| Part I Expression and clinical significance of PAK7protein expression inosteosarcomaBackground and purposep21-activated kinase7(PAK7)（also called PAK5） is a recently identified member ofPAKs that regulate many intracellular processes such as cytoskeleton remodeling, cellproliferation, cell differentiation, cell apoptosis and gene transcription. Recently, studiesfound that PAK7was over expressed in some cancer such as gastric and colon cancer.However, the expression status and biological function of PAK7in osteosarcoma are notclearly known. The objective of this study was to investigate the expression of PAK7inosteosarcoma tissue and their relationships with the prognosis of osteosarcoma.ObjectiveTo investigate the expression of PAK7in osteosarcoma tissue, analyze its correlationwith clinical and histopathological characteristics, and further discuss its role in theprognosis of osteosarcoma.MethodsThe expression of PAK7detected by using immune-histochemical MaxVision methodin92specimens of human osteosarcoma tissues and33cases of osteoclastoma tissue. Therelationship between expression of PAK7and clinicopathological parameters wascalculated by Chi-square test. Kaplan-Meier method was used to calculate the overallsurvival rate. The factors of gender, age, tumor location, tumor size, histological type, localrecurrence, Enneking grade and lung metastasis were included in univariate analysis. The univariate analysis was used to determine the prognostic factors related with survival rateby log-rank test. The COX proportional-hazard regression model was used to identify thecorrelation between the prognostic factor and survival.Results(1)66specimens showed positive staining of PAK7in all the92cases of osteosarcoma, aswell as none was detected in33cases of osteoclastoma tissue. The difference of positiverate was statistical significant.(2)The positive rate of PAK7in the osteosarcoma patients on the Enneking II stage is66.2%（49/74） and that is94.4%（17/18）on the Enneking III Stage. The difference ofthe positive rate of PAK7between Enneking II stage and Enneking III stage wassignificant（P=0.019）.(3) The positive rate of PAK7in the osteosarcoma patients with metastasis is90.4%（47/52）,however, the positive rate of PAK7in the osteosarcoma patients withoutmetastasis is47.5%（19/40）.The difference was significant（P=0.000）.(4) The positive rate of PAK7in the osteosarcoma patients who use neoadjuvantchemotherapy with tumor cell necrosis rate≥90%is54.8%(17/31),however, the positiverate of PAK7in the osteosarcoma patients with tumor cell necrosis rate <90%is80.3%（49/61），the high expression of PAK7may reduce the efficiency of chemotherapy.(5)PAK7expressions were not related to clinical variables such as gender, age, tumorlocation, tumor size, histological type and local recurrence, but significantly related toEnneking grade, tumor cell necrosis rate and lung metastasis by Chi-square test.(6)Survival analysis indicated that high expression of PAK7correlated with poor prognosisof patients with osteosarcoma. Univariate survival analysis showed that the significantprognostic factors were tumor size, Enneking grade, local recurrence, lung metastasisand expression levels of PAK7.COX multivariate regression identified that the PAK7expression levels (P=0.001) and lung metastasis (P=0.015) were independent prognosticfactors of patients with osteosarcoma. Conclusion(1) The positive expressions of PAK7closely correlate with Enneking grade, tumor cellnecrosis rate and lung metastasis. It may affect the biology behavior of theosteosarcoma.(2)Detection of PAK7may be used as a molecular marker for prognosis of osteosarcoma.The high expression of PAK7may reduce the efficiency of chemotherapy. Part II Clinical research of pemetrexed in combination with cisplatinin the treatment of osteosarcoma with lung metastasisObjectiveThe purpose of this study was to evaluate the efficacy and safety of pemetrexed incombination with cisplatin in the treatment of osteosarcoma with lung metastasis.failedwith first-line chemotherapyMethodsBetween Jan.2008and June2012,18patients with osteosarcoma patients with lungmetastasis were included in this analysis.Among the18cases,14cases were male and4were female,the median age was20years old, karnofsky performance status score is morethan or equal to70.The patients received pemetrexed500mg/m2on day1and cisplatin80～100mg/m2on day1and2by intravenous infusion, with21days as one cycle. Allpatients who received2cycles were evaluated for the efficacy and toxicity. The end pointwas overall survival time (OS), progression-free survival (PFS), the disease control rate(DCR) and toxicity.ResultsAll patients were given more than2cycles.18patients were entered and all of these patients could be evaluated. No case achieved CR and PR, one patient got minimalresponse, seven got stable disease and ten cases got progression disease. The diseasecontrol rate was44.4%(8/18). The median progression-free survival and overall survivaltime were9.0weeks (95%confidence interval:5～13weeks) and12.0months (95%confidence interval:9～16months), respectively. The common adverse effects weredigestive tract reaction (50.0%), anemia (44.4%) and fatigue (38.9%). The patients’conditions were apparently relieved after symptomatic treatments.ConclusionPemetrexed in combination with cisplatin tends to show modest treatment efficacyand is well tolerated in patients for osteosarcoma with lung metastasis. |
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