Ifosfamide plus doxorubicin in previously untreated patients with advanced soft tissue sarcoma

The objective of this phase II trial was to assess the therapeutic activity and toxicity of doxorubicin plus ifosfamide in previously untreated patients with advanced soft tissue sarcoma. Treatment was doxorubicin 50 mg/m² followed by a 24 h infusion of ifosfamide 5 g/m² plus mesna 2.5 g/m² repeated every 3 weeks until disease progression or unacceptable toxicity occurred. Of 203 patients entered, 175 were evaluable for response. The response rate was 35% (95% CI 28–42%), with 9% of the patients achieving a complete remission and 26% a partial remission. The median time to progression was 29 weeks for all evaluable patients, and 67, 40 and 28 weeks for complete and partial responders and patients with stable disease, respectively. The median duration of survival was 58 weeks. Myelosuppression was the dose-limiting toxicity, resulting in leukopenia (WHO grade 3 and 4) in 73% of evaluable treatment courses. Other side-effects were rare and usually well manageable.     

Effect of body mass index on adenocarcinoma of gastric cardia

AIM: Obesity has been proved as one of the main risk factors for gastric cardia adenocarcinoma (GCA) in the West.The objective of our research was to evaluate the relationship between obesity and the risk of GCA in people from North China.METHODS: A total of 300 patients who had been diagnosed as GCA and had accepted surgical operation at Beijing Cancer Hospital from 1995 to 2002 were enrolled. Data were collected from pathology materials and hospital records. Two hundred and fifty-eight healthy people who had accepted health examination at the same hospital during the same period were enrolled as controls. Height, weight and gender of them at the time of examination were also collected.Obesity was estimated by body mass index (BMI), computed as weight in kilograms per square surface area (Kg/m2).The degree of obesity was determined by using BMI≤18.5,24-27.9 and ≥28 (Kg/m^2) as the cut-off points for underweight/normal, overweight and obesity, respectively.Associations with obesity were estimated by odds ratios (ORs) and 95% confidence intervals (CIs). All ORs were adjusted for age and sex.RESULTS: The mean level of BMI was significantly lower in the patient group than that in the control group. The ORs for obesity in age groups 30-59 and 60-79 were 1.15 (95% CI=0.37-3.65) and 0.16 (95% CI=0.05-0.44) for males and 0.78 (95% CI=0.26-2.36) and 0.28 (95% CI=0.04-2.05) for females, respectively. The ORs for underweight were 2.42 (95% CI=0.56-10.53) and 4.68 (95% CI=1.13-19.40)for males in age subgroups 30-59 and 60-79 and 40.7 (95% CI=9.32-177.92) for females older than 60 yrs. BMI was significantly associated with GCA (P<0.01). Underweight people were at high risk for GCA.CONCLUSION: BMI is an independent risk factor for GCA.Underweight is positively associated with GCA.     

Positive selection signals of hepatitis B virus and their association with disease stages and viral genotypes

The hepatitis B virus (HBV) is a global health problem that causes different types of liver diseases. The high mutation rate of HBV, which results from a lack of proofreading activity of the viral polymerase, leads to the actively adaptive evolution of mutant strains under various selection pressures. This study focuses on the positive selection signals in the whole HBV genome and the association of these selection signals with the disease stages and/or viral genotypes. A total of 486 complete HBV genomes from HBV-infected individuals of different illness categories (i.e., acute, chronic, and severe hepatitis) were analyzed. To obtain a panoramic view of the selection signals, codon-based maximum likelihood analysis, three-dimensional (3D) mapping, and allele frequency comparison were conducted on genotypes B and C HBV from subjects with different stages of hepatitis. A total of 95 selected codons were resolved, and a significantly higher number of positive selection signatures were found in the chronic and severe hepatitis groups compared with the acute groups. Many of the selected codons were associated with either a unique disease stage or a specific genotype. The conservation analysis of the selection signals in the viral core protein (HBcAg) illustrated the occurrence of selected codons in the highly diversified regions. The allele-frequency-based analysis identified eight additional nucleotide substitutions, and the frequencies of these mutations were found to increase with disease progression. Moreover, we found that three substitutions, including A1762T, G1764A, and A2739C, were nearly fixed. The mapping of all of the selected codons and nucleotide substitutions to the functional domains of the viral proteins suggested that more than 60% of the mutations were subject to selection forces from host immune surveillance, antiviral therapy, and replication fitness.     

Prevalence of human papillomavirus infection in women in the Autonomous Region of Inner Mongolia: A population‐based study of a Chinese ethnic minority

Human papillomavirus (HPV) is one of the most common sexually transmitted infectious pathogens. Persistent infection has been linked to cancer development, in particular to cervical cancer. This study aims to investigate the epidemiology of HPV infection in women in Inner Mongolia of China and to dissect the disparities between the Han and Mongolian ethnic populations. Cervical cell samples from 5655 women (17‐68 years old) were collected during routine gynecologic examination. HPV infection was established using the HPV GenoArray kit detecting 21 HPV genotypes. The overall HPV prevalence was 14.5%. HPV16 (5.0%), HPV58 (2.2%), and HPV52 (1.5%) are the most common genotypes. Of the 21 genotypes investigated, high‐risk HPV genotypes dominate in all age groups. HPV16 and HPV58 are the most common genotypes in patients with cervical lesions. HPV prevalence among Han women is 11.5% and the most common genotypes are HPV16 (4%) and HPV58 (2.1%). HPV prevalence is significantly higher in Mongolian women (32.6%), with the most common genotypes being HPV16 (10.7%), HPV31 (7.1%), and HPV52 (4.3%). The multiple infection rate in Mongolian participants (14.9%) is also higher than that of Han participants (4.3%). Urbanization, the number of sex partners, and PAP history appear as risk factors for HPV infection in Han, but not in Mongolian participants. HPV infection is highly prevalent in women in Inner Mongolia, China. HPV16 remains the most common genotype in this area. However, there are clear ethnical disparities in respect to the HPV epidemiology between the Han and Mongolian population.     

免疫抑制剂治疗类风湿关节炎的研究进展

类风湿关节炎（rheumatoid arthritis,RA）是风湿免疫科一种常见的全身性自身免疫性疾病。根据病情进展的不同程度,治疗方案亦不同,包括改善病情抗风湿药（disease-modifying anti-rheumatic drugs,DMARDs）、非甾体抗炎药（non-steroidal anti-inflammatory drugs,NSAIDs）、生物制剂、植物制剂等药物治疗以及辅助疗法,如针对性的锻炼、改善膳食、热敷冷敷等。目前的治疗方法对于RA的病情是有明显改善的,其中免疫抑制剂（immunosupressive agents,ISA）起到了不可忽视的作用,故从免疫抑制的角度论述,它能够有效控制病情进展,达到缓解疾病、提高生活质量的目标,得到了广泛的应用和发展。本文简述了选择性免疫抑制剂和非选择性免疫抑制剂治疗类风湿关节炎的作用机制以及临床应用,为免疫抑制剂治疗RA方面提供理论依据。     

Cyr61基因的生物学功能及在肿瘤发生发展过程中的作用

Cyr61（cysteine-rich 61）是CCN家族第一个被克隆出来的、由生长因子诱导产生的富含半胱氨酸的即刻早期基因产物。作为一种重要的细胞基质调节因子,Cyr61在胚胎发育、伤口修复、血管性疾病及肿瘤的发生发展过程中均发挥重要的生物学作用。研究发现Cyr61在肿瘤组织中广泛表达,并且与肿瘤新生血管形成及肿瘤细胞的增殖与凋亡、转移密切相关。Cyr61在不同细胞中的表达受多种信号通路的调控,可与多种整联蛋白结合激活不同的下游通路,可能通过参与Wnt、NF-kB、Tyrosine Kinase（酪氨酸激酶）、Akt等信号转导通路调控其它癌基因、抑癌基因或凋亡调控因子的表达。     

DC-CIK细胞过继免疫治疗联合XELOX方案化疗对进展期结直肠癌患者的疗效分析

目的探讨树突状细胞-细胞因子诱导杀伤细胞(DC-CIK)细胞过继免疫治疗联合奥沙利铂+卡培他滨(XELOX)方案化疗对进展期结直肠癌(CRC)患者的疗效。方法将104例进展期CRC患者按随机数字表法分为观察组和对照组各52例,观察组行DC-CIK联合化疗,对照组行化疗。检测患者治疗前后血清糖类抗原242(CA242)、糖类抗原19-9(CA19-9)、癌胚抗原(CEA)、T淋巴细胞亚群[自然杀伤性T(NKT)细胞、自然杀伤(NK)细胞、CD4^+、CD3^+、CD8^+]及白细胞介素-6(IL-6)、白细胞介素-2(IL-2)、干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)水平,评价患者近期疗效。结果观察组患者的缓解率(RR)为61.54%(32/52),疾病控制率(DCR)为75.00%(39/52),分别高于对照组的40.38%(21/52)和55.77%(29/52),差异均有统计学意义(P<0.05)。治疗后,两组患者血清CEA水平均低于治疗前,差异均有统计学意义(P<0.05);治疗后,观察组患者血清IL-2、IFN-γ、TNF-α、CD4^+、CD3^+、CD8^+及NKT细胞水平均高于对照组,差异均有统计学意义(P<0.05)。结论 CRC患者行DC-CIK细胞过继免疫治疗联合XELOX方案化疗可改善机体免疫功能,弥补单纯化疗所造成的免疫抑制,为安全有效的疗法。     

Applying massively parallel sequencing to paternity testing on the Ion Torrent Personal Genome Machine

Massively parallel sequencing (MPS) is a promising supplementary method for forensic genetics and has gradually been applied to forensic casework. In this study, we applied MPS to forensic casework on an Ion Torrent Personal Genome Machine to evaluate its performance in paternity testing with mismatched STR loci. A total of 15 samples from seven cases containing one mismatched locus by capillary electrophoresis typing were analyzed. Combined paternity index (CPI) and relative chance of paternity were calculated according to the International Society for Forensic Genetics guidelines and the Chinese national standards recommended for paternity testing. With simultaneous analysis of enough STR loci, the results support the certainty of paternity, and the mismatched alleles were considered to be mutations (CPI > 10,000). With the detection of allele sequence structures, the origins of the mutations were inferred in some cases. Meanwhile, nine STRs (CSF1PO, D1S1656, D2S441, D2S1338, D3S1358, D8S1179, D12S391, D21S11 and D4S2408) were found in an increased number of unique alleles and three new alleles in three STRs (D2S441, D21S11, and FGA) that have not been reported before were detected. Therefore, MPS can provide valuable information for forensic genetics research and play a promising role in paternity testing.     

Studies on Lung Cancer Angiogenesis-Application of Interventional Therapy （A Report of 56 Cases）

OBJECTIVE To investigate the significance of angiogenesis of lung cancer, in order to provide a scientific basis for interventional therapy. METHODS Double-phase enhancement-scanning spiral CT and DSA were performed in 56 pathologically confirmed lung cancer cases, in order to evaluate angiogenesis of the tumors. The patients included 36 males and 20 females, with ages ranging from 33 to 76 years （average of 53）. Assessments and indexes for SCT and DSA examinations were as follows： a） Peak value （PV） of the cancerous focus was the difference between the maximum CT value after enhancement and the CT value of a plain scan; b） The abnormally distorted and expanded new vessels of the cancerous focus which could be macroscopically discriminated; c） DSA staining of the focus of cancer was sparse, grid-like and dense. Chemotherapy and embolotherapy via the bronchial artery （interventional therapy） were conducted. Radiotherapy was added for some of the solid tumors with a diameter exceeding 4 cm. RESULTS a） There were 25 cases with a central-type lesion, among which 4 were small cell lung cancers （SCLC） and 21 non-small cell lung cancers （NSCLC）. The cases with a peripheral location accounted for 31 of the total, with a maximum diameter of 1.5 to 13.5 cm and a median of 4.2 cm, including 5 small cell lung cancers and 26 NSCLC cases, b） The reinforced PVs of the cancerous foci were as follows： The PV ranged from 45 to 70 Hu in 34 cases, 25 to 45 Hu in 19, and 10 to 25 Hu in 3. Sparse DSA staining occurred in 3 cases, there was uneven grid-like staining in 22 and dense staining in 31; c） The interventional therapy via the bronchial artery was conducted twice in 5 cases with the SCLC, and three times in 4 SCLC cases. For 3 of the latter cases, a dose of 5,000 to 7,000 cGy radiation therapy was added during the interventional treatment. Complete remissions （CR） were seen in 88.9% of the cases （8/9） and partial remission （PR） in 11.1% （1/9）. Interventional therapy was conducted twice in 8 cases with NSCLC and three times in 30 with NSCLC and four times in 9 cases. Among the total cases, 13 received radiotherapy during interventional therapy, with a radiation dose of 5,000-7,000 cGy; The CR rate was 78.7% （37/47）, PR was 14.9% （7/47） and the rate of non-remission was 6.4% （3/47）. CONCLUSION Using imaging technology, analysis of angiogenesis of lung cancers was employed to accurately detect and quantify angiogenesis. This analysis was combined for interventional therapy, using embolizing agents and large doses of the anti-tumor drugs and angiogenesis inhibitors. The agents were selectively delivered into the tumor vessels to eliminate the primary tumor, in order to depress distant metastases and thus enhance the curative effect of the therapy.