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Saitama, Japan

Matsuo N.,Akita | Yomiya K.,Saitama Cancer Center
American Journal of Hospice and Palliative Medicine | Year: 2014

Steroids are commonly used for fatigue relief in terminally ill cancer patients. However, steroid-induced adverse effects including depression, myopathy, and hyperglycemia may contribute to fatigue. We report our experiences with aggravation of fatigue with steroid use in three cases. Case 1 was a 65-year-old man with advanced gastric cancer. He was started on betamethasone (2 mg/d) for fatigue, but the fatigue worsened due to steroid-induced depression. Discontinuation of steroids and initiation of an antidepressant ameliorated the fatigue. Case 2 was a 68-year-old man with advanced lung cancer. He complained of fatigue. Betamethasone (1 mg/d) was started and alleviated the fatigue. However, when the betamethasone dose was increased to 2 mg/d, the fatigue, with muscle weakness and myalgia, worsened due to steroid-induced myopathy. We therefore switched from betamethasone (2 mg/d) to prednisolone (10 mg /d). The fatigue resolved and the patient returned to his previous condition. Case 3 was a 73-year-old man with recurrent bile duct cancer. He also had diabetes mellitus. He developed fatigue, anorexia and fever. We started betamethasone (1.5 mg/d) for these symptoms, but the fatigue and anorexia worsened due to steroid-induced hyperglycemia. Blood glucose rose to 532 mg/dL. Therefore, insulin therapy was started, and the dose of betamethasone was reduced to 0.5 mg/d. His glucose level decreased to less than 320 mg/dL and he recovered from the fatigue while achieving moderate oral intake. In conclusion, the possibility of steroid-induced secondary fatigue in terminally ill cancer patients should be taken into consideration. © The Author(s) 2013. Source

Akagi K.,Saitama Cancer Center
Rinsho byori. The Japanese journal of clinical pathology | Year: 2011

Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor that, on ligand binding, triggers the RAS-RAF-MAPK signaling pathway which is mainly associated with cell proliferation. Drugs targeting EGFR have recently entered clinical practice and have proven to be effective in providing clinical benefits. However, the presence of mutated KRAS alleles in cancer is a predictive marker of anti-EGFR drug resistance. Similarly, alterations of other members of the RAS-RAF-MAPK signaling pathway may also be such predictive markers, especially the BRAF mutation in colorectal cancer. Therefore, the identification of KRAS and BRAF mutations may be important in predicting resistance to EGFR-targeted therapies. We looked at the Tm analysis for simultaneous detection of KRAS and BRAF mutations using a quenching probe. The oligonucleotide probes modified with certain fluorescent dyes at 5'-end cytosine are quenched by their interaction with a uniquely positioned guanine. When the probe is hybridized with target DNA, its fluorescence is quenched by the guanine in the target DNA. However, as the temperature is raised, perfect match probes and miss match probes dissociate at different temperatures. Dissociated probes generate fluorescence. This simple and rapid method for simultaneous detection of these mutations is useful in clinical practice. Source

Matsuo N.,Saitama Cancer Center | Morita T.,Seirei Mikatabara General Hospital | Iwase S.,University of Tokyo
Journal of Palliative Medicine | Year: 2011

Background and Methods: Corticosteroids are commonly used for symptom relief in the treatment of patients with advanced cancer. Consistent efficacy of corticosteroid treatment in palliative care remains controversial. A cross-sectional anonymous survey was mailed to representative managing physicians in certified palliative care units in Japan to clarify the physician-perceived efficacy of steroid treatment on anorexia, fatigue, and dyspnea in terminal cancer patients, to clarify physicians' experience of side effects of corticosteroid use, and to determine the Japanese palliative care physician-reported predictive factors for efficacy and lack of efficacy. Results and Conclusions: Many Japanese palliative care specialists perceived that corticosteroids are effective for each of the symptoms, are aware of the prevalence and importance of serious adverse effects, and predict the effectiveness of steroid therapy by etiological factors. © 2011, Mary Ann Liebert, Inc. Source

Kikuchi I.,Saitama Cancer Center
Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2011

We report a rare case of a 68-year-old man with long-term survival after a surgical treatment of solitary metachronous small intestinal metastasis from lung cancer. He underwent a right upper lobectomy for primary lung adenocarcinoma. Thirty -four months after the operation, a tumor of small bowel was detected by computed tomography. The tumor was resected and diagnosed as a metastasis from lung cancer. Eighteen months after resection of metastasis, a tumor located at mesentery of the jejunum was pointed out. The tumor was resected and also diagnosed as a metastasis from lung cancer. The postoperative course was uneventful, and the patient is still alive without recurrence for 3 years after the last operation. We reviewed of 222 Japanese cases that underwent a resection of small intestinal metastasis from lung cancer. Although the prognosis was extremely poor for those who underwent a resection of the primary lung cancer and who had no remnant metastatic lesion at the time of metastasectomy, they seem to have a longer survival time. Source

Lawson D.A.,University of California at San Francisco | Lawson D.A.,University of California at Irvine | Bhakta N.R.,University of California at San Francisco | Kessenbrock K.,University of California at San Francisco | And 14 more authors.
Nature | Year: 2015

Despite major advances in understanding the molecular and genetic basis of cancer, metastasis remains the cause of >90% of cancer-related mortality. Understanding metastasis initiation and progression is critical to developing new therapeutic strategies to treat and prevent metastatic disease. Prevailing theories hypothesize that metastases are seeded by rare tumour cells with unique properties, which may function like stem cells in their ability to initiate and propagate metastatic tumours. However, the identity of metastasis-initiating cells in human breast cancer remains elusive, and whether metastases are hierarchically organized is unknown. Here we show at the single-cell level that early stage metastatic cells possess a distinct stem-like gene expression signature. To identify and isolate metastatic cells from patient-derived xenograft models of human breast cancer, we developed a highly sensitive fluorescence-activated cell sorting (FACS)-based assay, which allowed us to enumerate metastatic cells in mouse peripheral tissues. We compared gene signatures in metastatic cells from tissues with low versus high metastatic burden. Metastatic cells from low-burden tissues were distinct owing to their increased expression of stem cell, epithelial-to-mesenchymal transition, pro-survival, and dormancy-associated genes. By contrast, metastatic cells from high-burden tissues were similar to primary tumour cells, which were more heterogeneous and expressed higher levels of luminal differentiation genes. Transplantation of stem-like metastatic cells from low-burden tissues showed that they have considerable tumour-initiating capacity, and can differentiate to produce luminal-like cancer cells. Progression to high metastatic burden was associated with increased proliferation and MYC expression, which could be attenuated by treatment with cyclin-dependent kinase (CDK) inhibitors. These findings support a hierarchical model for metastasis, in which metastases are initiated by stem-like cells that proliferate and differentiate to produce advanced metastatic disease. © 2015 Macmillan Publishers Limited. All rights reserved. Source

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