Cancer Biomarkers - Volume 18, issue 2

Authors: Huang, Xu-Hui | Liang, Rong-Hua | Su, Le | Guo, Wei | Wang, Chang-Jun

Article Type: Research Article

Abstract: PURPOSE: Research on the mechanism of Bushen Jianpi decoction (BJD) for preventing and treating osteoporosis caused by aromatase inhibitors (AI) during treatment for breast cancer resection. METHODS: An ovariectomized mouse model was established using random division into 6 groups: a sham ovariectomized group, a blank control group, a control group, an alendronate group, a BJD group, and a drug combination group. Mice breast cancer cell lines (4T1) were cultured and seeded into the armpits of 6 groups of BALB/c mice. The mouse breast cancer postoperative model was built when resecting the tumor after 3 weeks …following seeding tumor. After 1 weeks, the 6 groups of mice were given different drugs. Then the following analyses were made: estradiol (E2) levels and alkaline phosphatase (ALP) levels in the serum; detection of in vitro bone density and calcium and bone phosphorus content; tumor pathology and immunohistochemistry detection. RESULTS: The results suggested that BJD decreased levels of ALP in ovariectomized mice, and there was a trend for improved bone loss. BJD strengthened the trend of alendronate to improve bone loss, improved bone density, bone calcium and phosphorous, and reduced ALP. BJD had a certain role on the promotion of the expression of estrogen receptors (ERs) in the relapse of the tumor tissue. CONCLUSIONS: Combined therapy with BJD and alendronate can act synergistically against osteoporosis, which was possibly related to a reduced bone conversion rate through inhibiting bone resorption. BJD may block the MAPK signal pathway in breast cancer cells, increasing the expression of ERs and making cancer cells sensitive to endocrine treatment. Show more

Keywords: Bushen Jianpi decoction, breast cancer, AI treatment, osteoporosis

DOI: 10.3233/CBM-160281

Citation: Cancer Biomarkers, vol. 18, no. 2, pp. 183-190, 2017

Authors: Yan, Xiaorong | Kang, Dezhi | Pan, Jun | Jiang, Changzhen | Lin, Yuanxiang | Qi, Songtao

Article Type: Research Article

Abstract: BACKGROUND: The calcification of adamantinomatous craniopharyngioma (ACP) often creates difficulties for surgical therapy. Nevertheless, the mechanism of ACP calcification is unclear. Our previous studies demonstrated that osteoblastic factors might play important roles in ACP calcification. OBJECTIVE: We examined the effects of recombinant human Bmp2 on ACP cell differentiation by testing osteoblastic proteins and calcium deposition. METHODS: The expression of osteoblastic factors including osteopontin (OPN), Runx2, and osterix in Bmp2-treated ACP cells was examined by western blot and/or real time PCR. ALP activity and calcium deposition after Bmp2 induction were also tested. …RESULTS: Bmp2 significantly amplified the expression of Runx2, Osterix and OPN, as well as ALP activity. Both of these effects could be repressed by noggin treatment. Bmp2 also significantly induced the calcification of ACP, and noggin inhibited this calcium deposition. CONCLUSION: Our study demonstrated for the first time that ACP cells could differentiate into an osteoblastic lineage via induction by Bmp2. The mechanism of ACP calcification likely involves osteoblastic differentiation modulated by Bmp2. Further studies targeting Bmp2 cascades could result in novel therapeutic interventions for recurrent ACP. Show more

Keywords: Adamantinomatous craniopharyngioma calcification, bone morphogenetic protein-2, cell calcification, osteoblastic differentiation

DOI: 10.3233/CBM-161576

Citation: Cancer Biomarkers, vol. 18, no. 2, pp. 191-198, 2017

Authors: Donaires, Flávia S. | Godoy, Paulo R.D.V. | Leandro, Giovana S. | Puthier, Denis | Sakamoto-Hojo, Elza T.

Article Type: Research Article

Abstract: BACKGROUND: Glioblastoma is considered to the most common and malignant brain tumor in adults. Patients have a median survival of approximately one year from diagnosis due to poor response to therapy. OBJECTIVE: We applied bioinformatics approaches to predict transcription factors (TF) that are deregulated in glioblastoma in an attempt to point out molecular targets for therapy. METHODS: Up-regulated genes in glioblastoma selected from public microarray data were submitted to two TF association analyses. Thereafter, the expression levels of TF obtained in the overlap of analyses were assessed by RT-qPCR carried out in seven …glioblastoma cell lines (T98, U251, U138, U87, U343, M059J, and M059K). RESULTS: E2F1 and E2F4 were highlighted in both TF analyses. However, only E2F1 was confirmed as significantly up-regulated in all glioblastoma cell lines in vitro . CONCLUSION: E2F1 is a potential common regulator of differentially expressed genes in glioblastoma, despite the genetic heterogeneity of tumor cells. Show more

Keywords: Glioblastoma, E2F transcription factors

DOI: 10.3233/CBM-161628

Citation: Cancer Biomarkers, vol. 18, no. 2, pp. 199-208, 2017

Authors: Chen, Fan | Li, Xin-Feng | Fu, Dong-Sheng | Huang, Jian-Guo | Yang, Shun-E

Article Type: Research Article

Abstract: miRNA-221 is one of the over 700 kinds of currently known microRNAs (miRNAs) and is up-regulated in multiple tumors, suggesting that it may be a potential carcinogenic miRNA. Few studies have explored the relationship between miRNA-221 and hepatocellular carcinoma (HCC). We performed real-time quantitative polymerase chain reaction (qPCR) to detect miRNA-221 expression in HCC and para-carcinoma tissues and to explore the relationship between abnormal expression of miRNA-221 and clinicopathological features of HCC patients. miRNA-221 expression was significantly higher in HCC tissues than in adjacent tissues (P < 0.001). We analyzed the relationship between miRNA-221 expression level and clinicopathological characteristics of …HCC patients. Our results suggested that miRNA-221 expression level was closely related to tumor stage (P = 0.012), number of tumor nodes (P = 0.018), and microvascular invasion (P = 0.010) in HCC patients. The results of survival analysis suggested that HCC patients with up-regulated miRNA-221 expression had a shorter survival time. The high miRNA-221 expression indicates the poor prognosis of HCC patients; thus, miRNA-221 can be regarded an important molecular marker for HCC prognosis. Show more

Keywords: MicroRNA, real-time qPCR, prognosis, carcinoma, hepatocellular

DOI: 10.3233/CBM-161671

Citation: Cancer Biomarkers, vol. 18, no. 2, pp. 209-214, 2017

Authors: Caliò, Anna | Bria, Emilio | Pilotto, Sara | Gilioli, Eliana | Nottegar, Alessia | Eccher, Albino | Cima, Luca | Santo, Antonio | Pedron, Serena | Turri, Giona | Knuutila, Sakari | Chilosi, Marco | Vanzo, Francesca | Bogina, Giuseppe | Terzi, Alberto | Tortora, Giampaolo | Scarpa, Aldo | Loda, Massimo | Martignoni, Guido | Brunelli, Matteo

Article Type: Research Article

Abstract: BACKGROUND: Gains of a gene due to DNA polyploidy versus amplification of the specific locus are distinct molecular alterations in tumors. OBJECTIVE: We quantified copy number gains of ALK gene due to unspecific polyploidy versus amplifications of the specific locus in a series of non-small cell lung cancers. METHODS: The locus specific ALK copy (LSI) number status was evaluated in 205 cases by FISH. Ratio LSI ALK copy number corrected for control probes CEP2, CEP3 and CEP17 (CEPs) was scored. Amplification of the specific ALK locus was defined when …ratio set to ≥ 2 while polyploidy was interpreted when the increase in gene copy resulted < 2 in ratio (LSI/control CEPs). RESULTS: Twenty one cases (10.2%) showed ≥ 8 ALK signals, 68 cases (33.2%) 3-7 signals and 116 cases (56.6%) a mean of 2 signals. Only 2/21 cases of the cohort harboring ≥ 8 signals showed a ratio ≥ 2 after CEPs correction interpretable as amplified, showing numerous doubled fluorescent spots. All the remaining cases showed a mirrored number of fluorescent spots per each CEPs, interpretable as polyploidy. CONCLUSION: We detected a high prevalence of ALK gene copy number usually due to polyploidy rather than ALK locus amplification, the latter visible prevalently as double minutes. Show more

Keywords: ALK gene copy number, gains, polyploidy, amplification, double minutes

DOI: 10.3233/CBM-161680

Citation: Cancer Biomarkers, vol. 18, no. 2, pp. 215-220, 2017