Long-term cultured human neural stem cells undergo spontaneous transformation to tumor-initiating cells.

In this report, we describe the spontaneous malignant transformation of long-term cultured human fetal striatum neural stem cells (hsNSCs, passage 17). After subcutaneous transplantation of long-term cultured hsNSCs into immunodeficient nude mice, 2 out of 15 mice formed xenografts which expressed neuroendocrine tumor markers CgA and NSE. T1 cells, a cell line that we derived from one of the two subcutaneous xenografts, have undergone continuous expansion in vitro. These T1 cells showed stem cell-like features and expressed neural stem cell markers nestin and CD133. The T1 cells were involved in abnormal karyotype, genomic instability and fast proliferation. Importantly, after long-term in vitro culture, the T1 cells did not result in subcutaneous xenografts, but induced intracranial tumor formation, indicating that they adjusted themselves to the intracranial microenvironment. We further found that the T1 cells exhibited an overexpressed level of EGFR, and the CD133 positive T1 cells showed a truncation mutation in the exons 2-7 of the EGFR (EGFRvIII) gene. These results suggest that continuous expansion of neural stem cells in culture may lead to malignant spontaneous transformation. This phenomenon may be functionally related to EGFR by EGFRvIII gene mutation.

Prevention and treatment of amputation neuroma by an atelocollagen tube in rat sciatic nerves.

To evaluate the potential of the atelocollagen tube as a cap for amputation neuromas, the histological and histochemical characteristics of the neuroma and spinal cord were compared with those following silicone capping. Four weeks after the transection of 18 rat sciatic nerves, the amputated neuroma was resected, and the nerve stump inserted into an atelocollagen or silicone tube. The histological changes in the nerve ends and c-fos expression in the dorsal horn of the fourth lumbar spinal cord were evaluated at 4 weeks postoperatively. The regenerated nerve structure in the atelocollagen or silicone tube was very thin. In contrast, a typical bulbous neuroma was observed in the control group (the nerve stump was left in place). The atelocollagen and silicone tube groups demonstrated fewer c-fos-expressed cells in the spinal cord than the controls. These results suggest that capping by an atelocollagen tube, like that by a silicone tube, might successfully prevent an amputated neuroma from forming, and suppress induced pain. The atelocollagen tube may be a promising biomaterial for the prevention or treatment of a painful amputation neuroma.

Tumor spectrum in ARF-deficient mice.

The p19ARF product of the INK4a/ARF locus is induced in response to potentially oncogenic hyperproliferative signals and activates p53 by interfering with its negative regulator, Mdm2. Mice lacking ARF are highly prone to tumor development, and in this study, 80% of these animals spontaneously developed tumors and died within their first year of life. Mice that were heterozygous for ARF also developed tumors after a longer latency, whereas their wild-type littermates did not. In heterozygotes, tumor formation was accompanied by loss of the residual ARF allele and/or lack of ARF mRNA expression, implying that ARF can act as a canonical "two-hit" tumor suppressor gene. Tumors occurred earlier in life in ARF-null animals that were neonatally irradiated or given dimethylbenzanthrene, and several animals treated with carcinogen simultaneously developed multiple forms of malignancy arising from distinct cell lineages. Although p53-null mice primarily develop lymphomas and fibrosarcomas, the frequency of these two tumor types was inverted in ARF-null animals, with undifferentiated sarcomas predominating in a 3:2 ratio; 28% of ARF-null animals developed carcinomas and tumors of the nervous system, which have been rarely observed in untreated p53-null mice. The longer latency of tumor formation in ARF-null versus p53-null mice, therefore, appears to enable a broader spectrum of tumors to emerge.

Ulnar nerve palsy following fracture of the shaft of the humerus.

We present an unusual case of ulnar nerve palsy associated with humeral shaft fracture. Initial examination showed swelling and tenderness. No mention of neurological deficit was found in the patient's file. Radiography showed a displaced midshaft fracture. Closed reduction and intramedullary nailing were performed. Ulnar nerve palsy was noted by the attending physician afterward, and, after four months of nonoperative treatment without any obvious improvement, the patient was referred to our center. During surgery, the nerve was found to be transected and an end-to-end repair was performed. Five months after surgery, signs of motor recovery were present. This case demonstrates that ulnar nerve injury can occur with a closed fracture of the humeral shaft.

[Experimental study on prevention and treatment of neuroma by implanting nerve stump into muscle].

Prevention and treatment of traumatic neuroma by implanting the proximal neural stump into the muscle were studied. Sixteen SD rats were used for the experimental study. The proximal stump of the left sciatic nerve was implanted into the nearby muscle as the experiment side, whereas the proximal stump of the right sciatic nerve was left untreated as the control side. The results were assessed with histological and electrophysiological methods. The experiment demonstrated that neuroma was formed in the control side one month postoperatively, whereas in the experimental side the nerve fibers were dispersed among the muscle fibers and no definite neuroma was formed. Implantation of neural stump into muscle could prevent and treat traumatic neuroma.

Primitive neuroectodermal tumor of the chest wall in a patient with Jeune's syndrome and renal transplant.

Jeune's syndrome is a rare autosomal disorder characterized by osseous dysplasia, fetal respiratory distress, and renal failure in later life. We describe a 27-year-old man with Jeune's syndrome who underwent renal transplantation and 6 years later developed a sarcoma (primitive neuroectodermal tumor [PNET]) in the soft tissue of the chest wall, a principal site of dysplasia in this disorder.

Association between neuroepithelial tumor and multiple intestinal polyposis (Turcot's syndrome): report of a case and critical analysis of the literature.

We report a case of association of a brain tumor with multiple intestinal polyposis (Turcot's syndrome) and offer a critical analysis of the relevant literature with a view to revising the classification of the syndrome in relation to familial multiple polyposis and Gardner's syndrome. For this purpose, we considered only cases of intestinal polyposis associated with a primary neuroepithelial tumor (medulloblastoma, glioma, or glioblastoma) as originally described by Turcot. Differences emerged, depending on the central nervous system tumor type, which suggests that this neoplastic association may be classified as two distinct syndromes.

Nerve injury complications. Management of neurogenic pain syndromes.

Postural brachial plexus compression neuropathy occurs more frequently than usually realized. The cause is multifactorial with certain predisposing anatomic and congenital factors that are not uncommon. An inciting event is required to cause a clinically significant syndrome. The event can be a specific traumatic episode or cumulative trauma leading to an adoption of a guarding posture, which results in a self-perpetuating cycle and brachial plexus nerve compression. The diagnosis and management may be complicated by concurrent vascular compression, concurrent reflex sympathetic dystrophy, and associated inflammatory musculotendinous conditions. Diagnosis relies on the appreciation of a peculiar symptom complex of pain and paresthesias. The important clinical signs are a supraclavicular Tinel's sign and a positive stress abduction test. Treatment includes exercises, patient education, and behavior modification. However, misdiagnosis can lead to inappropriate treatment, such as unnecessary carpal and cubital tunnel releases. Operative treatment is reserved for those severe cases that are resistant to extended and intense physical therapy. The preferred surgical technique involves an anterior, supraclavicular approach allowing for complete visualization and release of intrinsic and extrinsic nerve compression. Awareness is the key to making the diagnosis, and successful treatment requires a multidisciplinary approach. It is generally accepted that injuries to peripheral nerves result in serious losses of function. Paresthesias and motor weakness cause immediate functional limitation, and place the hand at risk for further injury. The system has little regenerative capacity, and the chance for recovery is poor even under the best circumstances. Therefore the treatment of acute nerve injuries can be difficult and frustrating.(ABSTRACT TRUNCATED AT 250 WORDS)

Secondary tumors after high-dose cyclophosphamide and total-body irradiation followed by bone marrow transplantation in a rat model for human acute myelocytic leukemia (BNML).

Brown Norway (BN) rats carrying a transplantable acute myelocytic leukemia (BNML) were given a supralethal combination of cyclophosphamide (80-100 mg/kg i.p.) and total-body irradiation (9.0 Gy gamma rays or 8.5 Gy X-rays) followed by isologous bone marrow transplantation. Of 110 long-term survivors (greater than 95 days), 40 (45%) died of a secondary malignancy at a median posttreatment age of 450 days. At a comparable age, non-treated control BN rats show a spontaneous tumor incidence of 5% only, which increased to 83% during the aging process. Thus the latency period for the appearance of tumors was impressively shortened. Tumors of neurogenic origin and acute leukemias were the most prominent types, in contrast with non-treated control rats.