Renal cell carcinoma(RCC)is currently one of treatment-resistant malignancies and is not sensitive to conventional radiotherapy or chemotherapy.The effective rate of high dose of recombinant human interleukin-2(IL-2)and recombinant human interferon-α(IFN-α)was only 10%-15%.Advances in the understanding of cancer at molecular level have led to more progress in the development of anti-cancer agents.Recently,mutation of Von Hippel-Lindau(VHL),Ras,PTEN genes have been observed in RCC and the mutation can result in different expression levels of RTK.Among the newly invented medications for targeted cancer therapy,protein kinase inhibitors target intracellular molecules crucial in sighaling pathways of cancer cell survival and proliferation.Compared with conventional chemotherapy and immune therapy,targeted therapy is effective,with fewer adverse effects.According to 2009 NCCN Clinical Practice Guidelines in oncology,this article reviewed the clinical application of sunitinib,sorafenib,temsirolimus,and bevacizumab in the targeted therapy for renal cell carcinoma.

Heparanase is the only one endogenous glucuronidase found in mammalian cells up to now,and can degrade the heparan sulfate which is the side chain of heparin sulfate proteoglycans existing in the extracellular matrix and basement membrane.Heparanase is considered as an ideal target for the treatment of cancer metastasis.High expression of heparanase gene was found in breast cancer,and was closely associated with tumor size and lymph node metastasis.In vitro,high level of heparanase promoter activity was found in breast cancer cells.In vivo,compared with negative control group,breast cancer cells transfected with heparanase could generate higher tumor volume,tumor weight,microvessel density and longer survival time of cancer cells.Blockage or silencing of heparanase gene expression through antisense technology or RNA interference technology could reduce the ability of adhesion and invasion of breast cancer cells,indicating that heparanase played important roles in the invasion and metastasis of breast cancer.Mechanisms involved in the regulation of heparanase in the invasion and metastasis of breast cancer are as following.Estrogen could bind to its recaptor and then affect the specific region of heparanase gene which could activate heparanase transcription and the expression of hepamnase Mrna and protein.Heparanase could increase the secretion of osteoclast-stimulating factor which could cause the osteolytic lesions in the absence of detectable bone metastasis.Heparanase could also induce circulating lymphocytes to produce stimulating factors which might promote the invasion and metastasis of breast cancer.Furthermore,p53 gene,ETS gene,EGR1 gene,PI-88 factor,and Cox-2 could also regulate the expression of heparanase gene.This article reviewed the role of heparanase in the invasion and metastasis of breast cancer and summarized the corresponding regulation mechanisms.

Objective: To explore the effect of single-nostril transsphenoidal approach on pituitary adenoma. Methods: We retrospectively analyzed 46 cases of pituitary tumors treated with single-nostril transsphenoidal approach and the effects and complications of surgery.Dunng the surgery,a nasal speculum was inserted through right nostril slowly towards the anterior wall of sphenoid sinus.A nasal mucosa incision of about 1.5cm was made in the right nasal cavity at the level of the middle nasal turbinate.With a fracture of the bony septum,a space was developed between the bilateral nasal mucosa and bony septum to the sphenoid sinus.Then,the face of the sphenoid sinus was exposed.The remainder of the bony septum,the anterior sphenoid sinus wall,and the sphenoid mucosa were removed.The antenor sphenoidotomy should be less than 1.5cm wide.After confirming the tumor by dural puncture,a cross incision of dura was made and the tumor was removed.The saddle was usually Collapsed and visible after total tumor removal.When the tumor was resected,sevaral gelatin sponges were stuffed into the Surgical cavity to stop bleeding. Results: Thirty-four cases had total resection and 12 cases had subtotal resection.No deaths or disability occurred.Hormone levels in almost all patients were improved.Seventeen cases had a sign of diabetes insipidus.Electrolyte disturbance occuwed in 5 cases.NO postoperative cerebrospinal fluid rhinorrhea was observed. Conclusion: Single-nostril transsphenoidal approach has many advantages in treating pituitary adenomas such as simplified approach,brief technology and high security.

Objective: To discuss the clinical features of basaloid squamous carcinoma(BSC)and the factors relating to its prognosis and to compare patient survival between poorly differentiated squamous cell carcinoma(PDSC)and BSC. Methods: Clinical and pathological data of BSC and PDSC cases seen in our hospital between January 2004 and December 2008 were reviewed. Results: There were no statistical differences in demographic and clinical features between PDSC and BSC patients,with the exception that a larger proportion of BSC patients were female(P=-0.001).Additionally,higher tobacco consumption was observed among BSC male patients (P=0.003).There were no significant differences in survival rate between BSC and PDSC groups(X2=0.03,P=0.5470).The median survival time of BSC and PDSC patients was 19 months and 30 months，respectively.The 4-year survival rate was 22.4%and 36.1%，respectively(u=0.740,P=0.230).No significant difference was found in survival rate between stage Ⅰ and stage Ⅱ patients(X~2=0.109，P=0.2974).The median survival time of stage Ⅰ and stage Ⅱ patients was 19 months and 46 months，respectively；and the 4-year survival rate of stage Ⅰ and stage Ⅱ patients was 47.3% and 45.2%，respectively(u=0.122，P=0.450).Using Cox proportional hazard model，we found that surgical types and clinical stages of BSC were correlated with its prognosis.Compared with that of patients who received lobectomy,the postoperative mortality hazard of patients who received pneumonectomy and segmentectomy was increased by 1.379 times(P=0.031)and 1.634 times(P=0.061)，respectively.A more advanced clinical stage was associated with an increase in the postoperative morta,ty hazard ratio(X~2=14.12,P=0.000).The postoperative mortality hazard of patients of stage Ⅲ and stage Ⅳ was 2.437 times higher than that of stage Ⅰ patients(P=0.018).There were no statistical differences in postoperative mortality risk between stage Ⅰ patients and stage Ⅱ patients(P=0.057). Conclusion: Compared with that of PDSC,the incidence of BSC is higher among females.However,there is no difference in the prognosis between BSC and PDSC.BSC can be treated with the same therapies as those for other types of non-small cell lung cancer(NSCLC).

Objective: To study the clinicopathological characteristics，diagnosis，multiple modality therapy and prognosis of accessory breast cancer. Methods: Clinical data of 38 patients with accessory breast cancer seen in our hospital between October 1985 and November 2007. Results: The 38 cases of accessory breast cancer accounted for 0.15% of all 26,078 breast cancer cases during the same period.Six patients of stage Ⅰ and 3 patients of stage Ⅱ underwent breast-conserving local wide excision of the tumor plus axillary lymph node dissection,with the resection margins pathologically negative.The other 9 cases of stage Ⅱ patients were treated with Auchincloss mastectomy.Stage Ⅲ and stage Ⅳ patients were treated with Auchincloss or Halsted mastectomy.The most common histological type of accessory breast cancer was infiltrating ductal Carcinoma for 18 patients(47.4%)，of which 3 cases were associated with adenoma of the nipple tube.There were 6 cases of carcinoma simplex，6 cases of intraductal Carcinoma，3 cases of adenocarcinoma with focal squamous cancer cells differentiation，3 cases of medullary carcinoma，and 2 cases of mucinous adenocarcinoma.The most common pathological stages(according to AJCC staging of breast cancer,2002.6th edition)were stage Ⅱ and Ⅲ in 12 cases(31.6%)，stage Ⅰ in 6 cases，and stage Ⅳ in 8 cases.All patients were followed-up for 1 to 23 years.The median follow-up time was 6 years and 7 months，and the follow-up rate was 100%.Until November 2008，12 patients died of metastasis and the other 26 patients were still alive.The 5-year overall survival rate was 35.3%.significantly lower than that of breast cancer patients(66.8%).The 3-year survival rate was 77.8%.The 5-year disease free survivaI rate was 28.6%and the 3-year disease free survival rate was 63.6%. Conclusion: Accessory breast cancer is rarely seen but is aggressive.The diagnosis mainly depends on clinical characteristics，postoperative pathology and imaging examinations.Early diagnosis is essential.Surgery combined with other adjuvant therapies can improve patient survival.

Objective: To analyze the prognostic factors of non-Hodgkin's lymphoma(NHL)and to investigate the prognostic value of peripheral blood absolute lymphocyte count(ALC)at admission for patients with NHL. Methods: Clinical features and follow-up data of 108 patients with pathologically confirmed NHL seen in our hospital between January 2000 and January 2008 were reviewed.SPSS14.0 package was used for statistical analysis.Kaplan-Meier was applied to assess the survival probability.All parameters statistically significant concluded by univariate analysis were then computed as co-variates for multivariate analysis with Cox regression model. Results: The ratio of males to females was approximately 1.5:1.The median age of patients was 48 years.Before treatment.the Ann Arbor clinical classification showed that 61.1% of the cases were of stage Ⅰ and Ⅱ.Approximately 93%of the patients had ECOG performance status(PS)score of 0-1 and 19.2%of the cases had elevated serum lactate dehydrogenase(LDH).According to intemational prognosis index score.80.6%of the patients were in a low risk group.At admission，35.2%of the cases had ALC≤1×10~9/L.Hemoglobin (Hb)≤110g/L and B symptoms were seen in 29.6%and 26.9%of the patients.The mean Hb was 129.2±17.5g/L in cases with ALC>1×10~9/L(n=70)and 98.1±20.6g/L in cases with ALC≤1×10~9/L(n=38),with a statistically significant difference between the two groups(P<0.05).With a median follow-up duration of 2 years，the median overall survival(OS)time was 2.3 years for all patients.The 2-year and 5-year OS rates were 73.2%and 39.6%，respectively.ALC≤1×10~9/L,Hb≤110g/L,B symptoms and intemational prognostic index(IPI)≥2 were statistically significant unfavorable prognostic factors for NHL revealed by univariate analysis.Multivariate analysis showed that ALC≤1×10~9/L,B symptoms and IPI ≥2 were statistically significant unfavorable prognostic factors for NHL. Conclusion: ALC and B symptoms may be prognostic factors independent of IPI for NHL.Evaluation of the prognosis with IPI,ALC，and B symptoms is of clinical value for individualized therapy of NHL patients.

Objective: To observe the tolerability of Chinese melanoma patients to four-week high-dose interferon alfa-2b(INTRON A(R)，Schering-Plough)therapy. Methods:A total of 29 patients with high risk melanoma[American Joint Committee on Cancer Staging(AJCC)ⅡB-ⅢC]who received adjuvant interferon therapy in our hospital between September 2007 and May 2009 were retrospectively reviewed.Patients received 4 hours of intravenous infusion of interferon alfa-2b fdose range，22.00 million international unit(MIU)to 33.75 MIU]Ⅳ 5 days/week for 4 weeks.The adverse events were evaluated with National Cancer Institute Common Toxicity Criteria(NCI 2.0 version). Results: The average daily dose was 17.63 MIU/(m~2·d).The therapy was ended in two patients because of poor wound healing or intolerability to severe fatigue.The most common adverse events were myelosuppression.Grade 3/4 neutropenia was observed in 69% (20/29)patients and was rapidly reversed after conventional support interventions.Grade 1/2 abnormal hepatic function occurred in 18 cases(62%).Twenty-six patients were followed up for 3 to 22 months.Five patients developed early progression:one with local recurrence，two with regional lymph node metastasis one with in-transit metastasis in the affected limb,and one with distant metastasis. Conclusion: High-dose interferon alfa-2b regimen can be well tolerated by Chinese patients but cannot effectively inhibit subclinical lesions.

Objective: To explore the turnover and treament of postoperative remainder of giant nonfunctioning pituitary adenoma with suprasellar extension(SSE). Methods: The clinical data of 68 cases suffering from giant nonfunctioning pituitary adenoma with suprasellar extension(SSE)admitted into our department were retrospectively analyzed.These patients underwent primary transsphenoidal surgery. Results: Twenty cases had SSE adenomas totally removed(20.6%).In other 48 cases(79.34%)，SSE residues were shown in MRI recheck at one day after surgery.After 3 months，the 3rd MRI scanning was performed only to find that tumor residues descended to sellar floor in 21 cases,into intrasella in 8 cases，and down to the level of stalk hypophysial and the entrance to the sella in 3 cases.All of Patients with residual tumors received retranssphenoidal resection(the total removal rate of desending SSE residues was 96.9%).There were 2 cases with adenoma residues with slight descending.Obvious SSE adenomas were treated with transtranial approach.The twelve cases with small SSE residues were consecutively observed and two of them received gamma knife treatment because of unobvious postoperative visual improvement.The surgical mortality was 0%.There was no death during follow up in all of these patients.There were no cases with rhinorrhea.meningitis or visual deterioration.Two patients had supradiaphragmatic bleeding detected by routine postoperative CT. Conclusion: Staged surgery with two or multiple transsphenoidal resections is an appropriate treatment for giant nonfunctioning pituitary adenoma with supresellar extension(SSE)，with few complications.Futher study is warranted to investigate the growth pattern of pituitary adenoma.

Objective: To investigate the differential expression of Sox9 in conventional chondrosarcoma,dedifferentiated chondrosarcoma and normal cartilage. Methods: We reported 12 cases of chondrosarcomas,which were initially diagnosed as chondrosarcomas(6 cases of conventional chondrosarcoma and 6 cases of dedifferentiated chondrosarcoma)at Peking University People's Hospital between January 2003 and January 2007.We used genechip method to identify difierentially expressed genes involved in conventional chondrosarcoma,dedifferentiated chondrosarcoma and in normal cartilage(6 cases)and found thousands of differentially expressed genes after extensive statistical analysis.With Sox9 which played crucial roles in the process of both differentiation and maturation of chondrocyte as a candidate,we used Real-time PCR,Westem blot and immunohistochemistry to confirm the results found by gene chip. Results: DNA microarray results showed that Sox9 was up-regulated about 1.6 times in conventional chondrosarcoma compared with that in normal cartilage.But in dedifferentiated chondrosarcoma,the expression level of Sox9 was significantly down-regulated,0.082 times of that in normal cartilage.Real-time PCR results showed that the expression levels of Sox9 mRNA in conventional chondrosarcomas and dedifferentiated chondrosarcomas were 1.68±0.119 and 0.088±0.017,respectively.Sox9 protein level was significantly higher in humen conventional chondrosarcomas than that in normal cartilage.Sox9 protein level in dedifferentiated chondrosarcomas was significantly lower than that in normal cartilage tissue.All of the 6 cases of conventional chondrosarcomas showed diffuse and strong staining of Sox9.However,Only scattered staining was observed in dedifferentiated chondrosarcomas. Conclusion: Compared with that in normal cartilage,Sox9 expression is up-regulated in conventional chondrosarcomas and down-regulated in dedifferentiated chondrosarcomas.Decrease of Sox9 expression in dedifferentiated chondrosarcoma is correlated with poor survival,indicating that Sox9 may serve as a molecular prognostic marker for chondrosarcomas and disease progression.

Objective: To investigate differentially expressed protein profiles in B16-F10 grafted melanoma and its metastasis in the lung in order to identify molecular markers of melanoma metastasis. Methods: Differentially expressed proteins in B16-F10 grafted melanoma and its metastatic lesion in the lung were isolated and identified by fluorescence two-dimensional differential gel electrophoresis(2D-DIGE)coupled with matrix assisted laser desorption ionisation time-of-flight mass spectrometry(MALDI-TOF-MS).Some of identified proteins were further confirmed by Real-time PCR analysis. Results: High resolutional images of differential gel electrophoresis were obtained and 9 of 30 differentially expressed proteins (IRatiol≥2,P<0.01)were identified by MALDI-TOF-MS.The expression of Myoglobin(MB),vimentin(VIM),phosphoglycerate kinase 1(PGK1),Triosephosphate isomerase(TPI or TIM),heavy-chain binding protein(BiP),α-enolase,β-actin,γ-actin,and laminin-binding protein were up-regulated in the experimental group compared with the control group.These proteins were involved in the cytoskeletal formation,glycolysis and so on.Real-time PCR analysis showed up-regulation of mRNA expression of PGK1 and TPI in the experimental group(P=0.001 and 0.003),which was in consistent with the resuits of proteomic analysis. Conclusion: A variety of abnormally expressed proteins contribute to the metastasis of mice melanoma.Glycolytic enzymes PGK1 and TPI may be involved in this process.