OBJECTIVETo study the relationship between fibrotic focus (FF) and carbonic anhydrase (CA) IX in invasive ductal carcinomas (IDC) of the breast.

METHODSIn 167 cases of IDC, the FF was assessed morphologically, and expression of ER, PR and CA IX was evaluated using MaxVision immunohistochemistry.

RESULTSThe expression of CA IX in IDC with and without FF was 56.3% (45/80) and 28.7% (25/87) respectively, with significant difference (P=0.001). In IDC with FF, the CA IX expression of tumor cells in tumors with CA IX-positive fibroblasts (35/40, 87.5%) was significantly (P<0.001) higher than that in tumors with CA IX-negative fibroblasts (10/40, 25.0%). In IDC with FF, the CA IX expression of fibroblasts of FF in grade 3 IDC (23/33, 69.7%) was significantly (P=0.006) higher than that in grade 1+2 tumors (17/47, 36.2%). The ER and PR expression of tumor cells in tumors containing CA IX-negative fibroblasts was 72.5% (29/40) and 65.0% (26/40) respectively, whereas the ER and PR expression of tumor cells in tumors containing CA IX-positive fibroblasts was 50.0% (20/40) and 42.5% (17/40) respectively; the difference was statistically significant (for both ER and PR, P=0.04). The age of patients with tumors containing CA IX-negative fibroblasts was significantly (P=0.002) older than those containing CA IX-positive fibroblasts. The FF diameter/tumor diameter in tumors containing CA IX-positive fibroblasts was significantly larger than those containing CA IX-negative fibroblasts. (3) For the groups of tumor size≤2 cm and tumor size between 2 cm to 5 cm, the diameter of the fibrotic focus was significantly (P<0.01) smaller than the fibrotic focus size of tumors>5 cm in size.

CONCLUSIONSCA IX expression is correlated with FF, and that in fibroblasts of FF correlated with patients' age, tumor grade, hormone receptors and FF diameter/tumor diameter. CA IX expression in FF might be a marker for poor prognosis in patients with breast cancer.

Age Factors ; Antigens, Neoplasm ; Breast Neoplasms ; metabolism ; pathology ; Carbonic Anhydrase IX ; Carbonic Anhydrases ; Carcinoma, Ductal, Breast ; enzymology ; pathology ; Female ; Fibroblasts ; metabolism ; Humans ; Immunohistochemistry ; Neoplasm Grading ; Neoplasm Proteins ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

OBJECTIVE: To investigate the effect of rosuvastatin on homocysteine (Hcy) induced mousevascular smooth muscle cells(VSMCs) dedifferentiation and endoplasmic reticulum stress(ERS). METHODS: VSMCs were co-cultured with Hcy and different concentration of rosuvastatin (0.1, 1.0 and 10 μmol/L). Cytoskeleton remodeling, VSMCs phenotype markers (smooth muscle actin-α, calponin and osteopontin) and ERS marker mRNAs (Herpud1, XBP1s and GRP78) were detected at predicted time. Tunicamycin was used to induce, respectively 4-phenylbutyrate(4-PBA) inhibition, ERS in VSMCs and cellular migration, proliferation and expression of phenotype proteins were analyzed. Mammalian target of rapamycin(mTOR)-P70S6 kinase (P70S6K) signaling agonist phosphatidic acid and inhibitor rapamycin were used in Rsv treated VSMCs. And then mTOR signaling and ERS associated mRNAs were detected. RESULTS: Compared with Hcy group, Hcy+ Rsv group (1.0 and 10 μmol/L) showed enhanced α-SMA and calponin expression (<0.01), suppressed ERS mRNA levels (<0.01) and promoted polarity of cytoskeleton. Compared with Hcy group, Hcy+Rsv group and Hcy+4-PBA group showed suppressed proliferation, migration and enhanced contractile protein expression (<0.01); while tunicamycin could reverse the effect of Rsv on Hcy treated cells. Furthermore, alleviated mTOR-P70S6K phosphorylation and ERS (<0.01)were observed in Hcy+Rsv group and Hcy+rapamycin group, compared with Hcy group; while phosphatidic acid inhibited the effect of Rsv on mTOR signaling activation and ERS mRNA levels (<0.01). CONCLUSIONS Rosuvastatin could inhibit Hcy induced VSMCs dedifferentiation suppressing ERS, which might be regulated by mTOR-P70S6K signaling.
Actins ; metabolism ; Animals ; Calcium-Binding Proteins ; metabolism ; Cell Dedifferentiation ; drug effects ; Cells, Cultured ; Endoplasmic Reticulum Stress ; drug effects ; Heat-Shock Proteins ; metabolism ; Homocysteine ; Membrane Proteins ; metabolism ; Mice ; Microfilament Proteins ; metabolism ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; cytology ; drug effects ; Ribosomal Protein S6 Kinases, 70-kDa ; metabolism ; Rosuvastatin Calcium ; pharmacology ; TOR Serine-Threonine Kinases ; metabolism ; X-Box Binding Protein 1 ; metabolism

Objective To evaluate the clinical value of laparoscopy in adrenal surgery.Methods From December 2000 to May 2006,86 cases of adrenal space-occupying lesion received laparoscopic adrenalectomy via transperitoneal(n=1),retroperitoneal(n=81) and hand-assisted transperitoneal(n=4) approach,respectively.Results All the operations were successful without conversion to open surgery and severe complications.The mean operative time was 72 min(range,50-175 min).The mean blood loss was 54 ml(range,15-120 ml).The postoperative hospital stay was 6.3 d(range,5-8 d).Imaging examinations revealed no tumor recurrence and metastasis during the mean follow-up period of 26.5 months(range,2-65 months)in 86 patients.The symptoms of patients with functional tumor was alleviated or disappeared.Conclusions Laparoscopic adrenalectomy has advantages of minimal invasion,less blood loss,and quicker recovery,and it should be the fist choice for most adrenal space-occupying lesions.

Female ; Humans ; Adenocarcinoma in Situ ; Uterine Cervical Neoplasms/pathology* ; Papillomavirus Infections ; Cervix Uteri/pathology* ; Adenocarcinoma/pathology* ; Papillomaviridae ; DNA, Viral

OBJECTIVETo evaluate the efficacy and toxicity of concurrent chemoradiotherapy for patients with locally advanced unresectable extrahepatic cholangiocarcinoma.

METHODSThirty-eight patients with locally advanced unresectable extrahepatic cholangiocarcinoma admitted in Shaoxing People's Hospital from February 2007 to February 2012 were enrolled in the study. They were randomized into sequential chemoradiotherapy (n=19) or concurrent chemoradiotherapy group (n=19). All patients were treated with intensity modulated radiation therapy (IMRT). Patients in concurrent chemoradiotherapy group received the regimen of gemcitabine plus oxaliplatin. Tumor response and adverse effects were observed periodically. The primary end points were disease progression-free survival (PFS) and overall survival (OS).

RESULTSThe response rates of sequential chemoradiotherapy and concurrent chemoradiotherapy groups were 42.1% (8/19) and 63.2% (12/19). The disease control rates of them were 78.9% (15/19) and 84.2% (16/19))， respectively. The median PFS of sequential chemoradiotherapy group and concurrent chemoradiotherapy group was 8.3 (95%CI: 7.6-9.0) and 10.4 months (95%CI: 9.4-11.4, P=0.037), and the median OS in two groups were 14.2 (95%CI: 12.6-15.8) and 15.6 months (95%CI: 14.2-17.0, P=0.095), respectively. The major adverse reactions were controllable hematology toxicity and gastrointestinal reaction. There was no significant difference in incidence of adverse reactions between two groups (P>0.05).

CONCLUSIONSequential chemoradiotherapy and concurrent chemoradiotherapy may improve PFS and OS in patients with locally advanced unresectable extrahepatic cholangiocarcinoma, and both are well-tolerated. In addition, concurrent chemoradiotherapy might provide additional PFS benefit and would be preferable.

Bile Duct Neoplasms ; therapy ; Bile Ducts, Intrahepatic ; pathology ; Chemoradiotherapy ; Cholangiocarcinoma ; therapy ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Humans ; Organoplatinum Compounds ; therapeutic use ; Survival Rate

Breast ; Carcinoma ; Humans ; Mixed Tumor, Malignant

Objective To investigate the effects of the long non-coding RNA LOXL1 antisense RNA 1 （LOXL1-AS1） on the apoptosis and inflammatory factor expression of human brain microvascular endothelial cells （HBMECs） induced by oxygen-glucose deprivation （OGD）. Methods HBMECs were divided into control group （normal culture）， OGD group （OGD injury）， OGD+si-NC group （transfection with si-NC plus OGD injury）， OGD+si-LOXL1-AS1 group （transfection with si-LOXL1-AS1 plus OGD injury）， OGD+miR-NC group （transfection with miR-NC plus OGD injury）， OGD+miR-761 group （transfection with miR-761 mimic plus OGD injury）， OGD+si-LOXL1-AS1+negative control group （transfection with si-LOXL1-AS1 and anti-miR-NC plus OGD injury）， and OGD+si-LOXL1-AS1+miR-761 inhibitor group （transfection with si-LOXL1-AS1 and miR-761 inhibitor plus OGD injury）. The expression of LOXL1-AS1 and miR-761 was measured by RT-qPCR. Cell viability was measured using cell counting kit-8. Cell apoptosis was determined by flow cytometry. The expression of B-cell lymphoma/leukemia-2 （Bcl-2） protein and Bcl-2-associated X （Bax） protein was measured by Western blotting. The levels of interleukin （IL）-6， IL-1β， and tumor necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay. Dual luciferase reporter assay was used to detect the complementary binding of LOXL1-AS1 and miR-761. Results Compared with the control group， the OGD group showed significant increases in LOXL1-AS1 expression， the cell apoptosis rate， Bax expression， and IL-6， IL-1β， and TNF-α levels and significant decreases in the cell survival rate and Bcl-2 expression （all P<0.05）. After inhibiting LOXL1-AS1， the OGD+si-LOXL1-AS1 group showed significant decreases in LOXL1-AS1 expression， the apoptosis rate， Bax expression， and IL-6， IL-1β， and TNF-α levels and significant decreases in the survival rate and Bcl-2 expression， compared with the OGD group and the OGD+si-NC group （all P<0.05）. LOXL1-AS1 targeted the expression of miR-761. After overexpressing miR-761， the OGD+miR-761 group showed significant increases in the survival rate and Bcl-2 expression and significant decreases in the apoptosis rate， Bax expression， and IL-6， IL-1β， and TNF-α levels， compared with the OGD+miR-NC group （all P<0.05）. Compared with the OGD+si-LOXL1-AS1+negative control group， the OGD+si-LOXL1-AS1+miR-761 inhibitor group showed significantly decreased survival rate and Bcl-2 expression and significantly increased apoptosis rate， Bax expression， and IL-6， IL-1β， and TNF-α levels （all P<0.05）. Conclusion Inhibiting LOXL1-AS1 expression can up-regulate miR-761 to promote the survival of OGD-induced HBMECs and suppress the cells' apoptosis and expression of inflammatory factors.

Objective To compare the values of dynamic enhanced magnetic resonance imaging(DCE-MRI),digital breast tomosynthesis(DBT),and digital mammography(DM)in the early detection and diagnosis of breast cancer.Methods We retrospectively analyzed the clinical and imaging data of 65 cases with early breast cancer confirmed by surgical pathology from June 2017 to December 2018.All patients underwent breast DCE-MRI,DM and DBT before surgery.The receiver operating characteristic(ROC)curves were drawn,with the pathological results as the gold standard,to evaluate the diagnostic performance of different examination methods.The areas under ROC curves(AUCs)were compared using test.The differences among DCE-MRI,DBT and DM in detecting early breast cancer were compared using chi-square test in terms of positive rates,accuracy,sensitivity,and specificity.Pearson correlation analysis was performed to assess the accuracy of these imaging methods in detecting the size of early breast cancer.Results The AUCs of DCE-MRI,DBT,and DM based on the BI-RADS classification for early diagnosis of breast cancer were 0.910,0.832,and 0.700,respectively(=2.132,=0.001);the sensitivity of DCE-MRI,DBT,and DM for early breast cancer was 92.3%,70.8%,and 52.5%,the specificity was 65.0%,85.0%,and 79.3%,and the accuracy was 83.1%,70.8%,and 50.8%,indicating that DCE-MRI(=15.330,=0.0001) and DBT(=5.450,=0.020) had significantly higher diagnostic accuracy than DM.The measurement results of DM,DBT,and DCE-MRI were positively correlated with the pathological measurements(=0.781,=0.847,=0.946;all <0.01). Conclusions DCE-MRI and DBT have higher positive rates and accuracies than DM in detecting early breast cancer.Medical institutions where DCE-MRI is still not available can use DBT to improve the early detection of breast cancer.
Breast ; diagnostic imaging ; Breast Neoplasms ; diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging ; Mammography ; methods ; Retrospective Studies

OBJECTIVE: To explore the effect of oxidative stress on periprosthetic osteolysis induced by TCP wear particles in mouse calvaria and its mechanism. METHODS: Thirty-six male ICR mice were randomly divided into three groups (=12):sham group, TCP wear particles (TCP) group and N-acetyl-L-cysteine (NAC) group. Aperiprosthetic osteolysis model in mouse was established by implanting 30 mg of TCP wear particles onto the surface of bilateral parietal bones following removal of the periosteum. On the 2nd day post-operation, NAC (1.0 mg/kg) was locally injected to the calvarium under the periosteum every other day for 2 weeks. Then, all the mice were sacrificed to obtain blood and the calvaria. Periprosthetic osteolysis in the mouse calvaria was observed by tartrate resistant acid phosphatase (TRAP) staining; serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), interleukin-6 (IL-6); total anti-oxidation capacity (T-AOC) and superoxide dismutase (SOD) activity were examined by ELISA and chemical colorimetry, respectively; protein levels of glucose-regulated protein 78 (GRP78), protein kinase R-like ER kinase (PERK), phospho-PERK (p-PERK), eukaryotic initiation factor 2α (eIF2α) and phospho-eIF2α (p-eIF2α) in periprosthetic bone tissue were detected by Western blot. RESULTS: Compared with sham group, serum levels of TNF-α, IL-1β and IL-6, and osteolysis area were increased obviously in TCP group (<0.05), and serum level of T-AOC and SOD activity were decreased significantly in TCP group (<0.05), GRP78 expression, the ratio of p-PERK and PERK, p-eIF2α and eIF2α in the mouse calvaria of TCP group were up-regulated markedly. Compared with TCP group, serum levels of TNF-α, IL-1β and IL-6, and osteolysis area were decreased markedly in NAC group (<0.05), serum level of T-AOC and SOD activity were increased obviously in NAC group (<0.05), and GRP78 expression, the ratio of p-PERK/PERK and p-eIF2α/eIF2α were obviously down-regulated. CONCLUSIONS Inhibition of oxidative stress can prevent periprosthetic osteolysis induced by TCP wear particles, which may be mediated by inactivation of PERK/eIF2α signaling pathway.
Animals ; Male ; Mice ; Mice, Inbred ICR ; Osteolysis ; Oxidative Stress ; Skull ; Tumor Necrosis Factor-alpha

Adolescent ; Child ; Diagnostic Errors ; Female ; Humans ; Ovarian Diseases ; diagnosis ; pathology ; surgery