肿瘤干细胞与肝癌干细胞

肿瘤起源于干细胞的假说正在各种人类肿瘤中得到证实,肿瘤不单是一种基因病,而且是一种干细胞病,基因突变作用于干细胞,干细胞突变成为肿瘤干细胞,这是肿瘤发生、再生、转移和复发的关键。肝细胞癌是最常见的恶性肿瘤之一,其中是否存在“肝癌干细胞”的问题一直倍受人们关注。该文介绍肿瘤干细胞与肝癌干细胞的研究情况。     

Cement-within-cement stem exchange using the collarless polished double-taper stem

The clinical and radiographic outcomes of the cement-within-cement femoral stem exchange technique at revision hip arthroplasty were determined. Twenty-three revisions with a collarless polished double-taper stem design were prospectively monitored at up to 12 years. The most common indications for revision were recurrent dislocation and acetabular revision. Radiographic stem subsidence was measured by the Ein Bild Röentgen Analyse method. There was no stem re-revision and no radiographic loosening. Stem within cement subsidence, an intentional design feature of this stem, averaged 0.8 mm (range, 0-2 mm). The average subsidence was similar to that in primary hip arthroplasty. The excellent long-term results of cemented collarless polished taper stems for primary and revision hip arthroplasty can be extended even further by cement-within-cement exchange, which preserves the femur.     

Brain stem death

The concept of brain and brain stem death developed from the observation of apnoeic comatose patients. In the UK, the diagnosis of brain stem death is made by clinically testing brain stem function once specific preconditions have been met. The exact definition of brain death and some details regarding the tests required to make this diagnosis vary across the globe. However, the majority of tests carried out are similar to those in the UK. In this review we define brain stem death and the clinical tests used to confirm it. The use of ancillary testing can have a role in patients where clinical tests are not possible and this is also discussed.     

Brain stem death

The concept of brain and brain stem death developed from the observation of apnoeic comatose patients. In the UK, the diagnosis of brain stem death is made by clinically testing brain stem function once specific pre-conditions have been met. The exact definition of brain death and some details regarding the tests required to make this diagnosis vary across the globe. However, the majority of tests carried out are similar to those in the UK. In this review we define brain stem death and the clinical tests used to confirm it. The use of ancillary testing can have a role in patients where clinical tests are not possible and this is also discussed.     

Mesenchymal stem cells

Stem cells have two features: the ability to differentiate along different lineages and the ability of self-renewal. Two major types of stem cells have been described, namely, embryonic stem cells and adult stem cells. Embryonic stem cells (ESC) are obtained from the inner cell mass of the blastocyst and are associated with tumorigenesis, and the use of human ESCs involves ethical and legal considerations. The use of adult mesenchymal stem cells is less problematic with regard to these issues. Mesenchymal stem cells (MSCs) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as umbilical cord, endometrial polyps, menses blood, bone marrow, adipose tissue, etc. This is because the ease of harvest and quantity obtained make these sources most practical for experimental and possible clinical applications. Recently, MSCs have been found in new sources, such as menstrual blood and endometrium. There are likely more sources of MSCs waiting to be discovered, and MSCs may be a good candidate for future experimental or clinical applications. One of the major challenges is to elucidate the mechanisms of differentiation, mobilization, and homing of MSCs, which are highly complex. The multipotent properties of MSCs make them an attractive choice for possible development of clinical applications. Future studies should explore the role of MSCs in differentiation, transplantation, and immune response in various diseases.     

Brain stem tumors

Opinion statement Brain stem tumors are heterogeneous. They range from the diffuse pontine tumors, which are almost invariably fatal despite all known therapies, to lower-grade focal or exophytic tumors that often have a very good prognosis with surgery or observation only. In this article, we review the epidemiology of brain stem tumors and note that diffuse pontine tumors, although rare, are a significant contributor to mortality among pediatric oncology patients. Diagnosis in typical cases is made using a mag-netic resonance imaging scan without biopsy. No highly effective standard treatment exists; therefore, inclusion of eligible patients in well-designed clinical research stud-ies is extremely important. If an appropriate trial is not available, conventionally frac-tionated external beam radiation therapy can provide good short-term palliation to a significant proportion of patients. An important area of preclinical research that may soon be investigated in clinical trials for patients with diffuse pontine tumors is inter-stitial infusion of therapeutic agents, and the rationale for that approach is described in detail. Lastly, autopsy should be considered for patients who die of diffuse pontine tumors with the goal of obtaining tumor tissue for biological studies that may in the future lead to novel therapies.     

Mesenchymal stem cells

Mesenchymal Stem cells (MSCs) are stromal cells that can be readily harvested from adult bone marrow and adipose tissue, but also umbilical cords. With respect to respiratory disease, the therapeutic potential of these cells lies in their paracrine effects which underlie their ability to enhance tissue regeneration and modulate immune responses. MSCs have been shown to be effective in a range of murine models of respiratory disease, and there are currently five clinical trials involving the administration of MSCs for respiratory diseases, including COPD and emphysema. This paper summarises the features of MSCs.     

间充质干细胞联合输注促进造血干细胞移植后的造血重建

目的探讨间充质干细胞(MSCs)与造血干细胞(HSCs)共同移植对造血重建的影响。方法将扩增的Balb/c小鼠骨髓MSCs与骨髓共同经尾静脉输入经致死剂量照射的同系小鼠体内(联合输注组),并设单输骨髓细胞的HSCs组、单输间充质干细胞的MSCs组以及输培养基的对照组,每隔5d计数白细胞,计算动物死亡率。将乙酰乙酸碳氧荧光素标记的人间充质干细胞输入SCID小鼠尾静脉,24h后取肺、心、肝、脾、肾和小肠组织做冰冻切片;取骨髓、肝脏及脾脏,制成单细胞悬液,涂片,在荧光显微镜下观察计数;用逆转录聚合酶链反应测定鼠骨髓中人特异性β2-微球蛋白。结果细胞输注后,联合移植组的白细胞恢复快,12d左右恢复正常,死亡率(3/11)低于HSCs组(5/10)、MSCs组(4/4)、输培养基的对照组(11/11)。人MSCs输入SCID小鼠后24h,其在体内的分布依次为肺、肾、脾、肝,小肠及心脏组织中几乎无阳性细胞,骨髓中有极少MSCs。结论MSCs与造血干细胞共输能促进造血恢复。     

Investigations of prostate epithelial stem cells and prostate cancer stem cells

Although both prostate epithelial stem cells and prostate cancer stem cells are implicated in the differentiation of the normal prostate gland and carcinogenesis of prostate cancer, there has, until recently, been little information regarding their biology. This review summarizes the recent advancements in cell biological research including various in vitro culture systems that have offered the characterization and isolation of prostate epithelial stem cells and prostate cancer stem cells. In addition, the stromal niche or microenvironment of stem cells plays an essential role in proliferation and differentiation of normal stem cells. Stroma surrounding cancer cells, which also provide another unique niche, may involve the initiation and development of cancer stem cells. Investigation of stem cells and their microenvironments in the prostate should lead to the elucidation of biological features and the development of novel treatments for prostate cancer.     

Mesenchymal stem cells.

Bone and cartilage formation in the embryo and repair and turnover in the adult involve the progeny of a small number of cells called mesenchymal stem cells. These cells divide, and their progeny become committed to a specific and distinctive phenotypic pathway, a lineage with discrete steps and, finally, end-stage cells involved with fabrication of a unique tissue type, e.g., cartilage or bone. Local cuing (extrinsic factors) and the genomic potential (intrinsic factors) interact at each lineage step to control the rate and characteristic phenotype of the cells in the emerging tissue. The study of these mesenchymal stem cells, whether isolated from embryos or adults, provides the basis for the emergence of a new therapeutic technology of self-cell repair. The isolation, mitotic expansion, and site-directed delivery of autologous stem cells can govern the rapid and specific repair of skeletal tissues.     

Primary brain stem tumours

Summary The material consisted of 31 patients with primary brain stem tumours who were investigated retrospectively. Twenty patients were younger than 16 years of age (range: 1 1/2–65 years). The mean age was 11 years. The female/male sex ratio was 19/12. Histological diagnoses were available for 18 patients. All of the verified tumours were gliomas. The diagnoses in 12 cases were made by section or biopsy; in 15 by standard clinical and radiological examinations and in 4 by exploratory operations.Headaches, mental changes, speech and gait disturbances were the most common symptoms at the onset of the illness and at the time of diagnosis. The mean latency period between the emergence of symptom(s) until diagnosis was 4 months (range: 1/2–48 months). Amongst the dominant objective findings were failure of the V, VI and VII cranial nerves, pyramidal tract symptoms, ataxia and nystagmus, occurring singly or in combination.Pneumoencephalograms disclosed characteristic changes in 25 patients (83%).Fourteen patients (45%) received radiation treatment, from which 5 (36%) obtained a temporary remission in their symptoms. The postdiagnostic mean survival period for the patients was 15 months (range: 0–92 months).The survival time was found to depend on the number of damaged cranial nerve nuclei at the time of diagnosis and on the degree of severity and duration of the accompanying hydrocephalus. The prognosis was unfavourable, as the percentage of patients who survived for 2 years was only 6%, and a total duration of illness longer than 2 years occurred in only 7 patients. None of the patients were still surviving at the conclusion of this investigation.     

Short stem shoulder replacement

Context:

It is agreed that it is important to anatomically reproduce the proximal humeral anatomy when performing a prosthetic shoulder replacement. This can be difficult with a long stemmed prosthesis, in particular if there is little relationship of the metaphysis to the humeral shaft. The ‘short stem’ prosthesis can deal with this problem.

Aims:

A prospective study assessed the results of total shoulder arthroplasty using a short stem humeral prosthesis, a ceramic humeral head, and a pegged cemented polyethylene glenoid.

Materials and methods:

Patients with primary shoulder osteoarthritis were recruited into this prospective trial and pre-operatively had the ASES, Constant, SPADI, and DASH scores recorded. The patients were clinically reviewed at the two weeks, eight weeks, one year, and two year mark with completion of a data form. Radiological evaluation was at the eight week, one year and two year follow-up. At the one and two year follow-up the satisfaction rating, the range of passive and active motion, Constant, ASES, SPADI, DASH and pain results were recorded and analysed with SPPS 20.

Results:

During the study period 97 short stem, ceramic head total shoulder replacements were carried out. At the time of follow-up 12 were two years from operation and 38 one year from operation. Active elevation was overall mean 160 degrees. Constant scores were 76 at 1 year, and 86 at 2 years, ASES 88 and 93, and satisfaction 96% and 98% respectively at one and 2 year follow up. There were no problems during insertion of the humeral prosthesis, or any radiolucent lines or movement of the prosthesis on later radiographs.

Conclusion:

The short stem prosthesis had no complications, and on follow up radiographs good bone fixation. These fairly short term clinical results were overall good.     

Colorectal cancer stem cells

Somatic stem cells reside at the base of the crypts throughout the colonic mucosa. These cells are essential for the normal regeneration of the colonic epithelium. The stem cells reside within a special ‘niche’ comprised of intestinal sub‐epithlial myofibroblasts that tightly control their function. It has been postulated that mutations within these adult colonic stem cells may induce neoplastic changes. Such cells can then dissociate from the epithelium and travel into the mesenchyme and thus form invasive cancers. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumour. It is this group of cells that exhibits characteristics of colonic stem cells. Although anti‐neoplastic agents can induce remissions by inhibiting cell division, the stem cells appear to be remarkably resistant to both standard chemotherapy and radiotherapy. These stem cells may therefore persist after treatment and form the nucleus for cancer recurrence. Hence, future treatment modalities should focus specifically on controlling the cancer stem cells. In this review, we discuss the biology of normal and malignant colonic stem cells.