Han Chang

Luteolin Induces Apoptosis in Oral Squamous Cancer Cells

Oral squamous cell carcinoma is the most common malignancy of the oral cavity, and treatment approaches are inadequate. Luteolin, a natural flavonoid compound, has been shown to have anti-tumorigenic properties on various types of tumors. Therefore, we hypothesized that luteolin has anti-tumorigenic properties for oral squamous cell carcinoma, and may provide effective chemotherapy. Results revealed that luteolin reduced the viability of SCC-4 cells and induced apoptosis by decreasing the expression of cyclin-dependent kinase (CDKs), cyclins, and phosphor- retinoblastoma (p-Rb) anti-apoptotic protein, but increased the expression of pro-apoptotic proteins and activated caspase 9 and 3, with a concomitant increase in the levels of cleaved poly-ADP-ribose polymerase (PARP). Combination treatment of luteolin with paclitaxel enhanced the cytotoxic effect of paclitaxel in SCC-4 cells, and continuous administration of luteolin suppressed the growth of xenograft tumors in nude mice. These results suggest that luteolin could be an effective chemotherapeutic agent for the treatment of oral squamous cell carcinoma.

Changes in the extracellular matrix in the anterior vagina of women with or without prolapse

To investigate the changes in the connective tissues located in the upper portion of the anterior vaginal wall, which are associated with anterior vaginal wall prolapse, 23 women with anterior vaginal wall prolapse were included in the study group and 15 women with normal genital support served as control group. The anterior vaginal wall tissue samples were obtained for immunohistochemical staining of collagen (type I, III, IV, V, VI), elastin, and glycoproteins from the extracellular matrix (fibronectin, vitronectin, laminin). The number of capillaries per arteriole and mitochondria numbers per smooth muscle cell were evaluated for demonstrating whether the anatomical prolapse affect on blood supply to these tissues. Collagen III was significantly less in the anterior vaginal wall of patients with anterior vaginal wall prolapse. Quantitative immunoreactivity of collagen I and III had significant positive correlations with ageing.

Aryl hydrocarbon receptor activation and overexpression upregulated fibroblast growth factor-9 in human lung adenocarcinomas.

We had previously reported that aryl hydrocarbon receptors (AhRs) are overexpressed in lung adenocarcinomas. Benzo[a]pyrene (BaP), an AhR agonist, increased FGF‐9 expression in human lung adenocarcinoma cells. Similarly, several AhR agonists increased FGF‐9 mRNA levels, and BaP‐induced FGF‐9 expression was prevented by cotreatment with AhR antagonist in human lung adenocarcinoma cells. Furthermore, AhR agonists increased transcriptional activity of FGF‐9 promoter. Modulation of AhR expression via RNA interference or transient overexpression respectively reduced or increased both constitutive and BaP‐induced FGF‐9 expression in human lung cells. These results suggested that AhR activation and overexpression increased FGF‐9 expression in lung cells. FGF‐9 increased growth of lung fibroblasts but not that of lung adenocarcinoma cells. However, conditioned media collected from FGF‐9‐treated fibroblasts increased cell growth of lung adenocarcinoma cells. Furthermore, lung adenocarcinoma cells expressed FGF receptor 2 and cotreatment with anti‐FGF receptor 2 prevented the interaction between fibroblasts and tumor cells. It is likely that FGF‐9‐stimulated fibroblasts secreted unknown factors, which activated FGF receptor 2 and subsequently promoted growth of lung adenocarcinoma cells. We further compared AhR and FGF‐9 expression in 146 non‐small cell lung cancer (NSCLC) cases by immunohistochemistry. FGF‐9 expression was more common in adenocarcinomas than in squamous cell carcinomas. Furthermore, FGF‐9 and AhR expression were well correlated in lung adenocarcinomas. These results suggest that AhR expression correlated positively with FGF‐9 expression in lung adenocarcinomas, which might promote tumor growth by modulating communication between tumor cells and fibroblasts. Preventing AhR overexpression or disturbing FGF‐9 function may reduce the development of lung adenocarcinomas.

Clinical significance of high nm23-H1 expression in intraepithelial neoplasia and early-stage squamous cell carcinoma of the uterine cervix.

Seventy-two cervical pathology specimens, consisting of samples of cancer and high- and low-grade intraepithelial neoplasia, were used in a study exploring the involvement of nm23-H1/NDP kinase in carcinogenesis or recurrence. Additionally, the relationships between immunohistochemical expression of nm23-H1 and various clinicopathological variables for early-stage cervical cancer were evaluated. The nm23-H1 expression for high-grade cervical intraepithelial neoplasia and squamous cell carcinoma samples was significantly elevated when compared to low-grade analogs. Only deep stromal invasion was significantly associated with high nm23 expression. Moreover, a high cumulative recurrence hazard was demonstrated for the high nm23 expression group. In conclusion, high nm23-H1 expression may induce cellular proliferation for the progression from low- to high- grade intraepithelial neoplasia, with the subsequent emergence of invasive carcinoma as well as deep stromal invasion, and can be used as an indicator of prognosis.

High expression of human nonmetastatic clone 23 type 1 in cancer of uterine cervix and its association with poor cell differentiation and worse overall survival

The role of human nonmetastatic clone 23 type 1 (nm23‐H1), a metastasis‐associated gene, is less clear‐cut in cancer of uterine cervix; therefore, we investigate its expression in cancer tissues and its correlation with clinicopathologic variables and survival of patients.

High expression of human telomerase reverse transcriptase in high-grade intraepithelial neoplasia and carcinoma of uterine cervix and its correlation with human papillomavirus infection.

Most of cervical intraepithelial neoplasia 1 (CIN 1) will regress and 12% to 40% of high-grade CIN may progress to squamous cell carcinoma (SCC) of the uterine cervix. However, the differentiation of CIN 1 and high-grade CIN is sometimes controversial among pathologists. Human telomerase reverse transcriptase (hTERT) is therefore applied to detect the differences among normal, CIN 1, high-grade CIN, and SCC tissues of uterine cervix. One hundred six cervical specimens were collected for immunohistochemical study of hTERT. These data were compared with the human papillomavirus (HPV) DNA status. Expression of hTERT in high-grade CIN increased significantly compared to that in CIN 1 ( P < .001). A positive relationship was found between high hTERT expression and degree of malignant transformation ( P < .001). Most of the cases with high hTERT expression tested positive for the high-risk HPV groups. High hTERT expression was detected in 88.73% of the samples with cervical high-grade CIN or SCC. Low hTERT expression was found in 94.29% of low-grade CIN or normal tissues. Furthermore, 96.92% of the cervical tissues with high hTERT expression were high-grade CIN or SCC. A total of 80.49% of samples with low hTERT expression were low-grade CIN or normal tissues. A significantly increased hTERT expression between CIN 1 and high-grade CIN exhibits a critical progression in cervical carcinogenesis. hTERT can be offered as additional molecular information correlated with more severe dysplasia and SCC. Furthermore, this increased hTERT expression is correlated whigh-risk HPVs infection.

Synergism between 2,3,7,8-tetrachlorodibenzo-p-dioxin and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone on lung tumor incidence in mice.

Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is classified as a human carcinogen, TCDD only induced oxidative DNA damages. In our present study, we combined TCDD with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to investigate their tumorigenic effects on lung tumor formation in A/J mice. Application of NNK at a tumorigenic dose (2 mg/mouse) induced lung adenoma in both male and female A/J mice. Neither application of NNK at a non-tumorigenic dose (1 mg/mouse) nor repeated application of TCDD alone increased tumor incidence. Following the single injection of NNK at a non-tumorigenic dose (1 mg/mouse), repeated application of TCDD significantly increased the lung tumor incidence in female, but not in male, A/J mice 24 weeks later. Utilizing the real-time RT-PCR array, we found that P16 mRNA was significantly reduced in female lung, but not male lung, of NNK/TCDD co-treated A/J mice. With immunohistochemical staining, we confirmed that nuclear P16 protein was reduced in the lungs of NNK/TCDD co-treated female mice. These data suggest that P16 reduction at least partially contributed to synergistic effects of TCDD in lung tumorigenesis.

Lymph node metastases, not human telomerase reverse transcriptase or p53 proteins, as the strongest prognostic factor for survival in early stage cervical cancer

Aim:  Human telomerase reverse transcriptase (hTERT) is known to be significantly activated during immortalization, and p53 is thought to be a guardian of that apoptosis pathway in most cancer cells. The aim of this study was to assess the relationships among hTERT, p53 and various clinicopathological parameters of cervical cancer patients and overall survival.

Synchronous Primary Ovarian Sertoliform Variant of Endometrioid Adenocarcinoma and Primary Endometrial Well Differentiated Endometrioid Adenocarcinoma

Endometrioid carcinoma accounts for 10 to 20 percent of ovarian carcinomas. With only 23 cases reported in the literature, its sertoliform variant is rare. We report here the case of an 84-year-old female with the rare variant of ovarian endometrioid adenocarcinoma simulating a Sertoli cell tumor with a synchronous well-differentiated endometrioid adenocarcinoma of the endometrium. On histopathologic examination, small tubular structures resembling Sertoli cell tumors were found in the ovarian neoplasm. These stained positively for epithelial membrane antigen (EMA) and cytokeratin-8 (CK-8) a low molecular weight cytokeratin. There was also weak cytoplasmic granular staining pattern for CD99. A well-differentiated endometrioid carcinoma was present in the endometrium. This is the first reported case of ovarian sertoliform endometrioid carcinoma combined with endometrial endometrioid carcinoma.