Efficacy of percutaneous ethanol injection in the adjuvant treatment of hepatocellular carcinoma after TACE

Objective： To evaluate the efficacy of percutaneous ethanol injection （PEI） in the adjuvant treatment of hepatocellular carcinoma （HCC） after transcatheter arterial chemoembolization （TACE） by primary end points of time to progress （TTP）. Methods： The study population consisted of 73 consecutive patients with inoperable HCC （China Classification System IIN liB）. Among them, 22 patients were treated with TACE and PEI （experimental group）, and the rest 51 were treated only with TACE （control group）, and then the time to progress （TTP） and overall survival （OS） of these two groups were analyzed. Results： The median TTP was 10 months [95% confidence interval （CI）, 7.9-12.1 months] in experimental group and 6 months （95% CI, 4.7-7.3 months） in control group. The 3-month,6-month, and 1-year Progression Free Survival （PFS） rates were respectively 77.3%, 63.6%, and 48.1% in experimental group, and 76.5%, 42.15%, and 24.8% in control group. The TTP of experimental group was significantly longer than that of control group （P 〈 0.05）. The median survival period was 17 months [95% confidence interval （CI）, 11-23 months] of experimental group and 12 months （95% CI, 10-14 months） of control group （P 〉 0.05）. Conclusion： Compared with single TACE, the combination of TACE and PEI can obviously postpone disease progress and prolong survival of HCC patients.     

The predictive value of vascular endothelial growth factor and Ki-67 expression on neoadjuvant therapy in rectal cancer

Objective： To investigate the expressions of vascular endothelial growth factor （VEGF） and proliferating cell nuclear antigen （Ki-67） in patients with rectal adenocarcinoma and their associations with neoadjuvant therapy. Methods： The expressions of Ki-67 and VEGF in 32 cases of rectal adenocarcinoma, including both pretreatment tumor biopsies and postoperative specimen, were detected by immunohistochemistry using specific antibodies, and were correlated with clinicopathological factors. Results： The intensity of VEGF staining was significantly correlated with lymph nodal metastasis （P =0.033）, depth of tumor invasion （P =0.007） and tumor stage （P= 0.016）, but not with histological types, tumor sizes, patients＇ ages and genders （P 〉 0.05）. Low level of VEGF expression had significant correlation with the high sensitivity of response to neoadjuvant therapy （P = 0.016）. The transient increase of VEGF expression could be seen after neoadjuvant therapy （P = 0.035）. Ki-67 labeling index （Ki-67-LI） was significantly correlated with lymph node metastasis （P = 0.028）, but not correlated to tumor sizes, patients＇ ages and genders （P 〉 0.05）. Tumors with lower Ki-67-LI were more sensitive to neoadjuvant therapy （P = 0.032）. The Ki-67 level decreased after neoadjuvant therapy, but no statistical significance was found （P 〉 0.05）. Conclusion： Our results demonstrate that the expression of VEGF and Ki-67 in pretreatment rectal adenocarcinoma biopsies may be predictive of tumor response to neoadjuvant therapy.     

Clinicopathological significance and relations of Caspase-3 expression,cell proliferation and apoptosis in gastric cancer and the precancerous lesions

Objective： We investigated the relationship between the expression of Caspase-3, cell proliferation and apoptosis in gastric cancer and their precancerous lesions, to explore the tumorigenesis of the stomach mucosa. Methods： Caspase- 3 expression in 13 normal gastric mucosa, 6 chronic atrophic gastritis （CAG）, 31 intestinal metaplasia （IM）, 114 dysplasia （DYS） and 20 gastric carcinomas were investigated immunohistochemically. Cell proliferation was evaluated with anti-Ki-67 immunostaining and apoptosis was evaluated using DNA fragmentation in situ by TdT-mediated dUTP biotin nick end labeling （TUNEL） method. Results： Caspase-3 mild-moderately positive expression was observed in most of normal superficial epithelia, its positively polar distribution in normal mucosa, CAG, IM, DYS and gastric carcinomas changed as seen in TU- NEL, and so did the positive rate. Caspase-3 protein expression showed significantly positive correlation with the number of apoptotic cells labeled with TUNEL （correlation coefficient r = 0,94; P 〈 0101）. Ki-67 expression showed a negative but not significant correlation trend with Caspase-3 （correlation coefficient r = -0.23; P 〉 0.05）. Conclusion： Caspase-3 protein expression was up-regulated from CAG to IM and mild-moderate atypical dysplasia, but down-regulated in severe dysplasia and gastric carcinoma, indicating that inactivity or reduced expression of Caspase-3 is closely correlated with carcinogenesis of the stomach mucosa.     

Expression profile of CD10, Bcl-6, CD138, Bcl-2 and MUM1 and their prognostic value in 136 patients with diffuse large B-cell lymphoma

Objective： We evaluated the value of using a panel of GC B-cell （CD10 and Bcl-6） and activation （MUM1, CD138 and Bcl-2） markers by immunohistochemistry to define prognosis in patients with diffuse large B-cell lymphoma （DLBCL）. Methods： Two different models （Hans＇ and modified Chang＇s model） were applied on 136 de hove DLBCL patients. Median follow-up in all patients was 39 months （range 5-80 months）. Results： According to Hans＇ model, patients with GCB had much better overall survival （5-year OS, 75%） than those with non-GCB （5-year OS, 52%） （Kaplan-Meier survival analysis, P 〈 0.05, log rank test）. According to modified Chang＇s model, patients with group 1 had much better overall survival （5-year OS, 78%） than those with group 3 （5-year OS, 44%） while group 2 had no significant value compared with group 1 and group 3 in prognosis （Kaplan-Meier survival analysis, P 〈 0.05, log-rank test）. Using multivariate Cox proportional hazards regression analysis, the international prognostic index scores （IPI）, expression of CD138 and the expression pattern of modified Chang＇s model were independent prognostic indicators. Conclusion： Our results suggest that the expression patterns of the panel of GCB-cell and activation markers by immunohistochemistry correlate with prognosis of patients with DLBCL and both models can be used well in ordinary work.     

Breast secretory carcinoma： a clinicopathologic study of four cases

Objective： To explore the clinicopathologic features of secretory carcinoma of breast （SCB）. Methods： Four cases of SCB were analyzed by light microscopy, histochemistry, immunohistochemistry and electron microscopy. The clinical data were also analyzed. Special staining of periodic acid-Schiff reaction with diastase pretreatment, immunohistochemical staining of ER, PR, HER-2, p53, MIB-1, S-100, p63, CK8/18 and EMA by En Vision method were performed. Results： Solid, cribriform, tubular, or papillary architecture may be seen. Tumor forms cystic spaces filled with abundant pale pink secretory material, positive with diastase resistant periodic acid-Schiff （PAS-DR） stains. Tumor cells were small with bland nuclei and abundant pale, eosinophilic cytoplasm, rare mitotic activity and necrosis. Immunohistochemically, tumor cells were positive for CK8/18, EMA, negative for S-100, p63 and variable partially positive for p53, ER, PR, HER-2 and MIB-1. Under electron microscopy, the tumor cells possessed numerous membrane-bound secretory vacuoles in cytoplasm lined by microvilli. Conclusion： SCB is a rare, low-malignant neoplasm. SCB have pathology, clinical picture, treatment, follow-up, immunohistochemical and genetic features that distinguish them from invasive ductal carcinomas of the usual type.     

Statistic analysis of 6891 cancer-paining patients＇ information from Gansu Province Tumour Hospital,China

Objective： To analyze and gain the interlinking degree of the cancer pain with patients＇ cancer-species, sexuality and age etc. Methods： The information of narcotic drugs used for cancer pain patients in our hospital （Gansu Province Turnout Hospital, China） during 2002-2007 were typed in designed EXCEL form, then counted and analyzed. Results： The total number of cancer pain patients used narcotic drugs during 2002-2007 was 6891 （n = 6891 ）, among them, 4164 （60.44%） were males, and 2727 （39.56%） females. The top-range of cancer-species in those patients was as follows： lung cancer （20.39%）, gastric cancer （14.85%）, esophageal cancer （9.71%）, hysterocarcinoma （6.79%）, liver cancer （6.70%） and breast cancer （6.31%）. Conclusion： （a） The male number of cancer pain patients using narcotic drugs is higher than the female number （1.53：1）. （b） In the cases of lung cancer, gastric cancer, esophageal cancer, liver cancer and kidney cancer, the male numbers are twice more than the female numbers, and the difference between the two groups are significant. （c） Most of the cancer pain patients （over 87%） are over 40 years old.     

Biological effect of NK4 gene mediated by attenuated Salmonella typhimurium on hepatocellular carcinoma cell HepG2

Objective： The aim of the study was to construct a stable strain of recombined attenuated Salmonella typhimurium expressing NK4 gene, and observe the effect of the strain on the metastatic potentiality of HepG2 cells. Methods： The NK4 cDNA was isolated from PCAGGS/hNK4 plasmid by PCR, and subcloned into eukaryotic expression vector pcDNA4. The recombinant plasmid was electro-transferred into attenuated Salmonella typhimurium Ty21a to obtain the recombinant strain encoding NK4 gene （TPN）. Simultaneously, the recombinant attenuated Salmonella typhimurium carrying GFP gene （TPG） was also constructed. After the TPG and TPN were transferred into HepG2 cells, the transfection rate and the expression level of NK4 protein were detected by flow cytometry and ELISA, and the effects of expression product on the proliferation and migration of HepG2 and angiogenesis were observed. Results： The TPN and TPG were successfully constructed. Fortyeight hours after transfection with TPG, the infection rate was 82.58% ± 1.74%, and the expression level of NK4 protein in supernatant was （181.5 ± 11.7） ng/6 × 10^5 cells. The supematant had obviously depressant effect on the proliferative activity of HepG2 cells （P 〈 0.05）, and could obviously restrain the hepatocyte growth factor-mediated migration of tumor cells （P 〈 0.01）. The inhibitory effect of the expression product on the tumor angiopoiesis was obviously observed （P 〈 0.05）, without a dosage-effect relation. Conclusion： The TPN could effectively transfer tumor cells in vitro and express interest NK4 protein. The expression product could effectively inhibit the proliferation and migration of hepatocellular carcinoma cells and the tumor angiopoiesis.     

Impact of resveratrol on the expression of apoptosis related gene survivin and bax in human cancer cells

Objective： We explored the mechanism of apoptosis in human esophageal cancer Ecal09 cells by resveratrol. Methods： The suppressive ratio of resveratrol on Ecal09 cells proliferation was evaluated by MTT colorimetric assay and morphology was observed by transmission electron microscope. The expression of survivin and bax was analyzed by RT-PCR and Flow Cytometry （FCM）. Results： Resveratrol inhibited the growth of Ecal09 calls in a dose-and time-dependent man- ner, and the suppressive ratio arrived at 76.42%. Morphological apoptosis could be observed after treated with resveratrol.The bulk of some drug-treated cells turned small and the nuclear chromatin became condensed and rnarginated. The results determined by RT-PCR and FCM showed that resveratrol could down-regulate surviving, while up-regulate bax. Conclusion： Resveratrol could induce the apoptosis of human esophageal cancer Ecal09 cells, and its possible molecular mechanisms might be related to modulation the expression of survivin and bax.     

The diagnostic correlations of bone scintigraphy,pathological grade and PSA for metastatic prostate cancers

Objective： The aim of the study was to investigate the correlations between pathological grade, serum prostatespecific antigen （PSA） and bone scintigraphy in the diagnosis of metastasis diseases for prostate cancers, and to explore the characteristics of bone metastases for prostate cancer. Methods： Seventy-seven newly diagnosed prostate cancers were reviewed in the study. All the cases underwent bone scintigraphy, total serum PSA measurement by luminescent immunoassay before operation and were classified according to post-operative pathology diagnosis. We analyzed the correlations of the bone metastasis incidences and different pathological grades or different PSA levels. Results： Bone scans were indicative of metastases in 33 cases （42.86%）. Significantly higher incidence of bone metastasis was observed in patients with poorly differentiated prostate cancer compared with patients with well （X2 = 10.880, P = 0.001 〈 0.05） and moderately （X2 = 6.166, P = 0.013 〈 0.05） differentiated prostate cancers. No significant difference between the well differentiated and moderately differentiated prostate cancers was found （X2 = 0.612, P = 0.434 〉 0.05）. The serum PSA concentration had＇significant correlation with the incidence of bone metastasis. In 26 patients with PSA 〈 20 ng/mL, 5 cases （19.23%） had bone metastasis while 28 of 51 cases （54.90%） with PSA〉 20 ng/mL had bone metastasis. The serum PSA concentration had positive correlation with pathological grades of prostate cancer （r = 0.535, P = 0.01）. Conclusion： Bone scintigraphy plays a great role in the diagnosis of bone metastasis for prostate cancer patients currently. The poorly differentiated prostate cancer and PSA 〉 20 ng/mL most likely suggested the possibility of bone metastasis.     

Clinical progression of Iobaplatin in combination chemotherapy for patients with recurrence or metastatic cancer

The platinum-based combination chemotherapy has become one of the major modalities in anti-cancer treatment. After the first-line chemotherapy, many patients need further chemotherapy because of recurrence or metastasis. Lobaplatin is one of the third generation platinum drugs,and this article briefly reviews the clinical progression of Iobaplatin in combination chemotherapy for patients with recurrence or metastatic cancer.     

Study progress of cell endocytosis

Endocytosis is a process through which extracellular materials are transported into cell through membrane deformation. This process is not a simple step-by-step process in which a series of proteins function according to the chronological order, but rather a complex process comprising many members which are regulated precisely. The role of endocytosis is broadly divided into two categories, phagocytosis and pinocytosis, the latter is divided into four species in accordance with the size of endocytosis substances： clathrin dependent endocytosis, the diameter of clathrin-coated vesicle is 100-150 nm; caveolin dependent endocytosis, the diameter of caveolin protein-coated vesicle is 50-100 nm; macropinocytosis, the diam- eter of macropinocytosis is generally 0.5-2 μm, sometimes up to 5 μm; clathrin and caveolin independent endocytosis. Many proteins including endophilin A1, A2, A3, and endocytotic proteins B, B1a, and Blb as well as dynamin, actin and Rab protein families are involved in endocytosis and play an important role in different stages. The abnormal endocytosis may be involved in the development of certain diseases.     

Relationship between the expression of ERCC-1, survivin and both efficiency and prognosis of cisplatin contained first-line chemotherapy in advanced lung adenocarcinoma

Objective： We analyzed the relationship between the expression of ERCC-1 （excisition repair cross complement- 1）, survivin and sensitivity and prognosis of cisplatin contained regimens first-line chemotherapy in advanced lung adenocarcinoma. Methods： Immunohistochemical （IHC） method was used to evaluate the expression of ERCC-1 and survivin in 80 pathologically confirmed advanced lung adenocarcinoma patients given cisplatin-contained regimens first-line chemotherapy. The response rate and survival time were analyzed according to the expression of ERCC-1 and survivin. Results： Only 77 patients could be reviewed by IHC staining. The expression rates of ERCC-1 and survivin were 33.77% and 53.25 % respectively. The worse response rate and shorter TTP/PFS could be identified in ERCC-1 positive group. Patients with positive expression of survivin had worse survival time. Conclusion： Expression of ERCC-1 may be a molecular marker of cispla- tincontained regimens first-line chemotherapy resistance and poor prognosis in advanced lung adenocarcinoma patients. Positive expression of survivin predicates poor prognosis for patients with advanced lung adenocarcinoma.     

Effects of monoclonal antibodies against human stathmin I combined paclitaxel on proliferation of human hepatocellular carcinoma cell lines

Objective： We investigated the effects of monoclonal antibodies against stathmin 1 combined paclitaxel on the proliferation of HCC cells. Methods： HepG2 cells were treated with monoclonal antibodies against stathmin 1, paclitaxel alone or their combination, with the untreated cells used as the control, 24, 48, 72, 96 h later, the cell growth condition was observed by invert microscope and inhabitation rate was studied by MTT assay; The apoptosis was analyzed by flow cytometry with Annexin V/PI. Results： The population decreased and shape, size changed after treating with different concentration of experimental groups. Monoclonal antibodies against stathmin 1 and paclitaxel used alone or in combination both inhibited the proliferation of HepG2 cells, the inhibition ratio of their combination was more higher （P 〈 0.05）, and a synergistic effect of the two agents was noted in their combined action （P 〈 0.05）. Combined treatment of the cells resulted in significantly higher apoptosis rate than that in the other groups （P 〈 0.05）. Conclusion： Monoclonal antibodies against stathmin 1 and paclitaxel used alone or in combination both can inhibit proliferation of HepG2 cells and induce apoptosis. A synergistic effect is obsewed between the monoclonal antibodies against stathmin 1 and paclitaxel in their inhibition of HepG2 cell proliferation.     

Neck dissection for recurrent and persistent lymph nodes of nasopharyngeal carcinoma after radiotherapy： effect and choice

Objective： To investigate the best surgical mode for the patients of nasopharyngeal carcinoma with recurrent and persistent lymph nodes after radiotherapy. Methods： The clinical data of 88 patients of nasopharyngeal carcinoma with recurrent and persistent lymph nodes after radiotherapy were analyzed retrospectively. The levels of involved lymph nodes and the relationship among the levels were analyzed; the survival rate and recurrent rate of the surgical modes including radical neck dissection （RND）, modified radical neck dissection （MRND）, selective neck dissection （SND）, and lymph node resection （LNR） were analyzed; the role of postoperative radiotherapy was evaluated. Results： （1） The recurrent and persistent lymph nodes mainly located in level Ⅱ（55.6% and 58.6%, respectively）, next was level Ⅲ and rarely in level Ⅳ, Ⅴ, and Ⅰ, but the number of levels Ⅳ Ⅴ, and Ⅰ with cancer-bearing lymph nodes was relatively more than that of clinical measurement. （2） Patients with lymph nodes involved in level Ⅲ and Ⅳ, usually, have other levels involved simultaneously; the percentages were 63.6% and 88.9%, respectively. However, the lymph nodes in level Ⅱ and Ⅴ were mainly isolated. （3） The 5-year survival rate and recurrent rate of the whole group were 42.77% and 22.7%, respectively. （4） The 5-year survival rates of RND, MRND, SND, and LMR groups were 39.75%, 60.00%, 37.87%, and 44.10%, respectively; the differences were insignificant （Log-rank = 1.0, P = 0.8011）; the recurrent rate between the extensive and local surgery groups were insignificant （X^2 = 0.470, P = 0.493）. （5） The 5-year survival rates of the patients with and without postoperative radiotherapy were 39.06% and 45.26%, respectively; the difference was insignificant （Log-rank = 0.06, P = 0.8138）. Conclusion： The extensive surgery was recommended when the recurrent and persistent lymph nodes were more than one level involved or very large or immovable, otherwise, the SND should     

Construction of dual suicide gene therapy system pTRKH2/CD and pTRKH2/UPRT in Bifidobacterium infantis and its characterization

Objective： We recombine the suicide gene CD, UPRT into plasmid pTRKH2 and clone the recombinant dual suicide gene therapy system into tumor-hypoxia-targeting vector Bifidobacterium infantis and characterize its function. Methods： CD gene, UPRT gene and lactic acid bacteria expression plasmid pTRKH2 were digested by restriction endonuclease BamH I and Sal I, and constructed recombinant plasmids pTRKH2/CD and pTRKH2/UPRT in E. coli. The recombinant plasmids were then transfected into Bifidobacterium Infantis by electroporation. Identification of pTRKH2/CD and pTRKH2/UPRT was processed by dual restriction endonuclease digesting and sequencing. RT-PCR and SDS-PAGE were used to examine the expression of CD and UPRT genes at RNA and protein levels. The killing effects on Melanoma B16-F10 cells by pTRKH2/CD and pTRKH2/UPRT suicide gene therapy system with 5-FC were examined by MTT assay. Results： The CD gene and UPRT gene was successfully recombined into lactic acid bacteria expression plasmid pTRKH2, After dual endonuclease digestion of plasmid purified from the positively transfected E. coli, two fragments of 6.9 Kb and 1.3 Kb were found for CD gene and two fragments of 6.9 Kb and 620 bp were found for UPRT gene. The sequencing of CD gene and UPRT gene proved consistent sequences with Genebank published data. A fragment of 1.3 Kb for CD gene and fragment of 620 bp for UPRT gene was found in recombinant Bifidobacterium by RT-PCR. A 52 KDa protein for CD gene was identified in whole-cell protein of recombinant Bifidobacterium and a 26 KDa protein for UPRT gene was identified in supernatant fluid of recombinant Bifidobacterium. The survival rate of tumor cells treated by extracts from culture of recombinant Bifidobacterium with 5-FC showed a strong killing effects of pTRKH2/CD and pTRKH2/UPRT dual suicide gene therapy system on Melanoma B16-F10 cells. Conclusion： CD gene and U PRT gene are successfully inserted into pTRKH2 and transfected into tumor-hypoxia-targeting vector Bifidobacterium Infantis. This dual sui     

Comparison of diagnostic value of PET using 18- fluoro-2-deoxyglucose,CT and MR1 in detecting skull base invasion of nasopharyngeal carcinomas

Objective： We compared positron emission tomography （PET） using 18-fluoro-2-deoxyglucose （FDG）, enhanced computed tomography （CT） and magnetic resonance imaging （MRI） in detecting skull base invasion of nasopharyngeal carcinomas （NPC） and to evaluate the value of these three methods in determining the existence of skull base invasion of nasopharyngeal carcinomas. Methods： The images of enhanced CT, MRI and PET-CT scans, performed at intervals -〈 20 days on 57 NPC patients from July 2004 to February 2007, were selected and reviewed. The endpoints of the comparison were sensitivity, specificity, accuracy, positive predictive value （PPV） and negative predictive value （NPV） of Enhanced CT, MRI and PET-CT, based on histopathologic findings or clinical imaging follow-up for at least 6 months. Results： For detecting skull base invasion of NPC, the sensitivity of enhanced CT, MRI and PET-CT were 68.18%, 84.09%, 97.67% respectively; speci- ficity were 76.92%, 69.23%, 57.14% respectively; accuracy were 70.18%, 80.7%, 87.72% respectively; PPV were 90.9%, 90.24%, 87.5% respectively; NPV were 41.67%, 56.25%, 88.89% respectively. Conclusion： PET-CT has obvious advantages in sensitivity over CT （P 〈 0.05） and MRI, better than the two methods in accuracy and NPV and may be more valuable for new patients in detecting skull base invasion of NPC patients.     

Efficacy and safety profiles of cetuximab in Chinese patients with colorectal cancer

Objective： The aim of this study was to investigate the efficacy and safety profiles of cetuximab, the commonly used monoclonal antibody of epidermal growth factor receptor, based on Chinese patients with colorectal cancer. Methods： All the papers studied on Chinese patients with gastrointestinal cancer treated by cetuximab and found in both databases of Chinese journal database for fulltext and PubMed were collected. The commonly used efficacy index such as disease control rate （CR ＋ PR ＋ SD） and response rate （CR ＋ PR） were analyzed, and the cetuximab related side effects such acne-like rash and nail change and hypersensitivity were analyzed too. Results： （1） There were 10 original papers contained total 152 patients with gastrointestinal cancer who were the candidates to analyze the safety profiles, and contained 130 patients with colorectal cancer who were candidates to analyze the efficacy. （2） The disease control rate and response rate in the whole group was 73.5% （95% CI： 65.5%-81.5%） and 29.1% （95% CI： 20.9%-37.3%）, respectively; In first-line setting group they were 70.0% （95% CI： 55%-85%） and 41.7% （95% CI： 25.6%-57.8%）, respectively; In non-first line setting group they were 71.6% （95% CI： 61.8%-81.4%） and 23.5% （95% CI： 14.3%-32.7%）, respectively. The disease control rate between the two line-setting groups was insignificant, but the response rate between the two line-setting groups was significant （P = 0.045）. （3） The incidence of acne-like rash was 72.0% （95% CI： 64.8%-79.2%）, the degree Ⅰ-Ⅱ and degree Ⅲ-Ⅳ account for 56.0% （95% CI： 48.1%-63.9%） and 16.0% （95% CI： 10.1%-21.9%）, respectively. No treatment related death, and the hypersensitivity was under control. Conclusion： This study is the first study to summarize the data of Chinese patients with colorectal cancer treated by cetuximab-contained regimen, it showed that the monoclonal antibody was effective and safe for Chinese patients as the West p