In vitro Study of Interstitial Combination Chemotherapy in the Treatment of Glioma

Objective： To investigate the inhibitory effects of combination chemotherapy of Carboplatin （CBP）, Teniposide （Vm-26）, Methasquin （MTX）, and Nimodipine （NIM） on glioma, and to explore the sensitivity of glioma cells to different treatment regimens so as to provide some clues for clinical usage of interstitial combination chemotherapy. Methods： MTT assay and 3H-TdR incorporation assay were performed to evaluate the inhibitory effects upon the proliferation of glioma cells, and to compare the sen- sitivity of glioma cells to administration of CBP, Vm-26, MTX, and NIM with that of the administration of CBP＋NIM, Vm-26＋NIM, MTX＋NIM, CBP＋Vm-26＋MTX, or CBP＋Vm-26＋MTX＋NIM, respectively. Results： The inhibition rate of CBP＋Vm-26＋MTX＋NIM combination administration against glioma cells was 96.64%, higher than that of CBP＋NIM （69.03%）, Vm-26＋NIM （71.53%）, MTX＋NIM （52.75%）, CBP＋Vm-26＋MTX （78.59%） （P〈0.01）, and the dosage of CBP, Vm-26, and MTX was declined to 1/10- 1/100 that of respective use of CBP, Vm-26, and MTX. Conclusion： The curative effect of combination administration of CBP, Vm-26, MTX, and NIM was much better than that of respective administration, suggesting a higher inhibition rate and a lower dosage use.

Clinical Study of Photodynamic Therapy for Upper Gastrointestinal Tract Cancers

Objective： To evaluate the clinical effectiveness and adverse effects of photodynamic therapy （PDT） for the upper gastrointestinal tract cancers. Methods： 56 patients with upper gastrointestinal cancers in different clinical stages were treated with PDT. Diode laser （630 nm） was used as the light source and the parameters were as follows： power density 200 to 400 mW/cm, energy density 100 to 300 J/cm. PHOTOFRIN was used as photosensitizer, which was given in a dose of 2 mg/kg intravenously 12-24 h before irradiation. Results： Evaluation of the 56 patients＇ therapeutic effectiveness showed that 6 patients （10.7%） had a complete response （CR）, 33 patients （58.9%） partial response （PR）, 12 patients （21.4%） mild response （MR）, and 5 patients （8.9%） no response （NR）. The total response rate （CR＋PR） was 69.6%. No patients had severe adverse effects in this group. Conclusion： PDT is an effective and safe palliative modality for upper gastrointestinal tract cancers.

The Characteristics of Immunophenotype in Acute Lymphoblastic Leukemia and Its Clinical Significance

Objective： To study the characteristics of immunophenotype in acute lymphoblastic leukemia （ALL） and its clinical significance. Methods： Immunophenotyping was performed on 81 ALL patients by three-color flow cytometry analysis using CD45/SSC gating, meanwhile the cytogenetic analysis was performed on 45 cases out of 81 ALL patients. Results： （1） CD19 was the most commonly expressed of all B-lineage antigens detected with the positive rate being 100%. In T-ALL, the positive expression rate of CD5 and CD7 was the highest, being 90%. Both B-ALL and T-ALL overlapped in expression of lineage antigens. There was no significant difference in the complete remission rate （CR rate） between T-ALL and B-ALL. （2） The incidence of ALL with rayeloid antigens expression （My＋ALL） was 39.5%. CD13 was most often seen among the myeloid markers. My＋ALL always involved in B-lineage antigens and the CR rate in children and adults was 72.2% and 78.6% respectively. （3） The incidence of HAL was 19.8%. Coexpression of B-lineage and myeloid-assoeiated antigens was the commonest subtype in HAL. The expression of CD34 was commonly seen in HAL patients （81.3%）. The CR rate was low in HAL, 50% for children and 40% for adults. （4） Compared to T-ALL, B-ALL, My＋ALL, and HAL had a higher positive rate of CD34 expression with the difference being significant （P〈0.025）. Conclusion： Immunophenotyping had remarkable predominance in diagnosing special category of ALL （such as HAL and My＋ALL）; CD19 and CD5 were highly sensitive in diagnosing B-ALL and T-ALL, but less special, and overlapping was found in expression. No significant association was found between the expression of CD34 or myeloid antigens and CR rate, while low CR rate was found in HAL patients, especially for those coexpressing CD34 antigen.

Treatment of Primary Liver Cancer with Postoperative After-Loading Radiotherapy and Gemcitabine

Objective： To evaluate the curative effectiveness of postoperative after-loading radiotherapy with the use of gemcitabine in 22 patients with primary liver cancer. Methods： From Oct. 1999 to Dec. 2001, 22 patients with primary liver cancer underwent postoperative after-loading radiotherapy 3-10 days after hepatectomy and chemotherapy using gemcitabine （1400 mg every week for 3 weeks, repeated after one week interval, total cycles were 6） and compared with 22 cases of sole hepatectomy. Three-six catheters were placed for irradiation after hepatectomy. The single-dose of after-loading radiotherapy was 10 Gy, 24 sessions per person. Results＇. The rate of AFP negative-reversion was 100% （17/17） in the treated group, higher than in control group （62.5%, 10/16, P〈0.05）. In the treated group, the 1-year relapse rate, metastasis rate and survival rate were 18.2% （4/22）, 0 and 100% （22/22） respectively, while in the control group they were 45.5% （10/22）, 13.6% （3/22） and 77.3% （17/22） respectively. There were significant differences between the two groups in relapse rate, metastasis rate and survival rate within a year （P〈0.05）. Conclusion： Postoperative after-loading radiotherapy with gemcitabine is an effective way for the treatment of primary liver cancer.

Clinical Analysis of 81 Cases of Benign Retroperitoneal Schwannoma

Objective： To analyze the clinical manifestations of retroperitoneal schwannoma in order to improve the diagnosis and treatment of this rare disease. Methods： Between January 1951 and September 2004, 81 patients with retroperitoneal schwannoma were retrospectively analyzed. Results： All cases received operative therapy. Sixty cases （74.1%） received a total resection; 12 cases （14.9%） subtotal resection, and 9 cases （11.1%） exploration. During the surgical operation, a single tumor was found in 77 cases （95.1%）, and multiple tumors in 4 cases （4.9%）. Most of the retroperitoneal schwannomas located beside the spine. The tumor was a fusiform, round or oval mass that was sharply circumscribed and encapsulated. Pathologic results showed all 81 cases were benign schwannoma. In the 4 cases of multiple tumors, 2 （2.5%） were diagnosed as double-primary tumors associated with ascending colon adenocarcinoma and lung squamous-cell cancer. One case recurred postoperatively. Conclusion： Retroperitoneal schwannoma was rare and preoperative diagnosis was difficult. Most of retroperitoneal schwannoma were benign and the surgical treatment was the first choice.

Application of Support Vector Machine to Predict 5-year Survival Status of Patients with Nasopharyngeal Carcinoma after Treatment

Objective： Support Vector Machine （SVM） is a machine-learning method, based on the principle of structural risk minimization, which performs well when applied to data outside the training set. In this paper, SVM was applied to predict 5-year survival status of patients with nasopharyngeal carcinoma （NPC） after treatment, we expect to find a new way for prognosis studies in cancer so as to assist right clinical decision for individual patient. Methods： Two modelling methods were used in the study; SVM network and a standard parametric logistic regression were used to model 5-year survival status. And the two methods were compared on a prospective set of patients not used in model construction via receiver operating characteristic （ROC） curve analysis. Results： The SVM1, trained with the 25 original input variables without screening, yielded a ROC area of 0.868, at sensitivity to mortality of 79.2% and the specificity of 94.5%. Similarly, the SVM2, trained with 9 input variables which were obtained by optimal input variable selection from the 25 original variables by logistic regression screening, yielded a ROC area of 0.874, at a sensitivity to mortality of 79.2% and the specificity of 95.6%, while the logistic regression yielded a ROC area of 0.751 at a sensitivity to mortality of 66.7% and gave a specificity of 83.5%. Conclusion： SVM found a strong pattern in the database predictive of 5-year survival status. The logistic regression produces somewhat similar, but better, results. These results show that the SVM models have the potential to predict individual patient＇s 5-year survival status after treatment, and to assist the clinicians for making a good clinical decision.

Replication-selective Oncolytic Adenovirus CNHK300 in the Treatment of Breast Cancer Cell Lines in vitro

Objective： To evaluate the tumor selectivity and therapeutic efficiency of replication-competent adenovirus CNHK300 on human breast cancer cells. Methods： RT-PCR was used to detect the hTERT mRNA activity in various breast cancer and normal fibroblast cell lines. Virus proliferation assay, cell viability assay and Western blot were applied to evaluate the proliferation and cytolysis selectivity of CNHK300. Results： The telomerase activity of MCF-7, BT-549 and SK-BR-3 was positive, while telomerase in MRC-5 and BJ was negative. The progeny virus titers in MCF-7, BT-549 and SK-BR-3 after 48 h of CNHK300 exposure was 40 625, 1 265 and 20 000 fold higher than those of 0 h, even slightly higher than those of wtAd5 （except in SK-BR-3）. ONYX-015 virus proliferation ability was weaker than that of CNHK300 in cancer cells. However, CNHK300 exhibited attenuated replicative ability as compared with wtAd5 in MRC-5 and BJ. The CNHK300 replicatative multiple was 63 and 192 fold at 48 h respectively, while the wtAd5 still multiplied 3 160-4 846 fold. CNHK300 could cause about half of breast cancer cells to die within 7 days at MOI 10 pfu/cell and below, whereas the IC50 in BJ and MRC-5 was as high as MOI 100 pfu/cell. CNHK300 E1A protein could be detected in breast cancer cells and 293 cells but not in normal fibroblast cells. Conclusion： hTERT promoter can successfully modulate the CNHK300 to be selectively replicated in breast cancer cells positive for telomerase, which may be a potential treatment strategy in breast cancer.

Initial Study on Immune Escape Mechanism of Mouse Acute Myelomonocytic Leukemic Cell Line WEHI-3

Objective： To investigate the expression of Fas, Fas ligand （FasL） and CD80 on the cell surface of mouse acute myelomonocytic leukemia cell line WEHI-3 and the function of FasL. Methods： The expression of Fas, FasL and CD80 was detected on WEHI-3 cell surface by flow cytometry. Simultaneously the function of FasL was determined by Thymidine （^3H-TdR） Incorporation. Results： The expression of CD80 and Fas on WEHI-3 cell surface was 5.06%±0.41% and 6.75%±2.31% （n=5） respectively, and the expression of FasL was up to 63.73%±5.23% （n=5）. The apoptotic rate of YAC-1 cells was 26%±4.5%, 35%±3.2% and 43%±2.7% （n=5） respectively when WEHI-3 （effector cell, E） and Fas^＋ YAC-1 cells （target cell, T） were cultured in the ratio of 3：1, 10：1 and 30：1. Conclusion： WEHI-3 cells express high FasL, low Fas and CD80, and can induce apoptosis of Fas^＋ YAC-1 cells.

Patterns of Relapse and Management Options in Unknown Primary Cervical Metastatic Carcinoma

Objective: To analyze the patterns of relapse and management options in unknown primary cervical metastatic carcinoma (UPCMC) as well as to discuss its treatment strategies. Methods: Clinical data of 111 cases of eligible UPCMC were retrospectively studied. Neck control, primary relapse and long-term survival were compared among different groups. Results: Primary carcinomas ultimately appeared in 12 cases (10.8%, 12/111). Neck control rate was 36.9%. Overall 5-year survival rate was 41.4%. Neck control, N stage and primary control were prognostic factors for UPCMC. Neck control was affected by N stage and whether or not comprehensive radiotherapy was administered. Conclusion: UPCMC should primarily be treated by radiotherapy except for cases with N1 or N2 insensitive to radiation. Bilateral necks radiotherapy is the optimal choice in terms of neck radiotherapy. Selective total pharyngeal irradiation is recommended for potential primary treatment.

Studies on the Mechanism of Arsenic Trioxide-Induced Apoptosis in HepG_2 Human Hepatocellular Carcinoma Cells

OBJECTIVE To study the anti-tumor effect of arsenic trioxide on the HepG2 human hepatocellular carcinoma cell line, and to explore its mechanism of action. METHODS The MTT assay was used to determine the inhibitory effect of As2O3 on HepG2 cells at various As2O3 concentrations. The expression of p-JNK, caspase-3 and PARP was detected by Western blots. RESULTS As2O3 markedly inhibited the growth of the HepG2 cells and induced apoptosis. The results of Western blot analysis showed that the As2O3-induced apoptosis was accompanied by caspase-3 and PARP activation. p-JNK was detected at 10 min following As2O3 treatment, and preceded to peak at 20 min, and decreased by 30 min. The total protein content did not obviously change. The activation of JNK occurred prior to cell apoptosis. SP600125, a JNK inhibitor, suppressed the As2O3-induced activation of caspase-3 and PARP cleavage. CONCLUSION As2O3 inhibits the proliferation of human HepG2 hepatocellular carcinoma cells by inducing apoptosis in vitro. As2O3-induced apoptosis is accessed through the caspase-3 pathway. The JNK signal-transduction pathway and caspase-3 are involved upstream in the As2O3 induced HepG2 apoptotic response.

Efficacy Study on Six Antibiotic Methods for Treating Non-Gonococcal Urethritis and Cervicitis

Objective： To analyze the efficacy of six antibiotic methods for treating non- gonococcal urethritis /cervicitis and the factors influencing efficacy. Methods： Retrospective analysis of 878 nongonococcal urethritis / cervicitis cases which received regular treatment and follow-up in our institute from 1st Jan. 2001 to 31st Aug. 2003. Results： The mean cure rate of six methods for Chlamydia trachamatis （Ct） was 57.116%. There were distinct differences among these methods for Ct treatment.The mean cure rate of six methods for Ureaplasma urealyticum （Uu） was 69.556% and there was no difference among these methods for Uu treatment. Coinfection with Ct and Uu dramatically reduced the elimination rate of these two pathogens. Conclusion： The effectiveness of treatment of these antibodies for non-gonococcal urethritis / cervicitis is not currently satisfactory. Importantly, there were many antibiotic-resistant Ct and Uu strains. The factors influencing antibiotic efficacy and mechanisms need further study.

Local Recurrence of Low-Grade Myofibroblastic Sarcoma of the Chest Wall:Report of a Case and Literatures Review

Myofibroblastic sarcoma, composed primarily of myofibroblast, is a rare malignant tumor. Low-grade myofibroblastic sarcoma （LGMS） has been defined properly as a distinct entity in the 2002 WHO classification of soft tissue tumors. Primary sarcoma of the chest wall is also a rare disease. This article describes a case of locally recurrent LGMS of the chest wall.

Expression and Significance of LRIG1 Gene in Human Astrocytomas

Objective： LRIG1 gene is a newly found human gene that displays homologies to the Drosophila Kek-1 gene. Previous researches have shown that the LRIG1 gene almost expressed in all human tissues. However, its functions, particularly its functions in human tumors, are still unknown. The goals of the present study are to magnify the expression spectrum of the LRIG1 gene and determine their roles in the oncogenesis. Methods： A triphasic oligonucleotide probe was designed and used to detect the expression level of the LRIG1 gene in 16 astrocytomas and the corresponding tissues around the tumors by in situ hybridization. 11 primary astrocytoma cells were cultured. Among these, the expression level of the LRIG1 gene was checked by in situ hybridization and the expression of the Proliferating Cell Nuclear Antigen （PCNA） protein was detected by immunohistochemistry. Results： The expression of LRIG1 protein was detected in different degree in all the tumors and the surrounding tissues. Compared to the surrounding tissues, the expression of the tumors was lower. The decrease extends from the surrounding tissues to the tumors were correlation to the tumors＇ grades. The primary cultured cells also expressed LRIG1 to various extent and the expression of LRIG1 in the cultures was negatively correlated with the intensity of the PCNA staining. Conclusion： The LRIG1 protein may inhibit the growth of tumors of glial cells and the down-regulation of the LRIG1 gene may be involved in the development and progression of the tumor.

Role of radiation therapy in gastric adenocarcinoma

Outcomes in patients with gastric cancer in the United States remain disappointing, with a five-year overall survival rate of approximately 23%. Given high rates of local-regional control following surgery, a strong rationale exists for the use of adjuvant radiation therapy. Randomized trials have shown superior local control with adjuvant radiotherapy and improved overall survival with adjuvant chemoradiation. The benefit of adjuvant chemoradiation in patients who have undergone D2 lymph node dissection by an experienced surgeon is not known, and the benefit of adjuvant radiation therapy in addition to adjuvant chemotherapy continues to be defined. In unresectable disease, chemoradiation allows long-term survival in a small number of patients and provides effective palliation. Most trials show a benefit to combined modality therapy compared to chemotherapy or radiation therapy alone. The use of pre-operative, intra-operative, 3D conformal, and intensity modulated radiation therapy in gastric cancer is promising but requires further study. The current article reviews the role of radiation therapy in the treatment of resectable and unresectable gastric carcinoma, focusing on current recommendations in the United States.

Hepatocellular carcinoma: Therapy and prevention

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and limited therapeutic options. The therapeutic options fall into five main categories: surgical interventions including tumor resection and liver transplantation, percutaneous interventions including ethanol injection and radiofrequency thermal ablation, transarterial interventions including embolization and chemoembolization, radiation therapy and drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for therapeutic recommendations. Though surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, ＜5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce the morbidity and mortality of HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Furthermore, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets.

Progress in treatment of massive ascites and hepatorenal syndrome

Massive ascites and hepatorenal syndrome （HRS） are frequent complications of liver cirrhosis. Thus, effective therapy is of great clinical importance. This concise review provides an update of recent advances and new developments. Therapeutic paracentesis can be safely performed even in patients with severe coagulopathy. Selected patients with a refractory or recurrent ascites are good candidates for non-surgical portosysternic shunts （TIPS） and may have a survival benefit and improvement of quality of life. Novel pharmaceutical agents mobilizing free water （aquaretics） are currently under test for the therapeutic potential in patients with ascites. Prophylaxis of hepatorenal syndrome in patients with spontaneous bacterial peritonitis is recommended and should be considered in patients with alcoholic hepatitis. Liver transplantation is the best therapeutic option with long-term survival benefit for patients with HRS. To bridge the time until transplantation, TIPS or Terlipressin and albumin are good options. Albumin dialysis can not be recommended outside prospective trials.

Granular cell tumor of stomach: A case report and review of literature

Granular cell tumor （GCT） was described for the first time by Abrikosoff in 1926. It is a relatively rare neoplasm that may occur at many sites, but most commonly in the skin or soft tissues. The occurrence of GCT in the gastrointestinal tract is rare, accounting approximately for 8% of all tumors, among which the most common site is the esophagus, whereas gastric localization is very rare. Gastric GCTs can be solitary or, more frequently, associated with other gastrointestinal localization. Although GCTs are usually clinically and histologically benign, some malignant cases have been reported. Histologically, these tumors consist of polygonal and fusiform cells disposed in compact ＂nests＂ and immunohistochemical staining for S-100 protein supports the proposed derivation from Schwann cells. A correct preoperative diagnosis of this tumor can only be made in 50% of all patients and it is always based on endoscopic biopsy. Laparoscopic or conventional wedge resection represents the treatment of choice. In this study, the authors reported a case of a 49-year-old woman with a solitary granular cell tumor of the stomach with infiltrative pattern, successfully treated with surgical resection. A review of literature is also presented with emphasis on diagnostic criteria concerning the malignant form.

Ursodeoxycholic acid treatment of vanishing bile duct syndromes

Vanishing bile duct syndromes （VBDS） are characterized by progressive loss of small intrahepatic ducts caused by a variety of different diseases leading to chronic cholestasis, cirrhosis, and premature death from liver failure. The majority of adult patients with VBDS suffer from primary biliary cirrhosis （PBC） and primary sclerosing cholangitis （PSC）. Ursodeoxycholic acid （UDCA）, a hydrophilic dihydroxy bile acid, is the only drug currently approved for the treatment of patients with PBC, and anticholestatic effects have been reported for several other cholestatic syndromes. Several potential mechanisms of action of UDCA have been proposed including stimulation of hepatobiliary secretion, inhibition of apoptosis and protection of cholangiocytes against toxic effects of hydrophobic bile acids.

Therapeutic effect of traditional Chinese medicine on coagulation disorder and accompanying intractable jaundice in hepatitis B virus-related liver cirrhosis patients

AIM： TO observe the therapeutic effects of new traditional Chinese medicine （TClVl） therapy on coagulation disorder and accompanying intractable jaundice in HBV-related liver cirrhosis patients. METHODS： Using stratified random sampling according to fibrinogen （Fib） levels, 145 liver cirrhosis patients due to hepatitis B complicated by coagulation disorder were treated. Of them, 70 in research group were treated with TCM by ＂nourishing yin, cooling blood and invigorating blood circulation＂ and Western medicine, 75 in control group were treated with conventional Western medicine. The indexes of liver function, coagulation function and bleeding events were observed and compared. RESULTS： The prothrombin time （PT） was shorter and the fibrinogen （Fib） level was higher in the research group than in the control group （Fib = 1.6-2.0 g/L, 1.1-1.5 g/L, and ≤ 1.0 g/L）. The total bilirubin （TBIL） level was significantly lower in the research group than in the control group, except for the subgroup of FIB ≤ 1.0 g/L. CONCLUSION： TCM therapy can improve coagulation fuction and decrease TBIL.

Anti-hepatoma activity and mechanism of ursolic acid and its derivatives isolated from Aralia decaisneana

AIM： To investigate the anti-tumor activity of ursolic acid （UA） and its derivatives isolated from Aralia decaisneana on hepatocellular carcinoma both in vitro and in vivo. METHODS： In vivo cytotoxicity was first screened by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide （MTT） assay. Morphological observation, DNA ladder, flow cytometry analysis, Western blot and real time PCR were employed to elucidate the cytotoxic mechanism of UA. Implanted mouse hepatoma H22 was used to evaluate the growth inhibitory effect of UA in vivo . RESULTS： UA could significantly inhibit the proliferation of HepG2 and its drug-resistance strain, R-HepG2 cells, but had no inhibitory effect on primarily cultured normal mouse hepatocytes whereas all the six derivatives of UA could not inhibit the growth of all tested cell lines. Further study on mechanism demonstrated that apoptosis and G0/G1 arrest were involved in the cytotoxicity and cleavage of poly-（ADP-ribose）- polymerase （PARP）. Downregulation of cyclooxygenase-2 （COX-2） protein and upregulation of heat shock protein （HSP） 105 mRNA correlated to the apoptosis of HepG2 cells treated with UA. In addition, UA also could inhibit the growth of H22 hepatoma in vivo. CONCLUSION： UA is a promising anti-tumor agent, but further work needs to be done to improve its solubility.