AIM: To clarify the biological feature contributing to gastric cancer with diffuse bone metastases at diagnosis.METHODS: The participants visited the Department of Clinical Oncology, Akita University Hospital, from Ja...AIM: To clarify the biological feature contributing to gastric cancer with diffuse bone metastases at diagnosis.METHODS: The participants visited the Department of Clinical Oncology, Akita University Hospital, from January 2014 to August 2015. The selection criterion for gastric cancer with diffuse bone metastases at diagnosis includes over 29 hot spots of bone scintigraphy. Circulating tumor cell were collected from 20 m L of peripheral venous blood drawn using a Cell Search kit and a Cell Tracks Auto Prep system by SRL, a clinical laboratory. The endpoints of this study were correlations between circulating tumor cells(CTC) count and therapeutic outcomes. RESULTS: Among 39 patients with gastric cancer, 5 patients met the criterion. The incidence of this subtype was 12.8%. CTC counts ranged from 235 to 6440 cells/7.5 m L of peripheral blood(median of 1724). These values were much higher than common gastric cancers(2 cells). In chemo-sensitive cases, CTC counts decreased within 14 d(median) from 275, 235 and 1724 to 2, 7 and 66, respectively. On the other hand, CTC counts increased after treatment failure or insensitive case from 2, 7 and 6440 to 787, 513 and 7885, respectively. The correlation between CTC count and survival time showed a trend, but did not reach significance(Y = 234.6- 0.03 X, P = 0.085).CONCLUSION: High CTC count is a biological hallmark of this subtype, and can be used as a direct and definitive indicator of therapeutic outcome.展开更多
A number of studies have focused on the beneficial properties of Curcumin (diferuloyl methane, used in South Asian cuisine and traditional medicine) such as the chemoprevention of cancer. Recent studies have also indi...A number of studies have focused on the beneficial properties of Curcumin (diferuloyl methane, used in South Asian cuisine and traditional medicine) such as the chemoprevention of cancer. Recent studies have also indicated that this material has significant benefits for the treatment of cancer and is currently undergoing several clinical trials. We have been interested in the application of this compound as a therapeutic agent for advanced prostate cancer, particularly the skeletal complications in this malignancy. Our earlier work indicated that this compound could inhibit the osteomimetic properties which occur in castration resistant prostate cancer cells, by interfering with the common denominators between these cancer cells and the bone cells in the metastatic tumor microenvironment, namely the osteoblasts and the osteoclast. We predicted that curcumin could break the vicious cycle of reciprocal stimulation that results in uncontrolled osteolysis in the bony matrix. In this work, we have evaluated the potential of this compound in inhibiting the bone metastasis of hormone refractory prostate cancer cells in an established animal model. Our results strongly suggest that curcumin modulates the TGF-βsignaling that occurs due to bone matrix degradation by up-regulating the metastasis inhibitory bone morphogenic protein-7 (BMP-7). This enhancement of BMP-7 in the context of TGF-β in the tumor microenvironment is shown to enhance the mesenchymal-to-epithelial transition. Most importantly, we show that as a result of BMP-7 up-regulation, a novel brown/beige adipogenic differentiation program is also up-regulated which plays a role in the inhibition of bone metastasis. Our results suggest that curcumin may subvert the TGF-β signaling to an alternative adipogenic differentiation program in addition to the previously established interference with the osteomimetic properties, thus inhibiting the bone metastatic processes in a chemopreventive as well as therapeutic setting.展开更多
文摘AIM: To clarify the biological feature contributing to gastric cancer with diffuse bone metastases at diagnosis.METHODS: The participants visited the Department of Clinical Oncology, Akita University Hospital, from January 2014 to August 2015. The selection criterion for gastric cancer with diffuse bone metastases at diagnosis includes over 29 hot spots of bone scintigraphy. Circulating tumor cell were collected from 20 m L of peripheral venous blood drawn using a Cell Search kit and a Cell Tracks Auto Prep system by SRL, a clinical laboratory. The endpoints of this study were correlations between circulating tumor cells(CTC) count and therapeutic outcomes. RESULTS: Among 39 patients with gastric cancer, 5 patients met the criterion. The incidence of this subtype was 12.8%. CTC counts ranged from 235 to 6440 cells/7.5 m L of peripheral blood(median of 1724). These values were much higher than common gastric cancers(2 cells). In chemo-sensitive cases, CTC counts decreased within 14 d(median) from 275, 235 and 1724 to 2, 7 and 66, respectively. On the other hand, CTC counts increased after treatment failure or insensitive case from 2, 7 and 6440 to 787, 513 and 7885, respectively. The correlation between CTC count and survival time showed a trend, but did not reach significance(Y = 234.6- 0.03 X, P = 0.085).CONCLUSION: High CTC count is a biological hallmark of this subtype, and can be used as a direct and definitive indicator of therapeutic outcome.
文摘A number of studies have focused on the beneficial properties of Curcumin (diferuloyl methane, used in South Asian cuisine and traditional medicine) such as the chemoprevention of cancer. Recent studies have also indicated that this material has significant benefits for the treatment of cancer and is currently undergoing several clinical trials. We have been interested in the application of this compound as a therapeutic agent for advanced prostate cancer, particularly the skeletal complications in this malignancy. Our earlier work indicated that this compound could inhibit the osteomimetic properties which occur in castration resistant prostate cancer cells, by interfering with the common denominators between these cancer cells and the bone cells in the metastatic tumor microenvironment, namely the osteoblasts and the osteoclast. We predicted that curcumin could break the vicious cycle of reciprocal stimulation that results in uncontrolled osteolysis in the bony matrix. In this work, we have evaluated the potential of this compound in inhibiting the bone metastasis of hormone refractory prostate cancer cells in an established animal model. Our results strongly suggest that curcumin modulates the TGF-βsignaling that occurs due to bone matrix degradation by up-regulating the metastasis inhibitory bone morphogenic protein-7 (BMP-7). This enhancement of BMP-7 in the context of TGF-β in the tumor microenvironment is shown to enhance the mesenchymal-to-epithelial transition. Most importantly, we show that as a result of BMP-7 up-regulation, a novel brown/beige adipogenic differentiation program is also up-regulated which plays a role in the inhibition of bone metastasis. Our results suggest that curcumin may subvert the TGF-β signaling to an alternative adipogenic differentiation program in addition to the previously established interference with the osteomimetic properties, thus inhibiting the bone metastatic processes in a chemopreventive as well as therapeutic setting.
