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  1. Article ; Online: Tongue squamous cell carcinoma producing both parathyroid hormone-related protein and granulocyte colony-stimulating factor: a case report and literature review.

    Kaneko, Naoki / Kawano, Shintaro / Matsubara, Ryota / Goto, Yuichi / Jinno, Teppei / Maruse, Yasuyuki / Sakamoto, Taiki / Hashiguchi, Yuma / Iida, Masakazu / Nakamura, Seiji

    World journal of surgical oncology

    2016  Volume 14, Issue 1, Page(s) 161

    Abstract: Background: Paraneoplastic syndrome generally results from tumor-derived hormones or peptides that cause metabolic derangements. Common metabolic conditions include hyponatremia, hypercalcemia, hypoglycemia, and Cushing's syndrome. Herein, we report a ... ...

    Abstract Background: Paraneoplastic syndrome generally results from tumor-derived hormones or peptides that cause metabolic derangements. Common metabolic conditions include hyponatremia, hypercalcemia, hypoglycemia, and Cushing's syndrome. Herein, we report a very rare case of tongue carcinoma presenting with leukocytosis and hypercalcemia.
    Case presentation: A 57-year-old man was admitted to our hospital with tongue squamous cell carcinoma (cT4aN0M0, stage IV). He underwent radical resection following preoperative chemoradiotherapy, but locoregional recurrence was detected 2 months after surgery. He presented with marked leukocytosis and hypercalcemia with elevated serum levels of granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP). He was therefore managed with intravenous fluids, furosemide, prednisolone, elcatonin, and pamidronate. However, the patient died 1 month later of carcinomatous pleuritis following distant metastasis to the lung. Immunohistochemical analyses of the resected specimens revealed positive staining for PTHrP and G-CSF in the cancer cells.
    Conclusions: In this case, it was considered that tumor-derived G-CSF and PTHrP caused leukocytosis and hypercalcemia.
    MeSH term(s) Carcinoma, Squamous Cell/blood ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/pathology ; Fatal Outcome ; Granulocyte Colony-Stimulating Factor/blood ; Humans ; Hypercalcemia/blood ; Hypercalcemia/drug therapy ; Hypercalcemia/pathology ; Leukocytosis/blood ; Leukocytosis/drug therapy ; Leukocytosis/pathology ; Male ; Middle Aged ; Parathyroid Hormone-Related Protein/blood ; Tongue Neoplasms/blood ; Tongue Neoplasms/drug therapy ; Tongue Neoplasms/pathology
    Chemical Substances PTHLH protein, human ; Parathyroid Hormone-Related Protein ; Granulocyte Colony-Stimulating Factor (143011-72-7)
    Language English
    Publishing date 2016-06-17
    Publishing country England
    Document type Case Reports ; Journal Article ; Review
    ZDB-ID 2118383-1
    ISSN 1477-7819 ; 1477-7819
    ISSN (online) 1477-7819
    ISSN 1477-7819
    DOI 10.1186/s12957-016-0918-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Erratum to: Tongue squamous cell carcinoma producing both parathyroid hormone-related protein and granulocyte colony-stimulating factor: a case report and literature review.

    Kaneko, Naoki / Kawano, Shintaro / Matsubara, Ryota / Goto, Yuichi / Jinno, Teppei / Maruse, Yasuyuki / Sakamoto, Taiki / Hashiguchi, Yuma / Iida, Masakazu / Nakamura, Seiji

    World journal of surgical oncology

    2016  Volume 14, Issue 1, Page(s) 187

    Language English
    Publishing date 2016-07-19
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2118383-1
    ISSN 1477-7819 ; 1477-7819
    ISSN (online) 1477-7819
    ISSN 1477-7819
    DOI 10.1186/s12957-016-0945-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Tumor-suppressive roles of ΔNp63β-miR-205 axis in epithelial-mesenchymal transition of oral squamous cell carcinoma via targeting ZEB1 and ZEB2.

    Hashiguchi, Yuma / Kawano, Shintaro / Goto, Yuichi / Yasuda, Kaori / Kaneko, Naoki / Sakamoto, Taiki / Matsubara, Ryota / Jinno, Teppei / Maruse, Yasuyuki / Tanaka, Hideaki / Morioka, Masahiko / Hattori, Taichi / Tanaka, Shoichi / Kiyoshima, Tamotsu / Nakamura, Seiji

    Journal of cellular physiology

    2018  Volume 233, Issue 10, Page(s) 6565–6577

    Abstract: We previously revealed that epithelial-to-mesenchymal transition (EMT) was mediated by ΔNp63β, a splicing variant of ΔNp63, in oral squamous cell carcinoma (OSCC). Recent studies have highlighted the involvement of microRNA (miRNA) in EMT of cancer cells, ...

    Abstract We previously revealed that epithelial-to-mesenchymal transition (EMT) was mediated by ΔNp63β, a splicing variant of ΔNp63, in oral squamous cell carcinoma (OSCC). Recent studies have highlighted the involvement of microRNA (miRNA) in EMT of cancer cells, though the mechanism remains unclear. To identify miRNAs responsible for ΔNp63β-mediated EMT, miRNA microarray analyses were performed by ΔNp63β-overexpression in OSCC cells; SQUU-B, which lacks ΔNp63 expression and displays EMT phenotypes. miRNAs microarray analyses revealed miR-205 was the most up-regulated following ΔNp63β-overexpression. In OSCC cells, miR-205 expression was positively associated with ΔNp63 and negatively with zinc-finger E-box binding homeobox (ZEB) 1 and ZEB2, potential targets of miR-205. miR-205 overexpression by miR-205 mimic transfection into SQUU-B cells led to decreasing ZEB1, ZEB2, and mesenchymal markers, increasing epithelial markers, and reducing cell motilities, suggesting inhibition of EMT phenotype. Interestingly, the results opposite to this phenomenon were obtained by transfection of miR-205 inhibitor into OSCC cells, which express ΔNp63 and miR-205. Furthermore, target protector analyses revealed direct regulation by miR-205 of ZEB1 and ZEB2 expression. These results showed tumor-suppressive roles of ΔNp63β and miR-205 by inhibiting EMT thorough modulating ZEB1 and ZEB2 expression in OSCC.
    MeSH term(s) Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Epithelial-Mesenchymal Transition/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/genetics ; Mouth Neoplasms/genetics ; Mouth Neoplasms/pathology ; Transcription Factors/genetics ; Tumor Suppressor Proteins/genetics ; Zinc Finger E-box Binding Homeobox 2/genetics ; Zinc Finger E-box-Binding Homeobox 1/genetics
    Chemical Substances MIRN205 microRNA, human ; MicroRNAs ; TP63 protein, human ; Transcription Factors ; Tumor Suppressor Proteins ; ZEB1 protein, human ; ZEB2 protein, human ; Zinc Finger E-box Binding Homeobox 2 ; Zinc Finger E-box-Binding Homeobox 1
    Language English
    Publishing date 2018-05-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3116-1
    ISSN 1097-4652 ; 0021-9541
    ISSN (online) 1097-4652
    ISSN 0021-9541
    DOI 10.1002/jcp.26267
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Critical roles of Wnt5a-Ror2 signaling in aggressiveness of tongue squamous cell carcinoma and production of matrix metalloproteinase-2 via ΔNp63β-mediated epithelial-mesenchymal transition.

    Sakamoto, Taiki / Kawano, Shintaro / Matsubara, Ryota / Goto, Yuichi / Jinno, Teppei / Maruse, Yasuyuki / Kaneko, Naoki / Hashiguchi, Yuma / Hattori, Taichi / Tanaka, Shoichi / Kitamura, Ryoji / Kiyoshima, Tamotsu / Nakamura, Seiji

    Oral oncology

    2017  Volume 69, Page(s) 15–25

    Abstract: Objectives: We previously showed that ΔNp63β, a splicing variant of ΔNp63, mediated EMT and affected cell motility. DNA microarray was thus performed to elucidate the mechanism that ΔNp63β affects cell motility. As the results, Wnt5a was significantly ... ...

    Abstract Objectives: We previously showed that ΔNp63β, a splicing variant of ΔNp63, mediated EMT and affected cell motility. DNA microarray was thus performed to elucidate the mechanism that ΔNp63β affects cell motility. As the results, Wnt5a was significantly down-regulated by ΔNp63β overexpression in tongue SCC cell line (SQUU-B) with EMT phenotype.
    Materials and methods: Seven OSCC cell lines were used. Expression of ΔNp63, Wnt5a, its receptor Ror2, and matrix metalloproteinases (MMPs) were analyzed by RT-PCR, real-time PCR, and western blotting, and gelatin zymography. Furthermore, we examined the effects of siRNA for Wnt5a or Ror2 and recombinant human Wnt5a (rhWnt5a) on motility of tongue SCC cells. Biopsy specimens from tongue SCC patients were used for immunohistochemical staining of Wnt5a and Ror2.
    Results: Wnt5a and Ror2 were expressed only in SQUU-B cells without ΔNp63 expression, and negatively associated with ΔNp63 expression in other cells. ΔNp63β overexpression in SQUU-B cells decreased Wnt5a and Ror2 expression. By Wnt5a or Ror2 knockdown, cell motility was remarkably inhibited, but EMT markers expression was unaffected. MMP-2 expression and the activities inversely correlated with ΔNp63 expression, and were inhibited by Wnt5a or Ror2 knockdown. Cell motility and MMP-2 activities were recovered by adding rhWnt5a in the cells with Wnt5a knockdown, but not in those with Ror2 knockdown. Moreover, immunohistochemical analyses in tongue SCC specimens found that high expression of Wnt5a or Ror2 was associated with poorer prognosis.
    Conclusion: Wnt5a-Ror2 signaling enhanced tongue SCC cell aggressiveness and promoted production of MMP-2 following ΔNp63β-mediated EMT.
    Language English
    Publishing date 2017-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 1120465-5
    ISSN 1879-0593 ; 0964-1955 ; 1368-8375
    ISSN (online) 1879-0593
    ISSN 0964-1955 ; 1368-8375
    DOI 10.1016/j.oraloncology.2017.03.019
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    Zs.A 4869: Show issues Location:
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  5. Article ; Online: Differential roles of kallikrein-related peptidase 6 in malignant transformation and ΔNp63β-mediated epithelial-mesenchymal transition of oral squamous cell carcinoma.

    Kaneko, Naoki / Kawano, Shintaro / Yasuda, Kaori / Hashiguchi, Yuma / Sakamoto, Taiki / Matsubara, Ryota / Goto, Yuichi / Jinno, Teppei / Maruse, Yasuyuki / Morioka, Masahiko / Hattori, Taichi / Tanaka, Shoichi / Tanaka, Hideaki / Kiyoshima, Tamotsu / Nakamura, Seiji

    Oral oncology

    2017  Volume 75, Page(s) 148–157

    Abstract: We previously reported that epithelial-to-mesenchymal transition (EMT) was mediated by ΔNp63β in oral squamous cell carcinoma (OSCC). In this study, DNA microarray analyses were performed using ΔNp63β-overexpressing OSCC cells to identify genes ... ...

    Abstract We previously reported that epithelial-to-mesenchymal transition (EMT) was mediated by ΔNp63β in oral squamous cell carcinoma (OSCC). In this study, DNA microarray analyses were performed using ΔNp63β-overexpressing OSCC cells to identify genes associated with ΔNp63β-mediated EMT. Thereby, we focused on kallikrein-related peptidase (KLK) 6, most up-regulated following ΔNp63β-overexpression, that activates protease-activated receptors (PARs). In RT-PCR analyses, ΔNp63 was positively associated with KLK6 and PAR2 and negatively with PAR1 in OSCC cells. By ΔNp63 knockdown, KLK6 and PAR2 expression was decreased and PAR1 was increased. Furthermore, KLK6 knockdown led to enhancing migration and invasion, and inhibiting proliferation, suggesting EMT-phenotypes. Although, in the KLK6 or PAR2 knockdown cells, phosphorylation of ERK was reduced, it was restored in the KLK6 knockdown OSCC cells treated with recombinant KLK6 proteins. Immunohistochemistry showed ΔNp63, KLK6, and PAR2 were more strongly expressed in the epithelial dysplasia and central region of OSCC than normal oral epithelium, whereas PAR1 expression was undetectable. Interestingly, at the invasive front of OSCC, ΔNp63, KLK6, and PAR2 were reduced, but PAR1 was elevated. In addition, the OSCC patients with decreasing KLK6 expression at the invasive front had more unfavourable prognosis. These results suggested differential roles of KLK6 in malignant transformation and EMT; high ΔNp63β expression up-regulates KLK6-PAR2 and down-regulates PAR1, inducing malignant transformation in oral epithelium with stimulating proliferation through ERK signal activation. Moreover, KLK6-PAR2 expression is down-regulated and PAR1 is up-regulated when ΔNp63β expression is decreased, leading to EMT with enhancing migration and invasion through ERK signal reduction at the invasive front.
    MeSH term(s) Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/pathology ; Cell Transformation, Neoplastic ; Down-Regulation ; Epithelial-Mesenchymal Transition/physiology ; Female ; Gene Knockdown Techniques ; Humans ; Kallikreins/metabolism ; Male ; Mouth Neoplasms/metabolism ; Mouth Neoplasms/pathology ; Receptor, PAR-1/metabolism ; Receptor, PAR-2/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors/physiology ; Tumor Suppressor Proteins/physiology ; Up-Regulation
    Chemical Substances Receptor, PAR-1 ; Receptor, PAR-2 ; TP63 protein, human ; Transcription Factors ; Tumor Suppressor Proteins ; KLK6 protein, human (EC 3.4.21.-) ; Kallikreins (EC 3.4.21.-)
    Language English
    Publishing date 2017-11-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1120465-5
    ISSN 1879-0593 ; 0964-1955 ; 1368-8375
    ISSN (online) 1879-0593
    ISSN 0964-1955 ; 1368-8375
    DOI 10.1016/j.oraloncology.2017.11.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Increased expression of interleukin-6 predicts poor response to chemoradiotherapy and unfavorable prognosis in oral squamous cell carcinoma.

    Jinno, Teppei / Kawano, Shintaro / Maruse, Yasuyuki / Matsubara, Ryota / Goto, Yuichi / Sakamoto, Taiki / Hashiguchi, Yuma / Kaneko, Naoki / Tanaka, Hideaki / Kitamura, Ryoji / Toyoshima, Takeshi / Jinno, Akiko / Moriyama, Masafumi / Oobu, Kazunari / Kiyoshima, Tamotsu / Nakamura, Seiji

    Oncology reports

    2015  Volume 33, Issue 5, Page(s) 2161–2168

    Abstract: Recent studies have revealed that cancer cells are exacerbated by chronic inflammation. The present study examined the immunohistochemical expression for interleukin-6 (IL-6), a pleiotropic inflammatory cytokine, in oral squamous cell carcinoma (OSCC) to ...

    Abstract Recent studies have revealed that cancer cells are exacerbated by chronic inflammation. The present study examined the immunohistochemical expression for interleukin-6 (IL-6), a pleiotropic inflammatory cytokine, in oral squamous cell carcinoma (OSCC) to elucidate the association of IL-6 expression with tumor progression, chemoresistance and prognosis. Seventy-eight patients with primary OSCC were analyzed by immunohistochemical staining for IL-6. These labeling indexes (LIs) were calculated and evaluated in association with the clinicopathologic characteristics and prognosis in the OSCC patients. The patients were divided into three groups as follows: negative group = LI <5%; low IL-6 group = 5% ≤ LI <30%; high IL-6 group = LI ≥30%. The patient numbers of the negative, low and high expression groups were 24, 22 and 32, respectively. In the high IL-6 expression group, IL-6 receptor (IL-6R), phosphor-signal tranducer and activator of transcription 3 (p-STAT3) were also detected in almost all the cancer cells. The prevalence of the cervical lymph node or the distant metastasis in the high expression group was significantly higher than those in the negative and low expression groups. Furthermore, the high expression group had a significantly poorer tumor response to the preoperative chemoradiotherapy and a more unfavourable prognosis than the negative and the low expression groups. Interestingly, IL-6, IL-6R and p-STAT3 were expressed in the residual cancer cells of all the patients in the high expression group with poor response to chemoradiotherapy. These results suggested that IL-6 signaling possibly is involved in the progression and treatment-resistance of OSCC and IL-6 expression in cancer cells could be a useful predictive factor of poor response to chemoradiotherapy and unfavorable prognosis.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell/immunology ; Carcinoma, Squamous Cell/mortality ; Carcinoma, Squamous Cell/pathology ; Carcinoma, Squamous Cell/therapy ; Chemoradiotherapy ; Female ; Head and Neck Neoplasms/immunology ; Head and Neck Neoplasms/mortality ; Head and Neck Neoplasms/pathology ; Head and Neck Neoplasms/therapy ; Humans ; Immunohistochemistry ; Interleukin-6/biosynthesis ; Interleukin-6/immunology ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Mouth Neoplasms/immunology ; Mouth Neoplasms/mortality ; Mouth Neoplasms/pathology ; Mouth Neoplasms/therapy ; Prognosis ; Squamous Cell Carcinoma of Head and Neck ; Young Adult
    Chemical Substances IL6 protein, human ; Interleukin-6
    Language English
    Publishing date 2015-03-06
    Publishing country Greece
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1222484-4
    ISSN 1791-2431 ; 1021-335X
    ISSN (online) 1791-2431
    ISSN 1021-335X
    DOI 10.3892/or.2015.3838
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4213: Show issues Location:
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