<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04438564</url>
  </required_header>
  <id_info>
    <org_study_id>CMUH108-REC1-113</org_study_id>
    <nct_id>NCT04438564</nct_id>
  </id_info>
  <brief_title>Immunoassay and Regulation of Traditional Chinese Medicine on Cancer Patients</brief_title>
  <official_title>Immunoassay and Regulation of Traditional Chinese Medicine on Cancer Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>China Medical University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>China Medical University Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The immune system is our body's defense mechanism, which helps us to resist foreign pathogens&#xD;
      and cancer cells in the body. However, if the immune system is too weak, too strong, or&#xD;
      unbalanced, it will be susceptible to get bacterial and viral infections, unable to fight&#xD;
      cancer, or cause allergies, autoimmune and rheumatic diseases. At present, there is no good&#xD;
      western medicine to strengthen immunity when the body is insufficient immunity. However,&#xD;
      strong immunity causes autoimmune diseases and need to be treated by steroids and&#xD;
      immunosuppressive agents. These drugs have limited efficacy and often have many side effects.&#xD;
      In the clinical practice of traditional Chinese medicine, tonify qi, supplement blood and&#xD;
      nourish yin are often used to enhance immunity. However, there is no clinical test to&#xD;
      demonstrate the modulation of immune response after traditional Chinese medicine treatment.&#xD;
&#xD;
      In our preliminary study, the investigators identified that the basic immune response of&#xD;
      cancer patients is weaker than healthy people by testing the level of IFN-r (promoting T cell&#xD;
      activity, anti-tumor, anti-viral), TNF-a (promoting B cell proliferation, producing&#xD;
      antibodies, anti-tumor, anti-viral) and IL-2 (regulate the proliferation and&#xD;
      differentiation). Besides, some Chinese herbal extracts can significantly stimulate the&#xD;
      immune response higher than the general average basic immunity of cancer patients. Further,&#xD;
      we will use the stimulatory Chinese medicine extract to administer to cancer patients and&#xD;
      examine the immune response of cancer patients after taking them. Therefore, this test can&#xD;
      provide actual data on the basic immunity of healthy people or cancer patients and the&#xD;
      modulation of immune response by traditional Chinese medicine treatment. This analysis&#xD;
      platform provides patients to select the medicines that can enhance the immune response for&#xD;
      individuals and analyze the changes of the immune response after conditioning with the&#xD;
      candidate Chinese medicines. Therefore, this test could be applied clinically to validate the&#xD;
      immunological regulation of Chinese herbal medicine as well as analyze the immunological&#xD;
      modulation against different cancer by various Chinese herbal medicine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Traditional Chinese medicine (TCM) and dendritic cells (DCs) activation/maturation One of the&#xD;
      important approaches to successful cancer immunotherapy is generation of specific T cell&#xD;
      responses by dendritic cells (DCs). DCs are the most potent antigen-presenting cells for&#xD;
      naive T cells, because their high expression of MHC and co-stimulatory molecules. DCs&#xD;
      comprise several subsets, and their roles in the presentation of antigens derived from&#xD;
      pathogens, vaccines and self tissues are now beginning to be elucidated. Immature DCs (iDCs)&#xD;
      resided in periphery have a high ability to endocytose antigens and become to mature DCs&#xD;
      (mDCs) upon a variety of stimuli through Toll-like receptors (TLRs). However, iDCs facilitate&#xD;
      immune tolerance and fully mDCs can promote immune responses. Until now, there are some&#xD;
      studies have demonstrated that TCM could promote the activation status of DC to enhance&#xD;
      immune responses through TLR, which are characterized by increased expression of&#xD;
      co-stimulatory moleculars, MHC class II and several cytokines. Ganoderma lucidum and&#xD;
      Cordyceps sinensis have been widely used in Asian countries to have beneficial effects on&#xD;
      human health. Ganoderma lucidum polysaccharides have been reported to induce DCs maturation&#xD;
      and promote the cytotoxicity of specific CTL. Moreover, Ganoderma lucidum polysaccharides&#xD;
      were able to induce DC activation markers production and cytokines expression through TLR-4&#xD;
      signaling pathway. However, this character about TCM acted as TLR agonists could apply to&#xD;
      develop safe and effective adjuvant in vaccine generation.&#xD;
&#xD;
      Traditional Chinese medicine (TCM) and T cell activation T cells are the master regulators of&#xD;
      adaptive immune responses. Proper T cell responses are essential for the hosts to orchestrate&#xD;
      sufficient adaptive immunity. Classically, the TH1/TH2 hypothesis has served the immunology&#xD;
      community well, particularly in understanding infectious and allergic diseases. Regulatory T&#xD;
      cells (Treg) are suppressive T cells that regulate effector T cell immunity. Nevertheless,&#xD;
      this model dose not fit all systems when it comes to the study of organ-specific autoimmune&#xD;
      diseases. It has also become more and more clear, however, that many complicated pathological&#xD;
      situations cannot be simply explained by the TH1 cell and TH2 cell paradigm. Efforts to&#xD;
      resolve these issues in recent years have resulted in the discovery of TH17 cells.&#xD;
&#xD;
      T cell immunity is crucial for anti-tumor immunity. Given their importance in immune&#xD;
      responses and diseases, it is important to understand the regulation of T cell immunity. In&#xD;
      immune system, different lineages of immune cells were conventionally distinguished by the&#xD;
      morphology and expression of a cluster of differentiation markers on the cell surface. TH1&#xD;
      cells that make IL-2 and IFN-r are important for delayed-type hypersensitivity reactions,&#xD;
      whereas TH2 cells that make IL-4 promote IgE production and allergic reaction. The&#xD;
      differentiation of TH1 and TH2 cells mainly through the induction of distinct transcriptional&#xD;
      programs. Activation of Signal Transducers and Activators of Transcription 1 (STAT1) by IFN-r&#xD;
      and STAT4 by IL-12 drives expression of T-bet for TH1 programming. On the other hand,&#xD;
      activation of STAT6 by IL-4 promotes GATA3 expression in TH2 cells. A revise of the TH1/TH2&#xD;
      hypothesis was proposed until the discovery and IL-23 and IL-17. TH17 cell is a distinct T&#xD;
      helper cell population that plays a crucial role in CD4+ T cell-mediated adaptive immunity.&#xD;
      Commitment to the TH17 pathway requires the presence of both IL-6 and TGF-a during in vitro&#xD;
      culture. These cells, different from the classical TH1 and TH2 cells, do not produce IFN-r or&#xD;
      IL-4 but on the other hand express the IL-23 receptor and IL-21, IL-22, and IL-17F. ROR-rt ,&#xD;
      ROR-rt are also highly expressed in TH17cells and can be induced by TGF-a and IL-6. Our&#xD;
      previous studies showed for the first time an in vivo requirement for STAT3 in TH17 mediated&#xD;
      autoimmunity. In addition, the investigators found that STAT3 is required for the maintenance&#xD;
      of endogenous TH17 cells. In a more recent report, the investigators also found that CD8 T&#xD;
      cells, like their CD4 counterparts TH17, can be skewed toward IL-17 production in vitro and&#xD;
      in vitro.&#xD;
&#xD;
      Manipulating T cell immunity by Chinese herbs is a promising field to explore. Many herbs&#xD;
      were reported to regulate the T cell activation. Tanshinlactone A from Salvia miltiorrhiza&#xD;
      Bunge significantly decreased the IL-2 and IFN-γ gene expression through reduction of MAPK&#xD;
      activation in phytohemagglutinin-activated peripheral blood mononuclear cells. Periplocoside&#xD;
      E (PSE) was shown to dose-dependently inhibit anti-CD3 induced primary T cell proliferation,&#xD;
      activation for IL-2R (CD25) expression, and IFN-γ and IL-2 production at the transcriptional&#xD;
      level by inhibited the activation of ERK and JNK. Furthermore, kurarinol was reported to&#xD;
      increase level of HBV specific CTL by down-regulating peripheral blood HBV specific CTL&#xD;
      surface PD-1 expression of CHB patients.&#xD;
&#xD;
      All of these will support investigators' hypothesis that modulation of dendritic cell and T&#xD;
      cell immunity by Chinese herbs or cytokines may be an applicable intervention to modulate&#xD;
      immunity, for example, to promote anti-tumor immunity against cancer. The successful&#xD;
      completion of the proposed studies will provide a strong support for future development of&#xD;
      anti-cancer immunotherapy by Chinese herbs.&#xD;
&#xD;
      Traditional Chinese herbs as a pharmacologic approach to modulate immunity Cancer&#xD;
      immunotherapy, allergy, and autoimmune diseases are among the chronic illness that accounts&#xD;
      for the death and economic burdens in Taiwan and other modern countries. Diseases such of&#xD;
      Rheumatoid arthritis (RA), SLE, multiple sclerosis, ankylosing spondylitis, vasculitis,&#xD;
      psoriasis and Sjogren's syndrome are common autoimmune diseases that cause not only life-long&#xD;
      discomfort but also disabilities of the patients. Cancer immunotherapy is promising. Many of&#xD;
      autoimmune disease and difficult-to-treat allergies are now found to be associated with IL-17&#xD;
      mediated pathology. However, the current treatment is limited. Recently, targeted therapy&#xD;
      such as Etanercept (trade name Enbrel), a biopharmaceutical that interferes with tumor&#xD;
      necrosis factor (TNF; a soluble inflammatory cytokine), has been developed to treat some of&#xD;
      the autoimmune diseases. However, nhibition of TNF has substantially advanced the treatment&#xD;
      of inflammatory diseases. Because TNF and IL-17 have shared functions, the rationale for&#xD;
      testing IL-17 inhibitors in the clinic is often based on the concept that patients who do not&#xD;
      respond to TNF inhibitors may have an IL-17-driven disease. Autoimmune diseases such of&#xD;
      rheumatoid arthritis and multiple sclerosis are common autoimmune diseases that cause not&#xD;
      only life-long discomfort but also disabilities of the patients. The current treatment for&#xD;
      these autoimmune diseases is limited to analgesia, anti-inflammatory drugs, steroids,&#xD;
      disease-modifying antirheumatic drugs (DMARDs), and immunosuppressants. Recent studies in&#xD;
      mouse models and in humans have identified a key role of IL-17 and TH17 cells in the&#xD;
      pathogenesis of inflammation and autoimmunity as well as in host defense against certain&#xD;
      pathogens.&#xD;
&#xD;
      Meanwhile, there are some studies using Chinese herbs to modulate CD4 TH17 immunity. Compound&#xD;
      extracted from Chinese herbs, such as berberine exhibited potent efficacy inhibiting TH17 in&#xD;
      the EAE model. Triptolide also inhibited collagen-induced arthritis (CIA), a model of&#xD;
      rheumatoid arthritis, through inhibition of CD4 TH17 cells. Periplocoside A was found to&#xD;
      ameliorate EAE by suppressing IL-17 production and inhibited the differentiation of Th17&#xD;
      cells in vitro. Eriocalyxin B was also found to be effective to inhibit TH17 and EAE through&#xD;
      targeting Janus Kinase/Signal Transducer and Activator Of Transcription and Nuclear&#xD;
      factor-kappaB signaling pathways. TCM formula such as Qingkailing injection was found to&#xD;
      ameliorate rat experimental autoimmune uveitis (EAU). Qingkailing injection can alleviate&#xD;
      autoimmune uveitis in rats, inhibit the differentiation toward Th1 and Th17 effector cells&#xD;
      and the relevant cytokines secretion. Pure compound from Daphne odora var. marginata (D.&#xD;
      marginata) was also found to inhibit TH17 and thus exhibit inhibitory effects in CIA model.&#xD;
&#xD;
      One of the landmark study published in Science and Nature Chemical Biology is the example of&#xD;
      halofuginone, an active component of traditional Chinese herb hydrangea root (Dichroa&#xD;
      febrifuga), used to treat malaria for thousands of years. A collaborative research team led&#xD;
      by Dr. Mark Sundrud at the Department of Pathology, Harvard Medical School and Immune Disease&#xD;
      Institute, Boston, MA, has reported that halofuginone halted the progression of experimental&#xD;
      autoimmune encephalomyelitis (EAE) mice and TH17. Importantly, unlike other therapies for&#xD;
      autoimmune diseases, halofuginone does not have the undesirable effect of suppressing the&#xD;
      other immune system.&#xD;
&#xD;
      The investigators have established some platforms for screening Chinese herbs not only for&#xD;
      modulating PD-1/PD-L1, IL-17, but also for detection of dendritic cell and T cell activation&#xD;
      (Immunogen Test Panel).&#xD;
&#xD;
      The hypothesis is that modulation of dendritic cells and T cells by traditional Chinese&#xD;
      medicine may be an applicable intervention to treat some of the immunologic diseases such as&#xD;
      cancer, allergy, and autoimmune diseases. Studies that can fit the niche, understanding the&#xD;
      function and mechanism of Chinese herbs on immune cells and its pathway, will have broad&#xD;
      clinical and immunological significance. The successful completion of the proposed studies&#xD;
      will provide a strong support for a clinical trial of traditional Chinese medicine to treat&#xD;
      patients with immunologic diseases.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 18, 2020</start_date>
  <completion_date type="Anticipated">July 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The IL-2, TNF-alpha and IFN-gamma expression by traditional Chinese medicine treatment on cancer patients</measure>
    <time_frame>one year</time_frame>
    <description>The cytokines expression of immune cells in the blood by traditional Chinese medicine treatment in breast cancer, colon-rectal cancer, ovarian cancer, and endometrial cancer will be investigated.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Breast Cancer</condition>
  <condition>Colorectal Cancer</condition>
  <condition>Cancer of Ovary</condition>
  <condition>Cancer of Endometrium</condition>
  <arm_group>
    <arm_group_label>cancer of breast, colorectal, ovarian and endometrial</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patient who diagnostic of Breast cancer, Colorectal cancer, cancer of Ovary, and cancer of Endometrial are can recruit.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cases for patients diagnosed with breast cancer, colonrectal cancer, ovarian cancer and endometrial cancer</intervention_name>
    <description>Diagnosis and acceptance of breast cancer, colon rectal cancer, ovarian cancer, and endometrial cancer by the clinical Western medicine team.</description>
    <arm_group_label>cancer of breast, colorectal, ovarian and endometrial</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients diagnosed with ovarian cancer and endometrial cancer (cancer patients treated&#xD;
             with chemotherapy, radiotherapy, and surgery) can be included.&#xD;
&#xD;
          -  Breast cancer: Diagnosed by pathological diagnosis of biopsy, without chemotherapy or&#xD;
             radiotherapy.&#xD;
&#xD;
          -  Colorectal cancer: Diagnosed by pathological diagnosis of slices, without chemotherapy&#xD;
             or radiotherapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Minors under the age of 20.&#xD;
&#xD;
          -  Those who are currently using traditional Chinese medicine&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>China Medicine University</last_name>
    <role>Study Chair</role>
    <affiliation>China Medicine University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hung-Rong NA Yen</last_name>
    <phone>04-22053366</phone>
    <phone_ext>3005</phone_ext>
    <email>hungrongyen@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>China Medical University Hospital</name>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hung-Rong Yen</last_name>
      <phone>04-22053366</phone>
      <phone_ext>3005</phone_ext>
      <email>hungrongyen@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>June 14, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <last_update_submitted>February 6, 2023</last_update_submitted>
  <last_update_submitted_qc>February 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chinese Herbal Medicine, Immunity, T Cell, Dendritic Cell</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endometrial Neoplasms</mesh_term>
    <mesh_term>Ovarian Neoplasms</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04438564
org study id: CMUH108-REC1-113
nct id: NCT04438564
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The immune system is our body's defense mechanism, which helps us to resist foreign pathogens
      and cancer cells in the body. However, if the immune system is too weak, too strong, or
      unbalanced, it will be susceptible to get bacterial and viral infections, unable to fight
      cancer, or cause allergies, autoimmune and rheumatic diseases. At present, there is no good
      western medicine to strengthen immunity when the body is insufficient immunity. However,
      strong immunity causes autoimmune diseases and need to be treated by steroids and
      immunosuppressive agents. These drugs have limited efficacy and often have many side effects.
      In the clinical practice of traditional Chinese medicine, tonify qi, supplement blood and
      nourish yin are often used to enhance immunity. However, there is no clinical test to
      demonstrate the modulation of immune response after traditional Chinese medicine treatment.

      In our preliminary study, the investigators identified that the basic immune response of
      cancer patients is weaker than healthy people by testing the level of IFN-r (promoting T cell
      activity, anti-tumor, anti-viral), TNF-a (promoting B cell proliferation, producing
      antibodies, anti-tumor, anti-viral) and IL-2 (regulate the proliferation and
      differentiation). Besides, some Chinese herbal extracts can significantly stimulate the
      immune response higher than the general average basic immunity of cancer patients. Further,
      we will use the stimulatory Chinese medicine extract to administer to cancer patients and
      examine the immune response of cancer patients after taking them. Therefore, this test can
      provide actual data on the basic immunity of healthy people or cancer patients and the
      modulation of immune response by traditional Chinese medicine treatment. This analysis
      platform provides patients to select the medicines that can enhance the immune response for
      individuals and analyze the changes of the immune response after conditioning with the
      candidate Chinese medicines. Therefore, this test could be applied clinically to validate the
      immunological regulation of Chinese herbal medicine as well as analyze the immunological
      modulation against different cancer by various Chinese herbal medicine.
Traditional Chinese medicine (TCM) and dendritic cells (DCs) activation/maturation One of the
      important approaches to successful cancer immunotherapy is generation of specific T cell
      responses by dendritic cells (DCs). DCs are the most potent antigen-presenting cells for
      naive T cells, because their high expression of MHC and co-stimulatory molecules. DCs
      comprise several subsets, and their roles in the presentation of antigens derived from
      pathogens, vaccines and self tissues are now beginning to be elucidated. Immature DCs (iDCs)
      resided in periphery have a high ability to endocytose antigens and become to mature DCs
      (mDCs) upon a variety of stimuli through Toll-like receptors (TLRs). However, iDCs facilitate
      immune tolerance and fully mDCs can promote immune responses. Until now, there are some
      studies have demonstrated that TCM could promote the activation status of DC to enhance
      immune responses through TLR, which are characterized by increased expression of
      co-stimulatory moleculars, MHC class II and several cytokines. Ganoderma lucidum and
      Cordyceps sinensis have been widely used in Asian countries to have beneficial effects on
      human health. Ganoderma lucidum polysaccharides have been reported to induce DCs maturation
      and promote the cytotoxicity of specific CTL. Moreover, Ganoderma lucidum polysaccharides
      were able to induce DC activation markers production and cytokines expression through TLR-4
      signaling pathway. However, this character about TCM acted as TLR agonists could apply to
      develop safe and effective adjuvant in vaccine generation.

      Traditional Chinese medicine (TCM) and T cell activation T cells are the master regulators of
      adaptive immune responses. Proper T cell responses are essential for the hosts to orchestrate
      sufficient adaptive immunity. Classically, the TH1/TH2 hypothesis has served the immunology
      community well, particularly in understanding infectious and allergic diseases. Regulatory T
      cells (Treg) are suppressive T cells that regulate effector T cell immunity. Nevertheless,
      this model dose not fit all systems when it comes to the study of organ-specific autoimmune
      diseases. It has also become more and more clear, however, that many complicated pathological
      situations cannot be simply explained by the TH1 cell and TH2 cell paradigm. Efforts to
      resolve these issues in recent years have resulted in the discovery of TH17 cells.

      T cell immunity is crucial for anti-tumor immunity. Given their importance in immune
      responses and diseases, it is important to understand the regulation of T cell immunity. In
      immune system, different lineages of immune cells were conventionally distinguished by the
      morphology and expression of a cluster of differentiation markers on the cell surface. TH1
      cells that make IL-2 and IFN-r are important for delayed-type hypersensitivity reactions,
      whereas TH2 cells that make IL-4 promote IgE production and allergic reaction. The
      differentiation of TH1 and TH2 cells mainly through the induction of distinct transcriptional
      programs. Activation of Signal Transducers and Activators of Transcription 1 (STAT1) by IFN-r
      and STAT4 by IL-12 drives expression of T-bet for TH1 programming. On the other hand,
      activation of STAT6 by IL-4 promotes GATA3 expression in TH2 cells. A revise of the TH1/TH2
      hypothesis was proposed until the discovery and IL-23 and IL-17. TH17 cell is a distinct T
      helper cell population that plays a crucial role in CD4+ T cell-mediated adaptive immunity.
      Commitment to the TH17 pathway requires the presence of both IL-6 and TGF-a during in vitro
      culture. These cells, different from the classical TH1 and TH2 cells, do not produce IFN-r or
      IL-4 but on the other hand express the IL-23 receptor and IL-21, IL-22, and IL-17F. ROR-rt ,
      ROR-rt are also highly expressed in TH17cells and can be induced by TGF-a and IL-6. Our
      previous studies showed for the first time an in vivo requirement for STAT3 in TH17 mediated
      autoimmunity. In addition, the investigators found that STAT3 is required for the maintenance
      of endogenous TH17 cells. In a more recent report, the investigators also found that CD8 T
      cells, like their CD4 counterparts TH17, can be skewed toward IL-17 production in vitro and
      in vitro.

      Manipulating T cell immunity by Chinese herbs is a promising field to explore. Many herbs
      were reported to regulate the T cell activation. Tanshinlactone A from Salvia miltiorrhiza
      Bunge significantly decreased the IL-2 and IFN-γ gene expression through reduction of MAPK
      activation in phytohemagglutinin-activated peripheral blood mononuclear cells. Periplocoside
      E (PSE) was shown to dose-dependently inhibit anti-CD3 induced primary T cell proliferation,
      activation for IL-2R (CD25) expression, and IFN-γ and IL-2 production at the transcriptional
      level by inhibited the activation of ERK and JNK. Furthermore, kurarinol was reported to
      increase level of HBV specific CTL by down-regulating peripheral blood HBV specific CTL
      surface PD-1 expression of CHB patients.

      All of these will support investigators' hypothesis that modulation of dendritic cell and T
      cell immunity by Chinese herbs or cytokines may be an applicable intervention to modulate
      immunity, for example, to promote anti-tumor immunity against cancer. The successful
      completion of the proposed studies will provide a strong support for future development of
      anti-cancer immunotherapy by Chinese herbs.

      Traditional Chinese herbs as a pharmacologic approach to modulate immunity Cancer
      immunotherapy, allergy, and autoimmune diseases are among the chronic illness that accounts
      for the death and economic burdens in Taiwan and other modern countries. Diseases such of
      Rheumatoid arthritis (RA), SLE, multiple sclerosis, ankylosing spondylitis, vasculitis,
      psoriasis and Sjogren's syndrome are common autoimmune diseases that cause not only life-long
      discomfort but also disabilities of the patients. Cancer immunotherapy is promising. Many of
      autoimmune disease and difficult-to-treat allergies are now found to be associated with IL-17
      mediated pathology. However, the current treatment is limited. Recently, targeted therapy
      such as Etanercept (trade name Enbrel), a biopharmaceutical that interferes with tumor
      necrosis factor (TNF; a soluble inflammatory cytokine), has been developed to treat some of
      the autoimmune diseases. However, nhibition of TNF has substantially advanced the treatment
      of inflammatory diseases. Because TNF and IL-17 have shared functions, the rationale for
      testing IL-17 inhibitors in the clinic is often based on the concept that patients who do not
      respond to TNF inhibitors may have an IL-17-driven disease. Autoimmune diseases such of
      rheumatoid arthritis and multiple sclerosis are common autoimmune diseases that cause not
      only life-long discomfort but also disabilities of the patients. The current treatment for
      these autoimmune diseases is limited to analgesia, anti-inflammatory drugs, steroids,
      disease-modifying antirheumatic drugs (DMARDs), and immunosuppressants. Recent studies in
      mouse models and in humans have identified a key role of IL-17 and TH17 cells in the
      pathogenesis of inflammation and autoimmunity as well as in host defense against certain
      pathogens.

      Meanwhile, there are some studies using Chinese herbs to modulate CD4 TH17 immunity. Compound
      extracted from Chinese herbs, such as berberine exhibited potent efficacy inhibiting TH17 in
      the EAE model. Triptolide also inhibited collagen-induced arthritis (CIA), a model of
      rheumatoid arthritis, through inhibition of CD4 TH17 cells. Periplocoside A was found to
      ameliorate EAE by suppressing IL-17 production and inhibited the differentiation of Th17
      cells in vitro. Eriocalyxin B was also found to be effective to inhibit TH17 and EAE through
      targeting Janus Kinase/Signal Transducer and Activator Of Transcription and Nuclear
      factor-kappaB signaling pathways. TCM formula such as Qingkailing injection was found to
      ameliorate rat experimental autoimmune uveitis (EAU). Qingkailing injection can alleviate
      autoimmune uveitis in rats, inhibit the differentiation toward Th1 and Th17 effector cells
      and the relevant cytokines secretion. Pure compound from Daphne odora var. marginata (D.
      marginata) was also found to inhibit TH17 and thus exhibit inhibitory effects in CIA model.

      One of the landmark study published in Science and Nature Chemical Biology is the example of
      halofuginone, an active component of traditional Chinese herb hydrangea root (Dichroa
      febrifuga), used to treat malaria for thousands of years. A collaborative research team led
      by Dr. Mark Sundrud at the Department of Pathology, Harvard Medical School and Immune Disease
      Institute, Boston, MA, has reported that halofuginone halted the progression of experimental
      autoimmune encephalomyelitis (EAE) mice and TH17. Importantly, unlike other therapies for
      autoimmune diseases, halofuginone does not have the undesirable effect of suppressing the
      other immune system.

      The investigators have established some platforms for screening Chinese herbs not only for
      modulating PD-1/PD-L1, IL-17, but also for detection of dendritic cell and T cell activation
      (Immunogen Test Panel).

      The hypothesis is that modulation of dendritic cells and T cells by traditional Chinese
      medicine may be an applicable intervention to treat some of the immunologic diseases such as
      cancer, allergy, and autoimmune diseases. Studies that can fit the niche, understanding the
      function and mechanism of Chinese herbs on immune cells and its pathway, will have broad
      clinical and immunological significance. The successful completion of the proposed studies
      will provide a strong support for a clinical trial of traditional Chinese medicine to treat
      patients with immunologic diseases.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: The IL-2, TNF-alpha and IFN-gamma expression by traditional Chinese medicine treatment on cancer patients
time frame: one year
description: The cytokines expression of immune cells in the blood by traditional Chinese medicine treatment in breast cancer, colon-rectal cancer, ovarian cancer, and endometrial cancer will be investigated.
arm group label: cancer of breast, colorectal, ovarian and endometrial
arm group type: Other
description: Patient who diagnostic of Breast cancer, Colorectal cancer, cancer of Ovary, and cancer of Endometrial are can recruit.
intervention type: Other
intervention name: Cases for patients diagnosed with breast cancer, colonrectal cancer, ovarian cancer and endometrial cancer
description: Diagnosis and acceptance of breast cancer, colon rectal cancer, ovarian cancer, and endometrial cancer by the clinical Western medicine team.
arm group label: cancer of breast, colorectal, ovarian and endometrial
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: China Medicine University
role: Study Chair
affiliation: China Medicine University
last name: Hung-Rong NA Yen
phone: 04-22053366
phone ext: 3005
email: hungrongyen@gmail.com
facility: 
status: Recruiting
contact: 
country: Taiwan
responsible party type: Sponsor
mesh term: Endometrial Neoplasms
mesh term: Ovarian Neoplasms