察爾斯大夫 美麗殿堂 Dr. Charles Meridien Palace

Epitope：Antigenic determinant抗原決定位、抗原表位

Epitope, also known as Antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that recognizes the epitope is called a Paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized are also epitopes.

The epitopes of protein antigens are divided into two categories, Conformational epitopes and Linear epitopes, based on their structure and interaction with the paratope. A conformational epitope is composed of discontinuous sections of the antigen's amino acid sequence. These epitopes interact with the paratope based on the 3-D surface features and shape or tertiary structure of the antigen. The proportion of epitopes that are conformational is unknown.

By contrast, linear epitopes interact with the paratope based on their primary structure. A linear epitope is formed by a continuous sequence of amino acids from the antigen.

Epitope抗原決定位、抗原表位：是指抗原表面上決定抗原特異性的化學基團。

抗原表位可被免疫系統（尤其是抗體、B細胞或者T細胞）所識別。抗體中能識別抗原表位的區域叫做「互補位」或「抗體決定簇」（Paratope）。儘管通常抗原表位是指外來蛋白質等物質的其中一部分，但只要能被自身免疫系統所識別的表位，也被歸為抗原表位。

蛋白質抗原的表位根據它們的結構以及與互補位的交互作用，被分為構象表位Conformational epitopes和線性表位Linear epitopes這兩種類型。其中構象表位有抗原胺基酸序列中的不連續部分組成，因此互補位和抗原表位的交互作用是基於表面的三位特徵和形狀，或者是抗原的三級結構。大部分的抗原表位都屬於構象表位。與此相反，線性表位是由一段連續的抗原胺基酸序列構成，與抗原的交互作用的基礎是其一級結構。

抗原被抗体辨識或結合的地方叫抗原決定位antigenic determinant或epitope。

抗原上的決定位通常含6～8個胺基酸，它可以是三度空間的構造conformation structure，如抗体結合到蛋白質暴露在外面的位置，如果將蛋白質變性，另一種抗原決定位是二度空間的構造sequence determinant，T-細胞所辨認的抗原決定位，便是此種一連串胺基酸組成的抗原決定位，它和主要組織相容抗原（Major histocompatibility complex；MHC）上的class I/II在一起，而與T-細胞上的T-細胞受器（T cell receptor，TCR）結合，一個抗原通常有好幾個抗原決定位，構造越複雜，分子量越大，它的抗原決定位愈多。T-細胞和B-細胞辨認的抗原決定位可以是不同的。

APC：Antigen-presenting cell

An Antigen-presenting cell（APC）or Accessory cell is a cell that displays foreign antigens complexed with Major histocompatibility complexes（MHC's）on their surfaces. T-cells may recognize these complexes using their T-cell receptors（TCRs）. These cells process antigens and present them to T-cells.

APCs fall into two categories：professional or non-professional.

T cells cannot recognize, and therefore cannot respond to, 'free' antigen. T cells can only 'see' an antigen that has been processed and presented by cells via carrier molecules like MHC and CD1 molecules. Most cells in the body can present antigen to CD8+ T cells via MHC class I molecules and, thus, act as "APCs"; however, the term is often limited to specialized cells that can prime T cells（i.e., activate a T cell that has not been exposed to antigen, termed a naive T cell）. These cells, in general, express MHC class II as well as MHC class I molecules, and can stimulate CD4+（helper）cells as well as CD8+（cytotoxic）T cells, respectively.

Almost all nucleated cells express MHC class I receptors, including professional APCs. If a virus infects a macrophage or dendritic cell, it will try to promote its own destruction through cytotoxic T cells. However, dendritic cells can ingest viruses through pinocytosis and therefore activate the adaptive immune response to create antibodies for the virus through class II MHC receptors.

To help distinguish between the two types of APCs, those that express MHC class II molecules are often called professional antigen-presenting cells.

Concise review：Adipose-derived stem cells as a novel tool for future regenerative medicine.

Stem Cells. 2012 May;30(5):804-10. doi: 10.1002/stem.1076.

Mizuno H, Tobita M, Uysal AC.

Abstract

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in the genetic manipulation of human ESCs, even though these cells are, theoretically, highly beneficial.

Mesenchymal stem cells seem to be an ideal population of stem cells for practical regenerative medicine, because they are not subjected to the same restrictions. In particular, large number of Adipose-derived stem cells (ASCs) can be easily harvested from adipose tissue. Furthermore, recent basic research and preclinical studies have revealed that the use of ASCs in regenerative medicine is not limited to Mesodermal tissue but extends to both Ectodermal and Endodermal tissues and organs, although ASCs originate from mesodermal lineages. Based on this background knowledge, the primary purpose of this concise review is to summarize and describe the underlying biology of ASCs and their proliferation and differentiation capacities, together with current preclinical and clinical data from a variety of medical fields regarding the use of ASCs in regenerative medicine. In addition, future directions for ASCs in terms of cell-based therapies and regenerative medicine are discussed.

Copyright © 2012 AlphaMed Press.

Monocytes can be used to generate Dendritic cells in vitro by adding Cytokines（Granulocyte Monocyte Colony Stimulating Factor；GMCSF）and IL-4.

Phenotype表現型：Expression of an organism's Genes

Phenotype（from Greek phainein, 'to show' + typos, 'type'）is the composite of an organism's observable characteristics or traits, such as its morphology, development, biochemical or physiological properties, phenology, behavior, and products of behavior.

Phenotypes result from the expression of an organism's genes as well as the influence of environmental factors and the interactions between the two. When two or more clearly different phenotypes exist in the same population of a species, it is called polymorph.

The genotype of an organism is the inherited instructions it carries within its genetic code. Not all organisms with the same genotype look or act the same way because appearance and behavior are modified by environmental and developmental conditions. Likewise, not all organisms that look alike necessarily have the same genotype.

This genotype-phenotype distinction was proposed by Wilhelm Johannsen in 1911 to make clear the difference between an organism's heredity and what that heredity produces. The distinction is similar to that proposed by August Weismann, who distinguished between germ plasm (heredity) and somatic cells (the body). The genotype-phenotype distinction should not be confused with Francis Crick's central dogma of molecular biology, which is a statement about the directionality of molecular sequential information flowing from DNA to protein, and not the reverse.

一個基因的不同形式（例如S或s），稱為「對偶基因」（alleles）。當產生「配子」（gamate）時，這兩個對偶基因會分開。一個來自花粉的配子和一個來自柱頭的配子授粉後產生「合子」（zygote）。如果合子的對偶基因相同，則為「同基因合子」（homozygote），例如SS與ss。如果結合子的對偶基因不同，則為「異基因合子」（heterozygote），例如Ss。

後來出現「基因型」（genotype）和「表現型」（phenotype）這兩個名詞。外在表現的特徵稱為表現型，而表現型是由基因型來決定。SS與Ss雖擁有不同的基因型，卻有相同的表現型。我們如何能夠分辨SS和Ss呢？讓它們和ss（皺皮）種交配。交配得到的後代應該是平滑（Ss）與皺皮（ss）的比例各佔一半。這種鑑定基本型的方法稱為Testcross。

Epigenetics 表觀遺傳學

In biology, and specifically genetics, epigenetics is the study of heritable changes in gene activity that are not caused by changes in the DNA sequence; it also can be used to describe the study of stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable. Unlike simple genetics based on changes to the DNA sequence（the genotype）, the changes in gene expression or cellular phenotype of epigenetics have other causes.

The name epi-（Greek: επί- over, outside of, around）-genetics.

The term also refers to the changes themselves：functionally relevant changes to the genome that do not involve a change in the nucleotide sequence. Examples of mechanisms that produce such changes are DNA methylation and Histone modification, each of which alters how genes are expressed without altering the underlying DNA sequence. Gene expression can be controlled through the action of repressor proteins that attach to silencer regions of the DNA.

These epigenetic changes may last through cell divisions for the duration of the cell's life, and may also last for multiple generations even though they do not involve changes in the underlying DNA sequence of the organism; instead, non-genetic factors cause the organism's genes to behave or "express themselves" differently.

One example of an epigenetic change in eukaryotic biology is the process of Cellular differentiation. During morphogenesis, totipotent stem cells become the various pluripotent cell lines of the embryo, which in turn become fully differentiated cells. In other words, as a single fertilized egg cell – the zygote – continues to divide, the resulting daughter cells change into all the different cell types in an organism, including neurons, muscle cells, epithelium, endothelium of blood vessels, etc., by activating some genes while inhibiting the expression of others.

In 2011, it was demonstrated that the Methylation of mRNA plays a critical role in human energy homeostasis. The Obesity-associated FTO gene is shown to be able to demethylate N6-methyladenosine in RNA. This discovery launched the subfield of RNA epigenetics.

表觀遺傳學（Epigenetics），又稱「擬遺傳學」、「表遺傳學」、「外遺傳學」以及「後遺傳學」（Epigenetics），在生物學和特定的遺傳學領域，其研究的是在不改變DNA序列的前提下，通過某些機制引起可遺傳的基因表達或細胞表現型的變化。

表觀遺傳學是20世紀80年代逐漸興起的一門學科，是在研究與經典的孟德爾遺傳學遺傳法則不相符的許多生命現象過程中逐步發展起來的。

表觀遺傳現象包括DNA甲基化、RNA干擾、組蛋白修飾等。與經典遺傳學以研究基因序列影響生物學功能為核心相比，表觀遺傳學主要研究這些「表觀遺傳現象」建立和維持的機制。其研究內容主要包括兩類，一類為基因選擇性轉錄表達的調控，有DNA甲基化、基因印記、組蛋白共價修飾和染色質重塑；另一類為基因轉錄後的調控，包括基因組中非編碼RNA、微小RNA、反義RNA、內含子及核糖開關等。

表觀遺傳學指基因組相關功能改變而不涉及核苷酸序列變化。例如DNA甲基化和組蛋白修飾，兩者均能在不改變DNA序列的前提下調節基因的表達；阻遏蛋白通過結合沉默基因從而控制基因的表達。這些變化可能可以通過細胞分裂而得以保留，並且可能持續幾代。這些變化都僅是非基因因素導致的生物體基因表現（或「自我表達」）的不同，由於目前尚不清楚組蛋白的化學修飾是否可遺傳，有人對於用此術語描述組蛋白化學修飾提出了異議。

表觀遺傳學在真核生物中主要表現在細胞分化過程。在胚胎形態形成過程中，全能幹細胞將分化成完全不同的細胞，也就是說，一個受精卵細胞分化出各種不同類型的細胞，包括神經細胞、肌肉細胞、上皮細胞、血管內皮細胞等，並通過抑制其他細胞和激活相關基因而進行持續的細胞分裂。

2011年的相關研究已證實，mRNA甲基化對人體內能量平衡發揮著至關重要的作用，對RNA上的N6-甲基腺苷進行脫甲基治療可控制FTO基因相關肥胖症，並因此而開創了RNA表觀遺傳學的相關領域。

PBMC：Peripheral blood mononucleated（mononuclear）cell

A peripheral blood mononucleated cell（PBMC）is any blood cell having a round nucleus（opposed to a lobed nucleus）. For example：a lymphocyte, a monocyte or a macrophage. These blood cells are a critical component in the immune system to fight infection and adapt to intruders.

The lymphocyte population consists of T cells（CD4 and CD8 positive～75%）, B cells and NK cells（～25% combined）.

These cells can be extracted from whole blood using Ficoll™, a hydrophilic polysaccharide that separates layers of blood, which will separate the blood into a top layer of plasma, followed by a layer of PBMCs and a bottom fraction of polymorphonuclear cells (such as neutrophils and eosinophils) and erythrocytes. The polymorphonuclear cells can be further isolated by lysing the red blood cells.

PBMCs are widely used in research and clinical applications.

PBSCT：Peripheral stem cell transplantation周邊血液幹細胞移植

Peripheral blood stem cell transplantation（PBSCT）, also called peripheral stem cell support, is a method of replacing blood-forming stem cells destroyed, for example, by cancer treatment.

PBSCT is now a much more common procedure than its bone marrow harvest equivalent, this is in-part due to the ease and less invasive nature of the procedure.

Studies suggest, that PBSCT has a better outcomes in terms of the number of hematopoietic stem cell（CD34+ cells）yield.[4]

Immature blood cells hematopoietic stem cells in the circulating blood that are similar to those in the bone marrow are collected by apheresis from a potential donor（PBSC collection）. The product is then administered Intravenously to the patient after treatment.

The administered hematopoietic stem cells then migrate to the recipients bone marrow, a process known as Stem cell homing, where the transplanted cells override the previous bone marrow. This allows the bone marrow to recover, proliferate and continue producing healthy blood cells.

The transplantation may be Autologous（an individual's own blood cells saved earlier）, Allogeneic（blood cells donated by someone else with matching HLA）, or Syngeneic（blood cells donated by an identical twin）.

The procedure typically lasts for 4～6 hours, depending on the donors total blood volume.

Granulocyte colony stimulating factor（GCSF）are naturally occurring glycoproteins that stimulate white blood cell proliferation. Filgrastim is a synthetic form of GCSF produced in E.coli.

PBSC donors are given a course of GCSF prior to PBSC collection, this ensures a better outcome, as stem cell proliferation increases, thus increasing the number of peripheral stem cells in circulation. The course is usually given over a 4 day period prior to PBSC collection. Mild bone pain usually results due to the excessive stem cell crowding within the bone marrow.

Since allogeneic PBSCT involves transformation of blood between different individuals, this naturally carries more complications than autologous PBSCT. For example, calculations must be made to ensure consistency in the amount of total blood volume between the donor and recipient. If the total blood volume of the donor is less than that of the recipient（such as when a child is donating to an adult）, multiple PBSCT sessions may be required for adequate collection. Performing such a collection in a single setting could result in risks such as hypovolemia, which could lead to cardiac arrest, thus health care providers must exercise careful precaution when considering donor-recipient matching in allogeneic PBSCT.

何謂周邊血液幹細胞移植？

造血幹細胞（Stem cell）平常在骨髓內負責人體白血球，紅血球及血小板的製造，人類出生之後造血幹細胞主要分佈在人體的骨髓中，而周邊血液的造血幹細胞含量極低，無法分離得到足夠幹細胞作為臨床移植用。但是在病人接受高劑量的化學藥物治療，當白血球回升之際，骨髓中的幹細胞會被釋放至周邊血液中，若合併使用GCSF效果更好，才能抽取足夠的幹細胞，經過收集、分離、保存，然後回輸。

周邊血液幹細胞是在1990年代被發展出來的，主要是因為許多病患接受高劑量的化療或TBI，這些治療的毒性主要發生在骨髓造血細胞，一旦骨髓造血細胞被破壞，就無法被抽取利用；然而如事先收集起來的周邊血幹細胞則不受影響，因此可以用於重建骨髓造血細胞的功能。　

周邊血液幹細胞移植的優點

• 不需住院行全身麻醉抽取幹細胞，因此可免除因抽取導致的疼痛及麻醉的危險。

• 比骨髓移植較不受污染，可降低感染、死亡及住院天數。

• 移植後紅血球、白血球的恢復速度加快，血小板的恢復也比骨髓移植快14天以上，使輸血小板次數減少，降低因輸血的致病率及死亡率。

• 降低成本，且有經濟效益。

周邊血液幹細胞移植的用途

• 固態腫瘤的病患接受高劑量治療後，在癌細胞侵犯骨髓時，採用周邊血液幹細胞可減少癌細胞污染的可能性。

• 曾經接受骨盆腔放射線治療，無法從骨髓抽取足夠造血細胞進行自體骨髓移植者，周邊血液細胞是最好替代來源。

• 異體骨髓移植的骨髓移植捐贈者，因故無法收集骨髓時，也可用周邊血液幹細胞來代替。

Genome

The genome is the entirety of an organism's hereditary information.

The genome is encoded either in DNA or, for many types of viruses, in RNA.

The genome includes both the Genes and the Non-coding sequences of the DNA/RNA.

The term was created in 1920 by Hans Winkler, professor of botany at the University of Hamburg, Germany.

The Oxford English Dictionary suggests the name to be a blend of the words Gene and Chromosome.

A few related -ome words already existed—such as biome, rhizome and, more recently, connectome—forming a vocabulary into which genome fits systematically.

Kisspeptin（formerly known as Metastin）：a protein that in humans is encoded by the KISS1 gene

Kisspeptin（formerly known as Metastin）is a protein that in humans is encoded by the KISS1 gene.

Kisspeptin is a G-protein coupled receptor ligand for GPR54.

Kiss1 was originally identified as a human metastasis suppressor gene that has the ability to suppress melanoma and breast cancer metastasis. It recently became clear that Kisspeptin-GPR54 signaling has an important role in initiating secretion of Gonadotropin-releasing hormone（GnRH）at puberty, the extent of which is an area of ongoing research.

Kisspeptins are a family of peptides encoded by the KiSS-1 gene. This gene is located on the long arm of chromosome 1（1q32）and has four exons of which the 5' and 3' exons are only partly translated. The gene product is a 145 amino acid precursor peptide which is cleaved to 54 amino acids in length, which may be further truncated to 14, 13 or 10 amino acid carboxyl terminal fragments. These N-terminally truncated peptides are known as the Kisspeptins and belong to a larger family of peptides known as RFamides which all share a common arginine-phenylalanine-NH2 motif at their C-terminus.

A polymorphism in the terminal exon of this mRNA results in two protein isoforms. An adenosine present at the polymorphic site represents the third position in a stop codon. When the adenosine is absent, a downstream stop codon is utilized and the encoded protein extends for an additional seven amino acid residues.

DC：Dendritic cell

Dendritic cells（DCs）are Antigen-presenting cells（also known as Accessory cells）of the mammalian immune system.

Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system.

They act as messengers between the Innate and the Adaptive immune systems.

Dendritic cells are present in those tissues that are in contact with the external environment, such as the skin（where there is a specialized dendritic cell type called the Langerhans cell）and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood.

Once activated, they migrate to the lymph nodes where they interact with T cells and B cells to initiate and shape the adaptive immune response.

At certain development stages they grow branched projections, the dendrites that give the cell its name（δένδρον or déndron being Greek for "tree"）. While similar in appearance, these are distinct structures from the dendrites of neurons.

Immature dendritic cells are also called Veiled cells, as they possess large cytoplasmic 'veils' rather than dendrites.

M cells：Microfold cells or Epitheliocytus microplicatus)

M cells（Microfold cells or Epitheliocytus microplicatus）are cells found in the Follicle-associated epithelium of the Peyer's patch as well as in BALT（Bronchus-associated lymphoid tissue）. They transport organisms and particles from the gut lumen to immune cells across the epithelial barrier, and thus are important in stimulating Mucosal immunity.

Unlike their neighbouring cells, they have the unique ability to take up Antigen from the lumen of the Small intestine via Endocytosis or Phagocytosis, and then deliver it via Transcytosis to Dendritic cells（an antigen presenting cell）and T lymphocytes（namely T cells）located in a unique pocket-like structure on their basolateral side.

SVF：Stromal Vascular Fraction

Stromal vascular fraction（SVF）of adipose tissue is a rich source of Preadipocytes, Mesenchymal stem cells（MSC）, Endothelial progenitor cell, T cells, B cells, Mast cells as well as Adipose tissue macrophages.

Stromal Vascular Fraction（SVF）is the product of lipoaspirate which is obtained from liposuction of excess adipose tissue.

The Lipoaspirate, a disposable byproduct of liposuction in cosmetic surgery, contains a large population of stem cells called Adipose derived stem cells （ADSCs）, that shares a number of similarities with the Bone marrow stromal cells, including the multilineage differentiation capacity.

自體幹細胞移植第二線造血幹細胞驅動劑Plerixafor 血癌治療新希望

【中時健康黃筱雅／台北報導】2014.01.14

據統計，國內「非何杰金氏淋巴癌」（NHL）每年新增病患約2300人，「多發性骨髓瘤」（MM）每年新增約500人，患者除了接受化療，另可透過自體造血幹細胞移植以延長生命。一名70歲男性企業家因皮膚多處丘疹而就醫，確診為「非何杰金氏淋巴癌」第四期，接受自體造血幹細胞移植，目前復原情況良好。

台大醫院內科部骨髓移植病房主任唐季祿醫師表示，美國每年進行自體造血幹細胞移植，人數最多即「多發性骨髓瘤」與「非何杰金氏淋巴癌」的患者，不但如此，有至少3成的非何杰金氏淋巴癌患者，以及超過半數的多發性骨髓瘤患者，因為幹細胞移植，存活期有效延長6年。

唐季祿醫師說明，接受自體造血幹細胞移植的患者，需透過造血幹細胞驅動方式，收集至足夠的造血幹細胞，每公斤需達200萬顆、移植成功率才高。然而，現行健保給付的第一線造血幹細胞驅動方式，仍有2成5的非何杰金氏淋巴癌、近1成的多發性骨髓瘤患者，初次使用的成效不彰，只好放棄移植、回歸化療。

2013年12月中央健康保險署核准給付全新機轉造血幹細胞驅動劑（Plerixafor），於一線驅動失敗患者使用，可有效幫助超過7成以上患者，成功收集到足量的幹細胞進行移植，重獲寶貴健康。

該名70歲男性企業家使用二線全新驅動方式，2次收集到總數高達每公斤300萬顆以上造血幹細胞，為標準值的1.5倍。術後2週即出院並返回工作崗位，經追蹤病灶全數消失，復原狀況十分良好。

臨床研究發現，使用白血球生長激素（G-CSF）（Filgrastin injection例如Filgrastim；Lenograstim injection例如Granocyte)）搭配二線全新機轉造血幹細胞驅動劑，可幫助7成以上患者，刺激骨髓釋放出足夠的造血幹細胞，提供移植所需，健保已於去年12月核准給付，患者預估可減輕近60多萬元醫療負擔。

台大醫院血液腫瘤科主治醫師林建廷指出，根據過往臨床經驗，年長患者普遍較難成功驅動造血幹細胞，二線全新驅動方式可幫助年長患者，有機會接受幹細胞移植手術、提高術後的生活品質。不過。在使用過程中，會有2至3成患者出現嘔吐、噁心等副作用。

註：

Plerixafor（rINN and USAN, trade name Mozobil）is an immunostimulant used to mobilize hematopoietic stem cells in cancer patients. The stem cells are subsequently transplanted back to the patient. The drug was developed by AnorMED which was subsequently bought by Genzyme.

Peripheral blood stem cell mobilization, which is important as a source of hematopoietic stem cells for transplantation, is generally performed using granulocyte colony-stimulating factor（G-CSF）, but is ineffective in around 15 to 20% of patients. Combination of G-CSF with Plerixafor increases the percentage of persons that respond to the therapy and produce enough stem cells for transplantation.

The drug is approved for patients with Lymphoma and Multiple myeloma.

Researchers at Imperial College have demonstrated that plerixafor in combination with vascular endothelial growth factor（VEGF）can produce mesenchymal stem cells and endothelial progenitor cells in mice.

Receptor activator of nuclear factor kappa-B ligand（RANKL）

also known as Tumor necrosis factor ligand superfamily member 11（TNFSF11）、TNF-related activation-induced cytokine（TRANCE）、Osteoprotegerin ligand（OPGL）、and Osteoclast differentiation factor（ODF）