In the eighth decade of the last century extensive clinical delayed-type hypersensitivity (DTH) skin tests to an intradermal injection of a pharmaceutical allogeneic human Placenta Suspension (phPS) performed in obste...In the eighth decade of the last century extensive clinical delayed-type hypersensitivity (DTH) skin tests to an intradermal injection of a pharmaceutical allogeneic human Placenta Suspension (phPS) performed in obstetrical, gynecological and control group patients have shown positive reaction in 239 patients with clinical conditions having been as histopatrhological substratum, a hypoxia-induced adaptive/reactive epithelial cell proliferation, e.g. syncytiotrophoblastic cell hyperplasia, endometrial cell hyperplasia, or different gynecological cancers. Because the immune response against phPS has shown antigenc similarities between normal placental and endometrial hyperplastic cells and different kinds of cancer cells and because many cancers adopt an embryonic stem-like gene expression pattern, it is suggested that the profile of hypoxia-promoting placental and endometrial stem cell proliferation is more embryonic-like, and that the immune respose against phPS is expected to cross-react with tumor cells in vivo. In the process of persistent growth and accelerated oxygen consumption by hyperplastic cytotrophoblastic cells and neoplastic cells in a hypoxic microenvironment, a basic shift in energy metabolism is accompanied by appearance of heat shock proteins (HSPs), of fetal isoenzymes and of membrane glycoproteins (reappearance of oncofetal antigens, OFAs), which, as result of their overexpression/amplification may induce a host immunological response. Thus, it is assumed that phPS prepared from full-term human placentas delivered after a spontaneous labor comprises stem/progenitor cells reverted to a proliferative embryonic stem cell-like-state upon exposure to labor-inducing intrmittent placental hypoxia and that by expressing HSP/OFAs could immunize to generate immune response againjst a variety of antigens that are shared by different kinds of epithelial cancers. This immunological feature of phPS qualifies is as a vaccine-related product that may be used for a preventive cancer vaccine when mixed with a potent adjuvant (BCG-Vaccine) and given normal healthy individuals.展开更多
Ovarian cancer is the deadliest gynecological malignancy.It is typically diagnosed at advanced stages of the disease,with metastatic sites disseminated widely within the abdominal cavity.Ovarian cancer treatment is ch...Ovarian cancer is the deadliest gynecological malignancy.It is typically diagnosed at advanced stages of the disease,with metastatic sites disseminated widely within the abdominal cavity.Ovarian cancer treatment is challenging due to high disease recurrence and further complicated pursuant to acquired chemoresistance.Cancer stem cell(CSC)theory proposes that both tumor development and progression are driven by undifferentiated stem cells capable of self-renewal and tumor-initiation.The most recent evidence revealed that CSCs in terms of ovarian cancer are not only responsible for primary tumor growth,metastasis and relapse of disease,but also for the development of chemoresistance.As the elimination of this cell population is critical for increasing treatment success,a deeper understanding of ovarian CSCs pathobiology,including epithelial-mesenchymal transition,signaling pathways and tumor microenvironment,is needed.Finally,before introducing new therapeutic agents for ovarian cancer,targeting CSCs,accurate identification of different ovarian stem cell subpopulations,including the very small embryoniclike stem cells suggested as progenitors,is necessary.To these ends,reliable markers of ovarian CSCs should be identified.In this review,we present the current knowledge and a critical discussion concerning ovarian CSCs and their clinical role.展开更多
Accidental radiation exposure and the threat of deliberate radiation exposure have been in the news and are a public health concern. Experience with acute radiation sickness has been gathered from atomic blast survivo...Accidental radiation exposure and the threat of deliberate radiation exposure have been in the news and are a public health concern. Experience with acute radiation sickness has been gathered from atomic blast survivors of Hiroshima and Nagasaki and from civilian nuclear accidents as well as experience gained during the development of radiation therapy for cancer. This paper reviews the medical treatment reports relevant to acute radiation sickness among the survivors of atomic weapons at Hiroshima and Nagasaki, among the victims of Chernobyl, and the two cases described so far from the Fukushima Dai-Ichi disaster. The data supporting the use of hematopoietic stem cell transplantation and the new efforts to expand stem cell populations ex vivo for infusion to treat bone marrow failure are reviewed. Hematopoietic stem cells derived from bone marrow or blood have a broad ability to repair and replace radiation induced damaged blood and immune cell production and may promote blood vessel formation and tissue repair. Additionally, a constituent of bone marrow-derived, adult pluripotent stem cells, very small embryonic like stem cells, are highly resistant to ioniz-ing radiation and appear capable of regenerating radiation damaged tissue including skin, gut and lung.展开更多
文摘In the eighth decade of the last century extensive clinical delayed-type hypersensitivity (DTH) skin tests to an intradermal injection of a pharmaceutical allogeneic human Placenta Suspension (phPS) performed in obstetrical, gynecological and control group patients have shown positive reaction in 239 patients with clinical conditions having been as histopatrhological substratum, a hypoxia-induced adaptive/reactive epithelial cell proliferation, e.g. syncytiotrophoblastic cell hyperplasia, endometrial cell hyperplasia, or different gynecological cancers. Because the immune response against phPS has shown antigenc similarities between normal placental and endometrial hyperplastic cells and different kinds of cancer cells and because many cancers adopt an embryonic stem-like gene expression pattern, it is suggested that the profile of hypoxia-promoting placental and endometrial stem cell proliferation is more embryonic-like, and that the immune respose against phPS is expected to cross-react with tumor cells in vivo. In the process of persistent growth and accelerated oxygen consumption by hyperplastic cytotrophoblastic cells and neoplastic cells in a hypoxic microenvironment, a basic shift in energy metabolism is accompanied by appearance of heat shock proteins (HSPs), of fetal isoenzymes and of membrane glycoproteins (reappearance of oncofetal antigens, OFAs), which, as result of their overexpression/amplification may induce a host immunological response. Thus, it is assumed that phPS prepared from full-term human placentas delivered after a spontaneous labor comprises stem/progenitor cells reverted to a proliferative embryonic stem cell-like-state upon exposure to labor-inducing intrmittent placental hypoxia and that by expressing HSP/OFAs could immunize to generate immune response againjst a variety of antigens that are shared by different kinds of epithelial cancers. This immunological feature of phPS qualifies is as a vaccine-related product that may be used for a preventive cancer vaccine when mixed with a potent adjuvant (BCG-Vaccine) and given normal healthy individuals.
文摘Ovarian cancer is the deadliest gynecological malignancy.It is typically diagnosed at advanced stages of the disease,with metastatic sites disseminated widely within the abdominal cavity.Ovarian cancer treatment is challenging due to high disease recurrence and further complicated pursuant to acquired chemoresistance.Cancer stem cell(CSC)theory proposes that both tumor development and progression are driven by undifferentiated stem cells capable of self-renewal and tumor-initiation.The most recent evidence revealed that CSCs in terms of ovarian cancer are not only responsible for primary tumor growth,metastasis and relapse of disease,but also for the development of chemoresistance.As the elimination of this cell population is critical for increasing treatment success,a deeper understanding of ovarian CSCs pathobiology,including epithelial-mesenchymal transition,signaling pathways and tumor microenvironment,is needed.Finally,before introducing new therapeutic agents for ovarian cancer,targeting CSCs,accurate identification of different ovarian stem cell subpopulations,including the very small embryoniclike stem cells suggested as progenitors,is necessary.To these ends,reliable markers of ovarian CSCs should be identified.In this review,we present the current knowledge and a critical discussion concerning ovarian CSCs and their clinical role.
文摘Accidental radiation exposure and the threat of deliberate radiation exposure have been in the news and are a public health concern. Experience with acute radiation sickness has been gathered from atomic blast survivors of Hiroshima and Nagasaki and from civilian nuclear accidents as well as experience gained during the development of radiation therapy for cancer. This paper reviews the medical treatment reports relevant to acute radiation sickness among the survivors of atomic weapons at Hiroshima and Nagasaki, among the victims of Chernobyl, and the two cases described so far from the Fukushima Dai-Ichi disaster. The data supporting the use of hematopoietic stem cell transplantation and the new efforts to expand stem cell populations ex vivo for infusion to treat bone marrow failure are reviewed. Hematopoietic stem cells derived from bone marrow or blood have a broad ability to repair and replace radiation induced damaged blood and immune cell production and may promote blood vessel formation and tissue repair. Additionally, a constituent of bone marrow-derived, adult pluripotent stem cells, very small embryonic like stem cells, are highly resistant to ioniz-ing radiation and appear capable of regenerating radiation damaged tissue including skin, gut and lung.
