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1.
Yoshiyasu Umeda Hiroaki Hayashi Seiko Sugiyama Yumi Aoyama 《The Journal of dermatology》2020,47(11):1322-1325
Programmed death 1 (PD-1) inhibitors are increasingly used for the treatment of malignancies. Despite the clinical benefits, unpredictable and potentially fatal side-effects may occur. We report a psoriatic patient who developed systemic capillary leak syndrome (SCLS) after starting a PD-1 checkpoint inhibitor. In order to determine which factors could trigger the development of SCLS in a patient with stable psoriasis after starting anti-PD-1 therapy, serum cytokines were serially measured before and after the development of SCLS in this patient. We also retrospectively reviewed 28 previously reported patients presenting clinical exacerbations of pre-existing psoriasis or the de novo induction of psoriasis after anti-PD-1 therapy. In 16 of the 28 patients (57.1%), the interval between last anti-PD-1 therapy and exacerbations of pre-existing psoriasis or the de novo induction of psoriasis was less than 28 days. The timing of the onset of SCLS in this patient was coincident with the increase in lymphocyte counts and at 22 days after last anti-PD-1 therapy. In 75%, however, anti-PD-1 therapy was able to be restarted and was tolerated well. Increased levels of interleukin (IL)-2, IL-6, interferon-γ and tumor necrosis factor-α, in addition to a persistent increase in vascular endothelial growth factor (VEGF), were detected at onset of SCLS. An increase in pro-inflammatory cytokines and VEGF, when combined with a rapid and sequential recovery of neutrophils and lymphocytes after anti-PD-1 therapy, would predict the development of SCLS. Clinicians need to be aware that patients with psoriasis are at risk of a potentially fatal disease, SCLS, when anti-PD-1 therapy is started. 相似文献
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Kosuke Yoshihara Takayuki Enomoto Daisuke Aoki Yoh Watanabe Junzo Kigawa Nobuhiro Takeshima Hyoe Inomata Kana Hattori Masahisa Jinushi Hitoshi Tsuda Toru Sugiyama 《Cancer science》2020,111(9):3350-3358
Whether germline (g) breast cancer susceptibility gene (BRCA) mutations are located within or outside the ovarian cancer cluster region (OCCR) (1380‐4062 bp for gBRCA1, and between 3249‐5681 bp and 6645‐7471 bp for gBRCA2) may influence risk variations for ovarian cancers. This ad hoc analysis of the CHARLOTTE epidemiological study in Japan assessed the distribution of gBRCA1/2 mutations in patients with newly diagnosed ovarian cancer, and investigated an association between gBRCA1/2 mutation locations and ovarian cancer risk. Differences in patient background and clinical characteristics in subgroups stratified by gBRCA1/2 mutation locations were also evaluated. We analyzed the data of 93 patients (14.7%) from the CHARLOTTE study who were positive for gBRCA1/2 mutations. After excluding 16 cases with L63X founder mutation, 28 (65.1%) of gBRCA1 mutations were within the OCCR. Of 30 gBRCA2 mutations, 15 (50.0%) were within the OCCR. Of 27 patients (one patient excluded for unknown family history) with gBRCA1 mutations located in the OCCR, 11 (40.7%) had a family history of ovarian cancer; the proportion of patients with a family history of ovarian cancer and gBRCA1 mutations outside the OCCR was lower (13.3%). Sixty percent of patients with gBRCA1 mutations outside the OCCR had a family history of breast cancer; the proportion of patients with a family history of breast cancer and gBRCA1 mutations within the OCCR was relatively lower (33.3%). Understanding the mutation locations may contribute to more accurate risk assessments of susceptible individuals and early detection of ovarian cancer among gBRCA mutation carriers. 相似文献
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Tomohiro Saito Masahide Mizobuchi Yusuke Miwa Motonori Sugiyama Yuuki Mima Ayana Iida Nobuhiro Kanazawa Tomoki Morikawa Junichi Hayashi Kei Fukuda Yasuto Shikida Taihei Suzuki Hirokazu Honda 《Journal of clinical apheresis》2021,36(1):196-205
We present six cases of antimelanoma differentiation‐associated gene 5 antibody (anti‐MDA5‐Ab)‐positive clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP‐ILD), which is known to have a poor prognosis. The outcomes of these cases are described after treatment with therapeutic plasma exchange (TPE). Clinical and therapeutic data for patients with CADM with RP‐ILD were collected retrospectively from medical records. All six patients received early intensive care including high‐dose corticosteroids, intravenous cyclophosphamide, and a calcineurin inhibitor, but lung disease and hypoxia became more severe. TPE was performed over a median of 9.5 sessions (range 3‐14) per patient, and the median duration from admission to TPE was 23 days. Three patients received combined direct hemoperfusion using a polymyxin B‐immobilized fiber column (PMX‐DHP) therapy on successive days to manage acute respiratory failure. Four patients survived and two died due to respiratory failure. In the survival cases, ferritin decreased, and ferritin and KL‐6 were lower at diagnosis. The patients who died had a higher alveolar‐arterial oxygen difference and more severe lung lesions at the time of initiation of TPE. These findings indicate that a combination of conventional therapy and TPE may be useful for improvement of the prognosis of CADM with RP‐ILD at the early stage of onset. 相似文献
6.
Ryosuke Kobayashi Reika Kawabata-Iwakawa Makoto Sugiyama Tetsunari Oyama Masato Ohtsuka Takuro Horii Sumiyo Morita Masahiko Nishiyama Izuho Hatada 《International journal of cancer. Journal international du cancer》2023,152(11):2331-2337
Synergistic effects among multiple gene mutations are involved in cancer development and progression. However, developing genetically modified mouse models to analyze various combinations of mutations is extremely labor-intensive and time-consuming. To address these problems, we developed a novel method for in vivo multiplexed genome editing of the murine uterus to model human endometrial carcinoma (EMC). To do this, we injected a CRISPR-Cas9 ribonucleoprotein complex into the uterine cavity of adult female mice, followed by electroporation. Evaluation of reporter mice demonstrated that genome editing occurred specifically in uterine epithelial cells, which are the origin of EMCs. Simultaneous targeting of Pten/Trp53/Lkb1, or targeting of Pten/Lkb1 along with the Ctnnb1ΔEx3 mutation, resulted in efficient generation of invasive tumors in wild-type females within 3 months. This novel method will enable rapid and easy validation of many combinations of gene mutations that lead to endometrial carcinogenesis. 相似文献
7.
Hiroko Kobayashi Ryo Suzuki Kei Sato Takatoshi Ogami Hiroshi Tomozawa Masahito Tsubata Koji Ichinose Masaki Aburada Wataru Ochiai Kiyoshi Sugiyama Tsutomu Shimada 《Journal of natural medicines》2018,72(1):136-144
Knee osteoarthritis (OA) is becoming more prevalent worldwide due to increases in the numbers of elderly and obese patients. Currently, pharmaceutical medicines used for the treatment of OA are for symptomatic therapy and therefore new therapeutic agents are needed. Kaempferia parviflora (KP) is a plant growing naturally in Southeast Asia and has various pharmacological effects including an anti-inflammatory effect, but no effect on OA has yet been reported. We therefore conducted a search for the effects KP and the active components of KP extract (KPE) exert on OA as well as its mechanism of action. Results from a study of KPE using the monoiodoacetic acid rat OA model revealed that KPE reduced the pain threshold and severity of osteoarthritic cartilage lesions. The mechanism of action and active components were then investigated using IL-1β-treated human knee-derived chondrocytes. KPE, as well as 5,7-dimethoxyflavone and 5,7,4′-trimethoxyflavone, which are key constituents of KPE and highly absorbable into the body, reduced the expression of matrix metalloproteinases (MMPs), which are the main extracellular matrix enzymes that degrade collagen within cartilage. As mentioned above, KPE acted to suppress OA and 5,7-dimethoxyflavone and 5,7,4′-trimethoxyflavone were shown to be involved as part of KPE’s mechanism that inhibits MMPs. 相似文献
8.
Kentaro Ando Akira Takahara Yuji Nakamura Takeshi Wada Koki Chiba Ai Goto Nur Jaharat Lubna Mihoko Hagiwara-Nagasawa Hiroko Izumi-Nakaseko Kiyotaka Hoshiai Yasuki Akie Atsuhiko T. Naito Atsushi Sugiyama 《Journal of pharmacological sciences》2018,136(2):86-92
Microminipigs are expected as a novel animal model for cardiovascular pharmacological experiments. Since inherent vulnerability of coronary circulation of microminipigs has not been characterized, we performed dipyridamole-stress test to both microminipigs and beagle dogs, and compared the results. Dipyridamole in doses of 0.056 and 0.56 mg/kg were intravenously infused over 10 min (n = 4 for each animal). Dipyridamole decreased the systolic/diastolic blood pressures and double product in dogs as well as in microminipigs; but it did not significantly alter the heart rate or the global balance between the myocardial oxygen demand and supply in either animal. While organic coronary arterial stenosis was not detected in either animal, dogs have well-developed epicardial intracoronary networks unlike microminipigs. Like in humans, dipyridamole did not affect the ST segment of microminipigs, whereas it substantially depressed that in dogs. The results indicate the onset of subendocardial ischemia by dipyridamole in dogs may be partly associated with their well-developed native coronary collateral channels. Microminipigs would be more useful to evaluate the drugs which may affect the coronary circulation in the pre-clinical study than dogs. 相似文献
9.
Yi Hsun Tan Toshiyuki Shudo Tomoki Yoshida Yuma Sugiyama Jia Ying Si Chihiro Tsukano Yoshiji Takemoto Akira Kakizuka 《Genes to cells : devoted to molecular & cellular mechanisms》2019,24(11):688-704
In Chinese medicine, herbal medicine is commonly used to treat individuals suffering from many types of diseases. We thus expected that some herbal medicines would contain promising compounds for cancer chemotherapy. Indeed, we found that Sanguisorba officinalis extracts strongly inhibit the growth of B16F10 melanoma cells, and we identified ellagic acid (EA) as the responsible ingredient. B16F10 cells treated with EA exhibited strong G1 arrest accompanied by accumulation of p53, followed by inactivation of AKT. Addition of a PTEN inhibitor, but not a p53 inhibitor, abrogated the EA‐induced AKT inactivation and G1 arrest. The PTEN inhibitor also diminished EA‐induced p53 accumulation. Furthermore, EA apparently increased the protein phosphatase activity of PTEN, as demonstrated by the reduced phosphorylation level of FAK, a protein substrate of PTEN. Furthermore, an in vitro PTEN phosphatase assay on PIP3 showed the direct modulation of PTEN activity by EA. These results suggest that EA functions as an allosteric modulator of PTEN, enhancing its protein phosphatase activity while inhibiting its lipid phosphatase activity. It is notable that a combination of EA and cisplatin, a widely used chemotherapy agent, dramatically enhanced cell death in B16F10 cells, suggesting a promising strategy in chemotherapy. 相似文献
10.
Akitomo Yasunaga Ai Shibata Kaori Ishii Shigeru Inoue Takemi Sugiyama Neville Owen Koichiro Oka 《Health and quality of life outcomes》2018,16(1):240