A novel third generation bisphosphonate, minodronate (YM529), prevented proliferation and migration of hepatocellular carcinoma cells through inhibition of mevalonate pathway

Kogure, Takayuki; Ueno, Yoshiyuki; Kimura, Osamu; Kondo, Yasuteru; Inoue, Jun; Fukushima, Koji; Iwasaki, Takao; Shimosegawa, Tooru

doi:10.1111/j.1872-034x.2008.00484.x

Cited by 12 publications

(6 citation statements)

References 39 publications

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“…Indeed, whether systemic chemotherapy is effective and safe for MSCC from primary HCC remains controversial [45]. Besides, even though no significant association was found between bisphosphonate treatment and PFS ( p = 0.359) or OS ( p = 0.484) in our study, a published experimental study proved that bisphosphonate could prevent the proliferation and migration of HCC cells [46]. Knowing that bisphosphonate can definitely prevent or prolong the emergence of skeletal-related events to help improve the quality of life for patients with bone metastasis [47].…”

Section: Discussioncontrasting

confidence: 55%

Outcomes of metastatic spinal cord compression secondary to primary hepatocellular carcinoma with multidisciplinary treatments

Wei

et al. 2017

Oncotarget

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Few studies have reported progression-free survival (PFS) and overall survival (OS) of Metastatic spinal cord compression (MSCC) patients with primary hepatocellular carcinoma (HCC) following surgery and adjuvant therapies. Enrolled in this study were 155 MSCC patients with primary HCC who received surgery and adjuvant therapies between 2000 and 2015. Kaplan-Meier methods and Cox’s proportional hazards regression mode were performed to investigate the clinical features and prognostic factors affecting PFS and OS. The median PFS and OS was 7.0 months and 9.7 months, respectively. 92.9% patients responded well to surgery according to the Visual Analogue Scale, Frankel Score and postoperative complication occurrences. 68 (43.9%) patients who received circumferential decompression achieved better PFS than the remaining 87 (56.1%) patients who received laminectomy. Favorable outcomes were achieved after surgery during the perioperative period. Circumferential decompression was associated with better PFS than laminectomy. The postoperative Frankel Score E, Eastern Cooperative Oncology Group performance score of 1 or 2, no visceral metastasis, administration of postoperative radiation and the use of Sorafenib were found to be significant predictors of better PFS and OS. Patients who previously underwent resection of primary HCC with/without liver transplantation tended to have a better OS.

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Section: Discussioncontrasting

confidence: 55%

Outcomes of metastatic spinal cord compression secondary to primary hepatocellular carcinoma with multidisciplinary treatments

Wei

et al. 2017

Oncotarget

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“…In this study, we showed that statins inhibited the migration of B16BL6 cells. It has been reported that YM529/ONO-5920 and zoledronate, nitrogen-containing bisphosphonates, inhibited hepatocellular carcinoma and osteosarcoma cell migration by suppressing GGPP biosynthesis [30,31]. Collectively, the findings suggest that the inhibition of GGPP biosynthesis plays an important role in the suppression of B16BL6 cell migration by statins.…”

Section: Discussionmentioning

confidence: 88%

Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway

Kidera

Tsubaki

Yamazoe

et al. 2010

J Exp Clin Cancer Res

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BackgroundMelanomas are highly malignant and have high metastatic potential; hence, there is a need for new therapeutic strategies to prevent cell metastasis. In the present study, we investigated whether statins inhibit tumor cell migration, invasion, adhesion, and metastasis in the B16BL6 mouse melanoma cell line.MethodsThe cytotoxicity of statins toward the B16BL6 cells were evaluated using a cell viability assay. As an experimental model, B16BL6 cells were intravenously injected into C57BL/6 mice. Cell migration and invasion were assessed using Boyden chamber assays. Cell adhesion analysis was performed using type I collagen-, type IV collagen-, fibronectin-, and laminin-coated plates. The mRNA levels, enzyme activities and protein levels of matrix metalloproteinases (MMPs) were determined using RT-PCR, activity assay kits, and Western blot analysis, respectively; the mRNA and protein levels of vary late antigens (VLAs) were also determined. The effects of statins on signal transduction molecules were determined by western blot analyses.ResultsWe found that statins significantly inhibited lung metastasis, cell migration, invasion, and adhesion at concentrations that did not have cytotoxic effects on B16BL6 cells. Statins also inhibited the mRNA expressions and enzymatic activities of matrix metalloproteinases (MMPs). Moreover, they suppressed the mRNA and protein expressions of integrin α2, integrin α4, and integrin α5 and decreased the membrane localization of Rho, and phosphorylated LIM kinase (LIMK) and myosin light chain (MLC).ConclusionsThe results indicated that statins suppressed the Rho/Rho-associated coiled-coil-containing protein kinase (ROCK) pathways, thereby inhibiting B16BL6 cell migration, invasion, adhesion, and metastasis. Furthermore, they markedly inhibited clinically evident metastasis. Thus, these findings suggest that statins have potential clinical applications for the treatment of tumor cell metastasis.

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“…The effects of bisphosphonates on HCC have recently been attracting attention. Bisphosphonates have been demonstrated to inhibit the proliferation and migration of HCC cells, 23 and they are considered to be effective at preventing bone resorption, hypercalcemia, and pathological fractures and inhibiting local recurrence. 24 –27 According to the multivariate analysis, the use of BMA significantly influenced survival among our study population.…”

Section: Discussionmentioning

confidence: 99%

Prognostic scoring system for metastatic spine tumors derived from hepatocellular carcinoma

Uei

Tokuhashi

2020

J Orthop Surg (Hong Kong)

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Purpose: The prognosis of hepatocellular carcinoma (HCC) has recently improved, and so clinicians have greater opportunity to treat HCC-derived spinal metastases. Therefore, predicting life expectancy is important for determining the optimal treatment strategy for such tumors. This study aimed to investigate the prognostic factors for HCC-derived metastatic spine tumors and to develop a scoring system for predicting life expectancy in such cases. Methods: The posttreatment survival time and factors that might influence it were investigated in 62 patients with HCC-derived metastatic spine tumors who were treated at our department (surgery: 27 patients and conservative treatment: 35 patients), and a prognostic scoring system for predicting life expectancy was developed by combining the factors that significantly influenced survival. Results: In the univariate analyses, sex, the patient's general condition, the presence/ absence of major internal organ metastasis, the total revised Tokuhashi score, the serum albumin level, Child-Pugh class, spinal surgery, and bone-modifying agent (BMA) treatment were found to influence the posttreatment survival time. These factors were subjected to multivariate analysis, and a novel scoring system for predicting life expectancy based on the patient's general condition, the serum albumin level (or Child-Pugh class), and BMA treatment was developed. In the retrospective analysis, the concordance rate between the patients' life expectancy and actual survival times was 90.3%. Conclusion: The patient's general condition, the serum albumin level (or Child-Pugh class), and BMA treatment influenced the posttreatment survival times of patients with HCC-derived metastatic spine tumors. A prognostic scoring system based on these factors was proposed.

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A novel third generation bisphosphonate, minodronate (YM529), prevented proliferation and migration of hepatocellular carcinoma cells through inhibition of mevalonate pathway

Abstract: YM529 inhibited the cell proliferation and migration of HCC cells, implicating the involvement of the mevalonate pathway. These results suggest that N-BPs are potential agents for the treatment of HCC skeletal metastases.

Cited by 12 publications

References 39 publications

Outcomes of metastatic spinal cord compression secondary to primary hepatocellular carcinoma with multidisciplinary treatments

Outcomes of metastatic spinal cord compression secondary to primary hepatocellular carcinoma with multidisciplinary treatments

Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway

Prognostic scoring system for metastatic spine tumors derived from hepatocellular carcinoma

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