The document discusses evidence that hepatobiliary cancers can arise from stem cells based on several studies. It describes how stem cell mutations from chronic diseases can lead to carcinogenesis. While mutations can occur in any cell type, many hepatobiliary tumors contain cancer stem cells that have properties making them resistant to therapy and able to initiate tumor recurrence. Successful treatments may depend on targeting these cancer stem cells.
This is a lecture from the Ghana Emergency Medicine Collaborative (GEMC). To download the editable version (in PPT), to access additional learning modules, or to learn more about the project, see http://openmi.ch/em-gemc.
Brief description on the benign tumors of liver that includes hemangioma, focal nodular hyperplasia, regenerative nodular hyperplasia, dysplastic foci, dysplastic nodules and focal fatty change.
This is a lecture from the Ghana Emergency Medicine Collaborative (GEMC). To download the editable version (in PPT), to access additional learning modules, or to learn more about the project, see http://openmi.ch/em-gemc.
Brief description on the benign tumors of liver that includes hemangioma, focal nodular hyperplasia, regenerative nodular hyperplasia, dysplastic foci, dysplastic nodules and focal fatty change.
Sentience Everywhere: Complexity and the Role of Sentience in a Self-Organizi...Neil Theise
How viewing the world as a hierarchy of complex adaptive systems maps to quantum physics, insights about the structure of the universe from spiritual/contemplative traditions, and the relationships of these concepts to understanding the nature of consciousness.
Alternative models of the body: Opening science to cross-cultural dialogueNeil Theise
Complexity theory approaches to biology and universal structure. This construct may provide a linguistic and perhaps mathematical way to cross cultural boundaries when discussing biology, medicine, and healing.
Exosomes are smallest extracellular vesicles of size 30 to 100 nm originated from late endosomes. These are released by broad array of cells including B‐ cells, cells, dendritic cells (DCs), T‐cells, epithelial cells,
platelets and many more.
A seminar I gave as a PhD student reviewing the role of stem cells in the development of various different kinds of cancers, as well as emerging treatment options.
A normal cell can be transformed into a cancerous cell. Discuss the therapeutic strategies that are employed to target the cellular transformation process for cancer prevention and treatment.
Cirrhosis results from different mechanisms of liver injury that lead to necroinflammation and fibrogenesis; Patients
with liver cirrhosis often require liver transplantation but it is affected by many problems, including relative operative
damage, high costs, lack of donors, and risk of rejection. Currently studies are shown the Stem cell therapy has the
potential to provide a valuable adjunct to the management of disease, Stem cell should be the natural candidates to
provide a renewable source of cells for transplantation.
The main mechanism of stem cell therapy is that stem cell capacity to differentiate into any of the hundreds of distinct
cell types that comprise the human body. In addition to their potential in therapeutics can be used to study the earliest
stages of human development and disease modeling using human cells.
Keywords: Cell Therapy; Liver Cirrhosis; Stem Cell; Transplantation. limitlessly, and often play the principal role in
liver regeneration
GROUP 1 Case 967-- A Teenage Female with an Ovarian MassCLI.docxgilbertkpeters11344
GROUP 1: Case 967-- A Teenage Female with an Ovarian Mass
CLINICAL HISTORY
A teenage female presented with secondary amenorrhea (https://www.healthline.com/health/secondary-amenorrhea#causes). The patient had 1 menstrual cycle 3 years ago and has had no menses since. Laboratory work-up was negative for pregnancy test, mildly increased calcium level (11.7 mg/dL, normal range: 8.5-10.2 mg/dL) and CA 125 (43 Units/ml, normal range: 0-20 Units/ml). Prolactin, TSH, AFP, Inhibin A, Inhibin B and CEA were normal. Imaging revealed a 13 x 11.8 x 8.6 cm, predominately cystic left pelvis mass, with multiple internal septations. Her past medical history was not contributory. Patient underwent left salpingo-oophorectomy (https://www.healthline.com/health/salpingo-oophorectomy), omentectomy (https://moffitt.org/cancers/ovarian-cancer/omentectomy/) and tumor debulking (https://en.wikipedia.org/wiki/Debulking) with intraoperative frozen section consultation.
GROSS EXAMINATION
The 930.9 g tubo-ovarian complex consisted of a 20.0 x 16.0 x 8.0 cm large mass, with no recognizable normal ovarian parenchyma grossly and an unremarkable fallopian tube. The cut surface was gray, "fish-flesh", soft with foci of hemorrhage and necrosis.
MICROSCOPIC EXAMINATION
Microscopically, the majority of main tumor was growing in large nests, sheets and cords with focal follicle-like structures and geographic areas of necrosis. It was predominantly composed of small cells with hyperchromatic nuclei, round to oval nucleus with irregular nuclear contour, inconspicuous to occasional conspicuous nucleoli and minimal cytoplasm. This component was variably admixed with a population of larger cells, which as the name implies composed of cells with abundant eosinophilic cytoplasm, with central or eccentric round to oval nuclei, pale chromatin and prominent nuclei. Both, the small and large cell components demonstrated brisk mitotic activity. All staging biopsies and omentectomy were composed of large cell component.
An extensive panel of immunohistochemical stains was performed. Overall, the staining pattern was strong and diffuse in small cell component compared to patchy weak staining pattern in the large cell component.
FINAL DIAGNOSIS
Small cell carcinoma (https://en.wikipedia.org/wiki/Small-cell_carcinoma) of the ovary, hypercalcemic type (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939673/)
DISCUSSION
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive and highly malignant tumor affecting the women under 40. It was first described as a distinct entity by Dickersin et al in 1982 (1). Fewer than 500 cases have been described in the literature and it accounts for less than 1% of all ovarian cancer diagnoses. Due to the initial consideration of epithelial origin, the term of SCCOHT has been used to distinguish this entity from its mimicker, the neuroendocrine or pulmonary type (2). In fact epithelial origin of SCCOHT was recently challenged as new imm.
Discovering a "new organ": Tales of the InterstitiumNeil Theise
In vivo microscopy in humans reveals interstitial spaces with novel anatomy never before recognized, in every tissue and organ of the body. The fluid filled spaces comprise 20% of the volume of the body and they and the collagen bundles and lining cells that define the spaces is therefore the largest "organ" of the body.
Stem Cells, Complexity, and the Science of BeingNeil Theise
Implications of the universe as a self-organizing system. Bodies are comprised of cells, Cells are comprised of molecules. Molecules are comprised of atoms. Atoms are comprised of subatomic particles. Subatomic particles arise from the smallest possible entities (e.g. strings?), and these arise from the energy rich vacuum in a quantum foam. "Everything only looks like a thing"
Non material beings in a non-material worldNeil Theise
Our daily experience tells us that the world and our bodies are material things, made of “stuff.” Our Buddhist traditions however tell us otherwise, that the appearance of materiality is an illusion.
In past talks Dr. Neil Soten Theise has described his views that the universe is not material, but arises from the self-organization of quantum level entities that themselves arise out of pure Fundamental Awareness. Thus, contemporary science and philosophy can also view the world and ourselves as non-material.
But what of the non-material beings that fill Zen study texts and liturgy? Are they merely myths, metaphors, or Jungian archetypes? Or is it possible that gods, demons, angels, spirits are also as “real” as each of us? Can the Fundamental Awareness framework shed light on what is “real” and what is “not real” for us – living, sentient beings – in a non-material world?
1. Stem Cells and Hepatocarcinogenesis Neil Theise, MD Depts. of Pathology and Medicine Beth Israel Medical Center – Albert Einstein College of Medicine New York City www.neiltheise.com
2. Differentiation-Inducing Activity of Hydroxycamptothecin on Cancer Stem-Like Cells Derived from Hepatocellular Carcinoma. Zhang Y, Song WJ, Zhang FQ, Liu WH, Dou KF. Dig Dis Sci. 2011 Immunohistochemical study of hepatocyte, cholangiocyte and stem cell markers of hepatocellular carcinoma. Shibuya M, Kondo F, Sano K, Takada T, Asano T. J Hepatobiliary Pancreat Sci. 2011 MicroRNAs involved in neoplastic transformation of liver cancer stem cells. Li R, Qian N, Tao K, You N, Wang X, Dou K. J Exp Clin Cancer Res. 2010 Dec 23;29:169. Complete response in 5 out of 38 patients with advanced hepatocellular carcinoma treated with stem cell differentiation stage factors: case reports from a single centre. Livraghi T, Ceriani R, Palmisano A, Pedicini V, Pich MG, Tommasini MA, Torzilli G. Curr Pharm Biotechnol. 2011 Lupeol targets liver tumor-initiating cells through phosphatase and tensin homolog modulation. Lee TK, Castilho A, Cheung VC, Tang KH, Ma S, Ng IO. Hepatology. 2011 Jan;53(1):160-70. The cyclin E regulator cullin 3 prevents mouse hepatic progenitor cells from becoming tumor-initiating cells. Kossatz U, Breuhahn K, Wolf B, Hardtke-Wolenski M, Wilkens L, Steinemann D, Singer S, Brass F, Kubicka S, Schlegelberger B, Schirmacher P, Manns MP, Singer JD, Malek NP. J Clin Invest. 2010 Nov 1;120(11):3820-33 Invasion and EMT-associated genes are up-regulated in B viral hepatocellular carcinoma with high expression of CD133-human and cell culture study. Na DC, Lee JE, Yoo JE, Oh BK, Choi GH, Park YN. Exp Mol Pathol. 2011 Feb;90(1):66-73 Characterization of the epithelial cell adhesion molecule (EpCAM)+ cell population in hepatocellular carcinoma cell lines. Kimura O, Takahashi T, Ishii N, Inoue Y, Ueno Y, Kogure T, Fukushima K, Shiina M, Yamagiwa Y, Kondo Y, Inoue J, Kakazu E, Iwasaki T, Kawagishi N, Shimosegawa T, Sugamura K. Cancer Sci. 2010 Oct;101(10):2145-5 Cytoplasmic expression of CD133 is an important risk factor for overall survival in hepatocellular carcinoma. Sasaki A, Kamiyama T, Yokoo H, Nakanishi K, Kubota K, Haga H, Matsushita M, Ozaki M, Matsuno Y, Todo S. Oncol Rep. 2010 Aug;24(2):537-46. Collecting evidence for a stem cell hypothesis in HCC. Teufel A, Galle PR. Gut. 2010 Jul;59(7):870-1Expression of Oct4 in HCC and modulation to wnt/βcatenin and TGF-β signal pathways. Yuan F, Zhou W, Zou C, Zhang Z, Hu H, Dai Z, Zhang Y. Mol Cell Biochem. 2010 Oct;343(1-2):155-62Characterization of the epithelial cell adhesion molecule (EpCAM)+ cell population in hepatocellular carcinoma cell lines. Kimura O, Takahashi T, Ishii N, Inoue Y, Ueno Y, Kogure T, Fukushima K, Shiina M, Yamagiwa Y, Kondo Y, Inoue J, Kakazu E, Iwasaki T, Kawagishi N, Shimosegawa T, Sugamura K Cancer Sci. 2010 Oct;101(10):2145-55Oncostatin m renders epithelial cell adhesion molecule-positive liver cancer stem cells sensitive to 5-Fluorouracil by inducing hepatocytic differentiation. Yamashita T, Honda M, Nio K, Nakamoto Y, Yamashita T, Takamura H, Tani T, Zen Y, Kaneko S. Cancer Res. 2010 Jun 1;70(11):4687-97EpCAM, a new marker for cancer stem cells in hepatocellular carcinoma. Terris B, Cavard C, Perret C. J Hepatol. 2010 Feb;52(2):280-1. What is the relationship among microRNA-181, epithelial cell-adhesion molecule (EpCAM) and beta-catenin in hepatic cancer stem cells. Li JP, Zheng JY, Du JJ, Zhang R, Yang AG. Hepatology. 2009 Dec;50(6):2047-Hepatic progenitor cells in liver cancers from Asian children. Ward SC, Thung SN, Lim KH, Tran TT, Hong TK, Hoang PL, Jang JJ, Park YN, Abe K. Liver Int. 2010 Jan;30(1):102-11EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Yamashita T, Ji J, Budhu A, Forgues M, Yang W, Wang HY, Jia H, Ye Q, Qin LX, Wauthier E, Reid LM, Minato H, Honda M, Kaneko S, Tang ZY, Wang XW. Gastroenterology. 2009 Mar;136(3):1012-24Immunohistochemical staining of cancer stem cell markers in hepatocellular carcinoma. Lingala S, Cui YY, Chen X, Ruebner BH, Qian XF, Zern MA, Wu J. Exp Mol Pathol. 2010 Aug;89(1):27-35.
3. Neil Theise, MD Depts. of Pathology and Medicine Beth Israel Medical Center – Albert Einstein College of Medicine New York City www.neiltheise.com Cancer and Stem Cells and Stem Cell-derived Cancer and Cancer-derived Stem Cells and… and… and… and…
4. This talk has been posted on: www.slideshare.net Search: “Neil Theise”
17. Keratin 19 CD117 (c-kit) CD90 (thy-1) EpCAM CD 133 (prominin-1) ABC-G2 stem cell transit amplifying cells “ Side Population”
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22. 1. Combined HCC-ChC 2. Combined HCC-ChC with stem cell features A. typical subtype B. intermediate cell subtype C. cholangiocellular subtype Chapter 10-4, N. D. Theise, O. Nakashima, Y. N. Park, Y. Nakanuma
27. Immortal Strand Hypothesis Stem cell retention of original DNA template after replication and division SO: STEM CELLS SHOULD REMAIN FREE OF MUTATIONS
28. Disordered stem cell retention of original DNA template in chronic disease e.g. inflammatory bowel disease primary sclerosing cholangitis mammary fibrocystic disease chronic viral hepatitis H. pylori gastritis
55. In summary: Cancers can arise from stem cells or Cancers can arise from differentiated cells
56. In summary: Cancers can arise from stem cells or Cancers can arise from differentiated cells “ Cancer stem cells” may refer to the stem cells from which cancers start, BUT generally refer to:
57. In summary: Cancers can arise from stem cells or Cancers can arise from differentiated cells “ Cancer stem cells” can refer to the stem cells from which some cancers start, BUT generally refer to the: cells within a tumor that have stem cell-like properties :
58. In summary: Cancers can arise from stem cells or Cancers can arise from differentiated cells “ Cancer stem cells” can refer to the stem cells from which some cancers start, BUT generally refer to the: cells within a tumor that have stem cell like properties: i.e. slow cycling self-renewal multidrug resistance hypoxia resistant radio-insensitive
59. In summary: Cancers can arise from stem cells or Cancers can arise from differentiated cells “ Cancer stem cells” can refer to the stem cells from which some cancers start, BUT generally refer to the: cells within a tumor that have stem cell like properties: i.e. slow cycling self-renewal multidrug resistance hypoxia resistant radio-insensitive and therefore are resistant to therapy and responsible for tumor recurrence…
60. cells within a tumor that have stem cell like properties: i.e. slow cycling self-renewal multidrug resistance hypoxia resistant radio-insensitive and therefore are resistant to therapy and responsible for tumor recurrence… Antigenic Markers : CD133 c-kit EpCAM Keratin 19 Functional Markers : Side population Label retaining cells
61. Epigenetic regulation of cancer stem cells in liver cancer: current concepts and clinical implications. Marquardt JU, Factor VM, Thorgeirsson SS. J Hepatol. 2010; 53: 568. Stem cell plasticity: recapping the decade, mapping the future. Theise ND. Exp Hematol. 2010; 38: 529. FURTHER READING