原发性肝细胞癌中cyclin D1基因表达与P16 及CDK4蛋白表达的关系

目的研究cyclin D1基因在原发性肝细胞癌中的表达,并探讨其与P16及CDK4蛋白表达的关系.方法用原位杂交检测cyclin D1基因mRNA表达,免疫组化检测Cyclin D1蛋白表达.结果 6例(14.3%)HCC可检测到cyclin D1基因过表达,5例属Ⅲ-Ⅳ级,1例属Ⅱ级.6例HCC均有CDK4蛋白表达,其中3例为P16蛋白阳性.结论①cyclin D1表达增加只在小部分恶性程度高的HCC中起作用,可能与肿瘤侵袭有关.②在HCC中,cyclin D1基因过表达和(或)P16蛋白丢失均起重要作用.     

The role of leptin in human growth and puberty

Experimental animal studies demonstrate the effects of leptin on appetite, weight gain and metabolism. The biological effects of leptin in human adults are still to be determined, but recent reports show that congenital leptin deficiency leads to hyperphagia and excessive weight gain from early infancy as well as failure of pubertal onset in adolescence. Our recently reported data from two longitudinal cohorts suggest a role for leptin in the normal regulation of childhood weight gain, maturation and the development of secondary sexual features and body composition. Low leptin levels in cord blood closely reflected decreased adiposity at birth and stringly predicted high rates of weight gain in infancy and cath-up growth. In adolescents, leptin levels rose gradually with age prior to puberty, suggesting that a threshold effect may trigger puberty. In girls, low leptin levels at the start of puberty predicted large gains in the percentage of fat mass, perhaps suggesting a role in the preparation for childbearing.     

Turner syndrome: a pattern of early growth failure

The purpose of this study was to determine the pattern of early growth in girls with Turner syndrome. Analysis was performed on a total of 464 longitudinal measurements of height, obtained from birth to 8 years of age from 37 girls with Turner syndrome who did not have significant cardiac disease or autosomal abnormalities. All data were obtained prior to the initiation of any hormonal therapy. Mean height SDS fell from -0.5 at birth to -1.5 at age 1 year and -1.8 at age 1.5 years. Growth curves fitted using the first two components of the infancy-childhood-puberty model of growth revealed that growth failure was due to (a) mild growth retardation in utero , (b) slow growth during infancy, (c) delayed onset of the childhood component of growth and (d) slow growth during childhood. Physicians should consider the diagnosis of Turner syndrome in any girl with an unexplained failure to thrive or with short stature, even during the first 2 years of life.     

Restoration of spermatogenesis by hormone treatment after cytotoxic therapy

Cytotoxic therapy is effective in treating various cancers, but many of the agents used can cause sterility in men, regardless of the age at which they were treated. Originally, it was thought that infertility in individuals who had undergone cytotoxic therapy resulted from the destruction of stem spermatogonia. However, studies using rats suggest that some stem spermatogonia can survive cytotoxic therapy and that infertility is caused by the inability of these spermatogonia to differentiate. The author believes that the failure of these cells to differentiate may be related to the high levels of intratesticular testosterone encountered in these situations. In rats that have previously received cytotoxic therapy, the administration of a gonadotrophin-releasing hormone (GnRH) agonist restores the ability of spermatogonia to differentiate, and as a result normal spermatogenesis returns. This finding suggests that GnRH agonists show promise as treatment for male sterility induced by cytotoxic therapy, although further studies are required.     

Role of factor XIII Val 34 Leu polymorphism in patients with migraine

At present, it is contradictory to determine if the combination of certain prothrombotic polymorphisms and migraine increases the risk to develop ischaemic cerebrovascular disease. Recently, the common Val34Leu polymorphism of the A-chain factor XIII gene, associated with variations in factor XIII activity, has been suggested to play a significant role in the development of arterial and venous thrombotic disorders. We analysed the prevalence of this polymorphism in 17 patients with coexisting ischaemic cerebrovascular disease and migraine (5 with aura, and 12 without aura), 89 patients with migraine (43 with aura, and 46 without aura), 116 patients with ischaemic cerebrovascular disease, and 467 healthy Caucasian controls from the South of Spain. Genomic PCR amplification, using a mutated oligonucleotide, and allele-specific restriction assays were used for genotyping. The factor XIII Leu 34 variant was present in 47.1; 40.5; 34.9; and 35.1% of patients with coexisting ischaemic cerebrovascular disease and migraine, ischaemic cerebrovascular disease, migraine, and control subjects, respectively. These data suggest that the factor XIII Leu 34 allele does not play a protective role against these disorders in our population.     

Systemic Delivery of SapC-DOPS Has Antiangiogenic and Antitumor Effects Against Glioblastoma

Saposin C-dioleoylphosphatidylserine (SapC-DOPS) nanovesicles are a nanotherapeutic which effectively target and destroy cancer cells. Here, we explore the systemic use of SapC-DOPS in several models of brain cancer, including glioblastoma multiforme (GBM), and the molecular mechanism behind its tumor-selective targeting specificity. Using two validated spontaneous brain tumor models, we demonstrate the ability of SapC-DOPS to selectively and effectively cross the blood–brain tumor barrier (BBTB) to target brain tumors in vivo and reveal the targeting to be contingent on the exposure of the anionic phospholipid phosphatidylserine (PtdSer). Increased cell surface expression of PtdSer levels was found to correlate with SapC-DOPS–induced killing efficacy, and tumor targeting in vivo was inhibited by blocking PtdSer exposed on cells. Apart from cancer cell killing, SapC-DOPS also exerted a strong antiangiogenic activity in vitro and in vivo. Interestingly, unlike traditional chemotherapy, hypoxic cells were sensitized to SapC-DOPS–mediated killing. This study emphasizes the importance of PtdSer exposure for SapC-DOPS targeting and supports the further development of SapC-DOPS as a novel antitumor and antiangiogenic agent for brain tumors.     

Technetium-99m sestamibi scintimammography complements mammography in the detection of breast cancer

Mammography remains the technique of choice for the detection of early breast cancer. The sensitivity of mammography is 85%, but is decreased in patients with dense breasts. Sestamibi scintimammography (SCM) has been suggested as an adjunctive modality to improve the detection of breast cancer. We conducted a study to determine the impact of SCM in patient management. A prospective study was conducted in 95 patients presenting with palpable masses and/or abnormal mammography scheduled for biopsy. Injection of 20-30 mCi of technetium-99m (Tc-99m) sestamibi into a pedal vein was performed. Ten-minute images of the breast and axilla were obtained in multiple projections. The mammography and SCM were correlated with pathology and clinical findings. The median age was 44 years (range 28-86 years). The total number of lesions was 104, as eight patients had bilateral lesions and one patient had two lesions in the same breast. Fifty-nine patients presented with palpable lesions and 45 patients with nonpalpable lesions (42 with abnormal mammography only and 3 with nipple discharge). A comparison of sensitivity, specificity, positive and negative predictive values, and overall accuracy of SCM and mammography were performed. The sensitivity and specificity for SCM were 83% and 83%, respectively, and for mammography were 65%, and 72%, respectively. The sensitivity and specificity for combined SCM and mammography were 87% and 94%, respectively. The p-value for mammography versus combined SCM and mammography was 0.0003 and that for SCM versus SCM and mammography was 0.0098. There were 80 (77%) benign and 24 (23%) malignant lesions. Of the 24 malignancies, SCM missed six (25%), versus eight (33%) by mammography. In two patients (9%) SCM detected malignancy in the breast that was not visualized by mammography or found on clinical examination. Sestamibi SCM improves the sensitivity of mammography and it detects up to 9% of malignancies not detected by mammography or clinical examination. This testing could impact the management of 16,500 patients in the United States every year. More studies are needed to better define its role in breast cancer detection.     

Clonal analysis of transplant-associated lymphoproliferations based on the structure of the genomic termini of the Epstein-Barr virus

The clonal composition of various transplant-associated lymphoproliferations was assessed by means of Southern blot hybridizations using a DNA probe specific for the fused termini of the Epstein-Barr virus (EBV) genome. A single clonal band representing the joined EBV genomic termini was detected in most biopsies, demonstrating the presence of a monoclonal expansion of B lymphocytes carrying EBV DNA. Different configurations of immunoglobulin gene rearrangements and fused EBV genomic termini were frequently observed in tissues from different biopsy sites in individual patients, confirming the multiclonal origins for these lymphomas. In rare specimens, multiple forms of the joined termini were detected within individual lesions, which appeared polymorphous by histologic methods of analysis and polyclonal by immunologic and immunogenetic methods of analysis. These studies confirm that there is a spectrum of EBV-associated disorders of varying clonal composition that may arise in immunosuppressed organ- allograft recipients. The data are consistent with the proposal that the lymphoproliferations initiate as polyclonal expansions of EBV- carrying B cells, which progress to multiclonal lymphomas in most patients. Detection of homogeneous episomal EBV DNA in most lesions supports a primary role for the virus in the pathogenesis of these disorders.