目的 探讨多发性骨髓瘤外科治疗的手术指征、方式和效果。方法 总结分析了29例孤立性骨髓瘤和多发性骨髓瘤患者的临床表现及外科治疗情况。本组病例男17例，女12例。年龄38-76岁，平均59.5岁。原发病灶位于脊柱9例，肋骨1例，肱骨2例，股骨上端2例，股骨干4例， 骨盆5例，骶骨6例。这29例患者分别进行了下列外科治疗：行单纯病灶清除12例，其中6例为骶骨骨髓瘤，5例炎骨盆部骨髓瘤；行柱前路病灶清除减压、钛网置和钢板内固定6例； 行脊柱后路病灶清除减压、经椎弓根内固定3例；5例病理性骨折患者分别行肿瘤刮除、骨水泥填充，髓内钉或DHS内固定；3例患者行肿瘤切除，人工假体置换。文章评估了手术后疼痛、神经损害症状、脊柱不稳等症状的改善，生活质量及生存情况。结果 疼痛改善最明显，所有患者均有疼痛减轻。3例截瘫患者，一例由Frankal分级B级变为C级，2例由C级变为D级。术后平均随访1.5年。3例局部复发。结论 对有严重神经功能损害和严重影响患者生存质量的合并症的多发性骨髓瘤患者来说，外科手术治疗是一种有效可行的治疗方法，再结合化疗和放疗，对改善患者的生活质量和延长生存期是非常有意义的。

The INK4A gene, localized to human chromosorme 9p21, encodes P16INK4A, a tumor suppressor that functions at least in part through the inhibition of CDK4, a cyclin-dependet kinase encoded by a gent at 12q13. To examine INK4A gene alterations in uncultured samples of osteosarcoma and the relationship between INK4A adn CDK4 alterations, we ana-lyzed the INK4A and CDK4 genes in 87 specimens from 79 patients. INK4A deletion and CDK4 gene amplification were determined by quantiattive Southern blot analysis. INK4A exon 2 was screened for mutation by polymerase chain reaction and single-strand comformational polymorphism analysis. Methylation at the CpG island in INK4A, associated with loss of p16INK4A expression, was assessed by Southern blot analysis using methylation-sensitive restriction enzymes. INK4A deletion (4/55) or rearrangement (1/55) was found in 5 of 55 cases. No INK4A exon 2 poitnt mutations and methyl-ation were detected. CDK4 gene amplification was found in 6 of 67 samples, but not in tumors with INK4A alteration. Amplification analysis of other genes at 12q13 (GLI, CHOP, HMGI-C and MDM2) in these 6 cases supports the view that CDK4 and MDM2 are independent targets for amplification, with variable amplification of the intervening region comtain-ing HMGI-C. Of 46 patients studied for both INK4A alterations and CDK4 amplification, the tumors in 22% contained one or the other. The prevalence of these alterations, in conjunction with the reported inactivation of RB in up to 80% of cases, suggests that genetic lesions deregulating the G1 to S cell cycle checkpoint may be an almost constant feature in the pathogenesis of osteosarcoma. Int. J. Cancer 80: 199-204, 1999.

High-dose methotrexate is a major component of cur-rent protocols for the treatment of osteosarcoma, but some tumors seem to be resistant. Potential mechanisms of resist-ance include decreased transport throughthe reduced folate carrier (RFC) and increased expression of dihydrofolate reductase (DHFR). To investigate methotrexate resistance, tumors were obtained from 42 patients with high-grade osteosarcoma. RFC and DHFR mRNA expression were studied by semiquantiiative reverse transcription-PCR. The PFC and DHFR genes were studied for deletions and am-plification bySouthern blot. Thirteen of 20 (65%) osteosar-coma samples were found to have decreased RFC expression at the time of intial biopsy. At definitive surgery and re-lapse, 10 of 22 (45%) were found to have decreased RFC expression. Seventeen of 26 (65%) samples with a poor response to chemotherapy had decreased RFC expression, response to chemotherapy had decreased RFC expression, whereas 5 of 14 (36%) samples with a good response had a decrease (p=0.03). None of the samples had an RFC gene deletion. Two of 20 samples (10%) showed increased DHFR expression at inital biopsy. The frequency of increased DHFR expression was significanfly higher inmetastatic or recureent tumors (62%, p=0.014). None of the samples showed evidence of DHFR gene amplification. The high frequency of decreased RFC expression in the biopsy mate-rail suggests that impaired transport of methotrexate is a common mechanism of intrinsic resistance in osteosarcoma. Increased DHFR expression in the pulmonary metastases may be a mechanism of acquired methotrexate resistance or a difference between primary and metastatic lesions.

BACKGROUND. The primary genetic alteration, in > 95% of Ewing sarcomas (ES) is involoed in progression of ES are not well understood. A recent study found loss of the negative cell cyde rcgulator gene INK4A in 8 at 27 FS samples (13%) To confirm these findings and cvaluate their prognostic Significanoe, Lhe authors studied INK4A deletion in 41 ES samples from 39 patiens. METHODS Using Soulthem blot analysis with an INK4A p16 cDNA probe, the control probe and compared with nondeleted eonrol DNA; > 50% signal reduction was scored as evidence of deletion All NS tumor DNA samples previously were confirmed to have EWS rearrangremetnts on the same Soulhum blots, Using a cDNA probe spanning the EWS breakpoint region. RESULTS. Tumors from 7 Datients (18%) showed INK4A deletion indenendent of tasis INK4A was. strong negative facror for disease specific surviat in Univafate CONCLUSIONS. INK4A deletions appear to be the most frequent seeondary molec-ular genetic alteration faund la date in ES. Their possible clinical usefulness in identifying a subset or ES patents with poor prognosis merits systematic prospec tive analysts See related article on pages 783-92.

Bone morphogenetic proteins, which are capable of inducing mesenchymal tissue to form bone in mammals, have been implicated as important in normal skeletal developmetl. The expession of bone morphogenentic proteins and their recep-tors were studied In 36 osteosarcoma speelmens, six Ewing' s sarcomas, 20 synuvial sarcomas, and 20 ehondrcomas by reverse transcriptase-polyme rase chain reaction, and the flndings were co.elated with clinical data. Bane morphogene-tic protein-2, and -4 messages were detected in most sarcoma samples. Bone morphogenetic pratein-6 exprssion was detected in 22 of 32 os-teosarcomas and seven of eight chondrco-mas. Bone morphogenetic protein-7 and recep-tar IB were not detected in sarcoma sumples but were detected in three osteosarcoma cell lines and one malignant fibrous histiocytoma cetlline. Expression of bone morphogenetie protein re-ceptor II was found in 25 of 36 ostesarcomas, eight of 20 chondrosarcomas, four of six Ewing' s sarcomas, and 15 of 20 synovial sarcoma sam-pies. Expression of hone morphngenetic protein type 11 receptor was found to currelate with me-tastasis in osteosarcomas, which suggests that the hone morphogenetic protein pathway may participate in tumor aggressivenss or progres-sion. The expression of bone morphogenetic pro-rein receptor 11 in metastatic synovial sarcoma and dedifferentiated chondrosarcoma Iesions also supports this hypathesis. The current study showed that the ligauds fur hone morphogenetic protein receptors, bone morphagenetic proteins-2, -4, and -6 also are expressed in ostecrcoma and other other sarcoma tissues, indicating a potenlial for autocrine or paracrine growth stimulation in these tumors.