The microRNA-141-3p/ CDK8 pathway regulates the chemosensitivity of breast cancer cells to trastuzumab.

AIMS: This study was conducted to explore the function of microRNA-141-3p/cyclin-dependent kinase 8 (miR-141-3p/CDK8) in regulating trastuzumab resistance of breast cancer cells. MATERIALS AND METHODS: Microarray analysis was performed to screen microRNAs that are differentially expressed in wild type and trastuzumab-resistant (TR) breast cancer cell lines. TargetScan helped predict the target gene of miR-141-3p. The regulatory relationship was confirmed through a luciferase reporter assay, quantitative reverse transcriptase polymerase chain reaction, and Western blot analysis. The MTT assay, transwell invasion assay, and wound scratch assay were performed to measure the proliferative, invasive, and migratory ability of breast cancer cells, respectively. Tumor cell xenografts in nude mice were conducted to observe the effect of miR-141-3p on trastuzumab resistance in breast cancer cells in vivo. The enzyme-linked immunosorbent assay was used to detect protein secretion. RESULTS: miR-141-3p was downregulated in the drug-resistant cell lines. CDK8 was proved to be a target gene of miR-141-3p. Transfection of miR-141-3p or CDK8 small interfering RNA (siRNA) reversed the resistance to trastuzumab in TR cell lines and suppressed cell invasion and migration. Dysregulation of transforming growth factor beta (TGF-ß) was detected when the expression of CDK8 was silenced by CDK8 siRNA, and downregulation of TGF-ß had a notable effect on reducing the phosphorylation of SMAD2/SMAD3. CONCLUSION: miR-141-3p could restore the sensitivity to trastuzumab in breast cancer cells by repressing CDK8, which might regulate the phosphorylation levels of SMAD2/SMAD3 via TGF-ß.

Cervical human papillomavirus among 19 753 women attending gynecological department of a major comprehensive hospital in north Anhui China 2013-2016: Implication for cervical cancer screening and prevention.

Our study aimed to assess the prevalent, incident, and persistent infection, and clearance of HPV among 19 753 individual women attending the gynecological department at a major comprehensive hospital. HPV 16, 52, and 58 ranked top three types with the highest prevalence and incidence. The prevalence of high-risk (HR) HPV peaked among women aged 15 to 19 years, then sharply decreased with age, stabilized among women aged 25 to 44 years, and then surged again among women aged 45 years and older. HR HPV infection were more likely to be prevalent (15.9% vs 1.3%, P < 0.001), incident (17.3 vs 2.0 per 1000 person-months, P < 0.001), and persistent (33.0% vs 24.2%, P = 0.033), and less likely to clear (88 vs 115 per 1000 person-months, P = 0.040) compared to low-risk HPV types. The majority of women detected with HR HPV types did not retest within 12 months. Clinical guidelines on HPV DNA testing are needed and education and counseling about HPV infection and its implications for women detected with HPV at clinical settings are warranted.

Thyroid hormone receptor interactor 13 (TRIP13) overexpression associated with tumor progression and poor prognosis in lung adenocarcinoma.

Thyroid hormone receptor interactor 13 (TRIP13) is an AAA+-ATPase that plays a key role in mitotic checkpoint complex inactivation and is associated with the progression of several cancers. However, its role in lung adenocarcinogenesis remains unknown. Here, we report that TRIP13 is highly overexpressed in multiple lung adenocarcinoma cell lines and tumor tissues. Clinically, TRIP13 expression is positively associated with tumor size, T-stage, and N-stage, and Kaplan-Meier analysis revealed that heightened TRIP13 expression is associated with lower overall survival. TRIP13 promotes lung adenocarcinoma cell proliferation, clonogenicity, and migration while inhibiting apoptosis and G2/M phase shift in vitro. Accordingly, TRIP13-silenced xenograft tumors displayed significant growth inhibition in vivo. Bioinformatics analysis demonstrated that TRIP13 interacts with a protein network associated with dsDNA break repair and PI3K/Akt signaling. TRIP13 upregulatesAktSer473 and downregulatesAktThr308/mTORSer2448activity, which suppresses accurate dsDNA break repair. TRIP13 also downregulates pro-apoptotic BadSer136 and cleaved caspase-3 while upregulating survivin. In conclusion, heightened TRIP13 expression appears to promote lung adenocarcinoma tumor progression and displays potential as a therapeutic target or biomarker for lung adenocarcinoma.

[Expression of AXIN and MACC1 in Gastric Carcinoma and Its Clinical Significance].

OBJECTIVE: To investigate the expression of axis inhibition protein (AXIN) and metastasis-associated in colon cancer-1 (MACC1) in gastric carcinoma and their relationship to the clinicopathologic characteristics. METHODS: Expressions of AXIN and MACC1 proteins were examined by immunohistochemistry containing 100 specimens of gastric tissues (gastric carcinoma group) and 60 specimens of normal gastric mucosa tissues (control group,the nearby tissues of the excised specimen of gastric cancer patients,from the tumor of the gastric cancer >5.0 cm,and confirm that there were no cancer cells). RESULTS: The positive rates of AXIN and MACC1 proteins in gastric carcinoma and the control tissues were 37.0% vs. 83.3% and 58.0% vs. 6.7%,respectively. The difference were significant between the two groups (both P<0.05). The expressions of AXIN and MACC1 proteins were significantly related with grades of tumor,depth of invasion,lymph node metastasis,and Duke stages ( P<0.05). Spearman analysis showed that there was a negative relationship between the AXIN expression and MACC1 expression (r=-0.355, P<0.05). Kaplan-Meier survival analysis and log-rank single factor analysis showed that AXIN and MACC1 protein expressions were related to the 5-year survival rate of patients (both P<0.05). Cox regression analysis showed that the positive expression of AXIN and the negative expression MACC1 protein,and Duke stages (Ⅲ-Ⅳ) were the independent prognostic factors of gastric carcinoma. CONCLUSION: The expressions of AXIN and MACC1 proteins are related to the prognosis of gastric carcinoma patients,and are involved in the invasion and metastasis of gastric carcinoma.

Evaluation of the correlation of vasculogenic mimicry, ALDH1, KAI1 and microvessel density in the prediction of metastasis and prognosis in colorectal carcinoma.

BACKGROUND: Metastasis and recurrence are the most common reasons for treatment failure of colorectal carcinoma (CRC). Vasculogenic mimicry (VM, blood supply formation often seen in highly aggressive tumors), Aldehyde dehydrogenase 1 (ALDH1, a biomarker of cancer stem cells), KAI1 (a suppressor gene of tumor metastasis) are all valuable factors for metastasis and prognosis in diverse human cancers. However, the correlation of VM, ALDH1, KAI1 and microvessel density (MVD) in CRC is unclear. In this study, we analyzed the correlations among VM, ALDH1, KAI1 and MVD, as well as their respective correlations with clinicopathological parameters and survival in CRC. METHODS: The level of VM, ALDH1, KAI1 and MVD in 204 whole tissue samples of CRC were examined by immunhistochemistry. Clinical data was also collected. RESULTS: Levels of VM, ALDH1 and MVD were significantly higher, and levels of KAI1 significantly lower, in CRC tissues than in normal colorectal tissues. Levels of VM, ALDH1 and MVD were positively associated with invasion of depth, lymph node metastasis (LNM), distant metastasis and tumor-node-metastasis (TNM) stages, and negatively with patients' overall survival (OS). Levels of KAI1 was negatively correlated with invasion of depth, LNM, distant metastasis and TNM stages, and the KAI1 positive expression subgroup had significantly longer OS than did the KAI1- subgroup. In multivariate analysis, high levels of VM, ALDH1 and KAI1, as well as TNM stages were independently correlated with lower OS in patients with CRC. CONCLUSIONS: VM, MVD and the expression of ALDH1 and KAI1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets for CRC.

Metastasis-associated in colon cancer-1 and aldehyde dehydrogenase 1 are metastatic and prognostic biomarker for non-small cell lung cancer.

BACKGROUND: Tumor recurrence and metastasis are the most common reason for treatment failure. Metastasis-associate in colon cancer-1 (MACC1) has been identified as a metastatic and prognostic biomarker for colorectal cancer and other solid tumors. Aldehyde dehydrogenase 1 (ALDH1), a marker of cancer stem cells, is also associated with metastasis and poor prognosis in many tumors. However, the prognostic value of either MACC1 or ALDH1 in non-small cell lung cancer (NSCLC) is unclear. In this study, we explored the relationship between MACC1 and ALDH1 expression, as well as their respective associations with clinicopathological features, to determine if either could be useful for improvement of survival prognosis in NSCLC. METHODS: The expression levels of both MACC1 and ALDH1 in 240 whole tissue sections of NSCLC were examined by immunohistochemistry. Clinical data were also collected. RESULTS: MACC1 and ALDH1 were significantly overexpressed in NSCLC tissues when compared to levels in normal lung tissues. Investigation of associations between MACC1 or ALDH1 protein levels with clinicopathological parameters of NSCLC revealed correlations between the expression of each with tumor grade, lymph node metastasis, and tumor node metastasis. The overall survival of patients with MACC1- or ALDH1-positive NSCLC tumors was significantly lower than that of those who were negative. Importantly, multivariate analysis suggested that positive expression of either MACC1 or ALDH1, as well as TNM stage, could be independent prognostic factors for overall survival in patients with NSCLC. CONCLUSIONS: MACC1 and ALDH1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets, for NSCLC.

The expression of metastasis-associated in colon cancer-1 and KAI1 in gastric adenocarcinoma and their clinical significance.

BACKGROUND: The most common reason for malignant tumor treatment failure is recurrence and metastasis. Metastasis-associated in colon cancer-1 (MACC1) was originally identified as a metastatic and prognostic biomarker for colon cancer and later other solid tumors. Kangai 1 (KAI1), a marker of suppressor of metastasis, is also associated with metastasis and poor prognosis in many tumors. However, the prognostic value of either MACC1 or KAI1 in gastric adenocarcinoma (GAC) is unclear. In this study, we explored the relationship between MACC1 and KAI1 expression, as well as their respective correlation with clinicopathological features, to determine if either could be helpful for improvement of survival prognosis in GAC patients. METHODS: The expression levels of both MACC1 and KAI1 in 325 whole-tissue sections of GAC were examined by immunohistochemistry. Clinical data was also collected. RESULTS: MACC1 was significantly overexpressed in GAC tissues when compared to levels in normal gastric tissues; KAI1 was significantly down-expressed in GAC tissues when compared to levels in normal gastric tissues. Investigation of association between MACC1 and KAI1 protein levels with clinicopathological parameters of GAC indicated association between the expression of each with tumor grade, lymph node metastasis, invasive depth, and TNM stages. The overall survival time of patients with MACC1- or KAI1-positive GAC tumors was significantly shorter or longer than that of those who were negative. Importantly, multivariate analysis suggested that positive expression of either MACC1 or KAI1, as well as TNM stage, could be independent prognostic factors for overall survival in patients with GAC. CONCLUSIONS: MACC1 and KAI1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets, for GAC.

[Expressions of MACC1, Snail, and KISS-1 Proteins in Infiltrating Breast Carcinoma and Its Clinicopathological Features].

OBJECTIVES: To investigate the protein expressions of metastasis-associated in colon cancer 1 (MACC1), KISS-1 (a cancer ruppressor gene) and Snail (the marker of epithelial-mesenchymal transition) in infiltrating breast carcinoma (IBC) and explore the role of them in invasion, metastasis and prognosis in IBC. METHODS: Expressions of MACC1, Snail and KISS-1 were examined by immunohistochemistry in 250 specimens of IBC and 80 specimens of normal breast tissues. Their clinicopathological features were analyzed, and their influence on patients' survival was identified. RESULTS: The positive rate of MACC1, Snail and KISS-1 in normal breast tissues and IBC tissues was 7.5%, 5.0%, 87.5% and 63.6%, 58.8%, 38.0%, respectively. And there was a significant difference between the IBC group and control group ( P<0.05). The positive expressions of MACC1, Snail and KISS-1 were significantly different in different TNM stages, lymph node metastasis, types and grades of tumor ( P<0.05). The survival time of positive KISS-1 group was significantly longer than that of negative group ( P<0.001); the survival time was significantly shorter in positive MACC1 group or Snail group than that of negative groups (both P<0.001). Cox regression analysis indicated that the positive expressions of MACC1, Snail and negative expression of KISS-1 were independent risk factors of IBC (P<0.05). CONCLUSIONS: Abnormal expression of MACC1, Snail and KISS-1 should be involved in the invasion and metastasis of IBC. The combined detection in the expressions of MACC1, Snail and KISS-1 at the early stage may play an important role in predicting the progression and prognosis of IBC.

Clinicopathological significance of KAI1 expression and epithelial-mesenchymal transition in non-small cell lung cancer.

BACKGROUND: KAI1 and epithelial-mesenchymal transition (EMT) is related to both angiogenesis and lymphangiogenesis and is an important target in new cancer treatment strategies. We aimed to investigate the KAI1 and marker of EMT expression and correlation with lymph node metastasis (LNM) and explore their prognostic impact in non-small cell lung cancer (NSCLC). METHODS: Tumor tissue specimens from 312 resected patients with stage I-IIIA NSCLC were obtained. Immunohistochemistry was used to assess the expression of the molecular markers KAI1, E-cadherin (E-cad), vimentin, CD34, and D2-40. RESULTS: There were 153 N0 and 159 N+ patients. Tumor cell expression of KAI1and the marker of EMT, lymphatic vessel density (LVD), and microvessel density (MVD) were related to LNM. In multivariate analyses, the ages of patients, high tumor cell KAI1 expression, EMT, and the scores of MVD were independent factor of prognosis. CONCLUSIONS: Tumor cell KAI1 expression, EMT, LVD, and MVD correlate with LNM. Thus, the detection of KAI1, expression of markers of EMT, and the scores of MVD may be used as a potential indicator of NSCLC prognosis.

Clinicopathological significance of CD133 and CD44 expression in infiltrating ductal carcinoma and their relationship to angiogenesis.

BACKGROUND: Breast cancer is the leading cause of cancer death in females worldwide, and the majority type is infiltrating ductal carcinoma (IDC). Most of IDC patients died of metastasis and recurrence. Cancer stem cells (CSCs) are defined with the ability to be self-renewal and potentially promote proliferation and formation of tumors. CSCs are related to angiogenesis and are important targets in new cancer treatment strategies. In this study, we purposed to investigate on expression and clinical significances of CSCs marked by CD133 and CD44 in IDC and their relationship to angiogenesis. METHODS: The specimens of IDC from 325 Chinese patients with follow-up were analyzed for CD133, CD44, CD82, and CD34 protein expression by immunohistochemical staining. The Pearson chi-square test and t test were used to assess the associations among the positive staining of these markers and clinicopathological characteristics. Postoperative overall survival time in these patients with IDC was analyzed by univariate and multivariate analyses. RESULTS: In IDC tissues, positive rates of 48.6%, 53.8%, and 42.2% were obtained for CD133, CD44, and CD82 protein, respectively; the mean score of microvessel density (MVD) was 20.5 ± 7.0 in IDC group. And there was a significant difference between the two groups. There was a positive relationship between the expression of CD133, CD44, and the score of MVD and the grades of tumor, lymph node metastasis, tumor-node-metastasis (TNM) stages (all P < 0.05); and the expression of CD82 was negatively related to grades of tumor, lymph node metastasis, and TNM stages (all P < 0.05). The overall mean survival time of the patients with CD133, CD44, and the score of MVD (≥21) positive expression was lower than that of patients with negative expression. The overall mean survival time of patients of CD82-positive expression was longer than that of patients of the negative expression group. The positive expression of CD133 and CD82, and TNM stages were independent prognostic factors of IDC (P < 0.05). CONCLUSIONS: CSCs, angiogenesis, and aberrant expression of CD82 may be involved in the initiation, development, metastasis, and recurrence. It is suggested that CSCs, angiogenesis, and CD82 be possible as a therapeutic marker for anti-tumor therapy.

Clinicopathological significance of cancer stem cells marked by CD133 and KAI1/CD82 expression in laryngeal squamous cell carcinoma.

BACKGROUND: Presently, CD133 is one of the hottest markers to characterize cancer stem cells and KAI1/CD82 is reported as an important marker for the metastasis and prognosis of many cancers. The purpose of our study is to explore the relationship between cancer stem cells (CSCs) marked by CD133 and KAI1/CD82 expression and the clinicopathological characteristics of patients with laryngeal squamous cell carcinoma (LSCC). METHODS: Immunohistochemical analysis was used to detect the expression of CD133 and KAI1/CD82 in 83 archival surgical specimens of human LSCC and 83 cases of normal laryngeal tissues. RESULTS: In LSCC, positive rates of 49.4% and 41.0% were obtained for CD133 and KAI1/CD82, respectively. The expression of CD133 in LSCC tissues was significantly higher than that in normal tissues (P<0.001), and the expression of CD133 was positively associated with pTNM stage (P=0.005), pathological grade (P=0.001), and lymph node metastasis (P<0.001). The reduced expression of KAI1/CD82 was present in LSCC tissues. The positive rate of KAI1/CD82 expression was negatively correlated with pTNM stage (P=0.014), pathological grade (P<0.001), and lymph node metastasis (P=0.007). A correlation analysis showed that there was a negative relationship between the expression of CD133 and KAI1/CD82 protein in LSCC tissues (P<0.001). By Kaplan-Meier analysis, the expression of CD133 was negatively correlated with overall survival (OS) (log-rank=40.949, P<0.001) and disease-free survival (DFS) (log-rank=39.307, P<0.001) time of LSCC. The expression of KAI1/CD82 was positively correlated with OS (log-rank=40.279, P<0.001) and DFS (log-rank=39.271, P<0.001) time of LSCC. Cox regression analysis: the expression of CD133 and KAI1/CD82, and pTNM stages were independent prognostic factors of LSCC (P<0.05). CONCLUSIONS: Thus the detection of CD133 and KAI1/CD82 proteins may be used as a potential indicator of LSCC prognosis.

Clinicopathologic Features and Immune Cell Subtypes Analysis of Tumor-infiltrating Lymphocytes Rich Invasive Breast Carcinoma of No Special Type.

Tumor-infiltrating lymphocytes (TILs) rich invasive breast carcinoma no special type (IBC-NST) is an updated name introduced in the fifth edition WHO classification of breast tumors. Typical medullary breast carcinoma (MBC) represents one end of the spectrum of TILs-rich IBC-NST rather than a distinct morphologic subtype in the new category. A total of 42 cases of MBC and 180 cases of high-grade triple-negative breast cancer (TNBC) without medullary features were included. All samples were stained for CD20, CD4, CD8, and FoxP3 by immunohistochemistry staining. TILs infiltration was more prominent in the MBC tumor nests and in the stroma of high-grade TNBC without medullary features. The average stromal TILs percentage was 78.10% and 61.33%. MBC showed significantly lower numbers of lymphocytes expressing FoxP3 ( P < 0.001), no significant difference in the number of CD4 ( P = 0.154), CD8 ( P = 0.199), and a significantly higher CD8/FoxP3 ratio ( P < 0.001) than the other high-grade TNBC. MBC cases demonstrated less aggressive features such as lower TNM stage ( P = 0.031), smaller tumor size ( P = 0.010), and negative lymph node status ( P = 0.021) than the other high-grade TNBC. The 5-year disease-free survival and overall survival were significantly higher for MBC 82.50% and 85.00% compared with the other high-grade TNBC(54.49% and 58.68%). MBC is mostly triple-negative with higher nuclear atypia. Despite advanced staging based on cell morphology, it has low malignancy and a good prognosis. Differences in biological features and prognosis between MBC and high-grade TNBC without medullary features may be associated with the composition and function of TILs. Immune cell subtypes are complex in TILs-rich IBC-NST and deserve further investigation.

The Effect and Mechanism of New Processing Method of Codonopsis pilosula on Endocrine Physique Index in Rats.

Objective: To explore the effect and mechanism of a new processing method of Codonopsis pilosula (CP) on the endocrine physique index in rats. Methods: The rats were randomly assigned into the control group, model group, CP group (3.75 g/kg crude drug), rice-fried CP group (3.75 g/kg crude drug), and honey-roasted CP group (3.75 g/kg), with 10 rats in each group. All rats were gavaged according to the body weight of 1 mL/100 g every morning for 3 weeks. The water extracts of different processed products of CP were given to the drug group, the blank group, and the model group which were given the same volume of normal saline during the experiment. The model group and each administration group were fed every other day and drank freely for 21 days, during which the weight was weighed every 2 days. The changes of the organ index; the contents of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), adrenocorticotropic hormone (ACTH), and cortisol (Cor); and the activity of sodium and potassium adenosine triphosphate (Na+K+-ATP) were measured by enzyme-linked immunosorbent assay (ELISA). The expression of aquaporin-1 (AQP1) and aquaporin-2 (AQP2) mRNA was detected by RT-PCR. Results: Effect on the organ index: the organ index of the control group, CP group, rice-fried group, and honey moxibustion group was higher compared to that of the model group, and the organ index of the honey moxibustion group was the highest (P < 0.05). The level of cAMP and the ratio of cAMP/cGMP in the model group were significantly higher compared to those of the control group (P < 0.05); CGMP in the model group decreased significantly (P < 0.05). Compared with the model group, the level of cAMP in the CP group, rice-fried group, and honey moxibustion group decreased significantly, while the ratio of cGMP and cAMP/cGMP increased significantly (P < 0.05). Compared with the CP group, rice-fried group, and honey moxibustion group, the level of cAMP and the ratio of cAMP/cGMP in the honey moxibustion group were lower compared to those in the other two groups, and the ratio of cGMP in the honey moxibustion group was higher compared to that in the other two groups (P < 0.05). The contents of ACTH and Cor in the model group were significantly higher compared to those in the control group (P < 0.05). Compared with the model group, the contents of ACTH and Cor in the CP group, rice-fried group, and honey moxibustion group were significantly lower compared to those in the model group (P < 0.05). Compared with the CP group, rice-fried group, and honey moxibustion group, the contents of ACTH and Cor in the honey moxibustion group were higher compared to those in the other two groups (P < 0.05). The content of the Na+K+-ATP enzyme in the model group was significantly higher compared to that in the control group (P < 0.05). Compared with the model group, the content of the Na+K+-ATP enzyme in the CP group, rice-fried group, and honey moxibustion group decreased significantly (P < 0.05). Compared with the CP group, rice-fried group, and honey moxibustion group, the content of the Na+K+-ATP enzyme in the honey moxibustion group was higher compared to that in the other two groups (P < 0.05). The expression of AQP1 and AQP2 mRNA in the kidney tissue of the kidney yin deficiency model group was significantly higher compared to that of the control group (P < 0 05). Compared with the model group, the expression levels of AQP1 and AQP2 mRNA in the renal tissue of rats in the CP group, rice-fried group, and honey moxibustion group decreased in different degrees (P < 0.05). There was no statistical difference between the CP group, rice stir-frying group, and honey moxibustion group. Conclusion: This study proves that the new processing method of CP can improve the endocrine physique index of rats, enhance their organ quality, and regulate the disorder of water metabolism in kidney yin deficiency syndrome and has a certain therapeutic effect on kidney yin deficiency syndrome. Different new processing methods of CP have different effects on promoting endocrine physique indexes of rats. It is concluded that honey-roasted CP has the best effect on promoting spleen deficiency, which may be through glucose metabolism, amino acid metabolism, and nucleotide metabolism, increasing ATP energy metabolism, so as to strengthen the symptoms of spleen deficiency in rats. The experimental data of this study indicate that the effect of honey-roasted CP is better compared to that of other processed products, which provides an experimental basis for the rational clinical application of the new processed products.

Clinicopathological significances of PLOD2, epithelial-mesenchymal transition markers, and cancer stem cells in patients with esophageal squamous cell carcinoma.

BACKGROUND: To examine the expression level of procollagen-lysine2-oxoglutarate 5-dioxygenase 2 (PLOD2) in esophageal squamous cell carcinoma (ESCC) and analyze its correlation with clinicopathological parameters, in order to explore the mechanism of PLOD2 in regulating invasion and metastasis of ESCC. METHODS: Immunohistochemistry was used to detect the expression level of PLOD2 in tumor tissues and paired adjacent tissues of 172 patients with ESCC, and the relationship between PLOD2 expression and clinicopathological parameters was analyzed. The deposition of collagen fibers in tumor was detected by Sirius red staining. The correlation between tumor stem cells and epithelial-mesenchymal transition (EMT) markers ZEB1 was analyzed by multivariate logistic regression. RESULTS: The expression level of PLOD2 in tumor tissues of patients with ESCC (70.35%, 121/172) was significantly higher than that in paired adjacent tissues (29.65%, 51/172; P < .01). The positive expression rate of PLOD2 in ESCC was related to T classification, lymph node metastasis, and pathological tumor node metastasis of a tumor. The expression rates of ZEB1, CD44, and CD133 in ESCC were correlated with T classification, lymph node metastasis and pathological tumor node metastasis. Scarlet red staining showed that collagen fiber deposition in ESCC tissues with high expression of PLOD2 was significantly higher than that in tissues with low expression of PLOD2 (P < .01). A positive correlation was observed between the expression of PLOD2 and CD133, PLOD2 and CD44, and PLOD2 and N-cadherin (P < .01). Moreover, a negative correlation was noted between the expression of PLOD2 and E-cadherin (P < .01). The combined expression of PLOD2 and ZEB1 were independent prognostic factors for the total survival time of patients with ESCC. CONCLUSION: PLOD2 is highly expressed in ESCC and is closely related to tumor invasion and metastasis. The mechanism of PLOD2 for promoting invasion and metastasis of ESCC may be related to activation of the EMT signaling pathway to promote EMT and tumor stem cell transformation.

The synthesis of anticancer sulfonated indolo[2,1-a]isoquinoline and benzimidazo[2,1-a]isoquinolin-6(5H)-ones derivatives via a free radical cascade pathway.

A facile CuBr2 induced radical relay addition/cyclization of activated alkenes with substituted-thiosulfonates has been achieved, leading to a broad range of sulfonated indolo[2,1-a]isoquinolines and benzimidazo[2,1-a]isoquinolin-6(5H)-ones in moderate to good yields. In particular, some compounds exhibit bioactivity against cancer cell lines. This protocol shows advantages of low-cost, base-free, simple operation, and broad functional group tolerance.

Metaplastic breast carcinoma: a retrospective study of 26 cases.

Metaplastic breast carcinoma is a rare invasive breast cancer. Metaplastic breast carcinoma is mainly characterized by an epithelial or mesenchymal cell population mixed with adenocarcinoma. We collected 26 cases of metaplastic breast carcinoma in the First Affiliated Hospital of Bengbu Medical College from 2008 to 2014. Tumor size, tumor grade, vascular invasion, ER/PR status, histologic classification, and HER2/neu status were assessed for all cases and the literature was reviewed. Clinicopathologic characteristics of patients diagnosed with metaplastic breast carcinomas and its key points of differential diagnosis were discussed. All patients were female, with the median age of 50 years. The mean tumor size was 3.2 cm. 4 subtypes of metaplastic breast carcinomas were documented. Fibromatosis-like metaplastic carcinomas are typically characterized by wavy, intertwined, gentle spindle cells. When the tumor components are almost squamous cell carcinoma components and the primary squamous cell carcinoma of other organs and tissues are excluded, we can diagnose breast squamous cell carcinoma. In spindle cell carcinoma, atypical spindle cells are arranged in many ways and are usually accompanied by inflammatory cell infiltrate. Cancer with interstitial differentiation has mixed malignant epithelial and mesenchymal differentiation, and the mesenchymal components are diverse. Most tumors are triple negative. At present, surgical resection combined with chemotherapy or radiation therapy is the most effective and acceptable method for treating metaplastic breast carcinoma.

Fluorescence in situ hybridization for WWTR1-CAMTA1 has higher sensitivity and specificity for epithelioid hemangioendothelioma diagnosis.

Epithelioid hemangioendothelioma (EHE) is a rare medium-to-low-grade malignant vascular tumor characterized by vascular differentiation along with specific morphological and genetic alterations. Approximately 90% and 5% of EHE cases are associated with the WWTR1-CAMTA1 and YAP1/TFE3 fusion gene, respectively. Therefore, nuclear CAMTA1 protein expression is considered to be an effective marker for EHE diagnosis. However, the specificity and reliability of this approach have recently been put into question. The purpose of this study was to compare the detection of CAMTA1 expression in cases of EHE and histologic mimics using fluorescence in situ hybridization (FISH) and conventional protein immunohistochemistry via hematoxylin and eosin staining. Fifteen EHE and 37 histologic mimic samples were immunohistochemically stained with polyclonal anti-CAMTA1 antibody to evaluate the nuclear protein expression level of CAMTA1. In addition, 15 EHE samples and 10 vascular tumor samples were subjected to FISH to detect the WWTR1-CAMTA1 fusion gene. Histologically, EHE typically showed a mucous hyaline or cartilaginous stroma, often forming a primitive vascular lumen, and expressed vascular endothelial markers. Twelve of the 15 EHE samples showed positive nuclear CAMTA1 expression with immunohistochemistry, whereas six of the 37 histologic mimics showed positive nuclear expression. FISH detected a red-green signal fusion in 14 of the 15 cases of EHE, but in none of the 10 vascular tumors. These results indicate that CAMTA1 is an effective and useful EHE marker, but that FISH fusion gene detection has better diagnostic value and clinical significance.

Epithelial cell adhesion molecule and epithelial-mesenchymal transition are associated with vasculogenic mimicry, poor prognosis, and metastasis of triple negative breast cancer.

Triple-negative breast cancer (TNBC) is associated with epithelial-mesenchymal transition (EMT) and the phenotype of breast cancer stem cells (CSCs). Vasculogenic mimicry (VM) is a novel pattern of tumor blood supply and associated with aggression and metastasis of TNBC. Previous studies have shown that both CSCs and EMT are associated with VM, although the underlying mechanism is yet unclear. The present study aimed to analyze the immunohistochemical (IHC) expression of CSC marker, epithelial cell adhesion molecule (EpCAM), EMT-related markers, including transcription factors (TFs) (Slug, Twist1, and ZEB1), and EMT markers (E-cadherin and vimentin) in 137 TNBC. The expression of these markers was correlated to the clinicopathological features and VM channels of the tumors, including patient overall survival (OS) and disease-free survival (DFS). Furthermore, the expression of EpCAM and EMT-related markers showed a positive correlation with distant metastasis and lymph node metastasis (P < 0.05). A significant association was noted between VM and histological grade (P = 0.007). Moreover, VM showed a significant positive correlation with EpCAM, EMT-associated TFs, and VE-cadherin expression in TNBC. Furthermore, binary logistic analysis showed that VM expression was significantly correlated with lymph node metastasis and distant metastasis (P < 0.05). In survival analysis, the overexpression of EpCAM and ZEB1 predicted a poor prognosis with respect to OS and DFS. In addition, the presence of VM was significantly associated with poor OS and DFS. Multivariate Cox regression analysis revealed that VM expression is an independent prognostic factor for TNBC patients. In summary, VM was confirmed as a potential biomarker for TNBC associated with poor clinical outcomes and tumor metastasis. This study also suggested that EpCAM protein might be involved in VM formation by EMT in TNBC.

The correlation of the expressions of WWOX, LGR5 and vasohibin-1 in epithelial ovarian cancer and their clinical significance.

BACKGROUND: Recurrence and metastasis are the most common reasons for the treatment failure of epithelial ovarian carcinoma (EOC). WW domain-containing oxidoreductase (WWOX) is a tumor suppressor, which causes down- or lost-expression and is able to promote cell infiltration and progression in several human malignant tumors. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), an important marker of cancer stem cells (CSCs), has been considered a useful biomarker of tumor metastasis and patient prognosis. Vasohibin-1 (VASH1), also known as angiogenesis inhibiting protein-1, can be used as a biological marker for early infiltration and metastasis in many cancers. However, the correlations of WWOX, LGR5, and vasohibin-1 in EOC are still unclear. In this study, we analyzed the relationships of these three markers, as well as their respective correlations with clinicopathological characteristics, to determine whether they are useful biomarkers for the improvement and prognosis of EOC patients. METHODS: The positive rates of WWOX, LGR5, and vasohibin-1 in 210 whole tissue samples of EOC were detected by immunohistochemistry. Clinical data was also collected. RESULTS: The expressions of LGR5 and vasohibin-1 were significantly higher in EOC tissues than the levels in benign ovary tumors. However, WWOX expression was significantly lower in EOC tissues than the levels in benign ovary tumors. The investigation of the associations between WWOX, or LGR5, or vasohibin-1 positive rates with the clinicopathological characteristics of EOC showed associations between the positive rates of each with grade of tumor, lymph node metastasis (LNM), implantation, and International Federation of Gynecology and Obstetrics (FIGO) stage. The overall survival (OS) time of patients with LGR5-positive or vasohibin-1-positive EOC tissues was significantly shorter than that of those who were negative. On the contrary, the OS time of patients with WWOX-positive EOC tissues was significantly higher than the OS time of those who were negative. Importantly, a multivariate analysis indicated that the high level of WWOX, LGR5, and vasohibin-1, as well as implantation, LNM and FIGO stage could be independent prognostic biomarkers for OS in EOC patients. CONCLUSIONS: The expressions of WWOX, LGR5, and vasohibin-1 may represent useful promising biomarkers for metastasis and prognosis, as well as potential therapeutic targets in EOC.

Primary extramammary Paget's disease: a clinicopathological study of 28 cases.

To analyze the clinical and histopathological manifestations, immunohistochemistry, treatment, and prognostic factors of primary, extramammary Paget's disease (EMPD), we systematically reviewed the clinical presentations, histopathology and follow-up courses of 28 patients with primary EMPD. Clinically, their symptoms and morphology mimicked various types of dermatoses, such as seborrheic dermatitis, eczema, candidiasis, tinea cruris and erythrasma, so the initial diagnosis of EMPD was often delayed or missed. Histopathology showed invasive EMPD, and the tumor cells were mostly solid nests or had a glandular structure. The cellular atypia was obvious and signet ring Paget's cells could usually be observed. The acantholysis phenomenon in the epidermis could be seen. The condition was associated with stromal invasion, lymphatic metastasis, and even vascular invasion. Adnexal involvement in primary EMPD was a very common feature. The immunohistochemical markers CK7, GCDFP-15, CEA and HER-2 positive can identify other tumors similar to Paget's disease. We concluded that invasive EMPD is a rare malignant skin neoplasm with morphological diversity. Poorly differentiated cell morphology, extensive adnexal involvement, and an invasive pattern of solid sheets are significantly associated with lymph node metastasis and a worse prognosis. Pathologists should be alert to invasive lesions and make the correct diagnosis.