The clinical use of human recombinant TSH

The recent cloning of human TSH-beta gene has allowed the production of recombinant human TSH (rhTSH) by recombinant DNA technology in mammalian cells (Chinese hamster ovary cells). Studies aimed at biochemical and biological characterization have shown that rhTSH, unlike pituitary TSH, is highly sialylated and is biological active in stimulating c-AMP accumulation in FRTL-5 cells. Phase I/II and phase III clinical studies have been performed to evaluate the safety and efficacy of rhTSH in stimulating radioactive iodine uptake in patients after total thyroidectomy for differentiated thyroid cancer. In these patients therapy with thyroid hormones is performed to replace hormone production and to suppress TSH-stimulated tumor growth. To detect residual or recurrent cancer, the therapy has to be withdrawn in order to obtain rise in endogenous TSH to perform a total body scan. rhTSH, as a source of exogenous human TSH, has been shown as an additional diagnostic tool in the follow-up of patients with thyroid cancer. Used in patients maintained on thyroid hormone suppressive therapy, rhTSH enhances the sensitivity of serum Tg testing. Although the sensitivity of scans obtained after rhTSH administration is slightly lower than that after thyroid hormone withdrawal, the use of rhTSH avoids the clinical signs and symptom of hypothyroidism and can be used in selected patients.     

重组人粒细胞集落刺激因子在粒细胞减少患者中的应用

目前发现粒细胞减少最常见的原因是人类免疫缺陷病毒(HIV)感染、肿瘤的化学治疗和HIV治疗相关的骨髓抑制，而粒细胞减少以及随后发生的一系列感染并发症又限制了肿瘤化疗及HIV治疗的药物剂量，同时也延缓了必要的治疗，从而影响疗效。无论是治疗相关的还是疾病相关的粒细胞减少都会导致许多临床效应，如发生需住院治疗的发热及感染，感染相关病死率的升高，不能按时按原定剂量完成预定化疗，生活质量降低等。     

The evidence for the use of recombinant human activated factor VII in the treatment of bleeding patients with quantitative and qualitative platelet disorders

There are increasing reports suggesting that high-dose recombinant human activated factor VII (rFVIIa) is effective in the treatment and prevention of bleeding in patients with quantitative and qualitative platelet disorders. These clinical observations are supported by evidence that FVIIa binds weakly to activated platelet surface and at high concentration improves thrombin generation. In experimental models, this improved thrombin generation enhances platelet adhesion in thrombocytopenic conditions and enhances adhesion and aggregation of platelets lacking glycoprotein IIbIIIa (integrin alpha(IIb)beta(3)), characteristic of the qualitative platelet disorder Glanzmann thrombasthenia (GT). There is a need for clinical trials to confirm the safety and efficacy of rFVIIa in patients with various quantitative and qualitative platelet defects, either by itself or in combination with other hemostatic agents such as platelet transfusion. Pending the availability of such data, rFVIIa may be considered in severe bleeding in thrombocytopenia and GT patients with platelet antibodies and refractory to platelet transfusions and other standard treatments. An international survey suggests that rFVIIa at about 90 microg/kg every 2 hours for 3 or more doses could be used for GT patients with severe bleeding, but confirmation by larger studies is needed. For GT patients undergoing surgery and for treatment and prevention of bleeding in thrombocytopenic patients, the optimal rFVIIa regimen remains to be defined.     

The use of an insuflon device for the administration of G-CSF in pediatric cancer patients

In pediatric oncology, granulocyte colony-stimulating factor (G-CSF) is applied with the aim of shortening neutropenic periods after chemotherapy and for mobilization of peripheral blood stem cells for apheresis procedures. G-CSF is administered, subcutaneously or intravenously, on a daily basis. An insuflon device for the administration of G-CSF was used in 29 patients for 93 G-CSF periods. Retrospective evaluation shows that this administration route is feasible, safe and preferred by young children rather than by teenagers with cancer.     

Topical use of recombinant human thrombin for operative hemostasis

Background: The topical use of thrombin has a long history in surgery as an adjunct for achieving operative hemostasis. Until recently the majority of thrombin used topically was derived from bovine plasma. This preparation has been proven to be immunogenic and has led to safety concerns in recent years. Recombinant human thrombin (rhThrombin) has recently been developed as an alternative for topical use for surgical hemostasis. Objective: To review the clinical safety and efficacy data relating to rhThrombin using bovine-derived thrombin as a comparative standard. Methods: This review summaries recent literature regarding topical use of rhThrombin using bovine thrombin as the ‘gold standard’ for topical surgical hemostasis. Conclusions: The data indicates that topical rhThrombin is as effective as bovine thrombin for hemostasis and significantly less immunogenic.     

Development of recombinant human polyclonal antibodies for the treatment of complex human diseases

Antibodies are a central factor in the immunity against invading pathogens, such as bacteria and viruses, as well as against malignantly transformed cells. Natural antibody responses are polyclonal, comprising antibodies against several epitopes, thus increasing the probability of eliminating the invading pathogen or malignant cell. The pharmacological advantage of polyclonality is exploited in the plasma-derived immunoglobulin products used at present to treat a number of infectious diseases. However, the use of plasma-derived products is limited by their cost, inconvenience of use and potential for transferring diseases from the donor to the patient. Symphogen has developed technologies to capture the advantages of antibody polyclonality while eliminating the potential safety risk associated with the sourcing of human material. Hence, the Symplex technology has been developed to identify diverse repertoires of target-specific, fully human antibodies. For the controlled manufacture of recombinant polyclonal antibody drugs, Symphogen has developed the Sympress technology. Combined, these two technologies allow the identification and industrial manufacturing of recombinant human polyclonal antibodies for medical use in humans. The authors believe that this new class of therapeutic antibodies will be advantageous in the treatment of complex human diseases, such as cancer and infection, as it allows the combination of several treatment modalities in one drug.     

Development of recombinant human polyclonal antibodies for the treatment of complex human diseases

Antibodies are a central factor in the immunity against invading pathogens, such as bacteria and viruses, as well as against malignantly transformed cells. Natural antibody responses are polyclonal, comprising antibodies against several epitopes, thus increasing the probability of eliminating the invading pathogen or malignant cell. The pharmacological advantage of polyclonality is exploited in the plasma-derived immunoglobulin products used at present to treat a number of infectious diseases. However, the use of plasma-derived products is limited by their cost, inconvenience of use and potential for transferring diseases from the donor to the patient. Symphogen has developed technologies to capture the advantages of antibody polyclonality while eliminating the potential safety risk associated with the sourcing of human material. Hence, the Symplex? technology has been developed to identify diverse repertoires of target-specific, fully human antibodies. For the controlled manufacture of recombinant polyclonal antibody drugs, Symphogen has developed the Sympress? technology. Combined, these two technologies allow the identification and industrial manufacturing of recombinant human polyclonal antibodies for medical use in humans. The authors believe that this new class of therapeutic antibodies will be advantageous in the treatment of complex human diseases, such as cancer and infection, as it allows the combination of several treatment modalities in one drug.     

光动力联合重组人白介素-2治疗尖锐湿疣疗效观察

目的评价传统物理治疗和光动力联合注射重组人白介素-2治疗尖锐湿疣的治愈率和复发控制率。方法将84例患者随机分为2组,传统物理组患者仅做物理治疗,光动力加重组人白介素-2组在光动力治疗的同时联合应用肌肉注射重组人白介素-2治疗。结果传统物理组治愈率59.5%,复发控制率28.5%;光动力联合注射重组人白介素-2治疗组治愈率为88.0%,复发控制率47.6%,两组比较差异有统计学意义(P<0.05)。结论光动力联合注射重组人白介素-2治疗尖锐湿疣效果显著,治愈率高于传统物理治疗组,复发控制率高于传统物理治疗组。光动力联合注射重组人白介素-2是治疗尖锐湿疣的较好方法之一。     

The use of human insulin derived from baker's yeast by recombinant DNA technology.

Human insulin has gradually replaced animal insulin as the therapeutic agent of first choice among insulin-dependent and insulin-requiring patients with diabetes. Like animal insulin, human insulin manufactured by several different methods is available in Regular, NPH, Lente, and 70/30 (NPH/Regular) formulations. The most recently developed method of manufacturing human insulin uses recombinant DNA technology with baker's yeast as the host cell [rDNA HI (BY)], offering potentially limitless supplies of insulin structurally identical to that made by the human pancreas. Clinical studies have demonstrated that the extent of insulin absorption, the glucose-lowering effects, and the clinical effects on glycemic control and on incidence of hypoglycemia with rDNA HI (BY) are similar to those observed when patients are treated with semisynthetic human insulin (ssHI). Dose-for-dose transfer of patients from ssHI to rDNA HI (BY) is therefore appropriate. It is standard practice to recommend that any change in insulin be conducted under medical supervision.     

The use of recombinant factor VIII in the management of Hemophilia

Recombinant factor VIII is currently in the late stages of clinical trials. The available studies indicate that the product is safe and well-tolerated, and appears to be free of virus diseases such as HIV and hepatitis infections. Based on these early studies, recombinant coagulation factors appear to have enonnous promise and potential for transfusion medicine. The synthesis of large quantities of safe material may lead to the development of techniques for daily administration of factor VIII aimed at the prevention of joint and soft tissue bleedings. There is also the promise of decreased costs, as techniques for the efficient synthesis of recombinant proteins are refined further.     

重组人血管内皮抑制素治疗大鼠子宫内膜异位症的实验研究

目的：分析重组人血管内皮抑制素注射液（恩度）对大鼠子宫内膜异位症新生血管的抑制效果,探索治疗子宫内膜异位症的新手段。方法自体移植法建立子宫内膜异位症动物模型,将子宫内膜异位症大鼠随机分为对照组（腹腔注射等体积生理盐水）、恩度高剂量组（2 mg·kg-1·d-1）、恩度低剂量组（1 mg·kg-1·d-1）。用药治疗2周后,测量异位病灶体积变化,血清中血管内皮生长因子（VEGF）含量,免疫组化法检测异位内膜、正常内膜、在位内膜组织中VEGF表达。结果与对照组相比,恩度治疗组大鼠异位内膜体积缩小,血清中VEGF含量降低,内膜组织中VEGF表达下降,差异有统计学意义（P＜0.05）。结论重组人血管内皮抑制素对正常免疫状态大鼠（Wistar大鼠）异位内膜组织新生血管的形成和病灶生长有明显抑制作用,恩度高剂量组治疗大鼠子宫内膜异位症效果更明显。     

The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in orthopaedic applications

Preclinical proof-of-concept, feasibility and efficacy studies in lower animals resulted in the accumulation of data that served as a backbone for clinical trials with the recombinant, osteogenic bone morphogenetic protein-2 (BMP-2). Among the important observations was the dependence of dose and carrier on the outcome for osseous union in relation to the animal model used. Clinical outcome data for spinal applications indicate better overall results compared with traditional controls that utilised autogenous iliac crest bone graft for fusion. Parameters include less blood loss, less operating room time and costs, better fusion outcomes and increased patient satisfaction. At this juncture, the long journey from the identification of BMP-2 in demineralised bone fraction to FDA approval for use in a singular orthopaedic application has been completed. It has been demonstrated to be safe, efficacious and cost-effective, leading to increased patient satisfaction and improved clinical outcome.     

The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in orthopaedic applications

Preclinical proof-of-concept, feasibility and efficacy studies in lower animals resulted in the accumulation of data that served as a backbone for clinical trials with the recombinant, osteogenic bone morphogenetic protein-2 (BMP-2). Among the important observations was the dependence of dose and carrier on the outcome for osseous union in relation to the animal model used. Clinical outcome data for spinal applications indicate better overall results compared with traditional controls that utilised autogenous iliac crest bone graft for fusion. Parameters include less blood loss, less operating room time and costs, better fusion outcomes and increased patient satisfaction. At this juncture, the long journey from the identification of BMP-2 in demineralised bone fraction to FDA approval for use in a singular orthopaedic application has been completed. It has been demonstrated to be safe, efficacious and cost-effective, leading to increased patient satisfaction and improved clinical outcome.     

重组人白细胞介素-11治疗脓毒症相关血小板减少症的疗效观察

目的 观察重组人白细胞介素-11治疗脓毒症相关血小板减少症患者的疗效.方法 以入住天津市第一中心医院ICU并发生血小板减少的54例脓毒症患者为研究对象,分为治疗组和对照组.两组患者均接受积极抗感染、对症支持治疗,治疗组自血小板下降第1天予以皮下注射重组人白细胞介素-11 1.5 mg/kg,每日1次,疗程7~14 d,当血小板≥100×109/L时停药.结果 治疗组在第7天及第14天血小板计数显著高于对照组(P<0.05),血小板输注率显著低于对照组(P<0.05);治疗组血小板恢复到>50×109/L及>100×109/L所需的时间较对照组显著缩短(P<0.05);治疗组在第7天及第14天APACHEⅡ评分显著低于对照组(P<0.05).结论 脓毒症相关血小板减少症患者在积极抗感染治疗的同时加用重组人白细胞介素-11,可加速血小板数量的恢复,缩短血小板减少的持续时间,减少血小板输注,改善预后,而且重组人白细胞介素-11的不良反应轻微,可以安全有效地用于脓毒症相关血小板减少症.