• Oncology Letters
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• v.41 no.1
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• pp.711-717
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• 2019

In attempting to identify effective anticancer drugs from natural products that are harmless to humans, we found that the gomisin J from Schisandra chinensis fruit has anticancer activity. Schisandra chinensis fruits are used in traditional herbal medicine and gomisin J is one of their chemical constituents. In the present study, we examined the anticancer activity of gomisin J in MCF7 and MDA-MB-231 breast cancer cell lines and in MCF10A normal cell line, in a time- and concentration-dependent manner. Our data revealed that gomisin J exerted a much stronger cytotoxic effect on MCF7 and MDA-MB-231 cancer cells than on MCF10A normal cells. Gomisin J suppressed the proliferation and decreased the viability of MCF7 and MDA-MB-231 cells at relatively low (<10 ㎍/ml) and high (>30 ㎍/ml) concentrations, respectively. Our data also revealed that gomisin J induced necroptosis, a programmed form of necrosis, as well as apoptosis. Notably, gomisin J predominantly induced necroptosis in MCF7 cells that are known to have high resistance to many pro-apoptotic anticancer drugs, while MDA-MB-231 exhibited a much lower level of necroptosis but instead a higher level of apoptosis. This data indicated the possibility that it may be used as a more effective anticancer drug, especially in apoptosis-resistant malignant cancer cells. In an extended study, gomisin J exhibited a strong cytotoxic effect on all tested various types of 13 cancer cell lines, indicating its potential to be used against a wide range of different types of cancer cells.

• Investigative Magnetic Resonance Imaging
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• v.4 no.1
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• pp.34-41
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• 2000

Purpose: To evaluate the clinical usefulness of diffusion weighted MR imaging(DWI) in the differential diagnosis of brain tumors. Materials and methods: DWI and conventional MR images of nineteen patients with brain tumors(10 metastatic tumors, 4 high grade gliomas, 4 low grade astrocytomas, one oligodendroglioma)were obtained on 1.5T unit. DWI was obtained using single shot spin echo planar imaging with b-value near 1000. We analyzed the signal intensities of lesions including solid portion, necrotic or cystic portion and peritumoral edema of brain tumors (classified five grades comparison with the signal intensities of brain parenchyma and CSF)and calculate the SIR(signal intensity ratio)of lesions to the contralateral normal brain parenchyma. We analyzed statistically the signal intensities and SIR of tumors using independence T test. Results: In solid portions of tumors, all the metastatic tumors and high grade gliomas showed high signal intensities, but low grade astrocytomas and oligodendroglioma showed iso or slight high signal intensities to the normal brain parenchyma. The SIR of solid portion has positive correlation with malignant pot ential(metastatic tumors 1.52, high grade gliomas 1.38, low grade astrocytomas 1.16, oligodendroglioma 1.31)(p < 0.05). In peritumoral edema where seen in 14 tumors, seven of 10 metastatic tumors and two of 4 high grade gliomas showed iso signal intensities, whereas edemas in other 5 brain tumors showed hyperintense to the normal brain parenchyma. The SIRs of peritumoral edemas in metastatic tumors (1.14) was lower than high grade gliomas(1.31),but statistically insignificant. The SIR of cystic or necrotic portion of brain tumors was 0.63. In non enhancing solid portions, three of six cases showed hyperintense to the adjacent peritumoral edema. Conclusion: On DWI, the signal intensities of solid portion has positive correlation with malignant potential, and perilesional edema of brain tumors appear various signal intensities owing to "T2 shine through effect" and the extensiveness of vasogenic edema. Another merit using DWI on the evaluation of brain tumors is to improved better delineation of tumor margins from the adjacent edemas, especially at the non enhancing solid portion of the tumors.

• Archives of Reconstructive Microsurgery
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• v.9 no.2
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• pp.139-146
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• 2000

The aim of this study was to assess whether the functional regeneration of a lyophilized autografted cartilage could be improved by implanting a vascularized muscle flap into the medullary canal of autografted proximal humerus. A hemijoint reconstruction using a lyophilized osteochondral autograft in proximal humerus was done in 4 rabbits for control, and combined with an vascularized intramedullary muscle flap in another 4 rabbits for the experimental group. Graft healing and the repair process of osteochondral graft were followed by serial radiographs and histologic changes for 9 weeks after experiments. Each two rabbits in control and in experimental group on 5th and 9th week after implantation of hemijoint were sacrified. The results were as follows: 1. All of control and experimental froups on 5th week united solidly on osteotomized site radiologically, but their articular cartilages were destroyed more seriously in the control than that in experimental group with muscle flap on 5th and 9th week after experiment... 2. Histochemically, the cartilage surface are completely destroyed and revealed with severe osteoarthritic changes on all cartilage layers in control, but cartilaginous erosions are mild to moderate and their arthritic changes are also mild with somewhat regeneration of chondrocytes on deep layers more prominetly on 9th week of the experimental group. 3. The amount of collagen and protenized matrix which was determined by Masson-Trichrome stain was markedly decreased that means the weakness of bony strength and low osteogenic potential in lyophilized cartilage. These results suggest that an intramedullary vascularized muscle flap can improve the functional results of lyophilized osteochondral autograft by providing both increased vascularity and populations of mesenchymal cells to initiate new bone formation on osteotomized site as well as the regeneration of deep layers in articular cartilage. In clinical relevances, this lyophilized hemijoint autograft combined with an intramedullary vascularized muscle pedicle graft might be used very effectively for the treatment of malignant long bone tumors to preserve the joint functions, all or partly, and so to replace it with the artificial joint after tumor excision and hemijoint autograft.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1809-1817
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• 2012

Background: Gastric cancer is frequently lethal despite aggressive multimodal therapies, and new treatment approaches are therefore needed. Retinoids are potential candidate drugs: they prevent cell differentiation, proliferation and malignant transformation in gastric cancer cell lines. They interact with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors, each with three subclasses, ${\alpha}$, ${\beta}$ and ${\gamma}$. At present, little is known about retinoid expression and influence on prognosis in gastric cancers. Patients and Methods: We retrospectively analyzed the expression of the subtypes RARa, $RAR{\beta}$, $RAR{\gamma}$, RXRa, $RXR{\beta}$, $RXR{\gamma}$ by immunohistochemistry in 147 gastric cancers and 51 normal gastric epithelium tissues for whom clinical follow-up data were available and correlated the results with clinical characteristics. In addition, we quantified the expression of retinoid receptor mRNA using real-time PCR (RT-PCR) in another 6 gastric adenocarcinoma and 3 normal gastric tissues. From 2008 to 2010, 80 patients with gastric cancers were enrolled onto therapy with all-trans-retinoic acid (ATRA). Results: RARa, $RAR{\beta}$, $RAR{\gamma}$ and $RXR{\gamma}$ positively correlated with each other (p < 0.001) and demonstrated significantly lower levels in the carcinoma tissue sections (p < 0.01), with lower $RAR{\beta}$, $RAR{\gamma}$ and RXRa expression significantly related to advanced stages (p < =0.01). Tumors with poor histopathologic grade had lower levels of RARa and $RAR{\beta}$ in different histological types of gastric carcinoma (p < 0.01). Patients whose tumors exhibited low levels of RARa expression had significantly lower overall survival compared with patients who had higher expression levels of this receptor (p < 0.001, HR=0.42, 95.0% CI 0.24-0.73), and patients undergoing ATRA treatment had significantly longer median survival times (p = 0.007, HR=0.41, 95.0% CI 0.21-0.80). Conclusions: Retinoic acid receptors are frequently expressed in epithelial gastric cancer with a decreased tendency of expression and RARa may be an indicator of a positive prognosis. This study provides a molecular basis for the therapeutic use of retinoids against gastric cancer.