膝关节周围骨肿瘤手术的肢体康复

0　引言　膝关节周围是骨原发恶性肿瘤的好发部位 .病变组织广泛侵袭 ,切除肿瘤造成骨与软组织缺损 ,各种重建方法都需最大限度地保留膝关节功能 .如何采取早期系统的康复治疗 ,是临床骨肿瘤保肢手术的重要内容 .1　对象和方法　 1992 - 0 5 / 1999- 0 3,膝关节周围恶性骨肿瘤患者 6 4例接受保肢手术治疗 .男 38例 ,女 2 6例 ;骨肉瘤 5 2例 ,恶性骨巨细胞瘤 5例 ,尤文瘤 3例 ,母细胞瘤 2例 ,原发神经外胚层肿瘤 2例 .手术方式 :异体半关节移植术 37例 ;异体骨段移植术 16例 ;复合异体骨段的人工全膝关节表面置换术3例 ,动力旋转铰链式人工全…     

Targeted Next-generation Sequencing of Advanced Prostate Cancer Identifies Potential Therapeutic Targets and Disease Heterogeneity

Background

Most personalized cancer care strategies involving DNA sequencing are highly reliant on acquiring sufficient fresh or frozen tissue. It has been challenging to comprehensively evaluate the genome of advanced prostate cancer (PCa) because of limited access to metastatic tissue.

Objective

To demonstrate the feasibility of a novel next-generation sequencing (NGS)–based platform that can be used with archival formalin-fixed paraffin-embedded (FFPE) biopsy tissue to evaluate the spectrum of DNA alterations seen in advanced PCa.

Design, setting, and participants

FFPE samples (including archival prostatectomies and prostate needle biopsies) were obtained from 45 patients representing the spectrum of disease: localized PCa, metastatic hormone-naive PCa, and metastatic castration-resistant PCa (CRPC). We also assessed paired primaries and metastases to understand disease heterogeneity and disease progression.

Intervention

At least 50 ng of tumor DNA was extracted from FFPE samples and used for hybridization capture and NGS using the Illumina HiSeq 2000 platform.

Outcome measurements and statistical analysis

A total of 3320 exons of 182 cancer-associated genes and 37 introns of 14 commonly rearranged genes were evaluated for genomic alterations.

Results and limitations

We obtained an average sequencing depth of >900X. Overall, 44% of CRPCs harbored genomic alterations involving the androgen receptor gene (AR), including AR copy number gain (24% of CRPCs) or AR point mutation (20% of CRPCs). Other recurrent mutations included transmembrane protease, serine 2 gene (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) gene (ERG) fusion (44%); phosphatase and tensin homolog gene (PTEN) loss (44%); tumor protein p53 gene (TP53) mutation (40%); retinoblastoma gene (RB) loss (28%); v-myc myelocytomatosis viral oncogene homolog (avian) gene (MYC) gain (12%); and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α gene (PIK3CA) mutation (4%). There was a high incidence of genomic alterations involving key genes important for DNA repair, including breast cancer 2, early onset gene (BRCA2) loss (12%) and ataxia telangiectasia mutated gene (ATM) mutations (8%); these alterations are potentially targetable with poly(adenosine diphosphate-ribose)polymerase inhibitors. A novel and actionable rearrangement involving the v-raf murine sarcoma viral oncogene homolog B1 gene (BRAF) was also detected.

Conclusions

This first-in-principle study demonstrates the feasibility of performing in-depth DNA analyses using FFPE tissue and brings new insight toward understanding the genomic landscape within advanced PCa.     

Involvement of TSC genes and differential expression of other members of the mTOR signaling pathway in oral squamous cell carcinoma

Background  

Despite extensive research, the five-year survival rate of oral squamous cell carcinoma (OSCC) patients has not improved. Effective treatment of OSCC requires the identification of molecular targets and signaling pathways to design appropriate therapeutic strategies. Several genes from the mTOR signaling pathway are known to be dysregulated in a wide spectrum of cancers. However, not much is known about the involvement of this pathway in tumorigenesis of OSCC. We therefore investigated the role of the tumor suppressor genes, TSC1 and TSC2, and other members of this pathway in tumorigenesis of OSCC.     

Carriage of Haemophilus influenzae and Streptococcus pneumoniae in healthy Chinese and Vietnamese children in Hong Kong

Nasopharyngeal carriage of Haemophilus influenzae and Streptococcus pneumoniae was studied in 621 healthy Chinese children and 300 healthy Vietnamese children aged from 2 months to 5 years in Hong Kong. The carriage rate of H, influenzae type b in Vietnamese children was 1.3% (CI 0.04-2.63%); it was zero in Chinese. The carriage rate of non-typable H. influenzae was 5.8% (CI 1.4-7.6%) in Chinese and 65.4% (CI 58.9-69.8%) in Vietnamese. The carriage rates of S. pneumoniae were 10.8% (CI 8.3-13.2%) and 55.7% (CI 50.1-61.3%) in Chinese and Vietnamese children, respectively. Univariate and multivariate logistic regression analyses were performed to search for factors associated with differences in carriage rates of both H. influenzae and S. pneumoniae between Chinese and Vietnamese children. Although older age, smaller living area and parental smoking were associated with higher carriage rates, these could not explain the remarkably low carriage rates of both bacteria in Chinese children.     

DNA testing for fragile X syndrome in schools for learning difficulties

Fragile X syndrome is the most common inherited cause of mental retardation. Early diagnosis is important not only for appropriate management of individuals but also to identify carriers who are unaware of their high risk of having an affected child. The disorder is associated with a cytogenetically visible fragile site (FRAXA) at Xq27.3, caused by amplification of a (CGG)n repeat sequence within the gene at this locus designated FMR1. Clinical and molecular studies have been undertaken to screen for fragile X syndrome in 154 children with moderate and severe learning difficulties of previously unknown origin. Southern blot analysis of peripheral blood showed the characteristic abnormally large (CGG)n repeat sequence associated with fragile X syndrome in four of the 154 children. The findings were confirmed by cytogenetic observation of the fragile site and by further molecular studies. The families of the affected children were offered genetic counselling and DNA tests to determine their carrier status. These findings show that there are still unrecognised cases of fragile X syndrome. Given the difficulty of making a clinical diagnosis and the implications for families when the diagnosis is missed, screening in high risk populations may be justified. The issues involved in screening all children in special schools for fragile X syndrome are discussed.     

Growth, puberty and obesity after treatment for leukaemia

Final height, body proportions, pubertal growth and body mass index were studied retrospectively in 142 survivors of acute lymphoblastic leukaemia (ALL). Treatment consisted of combination chemotherapy and cranial irradiation (18 or 24 Gy). Significant standing height loss and disproportion, with a relatively short back, was seen in both radiation dose groups. Girls were more severely affected than boys. Pubertal growth was adversely affected, with a reduction in peak height velocity in both sexes. Puberty occurred early in girls but at the normal time in boys. Nearly half the group were obese at final height, with no significant difference in incidence between the sexes. The relative roles of cranial irradiation and chemotherapy in the disturbance of growth, puberty and body composition observed in survivors of childhood ALL remain unclear. The aetiology is almost certainly multifactorial, with radiation-induced growth hormone insufficiency, early puberty, steroids and chemotherapy all having a role.