Recent studies in secretory pathway calcium ATPases (SPCA) revealed novel functions of SPCA2 in interacting with store-operated Ca2+ channel Oral I and inducing Ca2+ influx at the cell surface. Importantly, SPCA2-...Recent studies in secretory pathway calcium ATPases (SPCA) revealed novel functions of SPCA2 in interacting with store-operated Ca2+ channel Oral I and inducing Ca2+ influx at the cell surface. Importantly, SPCA2-mediated Ca2+ signaling is uncoupled from its conventional role of Ca2+-ATPase and independent of store-operated Ca2+ signaling pathway. SPCA2-induced store-independent Ca2+ entry (SICE) plays essential roles in many important physiological processes, while unbalanced SICE leads to enhanced cell proliferation and tumorigenesis. Finally, we have summarized the clinical implication of SICE in oral cancer prognosis and treatment. Inhibition of SICE may be a new target for the development of cancer therapeutics.展开更多
DNA methylation, one of the best-characterized epigenetic modifications, plays essential roles in diseases, including human cancers. In recent years, our understanding on DNA methylation with human cancers has made si...DNA methylation, one of the best-characterized epigenetic modifications, plays essential roles in diseases, including human cancers. In recent years, our understanding on DNA methylation with human cancers has made significant progress, which was facilitated by stunning development in the analysis of the human methylome of multiple cancer types. In this review, recent developments in the characterization of aberrant DNA methylation involved in human cancers development were discussed with special emphasis on the mechanisms of aberrant DNA methylation in human cancers. We also summarize the recent treatment strategy for human cancers with de-methylation drugs.展开更多
Although chemotherapy is one of several therapeutic options for cancer patients, the outcomes have been less satisfactory with palpable side effects in many cases. To help improve the efficacy of chemotherapy, we exam...Although chemotherapy is one of several therapeutic options for cancer patients, the outcomes have been less satisfactory with palpable side effects in many cases. To help improve the efficacy of chemotherapy, we examined whether D-fraction (DF), a bioactive mushroom extract, would potentiate anticancer effects of those drugs in vitro. Seven types of cancer cell lines, including breast, lung, stomach, colon, prostate, bladder, and kidney cancers, were tested with various chemotherapeutic drugs and their combinations with DF. Compared to individual drugs alone, combinations of those drugs and DF have indeed improved anticancer activity, resulting in the significant (p 0.05) cell viability reduction in all cancer cells. As vitamin C (VC) has been insinuated to potentiate bioactivity of DF, combination of DF (300 μg/ml) and VC (200 μM) was also examined. Such studies showed that DF/VC combination led to the drastic (≥90%) viability reductions in 6 cancer cells and the 70% reduction in 1 cancer cell type. These results were superior to those from combinations of drugs and DF. To assess if such a profound cell viability reduction by DF/VC combination might be attributed to apoptosis, this possibility was tested by Western blots. Analyses revealed that anti-apoptotic bcl-2 was down-regulated while pro-apoptotic Bax was up-regulated with DF/VC combination, indicating induction of apoptosis. It is plausible that DF/VC combination may induce apoptosis, resulting in the severe cell viability reduction. Therefore, DF may have a great potential as an adjuvant agent that can be combined with chemotherapeutic drugs or with VC for the improved treatment of various human malignancies.展开更多
We examined the possibility that the anti-estrogens, tamoxifen (TX) and toremifen (TO) interacted?with the immune system. Indeed, both TX and TO stimulated cells mediated cytotoxicity reactions by various killer cells...We examined the possibility that the anti-estrogens, tamoxifen (TX) and toremifen (TO) interacted?with the immune system. Indeed, both TX and TO stimulated cells mediated cytotoxicity reactions by various killer cells: killer T (TK), natural killer (NK), lymphokine activated killer (LAK) cells. Both TX and TO inhibited the growth of tumors that express estrogen receptors. Thus these antiestrogens inhibited tumor growth and stimulated killer cells for cytotoxicty on such tumors. Therefore these agents were presumed to stimulate tumor immunity. We tested the P815 mouse mastcytoma with TK, LK, and TX or TO. A therapeutic effect was observed in both experiments. The SL2-5 murine lymphoma was tested with NK and TX cells or TO cells and successful immunotherapy was observed.?We digested human breast carcinomas and lung tumors with collagenase. The killer cells were separated from tumor cells on Ficoll gradients. TX and TO enhanced the cytotoxic effect of autologous killer cells on the corresponding tumor cells. This experiment indicates that the results obtained in animals are also valid for human malignant disease.展开更多
In recent years, human cancer genome projects provide unprecedented opportunities for the discovery of cancer genes and signaling pathways that contribute to tumor development. While numerous gene mutations can be ide...In recent years, human cancer genome projects provide unprecedented opportunities for the discovery of cancer genes and signaling pathways that contribute to tumor development. While numerous gene mutations can be identified from each cancer genome, what these muta- tions mean for cancer is a challenging question to address, especially for those from less understood putative new cancer genes. As a powerful approach, in silico bioinformatics analysis could efficiently sort out mutations that are predicted to damage gene function. Such an analysis of human large tumor suppressor genes, LATS1 and LATS2, has been carried out and the results support a role of hLATS1/12 as negative growth regulators and tumor suppressors.展开更多
This experiment was conducted in order to verify the role of Vitamin K1 as a cell growth inhibitor on the U937 cell line. This experiment was performed in two parts—one with a lesser concentration of Vitamin K1, and ...This experiment was conducted in order to verify the role of Vitamin K1 as a cell growth inhibitor on the U937 cell line. This experiment was performed in two parts—one with a lesser concentration of Vitamin K1, and the other with a range of concentrations from low-to-high. Through the remaining number of U937 cells, as well as cell areas, it was concluded that the presence of Vitamin K1 reduces the number of cancer cells. It was also concluded that as Vitamin K1 concentration increases, so does the frequency and effects of apoptosis.展开更多
基金supported by grant GM62142 from the National Institution of Health to Rajini RaoAmerican Heart Association Pre-doctoral Fellowship 0815058E to Ming-Ye Fengsupported by Open Fund of State Key Laboratory of Oral Diseases, Sichuan University
文摘Recent studies in secretory pathway calcium ATPases (SPCA) revealed novel functions of SPCA2 in interacting with store-operated Ca2+ channel Oral I and inducing Ca2+ influx at the cell surface. Importantly, SPCA2-mediated Ca2+ signaling is uncoupled from its conventional role of Ca2+-ATPase and independent of store-operated Ca2+ signaling pathway. SPCA2-induced store-independent Ca2+ entry (SICE) plays essential roles in many important physiological processes, while unbalanced SICE leads to enhanced cell proliferation and tumorigenesis. Finally, we have summarized the clinical implication of SICE in oral cancer prognosis and treatment. Inhibition of SICE may be a new target for the development of cancer therapeutics.
文摘DNA methylation, one of the best-characterized epigenetic modifications, plays essential roles in diseases, including human cancers. In recent years, our understanding on DNA methylation with human cancers has made significant progress, which was facilitated by stunning development in the analysis of the human methylome of multiple cancer types. In this review, recent developments in the characterization of aberrant DNA methylation involved in human cancers development were discussed with special emphasis on the mechanisms of aberrant DNA methylation in human cancers. We also summarize the recent treatment strategy for human cancers with de-methylation drugs.
文摘Although chemotherapy is one of several therapeutic options for cancer patients, the outcomes have been less satisfactory with palpable side effects in many cases. To help improve the efficacy of chemotherapy, we examined whether D-fraction (DF), a bioactive mushroom extract, would potentiate anticancer effects of those drugs in vitro. Seven types of cancer cell lines, including breast, lung, stomach, colon, prostate, bladder, and kidney cancers, were tested with various chemotherapeutic drugs and their combinations with DF. Compared to individual drugs alone, combinations of those drugs and DF have indeed improved anticancer activity, resulting in the significant (p 0.05) cell viability reduction in all cancer cells. As vitamin C (VC) has been insinuated to potentiate bioactivity of DF, combination of DF (300 μg/ml) and VC (200 μM) was also examined. Such studies showed that DF/VC combination led to the drastic (≥90%) viability reductions in 6 cancer cells and the 70% reduction in 1 cancer cell type. These results were superior to those from combinations of drugs and DF. To assess if such a profound cell viability reduction by DF/VC combination might be attributed to apoptosis, this possibility was tested by Western blots. Analyses revealed that anti-apoptotic bcl-2 was down-regulated while pro-apoptotic Bax was up-regulated with DF/VC combination, indicating induction of apoptosis. It is plausible that DF/VC combination may induce apoptosis, resulting in the severe cell viability reduction. Therefore, DF may have a great potential as an adjuvant agent that can be combined with chemotherapeutic drugs or with VC for the improved treatment of various human malignancies.
文摘We examined the possibility that the anti-estrogens, tamoxifen (TX) and toremifen (TO) interacted?with the immune system. Indeed, both TX and TO stimulated cells mediated cytotoxicity reactions by various killer cells: killer T (TK), natural killer (NK), lymphokine activated killer (LAK) cells. Both TX and TO inhibited the growth of tumors that express estrogen receptors. Thus these antiestrogens inhibited tumor growth and stimulated killer cells for cytotoxicty on such tumors. Therefore these agents were presumed to stimulate tumor immunity. We tested the P815 mouse mastcytoma with TK, LK, and TX or TO. A therapeutic effect was observed in both experiments. The SL2-5 murine lymphoma was tested with NK and TX cells or TO cells and successful immunotherapy was observed.?We digested human breast carcinomas and lung tumors with collagenase. The killer cells were separated from tumor cells on Ficoll gradients. TX and TO enhanced the cytotoxic effect of autologous killer cells on the corresponding tumor cells. This experiment indicates that the results obtained in animals are also valid for human malignant disease.
文摘In recent years, human cancer genome projects provide unprecedented opportunities for the discovery of cancer genes and signaling pathways that contribute to tumor development. While numerous gene mutations can be identified from each cancer genome, what these muta- tions mean for cancer is a challenging question to address, especially for those from less understood putative new cancer genes. As a powerful approach, in silico bioinformatics analysis could efficiently sort out mutations that are predicted to damage gene function. Such an analysis of human large tumor suppressor genes, LATS1 and LATS2, has been carried out and the results support a role of hLATS1/12 as negative growth regulators and tumor suppressors.
文摘This experiment was conducted in order to verify the role of Vitamin K1 as a cell growth inhibitor on the U937 cell line. This experiment was performed in two parts—one with a lesser concentration of Vitamin K1, and the other with a range of concentrations from low-to-high. Through the remaining number of U937 cells, as well as cell areas, it was concluded that the presence of Vitamin K1 reduces the number of cancer cells. It was also concluded that as Vitamin K1 concentration increases, so does the frequency and effects of apoptosis.