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  1. Article: Combination Therapies with Kinase Inhibitors for Acute Myeloid Leukemia Treatment.

    Takahashi, Shinichiro

    Hematology reports

    2023  Volume 15, Issue 2, Page(s) 331–346

    Abstract: Targeting kinase activity is considered to be an attractive therapeutic strategy to overcome acute myeloid leukemia (AML) since aberrant activation of the kinase pathway plays a pivotal role in leukemogenesis through abnormal cell proliferation and ... ...

    Abstract Targeting kinase activity is considered to be an attractive therapeutic strategy to overcome acute myeloid leukemia (AML) since aberrant activation of the kinase pathway plays a pivotal role in leukemogenesis through abnormal cell proliferation and differentiation block. Although clinical trials for kinase modulators as single agents remain scarce, combination therapies are an area of therapeutic interest. In this review, the author summarizes attractive kinase pathways for therapeutic targets and the combination strategies for these pathways. Specifically, the review focuses on combination therapies targeting the FLT3 pathways, as well as PI3K/AKT/mTOR, CDK and CHK1 pathways. From a literature review, combination therapies with the kinase inhibitors appear more promising than monotherapies with individual agents. Therefore, the development of efficient combination therapies with kinase inhibitors may result in effective therapeutic strategies for AML.
    Language English
    Publishing date 2023-05-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2586645-X
    ISSN 2038-8330 ; 2038-8322
    ISSN (online) 2038-8330
    ISSN 2038-8322
    DOI 10.3390/hematolrep15020035
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Kinase Inhibitors and Interferons as Other Myeloid Differentiation Inducers in Leukemia Therapy.

    Takahashi, Shinichiro

    Acta haematologica

    2021  Volume 145, Issue 2, Page(s) 113–121

    Abstract: Differentiation therapy using all-trans retinoic acid (ATRA) is well established for the treatment of acute promyelocytic leukemia (APL). Several attempts have been made to treat non-APL acute myeloid leukemia (AML) patients by employing differentiation ... ...

    Abstract Differentiation therapy using all-trans retinoic acid (ATRA) is well established for the treatment of acute promyelocytic leukemia (APL). Several attempts have been made to treat non-APL acute myeloid leukemia (AML) patients by employing differentiation inducers, such as hypomethylating agents and low-dose cytarabine, with encouraging results. In the present review, I focus on other possible differentiation inducers: kinase inhibitors and interferons (IFNs). A number of kinase inhibitors have been reported to induce differentiation, including CDK inhibitors, GSK3 inhibitors, Akt inhibitors, p38 MAPK inhibitors, Src family kinase inhibitors, Syk inhibitors, mTOR inhibitors, and HSP90 inhibitors. Other powerful inducers are IFNs, which were reported to enhance differentiation with ATRA. Although clinical trials for these kinase modulators remain scarce, their mechanisms of action have been, at least partly, clarified. The Raf/MEK/ERK MAPK pathway and the RARα downstream are affected by many of the kinase inhibitors and IFNs and seem to play a pivotal role for the induction of myeloid differentiation. Further clarification of the mechanisms, as well as the establishment of efficient combination therapies with the kinase inhibitors or IFNs, may lead to the development of effective therapeutic strategies for AML.
    MeSH term(s) Antineoplastic Agents/therapeutic use ; Cell Differentiation ; Glycogen Synthase Kinase 3/therapeutic use ; Humans ; Interferons/therapeutic use ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Promyelocytic, Acute/drug therapy ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Tretinoin/pharmacology ; Tretinoin/therapeutic use
    Chemical Substances Antineoplastic Agents ; Protein Kinase Inhibitors ; Tretinoin (5688UTC01R) ; Interferons (9008-11-1) ; Glycogen Synthase Kinase 3 (EC 2.7.11.26)
    Language English
    Publishing date 2021-10-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 80008-9
    ISSN 1421-9662 ; 0001-5792
    ISSN (online) 1421-9662
    ISSN 0001-5792
    DOI 10.1159/000519769
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Current Understandings of Myeloid Differentiation Inducers in Leukemia Therapy.

    Takahashi, Shinichiro

    Acta haematologica

    2020  Volume 144, Issue 4, Page(s) 380–388

    Abstract: Differentiation therapy using all-trans retinoic acid for acute promyelocytic leukemia (APL) is well established. Several attempts have been made to treat non-APL, AML patients by employing differentiation inducers, such as hypomethylating agents (HMAs), ...

    Abstract Differentiation therapy using all-trans retinoic acid for acute promyelocytic leukemia (APL) is well established. Several attempts have been made to treat non-APL, AML patients by employing differentiation inducers, such as hypomethylating agents (HMAs), and low-dose cytarabine (Ara-C) (LDAC), with encouraging results. Other than HMAs and LDAC, various inducers of myeloid cell differentiation have been identified. This review describes and categorizes these inducers, which include glycosylation modifiers, epigenetic modifiers, vitamin derivatives, cytokines, and chemotherapeutic agents. Some of these inducers are currently being used in clinical trials. I highlight the potential applications of glycosylation modifiers and epigenetic modifiers, which are attracting increasing attention in their use as differentiation therapy against AML. Among the agents described in this review, epigenomic modifiers seem particularly promising, and particular attention should also be paid to glycosylation modifiers. These drugs may signal a new era for AML differentiation therapy.
    MeSH term(s) Antineoplastic Agents/therapeutic use ; Cell Differentiation/drug effects ; Epigenomics ; Glycosylation/drug effects ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; MicroRNAs/metabolism ; Vitamins/chemistry ; Vitamins/pharmacology ; Vitamins/therapeutic use
    Chemical Substances Antineoplastic Agents ; MicroRNAs ; Vitamins
    Language English
    Publishing date 2020-11-20
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80008-9
    ISSN 1421-9662 ; 0001-5792
    ISSN (online) 1421-9662
    ISSN 0001-5792
    DOI 10.1159/000510980
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.145: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  4. Article: Peroral cholangioscopy for the evaluation of bile duct stricture in hepatocellular carcinoma on a preoperative examination.

    Chiba, Mitsuru / Aokawa, Masaki / Goto, Takashi / Sato, Wataru / Takahashi, Kenichi / Minami, Shinichiro / Iijima, Katsunori

    Journal of rural medicine : JRM

    2024  Volume 19, Issue 1, Page(s) 44–48

    Abstract: Objective: ...

    Abstract Objective:
    Language English
    Publishing date 2024-01-01
    Publishing country Japan
    Document type Case Reports
    ZDB-ID 2768933-5
    ISSN 1880-4888 ; 1880-487X
    ISSN (online) 1880-4888
    ISSN 1880-487X
    DOI 10.2185/jrm.2023-022
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  5. Article: Mutations of FLT3 receptor affect its surface glycosylation, intracellular localization, and downstream signaling.

    Takahashi, Shinichiro

    Leukemia research reports

    2019  Volume 13, Page(s) 100187

    Abstract: This review describes the effects of FLT3 mutations that alter its intracellular localization and modify its glycosylation, leading to differences in downstream signaling pathways. The most common type of FLT3 mutation, internal tandem duplication (FLT3- ... ...

    Abstract This review describes the effects of FLT3 mutations that alter its intracellular localization and modify its glycosylation, leading to differences in downstream signaling pathways. The most common type of FLT3 mutation, internal tandem duplication (FLT3-ITD), leads to localization in the endoplasmic reticulum and constitutive strong activation of STAT5. In contrast, the ligand-activated FLT3-wild type is mainly expressed on the cell surface and activates MAP kinases. Based on these backgrounds, several reports have demonstrated that glycosylation inhibitors are effective for inhibition of FLT3-ITD expression and intracellular localization. The general subcellular localization regulatory mechanisms for receptor tyrosine kinases are also discussed.
    Language English
    Publishing date 2019-11-27
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2706248-X
    ISSN 2213-0489
    ISSN 2213-0489
    DOI 10.1016/j.lrr.2019.100187
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  6. Article: Single-molecule analysis of intracellular insulin granule behavior and its application to analyzing cytoskeletal dependence and pathophysiological implications.

    Hatakeyama, Hiroyasu / Oshima, Tomomi / Ono, Shinichiro / Morimoto, Yuichi / Takahashi, Noriko

    Frontiers in physiology

    2023  Volume 14, Page(s) 1287275

    Abstract: Introduction: ...

    Abstract Introduction:
    Language English
    Publishing date 2023-12-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2023.1287275
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  7. Article: Molecular functions of SIRPα and its role in cancer.

    Takahashi, Shinichiro

    Biomedical reports

    2018  Volume 9, Issue 1, Page(s) 3–7

    Abstract: Signal regulatory protein α (SIRPα), also known as cluster of differentiation (CD)172a or Src homology 2 domain-containing phosphatase substrate-1, is a cell surface receptor expressed on myeloid and hematopoietic stem cells and neurons. Accumulating ... ...

    Abstract Signal regulatory protein α (SIRPα), also known as cluster of differentiation (CD)172a or Src homology 2 domain-containing phosphatase substrate-1, is a cell surface receptor expressed on myeloid and hematopoietic stem cells and neurons. Accumulating data suggests an important role of SIRPα in cell signaling as a negative regulator of the phosphatidylinositol 3-kinase signaling and mitogen-activated protein kinase pathways. In various cancers, including prostate, breast and liver, as well as astrocytoma and myeloid malignancies, downregulation of SIRPα is frequently observed, resulting in activation of these downstream signaling pathways. In turn, cell proliferation, transformation, migration and invasion may occur. Recently, it has been reported that blocking CD47, an anti-phagocytic signal expressed on tumor cells and an SIRPα ligand, may serve as a promising therapeutic approach, particular for the treatment of acute myeloid leukemia. In the present review, the current findings on SIRPα are summarized, with particular focus on its role in cancer.
    Language English
    Publishing date 2018-05-23
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2763624-0
    ISSN 2049-9442 ; 2049-9434
    ISSN (online) 2049-9442
    ISSN 2049-9434
    DOI 10.3892/br.2018.1102
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: How to treat borderline resectable pancreatic cancer: current challenges and future directions.

    Takahashi, Shinichiro

    Japanese journal of clinical oncology

    2018  Volume 48, Issue 3, Page(s) 205–213

    Abstract: Borderline resectable pancreatic cancer (BRPC) is an advanced tumor in contact with the surrounding major vessels, making R0 resection difficult to achieve. Neoadjuvant treatment is expected to provide substantial local control and prolong survival. ... ...

    Abstract Borderline resectable pancreatic cancer (BRPC) is an advanced tumor in contact with the surrounding major vessels, making R0 resection difficult to achieve. Neoadjuvant treatment is expected to provide substantial local control and prolong survival. However, there is no standard treatment. I therefore conducted a strategic literature search from January 2013 to September 2017 and identified 37 clinical studies of pancreatic cancer, including BRPC, to evaluate treatment interventions. Twenty (54%) studies were prospective. Neoadjuvant regimens were as follows: chemotherapy (CT) followed by chemoradiotherapy (CRT) or radiotherapy (RT) (n = 16, 43%), CT alone (n = 11, 30%), CRT alone (n = 9, 24%) and RT alone (n = 1, 3%). Radiotherapy was employed in 70% of the studies. Phase II studies were most frequent (55%), and we were unable to identify a Phase III study. The National Comprehensive Cancer Network's classifications were most frequently used as criteria for BRPC, although resectability status is not standardized. Radiological central review was used in three of eight multi-institutional studies. Assessing on-going or planned clinical trials for BRPC, administration of oxaliplatin, irinotecan, fluorouracil and leucovorin therapy or albumin-bound paclitaxel plus gemcitabine therapy, and randomized trials that evaluate the significance of CRT or RT combined with CT were identified as important topics for further consideration. Although standardization of classifications and improvement of infrastructure are required, a standard treatment of BRPC will likely be developed, which will improve prognosis in the near future because several important randomized trials are running.
    MeSH term(s) Clinical Trials as Topic ; Humans ; Neoadjuvant Therapy ; Pancreatic Neoplasms/classification ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/surgery ; Prognosis
    Language English
    Publishing date 2018-03-01
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 190978-2
    ISSN 1465-3621 ; 0368-2811
    ISSN (online) 1465-3621
    ISSN 0368-2811
    DOI 10.1093/jjco/hyx191
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  9. Article ; Online: Coronary sinus atresia with unroofed coronary Sinus: developed collateral coronary vein evaluated by cardiac computed tomography.

    Takahashi, Yu / Akita, Tomomi / Yamada, Shinichiro / Yoshida, Akihiro

    European heart journal. Case reports

    2022  Volume 6, Issue 10, Page(s) ytac392

    Language English
    Publishing date 2022-09-22
    Publishing country England
    Document type Case Reports
    ISSN 2514-2119
    ISSN (online) 2514-2119
    DOI 10.1093/ehjcr/ytac392
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  10. Article ; Online: Genetic parameter estimation for pork production and litter performance traits of Landrace, Large White, and Duroc pigs in Japan.

    Ogawa, Shinichiro / Takahashi, Hiroshi / Satoh, Masahiro

    Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie

    2023  Volume 140, Issue 6, Page(s) 607–623

    Abstract: We estimated genetic parameters for two pork production and six litter performance traits of Landrace, Large White, and Duroc pigs reared in Japan. Pork production traits were average daily gain from birth to end of performance testing and backfat ... ...

    Abstract We estimated genetic parameters for two pork production and six litter performance traits of Landrace, Large White, and Duroc pigs reared in Japan. Pork production traits were average daily gain from birth to end of performance testing and backfat thickness at end of testing (46,042 records for Landrace, 40,467 records for Large White, and 42,920 records for Duroc). Litter performance traits were number born alive, litter size at weaning (LSW), number of piglets dead during suckling (ND), survival rate of piglets during suckling (SV), total piglet weight at weaning (TWW), and average piglet weight at weaning (AWW) (27,410, 26,716, and 12,430 records for Landrace, Large White, and Duroc, respectively). ND was calculated as the difference between LSW and litter size at start of suckling (LSS). SV was calculated as LSW/LSS. AWW was calculated as TWW/LSW. Pedigree data for Landrace, Large White, and Duroc breeds contained 50,193, 44,077, and 45,336 pigs, respectively. Trait heritability was estimated via single-trait analysis and genetic correlation between two traits was estimated via two-trait analysis. When considering the linear covariate of LSS in the statistical model for LSW and TWW, for all breeds, the heritability was estimated to be 0.4-0.5 for pork production traits and below 0.2 for litter performance traits. Estimated genetic correlation between average daily gain and backfat thickness was small, ranging from 0.057 to 0.112, and those between pork production traits and litter performance traits were negligible to moderate, ranging from -0.493 to 0.487. A wide range of genetic correlation values among the litter performance traits was estimated, while that between LSW and ND could not be obtained. The results of genetic parameter estimation were affected by whether the linear covariate of LSS was included in the statistical model for LSW and TWW or not. This finding implies the necessity of carefully interpreting the results according to the choice of statistical model. Our results could give fundamental information on simultaneously improving productivity and female reproductivity for pigs.
    MeSH term(s) Pregnancy ; Swine/genetics ; Animals ; Female ; Birth Weight/genetics ; Japan ; Pork Meat ; Red Meat ; Genetic Variation ; Litter Size/genetics ; Weaning
    Language English
    Publishing date 2023-06-20
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 631363-2
    ISSN 1439-0388 ; 0044-3581 ; 0931-2668 ; 1742-4488
    ISSN (online) 1439-0388
    ISSN 0044-3581 ; 0931-2668 ; 1742-4488
    DOI 10.1111/jbg.12814
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    In stock of ZB MED Bonn / Germany

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