumor cell differentiation (P < 0.05) and did not correlate significantly with lymph node metastasis (P > 0.05). The cyclinE positive-expression rate in tumor tissues was 68.8%, which was higher than that in adjacent pancreatic tissues (P < 0.05). The cyclinE positive-expression also correlated significantly with tumor cell differentiation and lymph node metastasis (P < 0.05). The cyclinE protein positive-expression rate in the tumor tissues of the p57(kip2) protein positive-expression group was lower than that in the p57(kip2) protein negative-expression group, and there were no significant correlation between the two groups (r = -0.112, P > 0.05). CONCLUSION: Decreased expression of the p57(kip2) protein and/or over-expression of the cyclinE protein may play an important role in the genesis and progression of human pancreatic cancer.

Expression of p27(kip1), Rb protein and proliferating cell nuclear antigen and its relationship with clinicopathology in human pancreatic cancer.

OBJECTIVE: To investigate the effect of inhibiting factor of cell cycle regulation p27(kip1), retinoblastinoma protein (Rb protein), and proliferating cell nuclear antigen (PCNA) on the genesis and progression of human pancreatic cancer. METHODS: The expression of p27(kip1), Rb protein and PCNA in the tumor tissue and adjacent tissue of 32 patients with pancreatic cancer was detected by SP immunohistochemical technique. RESULTS: The p27(kip1) protein positive-expression rate in the tumor tissue of pancreatic cancer was 56.25%, which was lower than that in the adjacent pancreatic tissue (P<0.05). p27(kip1) protein positive-expression was correlated significantly with tumor cell differentiation and lymph node metastasis (P<0.05). The Rb gene protein positive-expression rate in the tumor tissue was 50%, which was also lower than that in the adjacent pancreatic tissue (P<0.05). The PCNA positive-expression rate was 71.87%, which was higher than that in the adjacent pancreatic tissue (P<0.05). PCNA positive-expression was also correlated significantly with tumor cell differentiation and lymph node metastasis (P<0.05). CONCLUSION: The decreased expression of p27(kip1), Rb protein and over-expression of PCNA may play an important role in the genesis and progression of pancreatic cancer.

Breast cancer metastasis to the stomach confirmed using gastroscopy: A case report.

Breast cancer metastasis to the stomach is relatively rare. Unlike infiltrating ductal carcinoma, invasive lobular carcinoma (ILC) has a high tendency to metastasize to the stomach. The present study reports a case of a 53-year-old female who had undergone a modified radical mastectomy of the left breast for ILC eight years previously and presented at the clinic seeking treatment for epigastric discomfort from sour regurgitation and belching that had persisted for one month. Gastroscopy revealed multiple apophysis lesions in the stomach, which were diagnosed as metastatic tumors to the stomach. The diagnosis was further established using histological and immunohistochemical analyses for gross cystic disease fluid protein-15, cytokeratin (CK) 7 and CK20. The patient was treated with systemic chemotherapy without surgery. During the treatment, two gastroscopy procedures revealed that the apophysis lesions in the gastric body had narrowed significantly. Few cases of breast cancer metastasizing to the stomach have been reported, particularly those that have been confirmed using gastroscopy. The present study reports a case of breast cancer metastasis to the stomach to raise awareness of the condition.

Soluble a­proliferation­inducing ligand (sAPRIL), a novel serum biomarker predicting the recurrence and metastasis of pancreatic adenocarcinoma after surgery.

Pancreatic adenocarcinoma (PA) is a leading cause of adult cancer mortality, and surgery is still the best available treatment strategy. However, PA can recur at any time and has limited prognosis. It is therefore necessary to explore novel serum biomarkers of PA to allow the early diagnosis of PA. Soluble a-proliferation-inducing ligand (sAPRIL), a promising inducer of the epithelial-mesenchymal transition (EMT), is often found overexpressed in a variety of autoimmune diseases. To determine whether serum sAPRIL can constitute a PA biomarker, the protein level of sAPRIL was examined by immunohistochemistry and western blot, and the mRNA level was quantified by RT-qPCR. The PA cell line PanC-1 was transfected with vectors bearing the sAPRIL gene and sAPRIL short hairpin RNA (shRNA) oligos. Increased expression of serum sAPRIL was observed in patients with PA recurrence or metastasis after five-year surgery compared to subjects without PA recurrence or metastasis. The growth rate of PanC-1 cells transfected with the sAPRIL expression vector was increased by 23% (P<0.01, vs. control group), and was reduced by 17% (P<0.01, vs. control group) in the sAPRIL shRNA-silenced cell line. Thus, sAPRIL is highly expressed in PA, and serum levels of sAPRIL can serve as a useful indicator for the recurrence or metastasis of PA after surgery. Additional validation studies on the use of serum sAPRIL as a diagnostic marker in PA are however needed.

Small breast epithelial mucin tumor tissue expression is associated with increased risk of recurrence and death in triple-negative breast cancer patients.

BACKGROUND: Small breast epithelial mucin (SBEM) has been implicated in tumor genesis and micrometastasis in breast cancer. Triple-negative breast cancer (TNBC) was characterized by high incidence in young women,early relapse and a very poor prognosis. The aim of this study was to evaluate the association of SBEM expression in tissues of TNBC with disease-free survival (DFS) and overall survival (OS). METHODS: SBEM protein expression was detected in 87 available formalin-fixed paraffin-embedded (FFPE) tissue specimens from TNBC patients by means of immunohistochemistry (IHC). We analyzed the correlation between the SBEM protein expression and DFS and OS during a 5 year follow-up period, respectively. And a SBEM cut-off value of prognosis was established associated with DFS and OS. SBEM was analyzed against other risk factors in multivariate analysis. RESULTS: SBEM 3+ score was cut-off value of prognosis and significantly correlated with DFS (p = 0.000) and OS (p = 0.001) in TNBC patients. There was a marked associations (p <0.05) between SBEM 3+ score and tumor size, grade, node status, TNM stage and Ki67. Multivariate analysis showed that patients with SBEM 3+ represented a higher risk of recurrence and mortality than those with a lower SBEM expression (HR = 3.370 with p = 0.008 for DFS and HR = 4.185 with p = 0.004 for OS). CONCLUSIONS: SBEM is an independent risk predictor and may offer utility as a prognostic marker in TNBC patients.

[Clinical and pathological analysis of 41 cases of acute leukemia combined with intracranial hemorrhage].

This study was aimed to summarize the clinical and pathological features of patients with acute leukemia combined with intracranial hemorrhage. The clinical and pathological data of 41 adult patients diagnosed as acute leukemia in our hospital from 1953 to 1990 year were analyzed retrospectively. The results showed that there were 35 cases of AML, 6 cases of ALL; 9 cases in clinical hematologic remission, 32 cases in non-remission, 3 cases of AL with hypertension, 2 cases of AL with diabetes, 4 cases of AL with sepsis, 19 cases with WBC ≥ 100×10(9)/L; the pathologic examination showed 4 cases of AL accompanied with disseminated intravascular coagulation, 10 cases with prothrombin time INR ≥ 1.5, 26 cases with multifocal intracranial hemorrhage, 7 cases with single intracranial hemorrhage, 8 cases with diffused spotting intracranial hemorrhage; the examination also showed that 84 hemorrhage foci were found in 41 cases of AL, among them 46 foci located under cerebral cortex, 23 foci in cerebellum, 6 in basal ganglia, 5 foci in pons, 2 foci in thalamus, 2 foci in spinal cord. It is concluded that the intracranial hemorrhage is a major cause resulting in death of AL patients which should be think highly, and the diagnosis and treatment should be conducted through comprehensive analysis.

Aspirin upregulates the expression of neuregulin 1 and survivin after focal cerebral ischemia/reperfusion in rats.

Neuregulin 1 (NGR1) and survivin have been shown to be neuroprotective. However, the link between their expression and aspirin in the treatment of cerebral ischemia remains unclear. Here, we investigated the effect of aspirin on NGR1 and survivin expression after focal cerebral ischemia/reperfusion in rats. Sprague Dawley rats were randomly divided into an aspirin treatment group (n=40) and a control group (n=40). Each group was further divided into five subgroups according to the time after reperfusion. A middle cerebral artery model was established by an occlusion suture. At 24 h, 3, 5 and 7 days after reperfusion, the Bederson neurological deficit scores were 1.47±0.11, 1.22±0.08, 0.85±0.15 and 0.59±0.12 in the treatment group, and 1.87±0.18, 1.45±0.14, 1.05±0.08 and 0.75±0.15 in the control group, respectively, indicating a significant difference at each time point (P<0.05). In the infarct center, the number of NGR1- and survivin-positive cells reached the maximum at 6 h and decreased gradually to a minimum at 7 days, while in the peri-infarct area, the number was few at 6 h, peaked at 3 days and then was reduced gradually with significant differences between the two time points (P<0.05). There were more NGR1- and survivin-positive cells in the treatment group compared to the control group (P<0.05). In conclusion, the neuroprotective effect of aspirin is at least partly mediated by the upregulation of NGR1 and survivin expression after ischemia.

[Relationship between expression of p57(kip2), cyclin E protein, PCNA, and clinicopathological factors in human pancreatic cancer].

BACKGROUND & OBJECTIVE: The abnormality of mammalian cell cycle regulation is an important cause of cell over-proliferation and oncogenesis. There were few reports about the relationship between p57(kip2) protein as negative factor of cell cycle regulation and pancreatic cancer. This article aims to investigate the effects of p57(kip2), cyclin E and proliferating cell nuclear antigen (PCNA) protein on the occurrence and progression of pancreatic cancer. METHODS: Expression of p57(kip2), cyclin E, and PCNA in tumor tissue and adjacent tissue from 32 patients with pancreatic cancer were detected using SP immunohistochemical technique. RESULTS: The positive-expression rate of p57(kip2) protein in tumor tissue of pancreatic cancer was 46.9%, which was lower than that in adjacent pancreatic tissue (75.0%) (Chi(2)=5.317, P< 0.05); p57(kip2) protein positive-expression was remarkably correlated with tumor cell differentiation (P< 0.05), but was not correlated with lymph node metastasis (P >0.05). The positive-expression rate of cyclin E in tumor tissues was 68.8%, which was higher than that in adjacent pancreatic tissue (43.8%) (Chi(2)=4.063,P< 0.05); Cyclin E positive-expression was remarkably correlated with tumor cell differentiation and lymph node metastasis (P< 0.05). The positive-expression rate of PCNA protein in tumor tissues was 71.9%, which was higher than that in adjacent pancreatic tissue (43.8%) (Chi(2)=5.189,P< 0.05); PCNA positive- expression was remarkably correlated with tumor cell differentiation and lymph node metastasis(P< 0.05). CONCLUSION: The decreased expression of p57(kip2) protein and over-expression of cyclin E and PCNA proteins may significantly related to genesis and progress of pancreatic cancer.