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Chung Che Chang - One of the best experts on this subject based on the ideXlab platform.

  • primary central nervous system Histiocytic Sarcoma with relapse to mediastinum a case report and review of the literature
    Archives of Pathology & Laboratory Medicine, 2007
    Co-Authors: Ming Cao, Camellia Eshoa, Christopher J Schultz, Jennifer O Black, Chung Che Chang
    Abstract:

    Abstract Histiocytic Sarcoma is a rare, malignant neoplasm of the lymphohematopoietic system that usually occurs in the skin, lymph node, and intestinal tract. Here we describe a unique case of primary central nervous system Histiocytic Sarcoma that initially showed an indolent clinical course following local resection and radiotherapy. However, relapse of disease within the mediastinum was noted 3½ years later. Biopsies of the initial brain lesion and subsequent mediastinal recurrence each revealed an identical, diffuse proliferation of histiocytes with expression of CD45, CD68, and CD163 but not pan-cytokeratin, epithelial membrane antigen, CD3, CD15, CD20, CD30, CD43, CD79a, CD138, myeloperoxidase, ALK-1, PAX-5, CAM 5.2, S100, CD1a, or glial fibrillary acidic protein. In the literature, central nervous system Histiocytic Sarcoma portends a poor prognosis with median survival of 4.5 months. To our knowledge, this case represents the first case of “low-grade” primary central nervous system Histiocytic sa...

  • primary central nervous system Histiocytic Sarcoma with relapse to mediastinum a case report and review of the literature
    Archives of Pathology & Laboratory Medicine, 2007
    Co-Authors: Ming Cao, Camellia Eshoa, Christopher J Schultz, Jennifer O Black, Chung Che Chang
    Abstract:

    Histiocytic Sarcoma is a rare, malignant neoplasm of the lymphohematopoietic system that usually occurs in the skin, lymph node, and intestinal tract. Here we describe a unique case of primary central nervous system Histiocytic Sarcoma that initially showed an indolent clinical course following local resection and radiotherapy. However, relapse of disease within the mediastinum was noted 3 1/2 years later. Biopsies of the initial brain lesion and subsequent mediastinal recurrence each revealed an identical, diffuse proliferation of histiocytes with expression of CD45, CD68, and CD163 but not pan-cytokeratin, epithelial membrane antigen, CD3, CD15, CD20, CD30, CD43, CD79a, CD138, myeloperoxidase, ALK-1, PAX-5, CAM 5.2, S100, CD1a, or glial fibrillary acidic protein. In the literature, central nervous system Histiocytic Sarcoma portends a poor prognosis with median survival of 4.5 months. To our knowledge, this case represents the first case of "low-grade" primary central nervous system Histiocytic Sarcoma with relatively indolent clinical course. A thorough discussion of the differential diagnosis of Histiocytic Sarcoma and a review of primary central nervous system Histiocytic Sarcoma are also presented.

Ming Cao - One of the best experts on this subject based on the ideXlab platform.

  • primary central nervous system Histiocytic Sarcoma with relapse to mediastinum a case report and review of the literature
    Archives of Pathology & Laboratory Medicine, 2007
    Co-Authors: Ming Cao, Camellia Eshoa, Christopher J Schultz, Jennifer O Black, Chung Che Chang
    Abstract:

    Abstract Histiocytic Sarcoma is a rare, malignant neoplasm of the lymphohematopoietic system that usually occurs in the skin, lymph node, and intestinal tract. Here we describe a unique case of primary central nervous system Histiocytic Sarcoma that initially showed an indolent clinical course following local resection and radiotherapy. However, relapse of disease within the mediastinum was noted 3½ years later. Biopsies of the initial brain lesion and subsequent mediastinal recurrence each revealed an identical, diffuse proliferation of histiocytes with expression of CD45, CD68, and CD163 but not pan-cytokeratin, epithelial membrane antigen, CD3, CD15, CD20, CD30, CD43, CD79a, CD138, myeloperoxidase, ALK-1, PAX-5, CAM 5.2, S100, CD1a, or glial fibrillary acidic protein. In the literature, central nervous system Histiocytic Sarcoma portends a poor prognosis with median survival of 4.5 months. To our knowledge, this case represents the first case of “low-grade” primary central nervous system Histiocytic sa...

  • primary central nervous system Histiocytic Sarcoma with relapse to mediastinum a case report and review of the literature
    Archives of Pathology & Laboratory Medicine, 2007
    Co-Authors: Ming Cao, Camellia Eshoa, Christopher J Schultz, Jennifer O Black, Chung Che Chang
    Abstract:

    Histiocytic Sarcoma is a rare, malignant neoplasm of the lymphohematopoietic system that usually occurs in the skin, lymph node, and intestinal tract. Here we describe a unique case of primary central nervous system Histiocytic Sarcoma that initially showed an indolent clinical course following local resection and radiotherapy. However, relapse of disease within the mediastinum was noted 3 1/2 years later. Biopsies of the initial brain lesion and subsequent mediastinal recurrence each revealed an identical, diffuse proliferation of histiocytes with expression of CD45, CD68, and CD163 but not pan-cytokeratin, epithelial membrane antigen, CD3, CD15, CD20, CD30, CD43, CD79a, CD138, myeloperoxidase, ALK-1, PAX-5, CAM 5.2, S100, CD1a, or glial fibrillary acidic protein. In the literature, central nervous system Histiocytic Sarcoma portends a poor prognosis with median survival of 4.5 months. To our knowledge, this case represents the first case of "low-grade" primary central nervous system Histiocytic Sarcoma with relatively indolent clinical course. A thorough discussion of the differential diagnosis of Histiocytic Sarcoma and a review of primary central nervous system Histiocytic Sarcoma are also presented.

Matti Kiupel - One of the best experts on this subject based on the ideXlab platform.

  • disseminated haemophagocytic Histiocytic Sarcoma in an african pygmy hedgehog atelerix albiventris
    Journal of Comparative Pathology, 2021
    Co-Authors: Sirintra Sirivisoot, Matti Kiupel, Nlin Arya, Pemika Kaenchan, Wasana Buayam, Tanit Kasantikul
    Abstract:

    A 3-year-old intact male African pygmy hedgehog (Atelerix albiventris) was found dead shortly after clinical onset of screaming, aerophagia and lethargy. On gross examination, the spleen was dark red and friable, and the liver was markedly enlarged with a prominent lobular pattern and multiple white nodules. Histopathological examination of liver and spleen revealed dense infiltrates of highly pleomorphic neoplastic, round to polyhedral cells with overt erythrophagocytosis. Similar neoplastic cells were found in the sinuses of the abdominal lymph nodes and in blood vessels in the heart, lung, brain and kidneys. Immunolabelling for CD204 confirmed the Histiocytic origin of the neoplastic cells. To our knowledge, this is the first report of a disseminated haemophagocytic Histiocytic Sarcoma in a hedgehog.

  • development of an orthotopic intrasplenic xenograft mouse model of canine Histiocytic Sarcoma and its use in evaluating the efficacy of treatment with dasatinib
    Comparative Medicine, 2019
    Co-Authors: Marilia Takada, Matti Kiupel, Jeremy M L Hix, Sarah Corner, Lauren A Smyth, Vilma Yuzbasiyangurkan
    Abstract:

    Canine Histiocytic Sarcoma is a highly aggressive and metastatic hematopoietic neoplasm that responds poorly to currently available treatment regimens. Our goal was to establish a clinically relevant xenograft mouse model to assess the preclinical efficacy of novel cancer treatment protocols for Histiocytic Sarcoma. We developed an intrasplenic xenograft mouse model characterized by consistent tumor growth and development of metastasis to the liver and other abdominal organs. This model represents the metastatic or disseminated form of canine Histiocytic Sarcoma, which is considered the most clinically challenging form of the disease. Transfection of tumor cells with a luciferase vector supported the use of in vivo bioluminescence imaging to track tumor progression over time and to assess the response of this murine model to novel chemotherapeutic agents. Dasatinib treatment of the mice with intrasplenic xenografts decreased tumor growth and increased survival times, compared with mice treated with vehicle only. Our findings indicate the potential of dasatinib for the treatment of Histiocytic Sarcoma in dogs and for similar diseases in humans. These results warrant additional studies to clinically test the efficacy of dasatinib in dogs with Histiocytic Sarcoma.

  • A novel canine Histiocytic Sarcoma cell line: initial characterization and utilization for drug screening studies
    BMC Cancer, 2018
    Co-Authors: Marilia Takada, Maciej Parys, Emmalena Gregory-bryson, Paulo Vilar Saavedra, Matti Kiupel, Vilma Yuzbasiyan-gurkan
    Abstract:

    Background Histiocytic Sarcoma is a rare disorder in humans, however it is seen with appreciable frequency in certain breeds of dogs, such as Bernese mountain dog. The purpose of this study was to fully characterize a novel canine Histiocytic Sarcoma cell line, and utilize it as a tool to screen for potential therapeutic drugs. Methods The Histiocytic Sarcoma cell line was characterized by expression of cellular markers as determined by immunohistochemistry and flow cytometry techniques. The neoplastic cells were also evaluated for their capability of phagocytizing beads particles, and their potential to grow as xenograft in an immunodeficient mouse. We investigated the in vitro cytotoxic activity of a panel of thirteen compounds using the MTS proliferation assay. Inhibitory effects of different drugs were compared using one-way ANOVA, and multiple means were compared using Tukey’s test. Results Neoplastic cells expressed CD11c, CD14, CD18, CD45, CD172a, CD204, MHC I, and vimentin. Expression of MHC II was upregulated after exposure to LPS. Furthermore, the established cell line clearly demonstrated phagocytic activity similar to positive controls of macrophage cell line. The xenograft mouse developed a palpable subcutaneous soft tissue mass after 29 days of inoculation, which histologically resembled the primary neoplasm. Dasatinib, a tyrosine kinase pan-inhibitor, significantly inhibited the growth of the cells in vitro within a clinically achievable and tolerable plasma concentration. The inhibitory response to dasatinib was augmented when combined with doxorubicin. Conclusions In the present study we demonstrated that a novel canine Histiocytic Sarcoma cell line presents a valuable tool to evaluate novel treatment approaches. The neoplastic cell line favorably responded to dasatinib, which represents a promising anticancer strategy for the treatment of this malignancy in dogs and similar disorders in humans.

  • a novel canine Histiocytic Sarcoma cell line initial characterization and utilization for drug screening studies
    BMC Cancer, 2018
    Co-Authors: Marilia Takada, Maciej Parys, Matti Kiupel, Emmalena Gregorybryson, Paulo Vilar Saavedra, Vilma Yuzbasiyangurkan
    Abstract:

    Histiocytic Sarcoma is a rare disorder in humans, however it is seen with appreciable frequency in certain breeds of dogs, such as Bernese mountain dog. The purpose of this study was to fully characterize a novel canine Histiocytic Sarcoma cell line, and utilize it as a tool to screen for potential therapeutic drugs. The Histiocytic Sarcoma cell line was characterized by expression of cellular markers as determined by immunohistochemistry and flow cytometry techniques. The neoplastic cells were also evaluated for their capability of phagocytizing beads particles, and their potential to grow as xenograft in an immunodeficient mouse. We investigated the in vitro cytotoxic activity of a panel of thirteen compounds using the MTS proliferation assay. Inhibitory effects of different drugs were compared using one-way ANOVA, and multiple means were compared using Tukey’s test. Neoplastic cells expressed CD11c, CD14, CD18, CD45, CD172a, CD204, MHC I, and vimentin. Expression of MHC II was upregulated after exposure to LPS. Furthermore, the established cell line clearly demonstrated phagocytic activity similar to positive controls of macrophage cell line. The xenograft mouse developed a palpable subcutaneous soft tissue mass after 29 days of inoculation, which histologically resembled the primary neoplasm. Dasatinib, a tyrosine kinase pan-inhibitor, significantly inhibited the growth of the cells in vitro within a clinically achievable and tolerable plasma concentration. The inhibitory response to dasatinib was augmented when combined with doxorubicin. In the present study we demonstrated that a novel canine Histiocytic Sarcoma cell line presents a valuable tool to evaluate novel treatment approaches. The neoplastic cell line favorably responded to dasatinib, which represents a promising anticancer strategy for the treatment of this malignancy in dogs and similar disorders in humans.

  • targeting mek in a translational model of Histiocytic Sarcoma
    Molecular Cancer Therapeutics, 2018
    Co-Authors: Marilia Takada, Matti Kiupel, Jeremy M L Hix, Sarah Corner, Peter Z Schall, Vilma Yuzbasiyangurkan
    Abstract:

    Histiocytic Sarcoma in humans is an aggressive orphan disease with a poor prognosis as treatment options are limited. Dogs are the only species that spontaneously develops Histiocytic Sarcoma with an appreciable frequency, and may have value as a translational model system. In the current study, high-throughput drug screening utilizing Histiocytic Sarcoma cells isolated from canine neoplasms identified these cells as particularly sensitive to a MEK inhibitor, trametinib. One of the canine cell lines carries a mutation in PTPN11 (E76K), and another one in KRAS (Q61H), which are associated with the activation of oncogenic MAPK signaling. Both mutations were previously reported in human Histiocytic Sarcoma. Trametinib inhibited sensitive cell lines by promoting cell apoptosis, indicated by a significant increase in caspase 3/7. Furthermore, in vitro findings were successfully recapitulated in an intrasplenic orthotopic xenograft mouse model, which represents a disseminated aggressive form of Histiocytic Sarcoma. Mice with Histiocytic Sarcoma xenograft neoplasms that were treated with trametinib had significantly longer survival times. Target engagement was validated as activity of ERK, downstream of MEK, was significantly downregulated in neoplasms of treated mice. Additionally, trametinib was found in plasma and neoplastic tissues within projected therapeutic levels. These findings demonstrate that in dogs, Histiocytic Sarcoma may be associated with a dysfunctional MAPK pathway, at least in some cases, and may be effectively targeted through MEK inhibition. Clinical trials to test safety and efficacy of trametinib in dogs with Histiocytic Sarcoma are warranted, and may provide valuable translational information to similar diseases in humans. Mol Cancer Ther; 17(11); 2439-50. ©2018 AACR.

Marilia Takada - One of the best experts on this subject based on the ideXlab platform.

  • development of an orthotopic intrasplenic xenograft mouse model of canine Histiocytic Sarcoma and its use in evaluating the efficacy of treatment with dasatinib
    Comparative Medicine, 2019
    Co-Authors: Marilia Takada, Matti Kiupel, Jeremy M L Hix, Sarah Corner, Lauren A Smyth, Vilma Yuzbasiyangurkan
    Abstract:

    Canine Histiocytic Sarcoma is a highly aggressive and metastatic hematopoietic neoplasm that responds poorly to currently available treatment regimens. Our goal was to establish a clinically relevant xenograft mouse model to assess the preclinical efficacy of novel cancer treatment protocols for Histiocytic Sarcoma. We developed an intrasplenic xenograft mouse model characterized by consistent tumor growth and development of metastasis to the liver and other abdominal organs. This model represents the metastatic or disseminated form of canine Histiocytic Sarcoma, which is considered the most clinically challenging form of the disease. Transfection of tumor cells with a luciferase vector supported the use of in vivo bioluminescence imaging to track tumor progression over time and to assess the response of this murine model to novel chemotherapeutic agents. Dasatinib treatment of the mice with intrasplenic xenografts decreased tumor growth and increased survival times, compared with mice treated with vehicle only. Our findings indicate the potential of dasatinib for the treatment of Histiocytic Sarcoma in dogs and for similar diseases in humans. These results warrant additional studies to clinically test the efficacy of dasatinib in dogs with Histiocytic Sarcoma.

  • A novel canine Histiocytic Sarcoma cell line: initial characterization and utilization for drug screening studies
    BMC Cancer, 2018
    Co-Authors: Marilia Takada, Maciej Parys, Emmalena Gregory-bryson, Paulo Vilar Saavedra, Matti Kiupel, Vilma Yuzbasiyan-gurkan
    Abstract:

    Background Histiocytic Sarcoma is a rare disorder in humans, however it is seen with appreciable frequency in certain breeds of dogs, such as Bernese mountain dog. The purpose of this study was to fully characterize a novel canine Histiocytic Sarcoma cell line, and utilize it as a tool to screen for potential therapeutic drugs. Methods The Histiocytic Sarcoma cell line was characterized by expression of cellular markers as determined by immunohistochemistry and flow cytometry techniques. The neoplastic cells were also evaluated for their capability of phagocytizing beads particles, and their potential to grow as xenograft in an immunodeficient mouse. We investigated the in vitro cytotoxic activity of a panel of thirteen compounds using the MTS proliferation assay. Inhibitory effects of different drugs were compared using one-way ANOVA, and multiple means were compared using Tukey’s test. Results Neoplastic cells expressed CD11c, CD14, CD18, CD45, CD172a, CD204, MHC I, and vimentin. Expression of MHC II was upregulated after exposure to LPS. Furthermore, the established cell line clearly demonstrated phagocytic activity similar to positive controls of macrophage cell line. The xenograft mouse developed a palpable subcutaneous soft tissue mass after 29 days of inoculation, which histologically resembled the primary neoplasm. Dasatinib, a tyrosine kinase pan-inhibitor, significantly inhibited the growth of the cells in vitro within a clinically achievable and tolerable plasma concentration. The inhibitory response to dasatinib was augmented when combined with doxorubicin. Conclusions In the present study we demonstrated that a novel canine Histiocytic Sarcoma cell line presents a valuable tool to evaluate novel treatment approaches. The neoplastic cell line favorably responded to dasatinib, which represents a promising anticancer strategy for the treatment of this malignancy in dogs and similar disorders in humans.

  • a novel canine Histiocytic Sarcoma cell line initial characterization and utilization for drug screening studies
    BMC Cancer, 2018
    Co-Authors: Marilia Takada, Maciej Parys, Matti Kiupel, Emmalena Gregorybryson, Paulo Vilar Saavedra, Vilma Yuzbasiyangurkan
    Abstract:

    Histiocytic Sarcoma is a rare disorder in humans, however it is seen with appreciable frequency in certain breeds of dogs, such as Bernese mountain dog. The purpose of this study was to fully characterize a novel canine Histiocytic Sarcoma cell line, and utilize it as a tool to screen for potential therapeutic drugs. The Histiocytic Sarcoma cell line was characterized by expression of cellular markers as determined by immunohistochemistry and flow cytometry techniques. The neoplastic cells were also evaluated for their capability of phagocytizing beads particles, and their potential to grow as xenograft in an immunodeficient mouse. We investigated the in vitro cytotoxic activity of a panel of thirteen compounds using the MTS proliferation assay. Inhibitory effects of different drugs were compared using one-way ANOVA, and multiple means were compared using Tukey’s test. Neoplastic cells expressed CD11c, CD14, CD18, CD45, CD172a, CD204, MHC I, and vimentin. Expression of MHC II was upregulated after exposure to LPS. Furthermore, the established cell line clearly demonstrated phagocytic activity similar to positive controls of macrophage cell line. The xenograft mouse developed a palpable subcutaneous soft tissue mass after 29 days of inoculation, which histologically resembled the primary neoplasm. Dasatinib, a tyrosine kinase pan-inhibitor, significantly inhibited the growth of the cells in vitro within a clinically achievable and tolerable plasma concentration. The inhibitory response to dasatinib was augmented when combined with doxorubicin. In the present study we demonstrated that a novel canine Histiocytic Sarcoma cell line presents a valuable tool to evaluate novel treatment approaches. The neoplastic cell line favorably responded to dasatinib, which represents a promising anticancer strategy for the treatment of this malignancy in dogs and similar disorders in humans.

  • targeting mek in a translational model of Histiocytic Sarcoma
    Molecular Cancer Therapeutics, 2018
    Co-Authors: Marilia Takada, Matti Kiupel, Jeremy M L Hix, Sarah Corner, Peter Z Schall, Vilma Yuzbasiyangurkan
    Abstract:

    Histiocytic Sarcoma in humans is an aggressive orphan disease with a poor prognosis as treatment options are limited. Dogs are the only species that spontaneously develops Histiocytic Sarcoma with an appreciable frequency, and may have value as a translational model system. In the current study, high-throughput drug screening utilizing Histiocytic Sarcoma cells isolated from canine neoplasms identified these cells as particularly sensitive to a MEK inhibitor, trametinib. One of the canine cell lines carries a mutation in PTPN11 (E76K), and another one in KRAS (Q61H), which are associated with the activation of oncogenic MAPK signaling. Both mutations were previously reported in human Histiocytic Sarcoma. Trametinib inhibited sensitive cell lines by promoting cell apoptosis, indicated by a significant increase in caspase 3/7. Furthermore, in vitro findings were successfully recapitulated in an intrasplenic orthotopic xenograft mouse model, which represents a disseminated aggressive form of Histiocytic Sarcoma. Mice with Histiocytic Sarcoma xenograft neoplasms that were treated with trametinib had significantly longer survival times. Target engagement was validated as activity of ERK, downstream of MEK, was significantly downregulated in neoplasms of treated mice. Additionally, trametinib was found in plasma and neoplastic tissues within projected therapeutic levels. These findings demonstrate that in dogs, Histiocytic Sarcoma may be associated with a dysfunctional MAPK pathway, at least in some cases, and may be effectively targeted through MEK inhibition. Clinical trials to test safety and efficacy of trametinib in dogs with Histiocytic Sarcoma are warranted, and may provide valuable translational information to similar diseases in humans. Mol Cancer Ther; 17(11); 2439-50. ©2018 AACR.

Endi Wang - One of the best experts on this subject based on the ideXlab platform.