Miwa S.,AntiCancer |
Yano S.,AntiCancer |
Kimura H.,Kanazawa University |
Yamamoto M.,AntiCancer |
And 11 more authors.
Cell Cycle | Year: 2015
Essentially every population of cancer cells within a tumor is heterogeneous, especially with regard to chemosensitivity and resistance. In the present study, we utilized the fluorescence ubiquitination-based cell cycle indicator (FUCCI) imaging system to investigate the correlation between cell-cycle behavior and apoptosis after treatment of cancer cells with chemotherapeutic drugs. HeLa cells expressing FUCCI were treated with doxorubicin (DOX) (5 mM) or cisplatinum (CDDP) (5 mM) for 3 h. Cell-cycle progression and apoptosis were monitored by time-lapse FUCCI imaging for 72 h. Time-lapse FUCCI imaging demonstrated that both DOX and CDDP could induce cell cycle arrest in S/G2/M in almost all the cells, but a subpopulation of the cells could escape the block and undergo mitosis. The subpopulation which went through mitosis subsequently underwent apoptosis, while the cells arrested in S/G2/M survived. The present results demonstrate that chemoresistant cells can be readily identified in a heterogeneous population of cancer cells by S/G2/M arrest, which can serve in future studies as a visible target for novel agents that kill cell-cycle-arrested cells. © 2015 Taylor & Francis Group, LLC.
Yano S.,AntiCancer |
Yano S.,University of California at San Diego |
Yano S.,Okayama University of Science |
Hiroshima Y.,AntiCancer |
And 19 more authors.
Cancer Gene Therapy | Year: 2015
Precise fluorescence-guided surgery (FGS) for pancreatic cancer has the potential to greatly improve the outcome in this recalcitrant disease. To achieve this goal, we have used genetic reporters to color code cancer and stroma cells in a patient-derived orthotopic xenograft (PDOX) model. The telomerase-dependent green fluorescent protein (GFP)-containing adenovirus OBP-401 was used to label the cancer cells of a pancreatic cancer PDOX. The PDOX was previously grown in a red fluorescent protein (RFP) transgenic mouse that stably labeled the PDOX stroma cells bright red. The color-coded PDOX model enabled FGS to completely resect the pancreatic tumors including stroma. Dual-colored FGS significantly prevented local recurrence, which bright-light surgery or single-color FGS could not. FGS, with color-coded cancer and stroma cells has important potential for improving the outcome of recalcitrant-cancer surgery. © 2015 Nature America, Inc. All rights reserved.
News Article | October 28, 2016
(Boston)--A new study has identified an effective combination therapy for treating ovarian cancer cells. The findings, published in the journal AntiCancer Research, may result in a new treatment option for different types of ovarian cancer, including those that develop resistance to chemotherapy and other treatments. Ovarian cancer accounts for about three percent of cancers among women, however it causes more deaths than any other cancer of the female reproductive system. Unfortunately it often goes undetected until it has spread within the pelvis and abdomen. At this late stage, it is more difficult to treat and is frequently fatal. Surgery and chemotherapy are generally used to treat this disease. In the absence of target specific drugs, platinum drugs are often used to treat ovarian cancer. Researchers at Boston University School of Medicine (BUSM) under the direction of Sibaji Sarkar, PhD, instructor of medicine, combined protease calpain inhibitor calpeptin with epigenetic (histone deacetylase) inhibitors sodium butyrate and SAHA. When used in suboptimal doses in combination, they produced enhanced ovarian cancer cell growth inhibition and induced ovarian cancer cell death. According to the researchers, one of the interesting observations of this study was the finding that calpeptin also works as an epigenetic drug as it is capable of removing the methyl tags from genes. Sarkar explains, "Calpeptin possibly has a dual role. It can kill cancer cells and in addition it may act as an epigenetic drug as well. We believe that epigenetic drugs alone are not the best choice for cancer therapy. We need other target specific and other types of inhibitors but the addition of epigenetic drugs can increase the efficacy of the therapy, inhibiting formation of new cancer progenitor/stem cells by re-expressing tumor suppressor genes and blocking the expression of growth promoting genes even after remission after standard therapy." In a previous study, this same research group had proposed that epigenetics (when genetically identical cells express their genes differently, causing different outcomes) play a significant role in the formation of cancer progenitor cells, cancer progression, metastasis and cancer drug resistance. They described an epigenetic switch concept, which is turned on during carcinogenesis. Results from other studies have shown that epigenetic drugs sensitize platinum drug resistance ovarian cancer cells and kill breast cancer stem cells, supporting this hypothesis. In a comparative analysis, the authors previously described the similarities in the genetic and epigenetic events of breast and ovarian cancer suggesting a common epigenetic origin. They have shown before that combination of histone deacetylase inhibitors with calpain inhibitor produced enhanced growth inhibition and cell death in different types of breast cancer cells including triple negative breast cancer cells as they observed in different types of ovarian cancer cells in this study. Other BUSM contributors to this study included Karolina Lapinska (first author), MS, Amber Willbanks and Anuja Oza, MD. Genevieve Housman, MS, from Arizona State University, Shannon Byler, MD, from Boston Children's Hospital/Harvard Medical School and Sarah Heerboth from Vanderbilt School of Medicine are also co-authors. The study was partially supported by a grant from American Cancer Society.