转基因动物乳腺反应器与生物制药

生物医药将成为21世纪的主导行业,并将改变我们的医疗结构.转基因动物乳腺反应器作为新型的动物制药厂,具有很多优势,可以生产许多具有临床价值的珍贵药物,它可以解决规模化生产,成本低,经济周期短,具有十分诱人的前景,一个新兴的转基因动物药业已开始崛起.     

转基因动物乳腺反应器与生物制药

生物医药将成为21世纪的主导行业，并将改变我们的医疗结构。转基因动物乳腺反应器作为新型的动物制药厂，具有很多优势，可以生产许多具有临床价值的珍贵药物，它可以解决规模化生产，成本低，经济周期短，具有十分诱人的前景，一个新兴的转基因动物药业已开始崛起。     

转基因动物乳腺生物反应器研究进展

文章综述了转基因动物乳腺生物反应器的原理、应用、优点、存在问题及国内外研究进展,并对其发展方向进行了小结及展望。     

转基因动物乳腺生物反应器研究进展

转基因动物乳腺生物反应器是利用动物乳腺特异性启动子调控元件指导外源基因在乳腺中特异性表达 ,并从转基因动物乳汁中获取重组蛋白。近年来 ,生物学和分子生物学研究领域的成就促进了该技术的蓬勃发展 ,并在生产药用蛋白领域展现出广阔前景。本文简要概述了转基因动物乳腺生物反应器的基本概念、原理、特点及应用 ,并重点阐述其研究现状及前景 ,从而探讨其存在的问题     

新型的动物生物制药厂——转基因动物乳腺反应器

1　生物医药产业的过去和现在生物医药产业的发展经历了三个不同的历史阶段 ,即天然药物阶段 ;化学合成药物阶段 ;基因工程药物阶段。基因药物的发展也经历了三个阶段。其一是细菌基因工程阶段 ,即用大肠杆菌等原核生物来表达目的基因蛋白 ,目前上市的基因工程药物绝大多数都采     

转基因动物生物反应器

概述了转基因动物生物反应器的原理、方法及研究进展，同时对其存在的问题和发展前景作了简要的探讨。     

转基因动物乳腺生物反应器研究概况

1992年,英国爱丁堡大学的一个研究组宣布他们已生产出6头转基因绵羊。这些绵羊可以在奶中生产抗胰蛋白酶,产量最低的是1g／L,产量高的可达35g／L。这一重大突破预示着一个以动物乳腺为主要生产手段（即乳房反应器系统）的巨大产业将要兴起,将为人类带来巨大的经济和社会效益。     

动物乳腺生物反应器的原理及研究进展

1　基本概念1 .1　转基因动物 (ｔｒａｎｓｇｅｎｉｃａｎｉｍａｌ)　转基因动物是指通过实验室的某些方法 ,将人为构建的外源目的基因导入动物的生殖细胞或早期胚胎 (原核或受精卵 ) ,使其稳定地整合到动物基因组中 ,并能遗传给后代的动物。最早的转基因动物是鸡 (Ｍｕｎｒｏ,1 968) ,其后是利用注射法和病毒感染法转基因鼠 (Ｊａｅｎｉｓｈ ,1 976)。1 .2　动物生物反应器 (ａｎｉｍａｌｂｉｏｒｅａｃｔｅｒ)　一般把目的基因在血液循环系统或乳腺中表达的转基因动物叫动物生物反应器。利用它来生产人类所需的生物活性物质或药用珍稀蛋白…     

转基因动物乳腺作为生物反应器生产药用蛋白质：影响表达水平因素分析

转基因动物乳腺作为生物反应器生产药用蛋白质──影响表达水平因素分析孙宪如，卢一凡（吉林农业大学动物科学系，长春１３０１１８）转基因动物最初以改变家畜的生产性状而受到重视。近年来，以转基因动物乳腺作为生物反应器来大规模生产有治疗价值的重组蛋白质，引起人...     

动物乳腺生物反应器在现代生物制药中的应用

目的基因在乳腺中表达的转基因动物称为动物乳腺生物反应器(mammary gland bioreaetor),又称为动物个体乳腺表达系统.动物乳腺生物反应器出现于20世纪90年代初,它是一项利用转基因动物的乳房代替生物发酵,大规模生产供人类疾病治疗和保健用的生物活性物质或药用珍稀蛋白的现代生物技术,其核心内容是利用乳蛋白基因的乳腺特异性调控成分驱动外源基因在动物乳腺中高效表达,以期通过源源不断地回收乳汁来提取大量有重要药用价值的生物活性外源蛋白.因此,动物乳腺生物反应器在现代生物制药领域中具有广阔的开发前景.     

转基因家畜生物反应器浅谈（续）

转基因家畜生物反应器浅谈（续）陈庄，魏平华（广东省农科院畜牧研究所广州５１０６４０）２转基因家畜生物反应器研究的进展目前，转基因动物研究有三大焦点：一是转基因方法研究；二是利用转基因动物来研究动物基因的表达调控机制；三是利用转基因动物生产非常规畜牧产...     

核移植技术在建立乳腺生物反应器中的应用

乳腺生物反应器的开发为制药业带来了生机,但目前采用的动物基因转移的方法,由于其各自固有的局限性,未能使得乳腺生物反应器的研究取得长足的进步。而核移植技术的发展为乳腺生物反应器的开发注入了活力。因此,笔者综合近年来国内外的文献,提出了核移植中供体细胞的选择以及处理方法,同时也从分子水平阐述了乳腺的一些调控机制,为核移植技术在乳腺生物反应器中的应用奠定了基础。     

转基因动物技术与动物育种

20世纪80年代以来，转基因动物技术一直是动物遗传育种领域的一个研究热点。它在改良动物生产性状、提高畜禽抗病力以及生产人药用蛋白等非常规畜牧产品等方面均有着广阔的应用前景。然而由于动物转基因的效率很低、难以控制转基因在宿主染色体中的行为、无法控制转基因表达的频率和水平等，转基因的稳定遗传问题也未能解决，以致难以形成转基因畜禽品种或品系，因而转基因动物技术在动物育种中的广泛应用尚需时日。随着动物基因组计划的深入进行，转基因技术将会得到不断的发展和完善，从而在未来的动物育种中大显身手。     

The expression of carbonic anhydrase in canine mammary gland and mammary gland tumor

Carbonic anhydrase (CA), a metallo-enzyme containing zinc, broadly distributes in mammalian tissues and participates in physiological regulation such as respiration, acid-base balance, ion transport, bone resorption, as well as the development of tumor by the reversible hydration of carbon dioxide. However the expression of CA in the tissue of mammary gland tumor was not documented. In this study we examine the histolocalization and gene expression of CA in both normal canine mammary gland tissue and mammary gland tumor by histochemical examination, and RT-PCR. Four mRNA expression of CA isoenzymes, such as CA II, IV, VI and IX were found under RT-PCR analysis and different band patterns were found between normal canine mammary tissue and canine mammary gland tumor tissue. CA II, IV, VI and IX gene mRNA expression were found in the normal mammary gland tissue, indicating CA II, IV, VI and IX are likely to be the essential enzymes to maintain the normal physiological condition of canine mammary gland tissue cells. However the expression of CA IV was not found in the tissue of malignant mammary gland tumor that may become the marker for the prognostic recognition of canine mammary gland tumor.     

Canine mammary gland tumors

An understanding of the known biologic facts of this disease and methodical evaluation of the individual patient are necessary prerequisites for outlining rational courses of therapy for dogs afflicted with mammary tumors. Because of the common occurrence of multiple tumors arising at various stages of development simultaneously and the heterogeneity of histology of the complex (mixed tissue types) tumors, presurgical biopsy is recommended only in cases in which mast cell tumor or anaplastic carcinoma is suspected. Although investigative work is being performed regarding the efficacy of chemotherapy, radiation therapy, and immunotherapy, surgery still remains the mainstay in treatment of this condition. No one surgical procedure fits the needs of all patients, although it seems logical to remove as much breast tissue as is reasonable in each circumstance owing to the multicentric nature of the disease. Ovariohysterectomy has not been demonstrated to be of value in treatment of dogs with mammary tumors, but it is a markedly effective method of preventing mammary tumors if it is performed before puberty; it is moderately effective if performed before the dog is 21/2 years of age.     

The mammary gland and neonatal immunity

The newborn pig and calf are normally devoid of immunoglobulins at birth and rely on colostrum for serum antibody and milk for intestinal antibody during their early life. Colostrum and milk are well adapted to their different immunological roles. Colostrum immunoglobulin is derived almost entirely from the serum of the dam and after absorption by the neonate is destined here to provide serum antibody. The main immunoglobulin in pig's milk is IgA which predominates also in intestinal juice of the adult. Intestinal IgA is locally formed in the lamina propria of the intestinal tract, whereas milk IgA is locally formed in the mammary gland. It seems likely, however, that IgA production at both sites results from antigenic stimulation of the gut associated lymphoid tissue and the immune systems of these organs are intimately linked. The role of IgA in mucosal defence in the calf appears to be assumed by IgG. Colostrum and milk IgG₁ is derived from serum; nonetheless it is likely that the main antigenic stimulus for its formation is obtained from the intestinal tract—the mammry gland immune system is present and its artificial stimulation could prove to be of great practical value.

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Kurzfassung Schweine und Kälber besitzen bei ihrer Geburt normalerweise keine Immunoglobuline und sind daher in ihrem ersten Lebensabschnitt auf Kolöstrum zur Bildung von Antikörperserum sowie auf Milch zur Bildung intestinaler Antikörper angewiesen. Kolöstrum und Milch eignen sich ganz besonders für die verschiedenen von ihnen zu erfüllenden immunologischen Zwecke. Kolöstrum-Immunoglobulin wird fast ausschliesslich dem Serum des Muttertiers entnommen und ist nach seiner Absorption durch das Neugeborene zur Bildung von Antikörperserum bestimmt. Wichtigstees Immunoglobulin in der Schweinemilch ist das IgA, das auch in der Intestinalflüssigkeit erwachsener Tiere überwiegt. Intestinal IgA wird lokal in der Lamina propria des Intestinaltrakts gebildet, während Milch-IgA örtlich in den Mammadrüsen entsteht. Wahrscheinlich ist jedoch, dass an beiden Stellen die IgA-Bildung durch die Antigenstimulierung der mit den Eingeweiden verbundenen lymphoiden Gewebe bewirkt wird; die Immunsysteme beider Organe sind eng miteinander verknüpft. Bei der mukösen Abwehr im Kalb scheint die Rolle des IgA von IgG₁ übernommen zu werden. Kolöstrum und Milch-IgG₁ werden vom Serum abgeleitet; es ist jedoch wahrscheinlich, dass der für seine Bildung wichtigste Antigenstimulus aus dem Intestinaltrakt kommt, wohingegen das Immunsystem der Mammadrüsen bei Rindern umgangen wird. Dort besteht allerdings ein lokales Immunsystem der Mammadrüsen, und seine künstliche Stimulierung könnte sich als äusserst nützlich erweisen.

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Resume Le porcelet et le veau sont normalement dépourvus d'immunoglobulines à la naissance; ils dépendent du colostrum pour l'acquisition d'anticorps sériques et du lait pour celle d'anticorps intestinaux pendant les premiers jours de leur vie. Le colostrum et le lait sont bien adaptés à leurs différents rôles immunologiques. L'immunoglobuline du colostrum provient presque entièrement du sérum de la mère et, après absorption par le nouveau-né, lui apporte les anticorps sériques. La principale immunoglobuline contenue dans le lait de la truie est l'IgA, qui prédomine également dans le suc intestinal de l'animal adulte. L'IgA intestinale se forme localement dans la lamina propria du tractus intestinal, tandis que l'IgA du lait se forme localement dans la glande mammaire. Toutefois, il semble probable que la production d'IgA dans ces deux organes résulte de la stimulation antigénique du tissu lympholde associé à l'intestin et que les systèmes immunitaires de ces organes sont intimement liés. Le rôle joué par l'IgA dans la réaction de défense de la muqueuse chez le veau semble assuré par l'IgG₁. L'IgG₁ du colostrum et du lait est dérivée du sérum; néanmoins, il est probable que le principal stimulus antigénique présidant à sa formation provienne du tractus intestinal—le système immunitaire de la glande mammaire n'intervenant pas chez les bovins. Cependant, il existe un système immunitaire local de la glande mammaire et sa stimulation artificielle pourrait s'avérer très utile sur le plan pratique.

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Riassunto Alla nascita, il suino ed il vitello sono normalmente privi di immunoglobuline, e nel primo periodo di vita dipendono dal colostro per gli anticorpi del siero, e dal latte per quelli intestinali. Il colostro ed il latte sono biologicamente ben adattati ai loro diversi ruoli immunologici. L'immunoglobulina del colostro proviene quasi per intero dal siero della madre e, dopo l'assorbimento da parte del neonato, è destinata a fornire gli anticorpi del siero. La principale immunoglobulina contenuta nel latte di suino è la IgA, che predomina anche nel succo intestinale dell'adulto. L'IgA intestinale si forma localmente nei lamina propria del tratto intestinale, mentre l'IgA del latte si forma localmente nella ghiandola mammaria. Sembra tuttavia probabile che le produzione di IgA in ambedue i siti risulti da stimolazione antigenica del tessuto linfoide associato all'intestino, e che i sistemi immunitari di questi organi siano intimamente collegati. Il ruolo dell'IgA nella difesa della mucosa nel vitello pare sia assunto dalla IgG₁. L'IgG₁ del colostro del latte è ricavata dal siero; tuttavia, è probabile che il principale stimolo antigenico per la sua formazione derivi dal tratto intestinale—in quanto nel bovino il sistema immunitario della ghiandola mammaria viene scavalcato. Tuttavia, un sistema immunitario locale della ghiandola mammaria esiste e, qualora stimolato artificialmente, potrebbe dimostrarsi di grande utilità pratica.

     

Canine mammary gland tumors.

The National Consensus Group recommends that all women with tumors larger than 1 cm be offered chemotherapy regardless of tumor histology of lymph node status. This recommendation is to ensure that everyone at risk for failing, even though the risk may be low in women with relatively small tumors and favorable histology, has a choice and receives the benefit of adjuvant chemotherapy. This type of treatment recommendation may also be made in dogs based on recognized, well-accepted prognostic factors such as tumor size, stage, type, and histologic differentiation. Based on the limited clinical information available in veterinary medicine, the drugs that are effective in human breast cancer, such as cyclophosphamide, 5-fluorouracil, and doxorubicin, may also have a role in the treatment of malignant mammary gland tumors in dogs. Randomized prospective studies are needed, however, to evaluate the efficacy of chemotherapy in dogs with high-risk mammary gland tumors and to determine which drugs and protocols are the most efficacious. Until such studies are performed, the treatment of canine mammary gland tumors will be based on the individual oncologist's understanding of tumor biology, experience, interpretation of the available studies, and a little bit of gut-feeling. Table 2 is a proposal for treatment guidelines for malignant canine mammary gland tumors according to established prognostic factors, results from published veterinary studies, and current recommendations for breast cancer treatment in women.