Targeted Therapy for Brain Metastases: Improving the Therapeutic Ratio

Patel, Rakesh; Mehta, Minesh P.

doi:10.1158/1078-0432.ccr-06-2489

Cited by 71 publications

(48 citation statements)

References 91 publications

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“…Brain metastases are the most common type of intracranial tumor in adults, accounting for ~40% of intracranial neoplasms (25). With the improving survival rates of cancer patients, the incidence of brain metastases has been rising (2).…”

Section: Discussionmentioning

confidence: 99%

TGF-β-induced miR10a/b expression promotes human glioma cell migration by targeting PTEN

Liu¹,

Sun²,

Lan³

2013

Molecular Medicine Reports

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Abstract. Human gliomas are associated with high rates of morbidity and mortality. In the brain, increased mRNA levels of transforming growth factor β (TGF-β) correlate with the degree of malignancy of human gliomas. miR10a/10b expression has been demonstrated to be associated with TGF-β expression in brain tumors, and it is reported that TGF-β induces miR10 expression. Therefore, miR10a/10b expression may be induced by TGF-β expression and may be involved in the TGF-β-induced migration of brain tumor cells. The present study examined the expression of TGF-β and miR10a/10b in the tissues of 10 patients with brain tumors using quantitative PCR (qPCR), and the correlation between TGF-β and miR10a or miR10b expression was analyzed. Additionally, U251 and SHG-44 cells were treated with TGF-β and the expression of miR10a/10b was examined. Further, cell migration was analyzed following transfection of U251 cells with miR10a/10b and the association between miR10a/10b and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was investigated. U251 cells were transfected with miR10a/10b inhibitors and a PTEN expression plasmid prior to TGF-β treatment and then cell migration was assessed. A significant correlation was identified between TGF-β and miR10a expression (r2=0.6936, P=0.007) and between TGF-β and miR10b expression (r2=0.5876, P=0.02) in the tissues of patients with brain tumors. The results also showed that TGF-β induces miR10a/10b expression and that TGF-β-induced miR10a/10b expression promotes cell migration through the suppression of PTEN. In conclusion, TGF-β-induced miR10a/10b promotes brain tumor migration. This study may provide a number of suggestions for the clinical treatment of brain tumors.

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Section: Discussionmentioning

confidence: 99%

TGF-β-induced miR10a/b expression promotes human glioma cell migration by targeting PTEN

Liu¹,

Sun²,

Lan³

2013

Molecular Medicine Reports

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“…Glioblastoma is currently treated with surgery, radiotherapy, and chemotherapy (Byun et al 2006;Chang et al 2007;Patel and Mehta 2007). The current therapeutic strategies are effective only in the less advanced stages of the disease, in which the tumor mass is localized (Feelders et al 2009;Schneider et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Static magnetic field controls cell cycle in cultured human glioblastoma cells

Kim

Shim

et al. 2016

Cytotechnology

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Magnetic field has been widely used in clinical diagnostics or for clinical treatment and is an important biomedical technology. Glioblastoma multiforme U87 and U251 are models of a fast growing malignant cancer. We focused on cellular level drafting of these cell lines as a time-dependent effect indicator of static magnetic fields (2000 ± 600 Gauss) by using their fast-growing properties. Cell viability showed a significant decrease (p \ 0.01). The results coincided with the occurrence of apoptotic signals or protein expression of cyclin B1 and cyclin dependent kinase 1 in a non-apoptotic manner. Cdk1 was decreased in proportion to ankyrin G and cyclin B1 (Chi-square test, p = 0.0366). Our findings suggest that static magnetic stimulation creates a specific cytoproliferative pattern, rather than producing randomized growth impairment.

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“…Similarly, the incidence of brain metastasis in non-small cell lung cancer patients has increased in recent years (9), likely resulting from improved therapy, diagnostic modalities, and screening programs for early detection. In addition, evidence suggests that improved targeted therapy in patients with HER-2-positive breast cancer may increase the incidence of brain metastases (10,11). Although there is no established targeted therapy for treating gastric cancer, novel therapeutics are being actively investigated in clinical trials (12,13).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-200 family members and ZEB2 are associated with brain metastasis in gastric adenocarcinoma

Minn

Lee

Hyung

et al. 2014

International Journal of Oncology

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Abstract. Although the incidence of brain metastasis in gastric cancer is relatively low, its prevalence may increase with improved therapy and longer survival tumors. The molecular mechanisms underlying brain metastases are not well understood. To gain insight into the mechanism of brain metastasis, we studied differences in microRNA (miRNA) expression levels in 8 cases of matched primary gastric adenocarcinoma and brain metastatic adenocarcinoma using the Illumina microRNA microarray chip. We identified 6 upregulated and 2 downregulated miRNAs in all 8 cases simultaneously. Interestingly, 2 out of 8 miRNAs (hsa-miR-141-3p and hsa-miR-200b-3p) belonged to the miR-200 family. Online microRNA database searching revealed that ZEB2 is the topranked target gene for hsa-miR141-3p and hsa-miR-200b-3p, prompting us to focus ZEB2 expression in brain metastatic adenocarcinoma. We confirmed that ZEB2 expression was markedly downregulated in some brain metastatic samples. In addition, decreased ZEB2 expression was noted by western blot analysis of 2 metastatic gastric adenocarcinoma cell types that were derived by in vivo selection following intracardiac injection of gastric cancer cell lines. In conclusion, we demonstrate that expression of miRNA-200 family members and ZEB2 are associated with brain metastases of gastric adenocarcinoma, not only in matched patient samples, but also in metastatic cell lines that were derived by in vivo selection. IntroductionAlthough the incidence of gastric cancer has been declining since 1950, gastric cancer remains the 4th most common cancer worldwide (1). The prevalence of gastric cancer shows wide geographic variations, with the highest rates found in Eastern Asia (including China, Japan and Korea), Eastern Europe, and Central and Latin America (1). In a recent report by the World Health Organization, gastric cancer was classified into 5 main types of adenocarcinomas and rare variants (2). In contrast to the better prognoses associated with early gastric cancers, advanced gastric cancers generally have poor prognoses, with known prognostic factors including stage and the number of lymph node metastases (2). Unlike lung or breast cancer, the brain metastases of gastric cancer are very rare and have been reported in <1% of clinical cases (3,4), most cases of which were reported as leptomeningeal carcinomatosis (5-7).Prolonged survival in gastric cancer patients accompanying improvements in systematic approaches and overall patient care has increased the likelihood of patients developing central nervous system metastases (8). Similarly, the incidence of brain metastasis in non-small cell lung cancer patients has increased in recent years (9), likely resulting from improved therapy, diagnostic modalities, and screening programs for early detection. In addition, evidence suggests that improved targeted therapy in patients with HER-2-positive breast cancer may increase the incidence of brain metastases (10,11). Although there is no established targeted therapy for treating gastric cancer,...

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Targeted Therapy for Brain Metastases: Improving the Therapeutic Ratio

Cited by 71 publications

References 91 publications

TGF-β-induced miR10a/b expression promotes human glioma cell migration by targeting PTEN

TGF-β-induced miR10a/b expression promotes human glioma cell migration by targeting PTEN

Static magnetic field controls cell cycle in cultured human glioblastoma cells

MicroRNA-200 family members and ZEB2 are associated with brain metastasis in gastric adenocarcinoma

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