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  1. Article: Proton Pump Inhibitors Enhance the Antitumor Effect of Chemotherapy for Esophageal Squamous Cell Carcinoma.

    Matsumura, Shinya / Ishikawa, Takeshi / Yoshida, Juichiro / Morita, Ryuichi / Sakakida, Tomoki / Endo, Yuki / Doi, Toshifumi / Hirose, Ryohei / Inoue, Ken / Dohi, Osamu / Yoshida, Naohisa / Uchiyama, Kazuhiko / Takagi, Tomohisa / Konishi, Hideyuki / Yasui, Kohichiroh / Naito, Yuji / Itoh, Yoshito

    Cancers

    2022  Volume 14, Issue 10

    Abstract: Background: Vacuolar ATPase (V-ATPase) is involved in cancer development. The use of proton pump inhibitors (PPIs) as V-ATPase inhibitors has been reported to enhance the effectiveness of chemotherapy in certain cancers. This study aimed to evaluate the ...

    Abstract Background: Vacuolar ATPase (V-ATPase) is involved in cancer development. The use of proton pump inhibitors (PPIs) as V-ATPase inhibitors has been reported to enhance the effectiveness of chemotherapy in certain cancers. This study aimed to evaluate the effect of PPIs on chemotherapy for esophageal cancer.
    Methods: To investigate the effects of PPIs on esophageal cancer cells, human KYSE50 and 70 cells were plated and 3 PPIs (lansoprazole, esomeprazole, vonoprazan) were added at various concentrations with 5-Fluorouracil (5-FU) to the corresponding cells for a cell viability assay. To investigate the effects of PPI treatment on patients undergoing 5-FU-based therapy in the clinical setting, we retrospectively analyzed the clinical outcomes and chemotherapy-related adverse events in 40 esophageal cancer patients who received 5-FU chemotherapy in our hospital between May 2013 and April 2017.
    Results: In the viability assays, all PPIs significantly enhanced the cytotoxic effect of 5-FU on the two esophageal cancer cell lines. In the clinical study, PPI-treated patients showed better overall survival (OS) than patients managed without PPI treatment. A multivariate analysis revealed that PPI treatment was independently associated with OS (
    Conclusions: PPI treatment may safely enhance chemosensitivity in esophageal cancer patients.
    Language English
    Publishing date 2022-05-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14102395
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Water-soluble dietary fiber alleviates cancer-induced muscle wasting through changes in gut microenvironment in mice.

    Sakakida, Tomoki / Ishikawa, Takeshi / Doi, Toshifumi / Morita, Ryuichi / Endo, Yuki / Matsumura, Shinya / Ota, Takayuki / Yoshida, Juichiro / Hirai, Yasuko / Mizushima, Katsura / Higashimura, Yasuki / Inoue, Ken / Okayama, Tetsuya / Uchiyama, Kazuhiko / Takagi, Tomohisa / Abe, Aya / Inoue, Ryo / Itoh, Yoshito / Naito, Yuji

    Cancer science

    2022  Volume 113, Issue 5, Page(s) 1789–1800

    Abstract: Cancer cachexia and the associated skeletal muscle wasting are considered poor prognostic factors, although effective treatment has not yet been established. Recent studies have indicated that the pathogenesis of skeletal muscle loss may involve ... ...

    Abstract Cancer cachexia and the associated skeletal muscle wasting are considered poor prognostic factors, although effective treatment has not yet been established. Recent studies have indicated that the pathogenesis of skeletal muscle loss may involve dysbiosis of the gut microbiota and the accompanying chronic inflammation or altered metabolism. In this study, we evaluated the possible effects of modifying the gut microenvironment with partially hydrolyzed guar gum (PHGG), a soluble dietary fiber, on cancer-related muscle wasting and its mechanism using a colon-26 murine cachexia model. Compared with a fiber-free (FF) diet, PHGG contained fiber-rich (FR) diet-attenuated skeletal muscle loss in cachectic mice by suppressing the elevation of the major muscle-specific ubiquitin ligases Atrogin-1 and MuRF1, as well as the autophagy markers LC3 and Bnip3. Although tight-junction markers were partially reduced in both FR and FF diet-fed cachectic mice, the abundance of Bifidobacterium, Akkermansia, and unclassified S24-7 family increased by FR diet, contributing to the retention of the colonic mucus layer. The reinforcement of the gut barrier function resulted in the controlled entry of pathogens into the host system and reduced circulating levels of lipopolysaccharide-binding protein (LBP) and IL-6, which in turn led to the suppression of proteolysis by downregulating the ubiquitin-proteasome system and autophagy pathway. These results suggest that dietary fiber may have the potential to alleviate skeletal muscle loss in cancer cachexia, providing new insights for developing effective strategies in the future.
    MeSH term(s) Animals ; Cachexia/etiology ; Cachexia/prevention & control ; Dietary Fiber/metabolism ; Dietary Fiber/pharmacology ; Humans ; Mice ; Muscle, Skeletal ; Muscular Atrophy/pathology ; Neoplasms/pathology ; Tumor Microenvironment ; Ubiquitin/metabolism ; Water/metabolism
    Chemical Substances Dietary Fiber ; Ubiquitin ; Water (059QF0KO0R)
    Language English
    Publishing date 2022-03-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2115647-5
    ISSN 1349-7006 ; 1349-7006
    ISSN (online) 1349-7006
    ISSN 1349-7006
    DOI 10.1111/cas.15306
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Metformin inhibits TGF‑β1‑induced epithelial‑mesenchymal transition and liver metastasis of pancreatic cancer cells.

    Yoshida, Juichiro / Ishikawa, Takeshi / Endo, Yuki / Matsumura, Shinya / Ota, Takayuki / Mizushima, Katsura / Hirai, Yasuko / Oka, Kaname / Okayama, Tetsuya / Sakamoto, Naoyuki / Inoue, Ken / Kamada, Kazuhiro / Uchiyama, Kazuhiko / Takagi, Tomohisa / Naito, Yuji / Itoh, Yoshito

    Oncology reports

    2020  Volume 44, Issue 1, Page(s) 371–381

    Abstract: Epithelial‑mesenchymal transition (EMT) is considered a crucial event in the development of cancer metastasis. Metformin is a drug used in the treatment of type 2 diabetes. Recently, increasing evidence has indicated that metformin possesses anti‑tumor ... ...

    Abstract Epithelial‑mesenchymal transition (EMT) is considered a crucial event in the development of cancer metastasis. Metformin is a drug used in the treatment of type 2 diabetes. Recently, increasing evidence has indicated that metformin possesses anti‑tumor activities. However, the effects of metformin on EMT and metastases in pancreatic cancer remain unknown. Thus, the present study investigated whether metformin inhibits EMT of human pancreatic cancer cell lines. Pancreatic cancer cells were stimulated with transforming growth factor β1 (TGF‑β1), an activator of EMT signaling, with or without metformin. After 48 h, the levels of epithelial and mesenchymal markers were evaluated by western blot analysis, immunocytochemistry and RT‑qPCR. Cancer cell migration was evaluated by an in vitro wound healing assay. The cells stimulated with TGF‑β1 acquired an elongated and fusiform morphology, which was inhibited by metformin. The wound healing assay revealed that metformin significantly suppressed the TGF‑β1‑stimulated migration of pancreatic cancer cells. Following treatment with metformin, E‑cadherin expression (epithelial marker) was upregulated, and the levels of mesenchymal markers were downregulated, which had been increased by TGF‑β1 in these cells. Exposure of the cells to TGF‑β1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF‑β1‑induced‑EMT through the down‑regulation of the Smad pathway in PANC‑1 cells and the downregulation of the Akt/mTOR pathway in BxPC‑3 cells. In an animal model of surgical orthotopic implantation, metformin inhibited liver metastasis without a significant reduction in the size of the primary pancreatic tumor. On the whole, the findings of the present study suggest that metformin inhibits EMT and cancer metastasis through the Smad or Akt/mTOR pathway.
    MeSH term(s) Animals ; Antigens, CD/genetics ; Cadherins/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Epithelial-Mesenchymal Transition/drug effects ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Liver Neoplasms/secondary ; Metformin/administration & dosage ; Metformin/pharmacology ; Mice ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/metabolism ; Signal Transduction/drug effects ; Transforming Growth Factor beta1/pharmacology ; Xenograft Model Antitumor Assays
    Chemical Substances Antigens, CD ; CDH1 protein, human ; Cadherins ; Transforming Growth Factor beta1 ; Metformin (9100L32L2N)
    Language English
    Publishing date 2020-04-23
    Publishing country Greece
    Document type Journal Article
    ZDB-ID 1222484-4
    ISSN 1791-2431 ; 1021-335X
    ISSN (online) 1791-2431
    ISSN 1021-335X
    DOI 10.3892/or.2020.7595
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4213: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  4. Article ; Online: Clinical significance of soluble forms of immune checkpoint molecules in advanced esophageal cancer.

    Yoshida, Juichiro / Ishikawa, Takeshi / Doi, Toshifumi / Ota, Takayuki / Yasuda, Tomoyo / Okayama, Tetsuya / Sakamoto, Naoyuki / Inoue, Ken / Dohi, Osamu / Yoshida, Naohisa / Kamada, Kazuhiro / Uchiyama, Kazuhiko / Takagi, Tomohisa / Konishi, Hideyuki / Naito, Yuji / Itoh, Yoshito

    Medical oncology (Northwood, London, England)

    2019  Volume 36, Issue 7, Page(s) 60

    Abstract: Immune checkpoint molecules are expressed on cancer cells and regulate tumor immunity by binding to ligands on immune cells. Although soluble forms of immune checkpoint molecules have been detected in the blood of patients with some types of tumors, ... ...

    Abstract Immune checkpoint molecules are expressed on cancer cells and regulate tumor immunity by binding to ligands on immune cells. Although soluble forms of immune checkpoint molecules have been detected in the blood of patients with some types of tumors, their roles have not been fully elucidated. Soluble PD-L1, PD-1, CD155, LAG3, and CD226 (sPD-L1, sPD-1, sCD155, sLAG3, and sCD226, respectively) were measured in the sera of 47 patients with advanced esophageal cancer and compared with those of 24 control subjects. Pretreatment levels of sPD-1 and sCD155 were significantly higher in the patients with cancer than in the control subjects (P = 0.023, P = 0.001). The sPD-1 levels tended to be higher in the patients with lymph node metastasis, a large tumor diameter, and higher levels of serum SCC antigen (P = 0.150, P = 0.189, and P = 0.078, respectively). However, higher levels of sCD155 were associated with a better response to chemotherapy and favorable overall survival (P = 0.111 and P = 0.068, respectively). After 2 courses of chemotherapy, the levels of sCD155 and sCD226 were significantly increased (P < 0.001 and P = 0.002, respectively). Moreover, the increase in sCD226 during chemotherapy was associated with poor treatment response (P = 0.019). sPD-1 levels are possibly dependent on the tumor aggressiveness of the esophageal cancer. Furthermore, the pretreatment levels of sCD155 and kinetic change of sCD226 after chemotherapy may be used as biomarkers of the treatment response and prognosis in patients with esophageal cancer.
    MeSH term(s) Adult ; Aged, 80 and over ; Antigens, CD/blood ; Antigens, Differentiation, T-Lymphocyte/blood ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; B7-H1 Antigen/blood ; Case-Control Studies ; Cisplatin/administration & dosage ; Docetaxel/administration & dosage ; Esophageal Neoplasms/blood ; Esophageal Neoplasms/drug therapy ; Esophageal Neoplasms/immunology ; Esophageal Squamous Cell Carcinoma/blood ; Esophageal Squamous Cell Carcinoma/drug therapy ; Esophageal Squamous Cell Carcinoma/immunology ; Female ; Fluorouracil/administration & dosage ; Humans ; Male ; Middle Aged ; Prognosis ; Programmed Cell Death 1 Receptor/blood ; Receptors, Virus/blood
    Chemical Substances Antigens, CD ; Antigens, Differentiation, T-Lymphocyte ; B7-H1 Antigen ; CD223 antigen ; CD226 antigen ; CD274 protein, human ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; Receptors, Virus ; poliovirus receptor ; Docetaxel (15H5577CQD) ; Cisplatin (Q20Q21Q62J) ; Fluorouracil (U3P01618RT)
    Language English
    Publishing date 2019-05-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1201189-7
    ISSN 1559-131X ; 0736-0118 ; 1357-0560
    ISSN (online) 1559-131X
    ISSN 0736-0118 ; 1357-0560
    DOI 10.1007/s12032-019-1285-x
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    Zs.A 1899: Show issues Location:
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  5. Article: [A case of freeze-dried gas gangrene antitoxin for the treatment of Clostridium perfringens sepsis].

    Yoshida, Juichiro / Nakamura, Hideki / Yamada, Shinya / Sekoguchi, Satoru / Suzuki, Takahiro / Tomatsuri, Naoya / Sato, Hideki / Okuyama, Yusuke / Kimura, Hiroyuki / Yoshida, Norimasa

    Nihon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology

    2015  Volume 112, Issue 2, Page(s) 332–338

    Abstract: A 66-year-old man was admitted to our hospital with high fever. We diagnosed a gas-containing liver abscess and performed percutaneous abscess drainage. However, 15 hours after admission, he developed massive intravascular hemolysis and acidosis. Sepsis ... ...

    Abstract A 66-year-old man was admitted to our hospital with high fever. We diagnosed a gas-containing liver abscess and performed percutaneous abscess drainage. However, 15 hours after admission, he developed massive intravascular hemolysis and acidosis. Sepsis due to Clostridium perfringens was suspected and we treated the patient intensively with multidisciplinary approaches, including antibiotics, mechanical ventilation, and renal replacement therapy. Furthermore, we administered freeze-dried gas gangrene antitoxin. Despite intensive care, the patient died 43 hours after admission.
    MeSH term(s) Aged ; Antitoxins/therapeutic use ; Freeze Drying ; Gas Gangrene/therapy ; Humans ; Liver Abscess, Pyogenic/therapy ; Male
    Chemical Substances Antitoxins
    Language Japanese
    Publishing date 2015-03-06
    Publishing country Japan
    Document type Case Reports ; English Abstract ; Journal Article
    ZDB-ID 708695-7
    ISSN 1349-7693 ; 0446-6586
    ISSN (online) 1349-7693
    ISSN 0446-6586
    DOI 10.11405/nisshoshi.112.332
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  6. Article: [Impact of Primary Prophylaxis with Pegfilgrastim on Clinical Outcomes in Patients with Advanced Esophageal Cancer Receiving Chemotherapy with Docetaxel, Cisplatin ,and 5-FU].

    Yasuda, Tomoyo / Ishikawa, Takeshi / Ohta, Takayuki / Yoshida, Juichiro / Doi, Toshifumi / Dohi, Osamu / Okayama, Tetsuya / Yoshida, Naohisa / Kamada, Kazuhiro / Uchiyama, Kazuhiko / Handa, Osamu / Takagi, Tomohisa / Konishi, Hideyuki / Shiozaki, Atsushi / Fujiwara, Hitoshi / Naito, Yuji / Itoh, Yoshito

    Gan to kagaku ryoho. Cancer & chemotherapy

    2018  Volume 45, Issue 12, Page(s) 1733–1736

    Abstract: It has been reported that docetaxel, cisplatin, and 5-FU combination chemotherapy(DCF)is effective for advanced esophageal cancer. However, we often encounter severe hematotoxicity during DCF therapy. Here, we retrospectively analyzed the data of ... ...

    Abstract It has been reported that docetaxel, cisplatin, and 5-FU combination chemotherapy(DCF)is effective for advanced esophageal cancer. However, we often encounter severe hematotoxicity during DCF therapy. Here, we retrospectively analyzed the data of patients with advanced esophageal cancer treated with DCF at our department, and assessed the efficacy of pegfilgrastim and the issues associated with its use. According to the results, pegfilgrastim may reduce the severe hematotoxicity associated with DCF therapy and may contribute to the maintenance of the intensity of DCF. However, neutropenia had already occurred before pegfilgrastim administration on day 7 in most patients. Therefore, the appropriate timing of pegfilgrastim administration in DCF must be determined in a future prospective study.
    MeSH term(s) Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cisplatin/administration & dosage ; Docetaxel/administration & dosage ; Esophageal Neoplasms/drug therapy ; Filgrastim/therapeutic use ; Fluorouracil/administration & dosage ; Humans ; Neutropenia/chemically induced ; Neutropenia/prevention & control ; Polyethylene Glycols/therapeutic use ; Prospective Studies ; Retrospective Studies ; Taxoids
    Chemical Substances Taxoids ; Docetaxel (15H5577CQD) ; pegfilgrastim (3A58010674) ; Polyethylene Glycols (3WJQ0SDW1A) ; Filgrastim (PVI5M0M1GW) ; Cisplatin (Q20Q21Q62J) ; Fluorouracil (U3P01618RT)
    Language Japanese
    Publishing date 2018-12-23
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 604842-0
    ISSN 0385-0684
    ISSN 0385-0684
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.B 2573: Show issues Location:
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