Effects of ursolic acid and oleanolic acid on human colon carcinoma cell line HCT15

AIM: Ursolic acid (UA) and oleanolic acid (OA) aretriperpene acids having a similar chemical structure and aredistributed wildly in plants all over the world. In recentyearn, it was found that they had marked anti-tumor effects.There is little literature currently available regarding theireffects on colon carcinoma cells. The present study wasdesigned to investigate their inhibitory effects on humancolon carcinoma cell line HCT15 METHODS: HCT15 cells were cultured with different drugs.The treated cells were stained with hematoxylin-eosin andtheir morphologic changes observed under a lightmicroscope. The cytotoxicity of these drugs was evaluatedby tetrazolium dye assay. Cell cycle analysis was performedby flow cytometry (FCM). Data were expressed as means +SEM and Analysis of variance and Student' t-test forindividual comparisons.RESULTS: Twenty-four to 72 h after UA or OA 60 μmol/Ltreatment, the numbers of dead cells and cell fragmentswere increased and most cells were dead at the 72 nd hour.The cytotoxicity of UA was stronger than that of OA.Seventy-eight hours after 30 μmol/L of UA or OA treatment,a number of cells were degenerated, but cell fragments wererarely seen. The IC50 values for UA and OA were 30 and 60μmol/L, respectively. Proliferation assay showed thatproliferation of UA and OA-treated cells was slightlyincreased at 24 h and significantly decreased at 48 h and 60h, whereas untreated control cells maintained anexponential growth curve. Cell cycle analysis by FCMshowed HCT15 cells treated with UA 30 and OA 60 for 36 h and72 h gradually accumulated in G0/G1 phase (both drugs P＜ 0.05 for 72 h), with a concomitant decrease of cell populationsin S phase (both drugs P＜ 0.01 for 72 h) and no detectableapoptotic fraction.CONCLUSION: UA and OA have significant anti-ttumor activity.The effect of UA is stronger than that of OA. The possiblemechanism of action is that both drugs have an inhibitoryeffect on tumor cell proliferation through cell-cycle arrest.

Intra-tumor injection of H101,a recombinant adenovirus,in combination with chemotherapy in patients with advanced cancers:A pilot phase Ⅱ clinical trial

AIM: HI01, an EIB 55 kD gene deleted adenovirus, has been shown to possess oncolysis activity experimentally and proved to be safe in preliminary phase I study. The current study was designed to evaluate its anti-tumor activity and toxicity in combination with chemotherapy in patients with late stage cancers.METHODS: H101 5.0×10^11 virus particles were given by intra-tumor injection daily for five consecutive days at every three-week cycle, combined with routine chemotherapy,to one of the tumor lesions of 50 patients with different malignant tumors. Tumor lesions without H101 injection in the same individuals were used as controls. The efficacy and toxicity were recorded.RESULTS: Forty-six patients were evaluable with a 30.4% response rate. H101 injection in combination with chemotherapy induced three complete response (CR) and 11 partial response (PR), giving an overall response rate of 28.0% (14/50) among intention-to-treat patients. The response rate for the control lesions was 13.0%, including one case with CR and five cases with PR, which was significantly lower than that for the injected lesions (P<0.05).Main side effects were fever (30.2%) and pain at the injected sites (26.9%). Grade 1 hepatic dysfunction was found in four patients, grade 2 in one patient, and grade 4 in one patient. Hematological toxicity (grade 4) was found in four patients.CONCLUSION: Intra-tumor injection of the genetically engineered adenovirus H101 exhibits potential anti-tumor activity to refractory malignant tumors in combination with chemotherapy. Low toxicity and good tolerance of patients to H101were observed.

Meta-analysis of intraperitoneal chemotherapy for gastric cancer

AIM: To assess the efficacy and safety of intraperitoneal chemotherapy in patients undergoing curative resection for gastric cancer through literature review.METHODS: Medline (PubMed) (1980-2003/i), Embase(1980-2003/1), Cancerlit Database (1983-2003/1) and Chinese Biomedicine Database (1990-2003/1) were searched. Language was restricted to Chinese and English.The statistical analysis was performed by RevMan4.2 software provided by the Cochrane Collaboration. The results were expressed with odds ratio for the categorical variables.RESULTS: Eleven trials involving 1 161 cases were included.The pooled odds ratio was 0.51, with a 95% confidence interval (0.40-0.65). Intraperitoneal chemotherapy may benefit the patients after curative resection for locally advanced gastric cancer, and the combination of intraperitoneal chemotherapy with hyperthermia or activated carbon particles may provide more benefits to patients due to the enhanced antitumor activity of drugs. Sensitivity analysis and fail-safe number suggested that the result was comparatively reliable.However, of 11 trials, only 3 studies were of high quality.CONCLUSION: Intraperitoneal chemotherapy after curative resection for locally advanced gastric cancer may be beneficial to patients. Continuous multicenter, randomized,double blind, rigorously designed trials should be conducted to draw definitive conclusions.

Analysis of clinical effect of high-intensity focused ultrasound on liver cancer

AIM: To evaluate the clinical effect of high-intensity focused ultrasound (HIFU) in the treatment of patients with liver cancer.METHODS: HIFU treatment was performed in 100 patients with liver cancer under general anesthesia and by a targeted ultrasound. Evaluation of efficacy was made on the basis of clinical symptoms, liver function tests, AFP,MRI or CT before and after the treatment.RESULTS: After HIFU treatment, clinical symptoms were relieved in 86.6%(71/82) of patients. The ascites disappeared in 6 patients. ALT (95±44) U/L and AST(114±58) U/L before HIFU treatment were reduced to normal in 83.3%(30/36) and 72.9%(35/48) patients,respectively, after the treatment. AFP was lowered by more than 50% in 65.3%(32/49) patients. After HIFU treatment,MRI or CT findings indicated coagulation necrosis and blood supply reduction or disappearance of tumor in the target region.CONCLUSION: HIFU can efficiently treat the patients with liver cancer. It will offer a significant noninvasive therapy for local treatment of liver tumor.

Current status and future strategies of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis

This article is to offer a concise review on the use of cytoreductive surgery (CRS) plus intraperitoneal hyperthermic chemotherapy (IPHC) for the treatment of peritoneal carcinomatosis (PC). Traditionally, PC was treated with systemic chemotherapy alone with very poor response and a median survival of less than 6 mo. With the establishment of several phase Ⅱ studies, a new trend has been developed toward the use of CRS plus IPHC as a standard method for treating selected patients with PC, in whom sufficient cytoreduction could be achieved. In spite of the need for more high quality phase Ⅲ studies, there is now a consensus among many surgical oncology experts throughout the world about the use of this new treatment strategy as standard care for colorectal cancer patients with PC. This review summarizes the current status and possible progress in future.

Multi-phasic CT arterial portography and CT hepatic arteriography improving the accuracy of liver cancer detection

AIM: To evaluate the value of multi-phasic CT arterial portography (CTAP) and CT hepatic arteriography (CTHA) in differential diagnosis of liver diseases, and to improve the specificity of CTAP and CTHA for liver cancerdetection. METHODS: From January 1999 to December 2002, multiphasic CTAP and CTHA were performed in 20 patients with suspected liver disease. CT scanning was begun 25s, 60s and 120s for the early-, late- and delayed-phase CTAP examinations, and 6sec, 40 s and 120 s for the early-, lateand delayed-phase CTHA examinations respectively, after a transcatheter arterial injection of non-ionic contrast material. If a lesion was diagnosed as a liver cancer, transcatheter hepatic arterial chemoembolization (TACE) treatment was performed, and the follow-up CT was performed three or four weeks later.RESULTS: All eighteen HCCs in 12 cases were shown as nodular enhancement on early-phasic CTHA. The density of the whole tumor decreased rapidly on late and delayed phases, and the edge of 12 tumors (12/18) remained relatively hyperdense compared with the surrounding liver tissue, and demonstrated as rim enhancement. All HCCs were shown as perfusion defect nodules on multi-phasic CTAP. Five tumors (5/18) were shown as rim enhancement on delayed-phasic CTAP. Rim enhancement was shown as 1 to 2-mm-wide irregular, uneven and discontinuous circumferential enhancement at late-, and delayed-phase of CTHA or CTAP. Five pseudolesions and 4 hemoangiomas were found in multi-phasic CTAP and CTHA. No pseudolesions and hemoangiomas were shown as rim enhancement on late- or delayed-phasic CTHA and CTAP.CONCLUSION: Multi-phasic CTAP and CTHA could help to recognize the false-positive findings in CTAP and CTHA images, and improve the accuracy of CTAP and CTHA of liver cancer detection.

Advantages of assaying telomerase activity in ascites for diagnosis of digestive tract malignancies

AIM： To evaluate the diagnostic value of assaying telomerase activity in ascites cells for the differential diagnosis of malignant and non-malignant ascites.METHODS: Ascites from 40 patients with hepatocellular carcinoma (HCC), 31 with non-HCC gastrointestinal carcinoma (CA), and 24 with liver cirrhosis (LC) were analyzed for telomerase activity. The telomerase activities in cell pellets from ascites were measured according to the Telomeric Repeat Amplification Protocol (TRAP) and quantified with a densitometer.RESULTS: Positive telomerase activity was detected in 16 of 31 (52%) CA patients, 10 of 40 (25%) HCC patients, and 1 of 24 (4%) LC patients (P<0.001). The telomerase activity was higher in the ascites of CA patients than in the ascites of HCC or LC patients (CA: 22.9±5.8, HCC: 6.7±2.5, LC:1.3±1.3, P= 0.001). Cytology was positive in 18 CA patients (58%) and 1 HCC patient (2.5%), respectively. The positive telomerase activity was not related to patients' age, gender,and ascitic protein concentration, but to white blood count (r = 0.31, P = 0.002), neutrophil count (r= 0.29, P = 0.005),and the C-reactive protein level (r = 0.29, P = 0.018). When the results of both cytological examination and telomerase assay were considered together, the sensitivity increased to 77% for CA patients, 25% for HCC patients, and 48% for all 71 gastrointestinal cancer patients.CONCLUSION: Combining cytological examination of ascites with telomerase activity assay significantly improves the differential diagnosis between malignant and non-malignant ascites.

Endostatin gene therapy for liver cancer by a recombinant adenovirus delivery

AIM: To investigate the expression of adenovirus-mediated human endostatin (Ad/hEndo) gene transfer and its effect on the growth of hepatocellular carcinoma (HCC) BEL-7402 xenografted tumors.METHODS: Immunohistochemistry analysis with an antiendostatin antibody was preformed to detect endostatin protein expression in HCC BEL-7402 cells infected with Ad/hEndo. MTT assay was used to investigate the effects of Ad/hEndo on proliferation of human umbilical vein endothelial cells (HUVEC). Intra-tumoral injections of lx10^9 pfu Ad/hEndo was given to treat BEL-7402 xenografted tumors in nude mice once weekly for 6 wk. Mice received injections of Ad/LacZ and DMEM were regarded as control groups. After intra-turmoral administration with Ad/hEndo, the endostatin mRNA expression in tumor tissue was analyzed by Northern blotting, and plasma endostatin levels were determined using enzyme-linked immunosorbent assay (ELISA).RESULTS: High level expression of endostatin gene was detected in the infected HCC BEL-7402 cells. Ad/hEndo significantly inhibited HUVEC cell proliferation by 57.2% at a multiplicity of infection (MOI) of 20. After 6-week treatment with Ad/hEndo, the growth of treated tumors was inhibited by 46.50% compared to the Ad/LacZcontrol group (t=-2.729, P<0.05) and by 48.56% compared to the DMEM control group (t=2.485, P<0.05). The ratio of mean tumor volume in treated animals to mean tumor volume in the control animals (T:C ratio) was less than 50% after 24 d of treatment. Endostatin mRNA in tumor tissue was clearly demonstrated as a band of approximately 1.2 kb, which was the expected size of intact and functional endostatin.Plasma endostatin levels peaked at 87.52+8.34 ng/mL at d 3 after Ad/hEndo injection, which was significantly higher than the basal level (12.23+2.54 ng/mL). By d 7,plasma levels dropped to nearly half the peak level(40.34+4.80 nglmL).CONCLUSION: Adenovirus-mediated human endostatin gene can successfully express endogenous endostatin in vitro and in vivo, and significantly inhibit the growth of BEL-7402 xenografted liver tumors in nude mice.

Co-mutation of p53,K-rasgenes and accumulation of p53 protein and its correlation to clinicopathological features in rectal cancer

AIM: To determine bhe accuracy of p53 gene mutations predicted by overexpression of p53 protein immunohistochemically,and to investigate the co-mutation of p53 and K-ras genes in rectal cancer and its effect on promoting malignant biologic behaviors of tumors.METHODS: Ninety-seven specimens of rectal cancer were surgically resected in our hospital from August 1996 to October 1997. The hot mutation areas of p53 gene (in exons 5-8) and K-rasgene (in codon 5/12 and 13) were detected with polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), and overexpression of p53 protein was detected with immunohistochemistry (IHC) in the 97 specimens of rectal cancer. Correlation between gene mutations and tumor clinicopathologic factors was studied, and survival analysis was penfomed as well.RESULTS: There were 36 cases of p53 gene mutations in 61 p53 protein positive cases, and 21 cases of p53 gene non-mutation in 36 p53 protein negative cases respectively.The coincidence rate of p53 gene mutation by IHC method with PCR-SSCP method was 58.8% (57/97). The mutation rate of p53 gene was 52.6% (51/97), while K-ras gene mutation was observed in codons 12 and 13 in 61 cases with a mutation rate of 62.9% (61/97). Single gene mutation of p53 or K-raswas found in 32 cases. Both p53 and K-ras gene mutation were found in 48 cases. Statistical analysis showed that p53 and K-ras gene mutations were not related to the dinicopathologic factors, including tumor size, gross tumor type, histological dassification, differentiation, invasion to intestinal veins, lymphatics and nerves, invasive depth to.wall, lymph node metastasis, and Dukes' stages (P>0.05).The survival in patients with no gene mutation, single gene mutation and both gene mutations were similar (P>0.05).CONCLUSION: IHC has a certain false positive and false negative rate in detecting p53 gene mutations. Malignant biological behaviours of rectal cancer are not enhanced by p53 and K-rasgene mutations. Co-mutation of p53 and K-ras gene has neither synergic carcinogenesis-promoting effect,nor prognostic effect on rectal cancer.

Effect of retinoic acid on cell proliferation kinetics and retinoic acid receptor expression of colorectal mucosa

AIM: To investigate the effect of retinoic acid (RA) on cell proliferation kinetics and retinoic acid receptor (RAR)expression of colorectal mucosa.METHODS:One hundred sixty healthy male Wistar rats were randomly divided into 4 groups. Rats in groups Ⅰ and Ⅱ were subcutaneously injected with dimethylhydrazine (DMH) (20 mg/kg, once a week,) for 7 to 13 weeks, while groups Ⅲ and Ⅳ were injected with normal saline. Rats in groups Ⅱ and Ⅲ were also treated with RA (50 mg/kg,every day, orally) from 7th to 15th week, thus group Ⅳ was used as a control. The rats were killed in different batches.The expressions of proliferating cell nuclear antigen (PCNA),nucleolar organizer region-associated protein (AgNOR) and RAR were detected.RESULTS: The incidence of colorectal carcinoma was different between groupsⅠ(100 %) and Ⅱ (15 %) (P＜0.01).The PCNA indices and mean AgNOR count in group Ⅱ were significantly lower than those in group Ⅰ(F=5.418 and 4.243,P＜0.01). The PCNA indices and mean AgNOR count in groups Ⅰ and Ⅱ were significantly higher than those in the groups Ⅲ and Ⅳ (in which carcinogen was not used) (F=5.927and 4.348, P＜0.01). There was a tendency in group Ⅰ that the longer the induction with DMH the higher PCNA index and AgNOR count expressed (F=7.634 and 6.826, P＜0.05).However, there was no such tendency in groups Ⅱ, Ⅲ and Ⅳ(F=1.662 and 1.984, P＞0.05). The levels of RAR in normal and cancerous tissues in groups treated with RA were significantly higher than those in groups not treated with RA (F=6.343 and 6.024, P＜0.05).CONCLUSION: RA decreases the incidence of colorectal carcinoma induced by DMH. Coiorectal cancer tissue is associated with abnormal expression of PCNA, AgNOR and RAR. RA inhibits the expression of PCNA and AgNOR, and increases RAR concentration in colorectal tissues.

Establishment and primary application of a mouse model with hepatitis B virus replication

瞄准：与肝炎 B (HBV ) 复制建立一个快速、方便的动物模型。方法：HBV-replication-competent 原生质标志的一个裸体 DNA 解决方案经由尾巴静脉被转移到 BALB/C 鼠标，用一个水动力学在活体内 transfection 过程。在注射以后，这些老鼠在 d 上被牺牲 1， 3， 4， 5， 7 和 10。在肝的 HBV DNA 复制中介被南部的污点杂交分析。肝炎 B 核心抗原(HBcAg ) 和在肝的肝炎 B 表面抗原(HBsAg ) 的表示被免疫组织化学检查。浆液 HBsAg 和肝炎 B e 抗原(HBeAg ) 被连接酶的免疫吸着剂试金(ELISA ) 检测。HBV 复制的抑制在与 polyinosinic-polytidylin 酸(polyIC ) intraperitoneally 对待的 HBV 复制模型老鼠被比较或缓冲磷酸盐 saline (PBS ) 。结果：在水动力学在活体内 transfection 以后，在老鼠肝的 HBV DNA 复制中介在 d 上是可检测的 1 并且在 d 上丰富 3 和 4，层次稍微被减少并且在 d 之间仍然保持相对稳定 5 和 7，并且在 d 上是几乎无法发现的 10。HBcAg 和 HBsAg 的表示模式类似于 HBV 复制中介 DNA 的，除了他们在 d 上到达了一座山峰之外 1 在注射以后。在 HBV DNA 复制中介的明显的差别都没在肝的左、正确、中间的脑叶被观察。有 polyIC 的术后疗法，在肝的 HBV 中间的 DNA 的水平在与 PBS 注射的控制老鼠是比那低的。结论：有 HBV 复制的高水平的一个快速、方便的老鼠模型被开发并且过去常在 HBV 复制上调查 polyIC 的禁止的效果，它为未来提供一个有用工具 HBV 染色体的功能的研究。

Quantitative detection of common deletion of mitochondrial DNA in hepatocellular carcinoma and hepatocellular nodular hyperplasia

AIM: To study the deletion of mitochondiral DNA in hepatocellular carcinoma and hepatocellular nodular hyperplasia and its significance in the development of cancer. METHODS: Deleted mtDNA (CD-mtDNA) and wild type mtDNA (WT-mtDNA) were quantitatively analyzed by using real-time PCR in 27 hepatocellular carcinomas (HCC) and corresponding noncancerous liver tissues and 27 hepatocellular nodular hyperplasiae (HNH). RESULTS: A novel CD (4 981 bp) was detected in 85% (23/27) and 83%(22/27) of HCC and HNH tumor tissues, respectively, which were significantly higher than that in paired noncancerous liver tissues (57%, 15/27) (P<0.05). The CD/WT-mtDNA ratio in HCC tumors was 0.00092 (median, interquartile range, 0.0001202-0.00105), which was significantly higher than that in paired noncancerous liver tissues (median, 0.000, quartile range, 0-0) (P=0.002, Mann-Whitney Test), and was 25 of times of that in HNH tissues (median, 0.0000374, quartile range, 0-0.0004225) (P=0.002, Mann-Whitney test). CONCLUSION: CD-mtDNA mutation plays an important role in the development and progression of HCC.

Inhibition of DNA primase and induction of apoptosis by 3,3'-diethyl-9-methylthia-carbocyanine iodide in hepatocellular carcinoma BEL-7402 cells

AIM:To evaluate the effects of 3,3′-diethyl-9-methylthia-carbocyanine iodide (DMTCCI) on DNA primase activity and on apoptosis of human hepatocellular carcinoma BEL-7402 cells.METHODS: DNA primase assay was used to investigate DNA primase activity. MTT assay was applied to determine cell proliferation. Flow cytometric analysis, transmission electron microscopy, DNA fragmentation assay were performed to detect DMTCCI-induced apoptosis. Expression levels of p53, Bcl-2, Bcl-xL, Bad, Bax, survivin, Caspase-3 and poly (ADP-ribose) polymerase (PARP) were evaluated by immunoblot analysis. Caspase-3 activity was assessed with ApoAlert Caspase-3 colorimetric assay kit.RESULTS:DMTCCI had inhibitory effects on eukaryotic DNA primase activity with IC50 value of 162.2 nmol/L. It also inhibited proliferation of human hepatocellular carcinoma BEL-7402 cells with IC50 value of 2.09μmol/L. Furthermore,DMTCCI-induced BEL-7402 cell apoptosis was confirmed by DNA fragmentation (DNA ladders and sub-G1 formation) and transmission electron microscopy (apoptotic bodies formation). During the induction of apoptosis, expression of Bcl-2, Bcl-xL and survivin was decreased, and that of p53,Bad and Bax was increased. Caspase-3 was activated and poly (ADP-ribose) polymerase (PARP) was cleaved in BEL-7402 cells treated with DMTCCI.CONCLUSION: The present data suggest that DMTCCI has inhibitory effects on eukaryotic DNA primase and can induce apoptosis of BEL-7402 cells. The modulation of expression of p53 and Bcl-2 family proteins, and activation of Caspase-3 might be involved in the induction of apoptosis.

Significance of Cell-Free Epstein-Barr Virus DNA in Monitoring Prognosis of Nasopharyngeal Carcinoma

OBJECTIVE It has been reported that cell-free Epstein-Barr virus (EBVDNA) in plasma was useful in diagnosing and monitoring nasopharyngeal carcinoma (NPC). The current study was designed to evaluate the significance of EBV-DNA in monitoring the prognosis of nasopharyngeal carcinoma and comparing its significance with that of plasma VCA/IgA and EA/IgA levels. METHODS EBV-DNA, VCA/IgA, and EA/IgA levels in plasma were determined in NPC patients with different prognosis after radiotherapy, including 30 distant metastatic patients, 22 local recurrence patients and 24 individuals with remission who had been followed-up for more than 2 years after treatment. EBV-DNA was determined using a real-time quantitative PCR system, and levels of VCA/IgA and EA/IgA were measured using standard immunofluorescence. In a cohort study, the indexes were determined after different radiation periods for the 20 new cases of nasopharyngeal carcinoma. RESULTS The median plasma EBV-DNA concentration was 135,100 copies/ml (interquartile range: 5,525-1,003 750)in metastatic group, 20,500 copies/ml (interquartile range: 0-58,500) in the local recurrence group and 0 copies/ml (interquartile range: 0-0) in the continuous remission group (P<0.05). The levels of VCA/IgA and EA/IgA showed no significant differences among the different groups. The high level of EBV-DNA concentration in the metastatic group was more than that in the local recurrence group. A level of 1,000,000 copies/ml of EBV DNA was an indication of distant metastasis of the NPC patients with a sensitivity of 27.3%. However, the sensitivity was 0 in the local recurrence group. For the 20 new patients, EBV-DNA concentration gradually decreased during the radiation period. Before radiation there were 32,050 copies/ml (interquartile range: 3,880-317,750), 0 copies/ml (interquartile range: 0-14 375) after a 40 Gy radiation dose and 0 copies/ml (interquartile range: 0-2940)after the radiation was finished (P<0.05). However, the levels of VCA/IgA and EA/IgA showed no significantdifference. CONCLUSION Determination of plasma cell-free EBV-DNA level is more valuable than evaluation of VCA/IgA and EA/IgA for monitoring the prognosis of NPC patients.

Heterogeneity of neutrophils in cancer:one size does not fit all

Neutrophils play an essential role in the defense against bacterial infections and orchestrate both the innate and adaptive immune responses.With their abundant numbers,diverse function and short life span,these cells are at the forefront of immune responses,and have gained attention in recent years because of their presence in tumor sites.Neutrophil involvement pertains to tumor cells'ability to construct a suitable tumor microenvironment(TME)that accelerates their own growth and malignancy,by facilitating their interaction with surrounding cells through the circulatory and lymphatic systems,thereby influencing tumor development and progression.Studies have indicated both pro-and anti-tumor properties of infiltrating neutrophils.The TME can exploit neutrophil function,recruitment,and even production,thus resulting in pro-tumor properties of neutrophils,including promotion of genetic instability,tumor cell proliferation,angiogenesis and suppression of anti-tumor or inflammatory response.In contrast,neutrophils can mediate anti-tumor resistance by direct cytotoxicity to the tumor cells or by facilitating anti-tumor functions via crosstalk with T cells.Here,we summarize current knowledge regarding the effects of neutrophil heterogeneity under homeostatic and tumor conditions,including neutrophil phenotype and function,in cancer biology.

Treatment of Hodgkin＇s Disease with Chemotherapy Based- Regimens： Long-term Follow-up Results with 295 Patients

OBJECTIVE Hodgkin's disease (HD) is a chemo and radio-sensitive hematologic malignancy. At the present time, improvement of its cure rate, reduction of its long-term detrimental effects, and maintenance of a good quality of life are the major concerns in the treatment of HD. In this study the results of a long -term follow-up from our cancer center was analyzed retrospectively in terms of efficacy and collateral side effects. METHODS The results were analyzed for 295 patients with histologicallyverified HD who were treated from 1970 to 2000, especially 182 patients treated from 1980 to 2000. Multivariant analysis (COX model ) was employed to elucidate the prognostic determinants. RESULTS The 5, 10 and 20-year survival for 295 patients with HD were 63.5%, 55.8% and 47.1% respectively with a median survival time of 172 months (28-352 months ). The median follow-up time was 43 months (17-352 months). The 5, 10 and 20 years overall survival and disease-free survival were 79.6%, 74.5%, 66.8% and 74.5% ,69.4%, 69.4% respectively for patients treated by regular chemotherapy and radiotherapy from 1980 to 2000. The incidence of late toxicities was low. An age of≥45 years, B symptoms and stage Ⅲ / Ⅳ were the main prognostic determinants (P=0.000, P=0.035 and P=0.047) in this clinical study. Stage Ⅰ/Ⅱ and nodularsclerosis were favorable factors in comparison with stages Ⅲ/Ⅳ and other histologic subtypes. CONCLUSIONS A chemotherapy-predominant modality plays an important role in the treatment of HD with promising long-term survival and fewer late toxicities. Further investigation for this simplified convenient comprehensive therapy is warranted.

Analysis of Clinical Treatment Efficiency for 179 Geriatric Women with Stage I or II Cervical Carcinoma

OBJECTIVE To evaluate the efficiency of surgery plus radiotherapy and chemotherapy versus radiotherapy plus chemotherapy in the treatment of older patients with stage I or II cervical carcinoma and to seek suitable treatment for such patients. METHODS The clinical data of 179 elderly women with stage la or lib cervical cancer were analyzed retrospectively. One hundred and thirty-four cases underwent radical hysterectomy followed by adjuvant radiotherapy and/or chemotherapy (Group 1). Forty-five cases underwent radiation therapy plus adjuvant chemotherapy (Group 2). RESULTS The 5-year survival rates in group 1 and group 2 were 78.3% and 49.1%(P=0.04), respectively. The incidence of complications in group1 was 47.0%. Three patients died of complications after radical hysterectomy. The incidence of complications in group 2 was 75.6%. CONCLUSION Elderly patients with stage I or II cervical carcinoma should receive an operation if possible. In addition they should receive adjuvant treatments according to their personal conditions, and be treated with appropriate adjuvant chemo-and/or radiotherapy.

Influence of the Application of MRI on the T, N Staging System of Nasopharyngeal Carcinoma

OBJECTIVE To investigate the influence of utilizing MRI on the T, N staging system (the 5th edition, UICC) and on the 1992 China staging systems (Fuzhou-Guangzhou,China) by comparing the results of CT and MRI examinations of nasopharyngeal carcinoma (NPC).METHODS All 56 NPC patients, which were confirmed by histology,accepted both CT and MRI examinations. CT system scans were obtained by using an Elscient CT Twin Flash with the conventional axial scan. Three cases were examined by an additional coronary scan and 16 patients received an enhanced CT. The MR imaging was performed with a 0.5T MR system (Philips T5- II Ultra-Magnetic). The conventional axial, sagittal and coronary sections with SE sequences were obtained. The scan field was from the supra sellar cistern to the inferior border of C2. Most patients (50/56) accepted contrast enhanced MRI.RESULTS The pharyngobasilar fascia can clearly be seen on MRI but not on CT, so MRI can accurately determine the lesion in the nasopharyngeal cavity. MRI is more sensitive for evaluation of tumor involvement of soft tissue such as the Iongus colli muscle (14 cases by CT and 26 by MRI), tensor veli patalini muscle and levator veli palatini muscle (17 cases by CT and 23 by MRI), and skull-base bone marrow invasion (15 cases by CT and 42 by MRI). MRI can also demonstrate the invasion of the carotid sheath area and the enlargement of retropharyngeal lymph nodes more definitely than CT.The involvement of the trigeminal nerve can be detected on MRI, which may influence the clinical staging directly.CONCLUSION Of the 56 cases examined, 16 (28.6%) changed the staging based on UICC staging; while 33.9% (19/56) cases changed based on the 1992 China-stagin9 system. The major influence of MRI examinations on the 1992 staging was to differentiate the involvement of the carotid sheath area from metastasis of the retropharyngeal lymph nodes. There also was a significant difference in finding early invasion of the skull base.

Clinical Analysis of 57 Patients with Ovarian Dysgerminoma

OBJECTIVE Ovarian dysgerminoma is an uncommon ovarian malignancy. Its clinical features are special and there are many factors affecting its prognosis. If treated properly, the patient can be cured. Otherwise it may endanger the patient's life. The aim of this study is to investigate the clinical features and factors related to prognosis of ovarian dysgerminoma. METHODS Data from 57 patients with pure ovarian dysgerminoma were analyzed retrospectively. The patients were admitted to the Cancer Center, Sun Yat-sen University from January 1,1964 to December 31,2000. RESULTS The main clinical features were abdominal mass (56.1%), abdominal pain (21.1%), abdominal swelling (17.5%), vaginal bleeding (5.3%)and genital tract abnormalities (5.3%). Twenty-six patients had stage Ⅰ diseases,8 stage Ⅱ,9 stage Ⅲ,1 stage Ⅳ and 13 recurrent and persistent diseases. The uterus was involved in 41.2% of patients with stage Ⅱ-Ⅲ diseases. Combined modality was given to 52 cases and a singlemethod treatment to 5 cases. The total overall 5 and 10-year survival rates for stages Ⅰ-Ⅳ was 80.1% and 70.0% respectively. The 5-year survival rate for stage Ⅰ was 100%, stage Ⅱ 55.2% ,stage Ⅲ 55.6% and stage Ⅳ 0% ; for recurrent and persistent diseases, 72.7%. The stage I group of 12 patients received adnexectomy and 14 patients underwent hysterectomy and adnexa removal. There was no significant difference between the 5 and 10-year survival rates (all 100%). Of the 23 patients in the stage Ⅰ group to whomonly chemotherapy was given after operation, 19 cases received 3 or morecourses and were well without recurrence; 4 patients received only onecourse and one of them recurred 21 months after the operation. In the group of stages Ⅱ and Ⅲ cases, the 5-year survival rate was 86.7% for those whose chemotherapy courses were t> 4 and 25.0% for patients who received less than 4 courses of chemotherapy (P<0.05). CONCLUSIONS The prognosis of ovarian dysgerminoma is closely related to the disease stage and treatment modality. A fertility-preserving operation can be considered in early-staged patients, but caution needs to be exercised in the middle to late staged cases. Good results can be achieved with an operation-based combined modality in recurrent patients.