With the aim of establishing bio-indices for the development of multistep hepatotumorigenesis, rats were fed water containing 0.01% diethylnitrosamine (DEN) ad libitum for 13 weeks. This treatment with DEN only made it possible to induce hepatic tumors in 100%. After the DEN administration, several clinical symptoms were observed including minor behavioral changes, brittleness of hair and a decrease in water and food intake. The concentration of total serum protein and albumin in all treated groups was significantly lower than in non-treated controls (p<0.05). Increase of specific enzyme (AST, ALT and GGT) activity (p<0.05), variable tumor size and hepatomegaly of the liver was observed in all rats treated with DEN for 10 weeks. Both hepatocellular carcinoma and cholangiocarcinoma were found in the same livers at the same time, and were prominently developed after 12 weeks. In case of carcinoma, some of the livers showed more or less advanced states over the 12-15 weeks period. In the present study, hepatocellular carcinoma was developed by treating DEN in only the drinking water, without any other carcinogens or without partial hepatectomy. These results indicate that DEN is a new carcinogen that acts directly on it the liver, moreover, it might be very useful for investigating hepatotumorigenesis.
Alanine Transaminase/blood ; Animals ; Aspartate Aminotransferases/blood ; Biological Markers/blood ; Carcinogens ; *Cell Transformation, Neoplastic ; Diethylnitrosamine/toxicity ; Liver/drug effects/*pathology ; Liver Neoplasms/blood/chemically induced/*pathology ; Liver Neoplasms, Experimental/blood/*pathology ; Male ; Rats ; Rats, Sprague-Dawley ; gamma-Glutamyltransferase/blood

To investigate the influence of bear bile on rat hepatocarcinoma induced by diethylnitrosamine (DEN), a total of 40 rats were randomly divided into 4 groups: normal control group, model group, and two bear bile treatment groups. The rat liver cancer model was induced by breeding with water containing 100 mg x L(-1) DEN for 14 weeks. The rats of the bear bile groups received bear bile powder (200 or 400 mg x kg(-1)) orally 5 times per week for 18 weeks. The general condition and the body weight of rats were examined every day. After 18 weeks the activities of serum alanine transaminase (ALT), aspartate transaminase (AST) and total bilirubin (TBIL) were detected. Meanwhile, the pathological changes of liver tissues were observed after H&E staining. The expression of proliferative cell nuclear antigen (PCNA) and a-smooth muscle actin (alpha-SMA) in liver tissue were detected by immunohistochemical method. After 4 weeks the body weights of rats in normal group were significantly more than that in other groups (P < 0.05); and that in the two bile groups was significantly more than that in the model group. Compared with normal group, the level of serum glutamic-pyruvic transaminase and total bilirubin increased significantly in other groups; compared with model group, these two indexes decreased significantly in two bile groups. Hepatocellular carcinoma occurred in all rats except for normal group; there were classic cirrhosis and cancer in model group while there were mild cirrhosis and high differentiation in two bile groups. There were almost no expressions of PCNA and alpha-SMA in normal group while there were high expressions in model group; the two bile groups had some expressions but were inferior to the model group, and alpha-SMA reduced markedly. It indicated that bear bile restrained the development of liver cancer during DEN inducing rat hepatocarcinoma, which may be related to its depressing hepatic stellate cell activation and relieving hepatic lesion and cirrhosis.
Actins ; metabolism ; Alanine Transaminase ; blood ; Animals ; Antineoplastic Agents ; pharmacology ; Aspartate Aminotransferases ; blood ; Bile ; chemistry ; Bilirubin ; blood ; Body Weight ; drug effects ; Carcinoma, Hepatocellular ; blood ; chemically induced ; pathology ; Diethylnitrosamine ; Liver ; metabolism ; pathology ; Liver Cirrhosis ; chemically induced ; pathology ; Liver Neoplasms, Experimental ; blood ; chemically induced ; pathology ; Male ; Powders ; pharmacology ; Proliferating Cell Nuclear Antigen ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Ursidae

OBJECTIVETo evaluate the toxicity of Radix Aristolochiae and Radix Inulae, and to supply the toxicity experimental data that Radix Inulae supersedes Radix Aristolochiae in clinic.

METHODA long dose of Radix Aristolochice and Radix Inulae was given intragastrically to rats for six months, then drug withdrawal for a month. The hematology and biochemical indicators were measured, and the pathologic changes of kidney, liver, stomach and urinary bladder were examined.

RESULTThe rats of Radix Aristolochice showed serious toxic responses of renal tubule atrophy and necrosis, meanwhile, the levels of BUN, Cr and NAG were increased obviously. Hepatonecrosis, renal tubular necrosis, gastric carcinoma and bladder carcinoma were discovered with pathologic assaying. But the rats of Radix Inulae did not.

CONCLUSIONRadix Aristolochiae could damage kidney and liver, and cause gastric carcinoma and bladder carcinoma by intensive toxicity. Radix Inulae could take the place of Radix Aristolochiae to use in clinic.

Acetylglucosaminidase ; urine ; Animals ; Aristolochia ; chemistry ; Blood Urea Nitrogen ; Creatinine ; blood ; Drugs, Chinese Herbal ; isolation & purification ; toxicity ; Female ; Inula ; chemistry ; Kidney Tubules ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Male ; Necrosis ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stomach ; drug effects ; pathology ; Stomach Neoplasms ; chemically induced ; Urinary Bladder ; drug effects ; pathology ; Urinary Bladder Neoplasms ; chemically induced

OBJECTIVETo evaluate the effect and adverse effects of arsenic trioxide (As2O3) in the treatment of primary hepatocarcinoma patients, and conduct the pharmacokinetics study.

METHODSA total of one hundred and eleven advanced primary hepatocarcinoma patients in five centers were treated with As2O3 injection 7 - 8 mg/m(2) i.v. qd for 14 days and was repeated after 7 - 14 days. Evaluation of the clinical response and adverse effects was conducted after two cycles of treatment. The patient who had reached partial PR and SD was treated continuously until disease progression or intolerance.

RESULTSAmong the 102 patients evaluable for clinical efficacy analysis, there were 7 PR, 71 SD and 24 PD, the response rate was 6.9% and the clinical benefit rate was 76.5%. The quality of life was improved in 22.5% of patients. The pain relief rate was 71.7%, time to progress (TTP) was 97 days, and the median survival time (MST) was 195 days. The major adverse effects were reversible WHO I-II grade gastrointestinal reactions and bone marrow suppression. The results of pharmacokinetic study showed that the distribution and elimination characteristics in vivo was found to be a two-compartment model. The plasma elimination half-life was (23.94 ± 18.39) h.

CONCLUSIONSAs2O3 is effective in the management of primary hepatocarcinoma, with a significant analgesic effect. To some extent, it can extend TTP and MST in advanced liver cancer patients, while the treatment is well tolerated in the majority of patients.

Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Arsenicals ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Carcinoma, Hepatocellular ; blood ; drug therapy ; pathology ; Disease Progression ; Female ; Follow-Up Studies ; Half-Life ; Humans ; Injections ; Leukopenia ; chemically induced ; Liver Neoplasms ; blood ; drug therapy ; pathology ; Lung Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Oxides ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Quality of Life ; Remission Induction ; Survival Rate ; Vomiting ; chemically induced

OBJECTIVETo investigate the efficacy, safety and the life quality improvement of uroacitides injection in the treatment for patients with advanced malignant tumors.

METHODSA total of 160 patients with advanced stage cancers were enrolled into this multicenter, open and non-randomized phase II clinical trial, including cancers of the lung (33 cases), liver (45 cases), breast (17 cases), esophagus (11 cases), stomach (18 cases), colon (19 cases), pancreas (3 cases) and kidney (4 cases), and glioma (10 cases). Uroacitides was administrated in a dose of 300 ml daily via the superior vena cava catheter for consecutive 4-8 weeks.

RESULTSOf the 160 patients, 21 dropped out and one patient died during the trial. Efficacy could be evaluated in 138 patients and safety in 160. The total objective response rate (ORR, CR + PR)) and tumor control rate (CR + PR + MR + SD) of the 138 evaluable patients were 5.8% and 65.2%, respectively. Clinical benefit response (CBR) rate was 57.2%. Major adverse effects were grade I - II and reversible nausea/vomiting (21.9%) and pain (6.3%).

CONCLUSIONUroacitides injection is effective in the control for various kinds of advanced cancers with mild, reversible and tolerable adverse effects, and can also improve the patient's quality of life. It is worth being studied further.

Breast Neoplasms ; blood ; drug therapy ; pathology ; CA-19-9 Antigen ; blood ; Carcinoembryonic Antigen ; blood ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; pathology ; Catheterization, Central Venous ; Colorectal Neoplasms ; blood ; drug therapy ; pathology ; Humans ; Liver Neoplasms ; blood ; drug therapy ; pathology ; Lung Neoplasms ; blood ; drug therapy ; pathology ; Methyltransferases ; administration & dosage ; adverse effects ; antagonists & inhibitors ; therapeutic use ; Nausea ; chemically induced ; Neoplasm Staging ; Peptides ; administration & dosage ; adverse effects ; therapeutic use ; Phenylacetates ; administration & dosage ; adverse effects ; therapeutic use ; Quality of Life ; Remission Induction ; Salvage Therapy ; Treatment Outcome ; Vomiting ; chemically induced ; alpha-Fetoproteins ; metabolism

OBJECTIVETo evaluate the efficiency and safety of transhepatic arterial chemoembolization (TACE) with gemcitabine and carboplatin for the treatment of stage III hepatocellular carcinoma (HCC).

METHODSSixty-one HCC patients were treated by TACE. During TACE, At first, intra-arterial infusion of carboplatin 300 mg/m2, then gemcitabine 1000 mg/m2 with 5-30 ml of ultra-lipoidal iodide oil emulsion was used for arterial embolization. The toxicity and hepatic damage were observed according to WHO anticancer drug toxicity criteria and Child-Pugh classification criteria, respectively. The survival time was also observed during follow-up.

RESULTSThe blood toxicity was bone marrow suppression presented as grade I leucopenia in 39.3%, grade II in 29.5%, grade III-IV in 18.0%. Grade II-III nausea and vomiting developed in 96.8% of the patients. Hepatic function damage became aggravated in 16 patients from A to B class, in 2 from A to C class, and in 6 from B to C class according to Child-Pugh classification criteria. The median survival time was 20 months with a range of 5 to 3 5 months.

CONCLUSIONTranshepatic arterial chemoembolization using carboplatin and mixture of gemcitabine with ultra-lipoidal iodide oil emulsion is safe and effective in the management of stage III hepatocellular carcinoma. This regimen can also improve their quality of life.

Adult ; Aged ; Alanine Transaminase ; blood ; Antimetabolites, Antineoplastic ; administration & dosage ; adverse effects ; Antineoplastic Agents ; administration & dosage ; adverse effects ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Hepatocellular ; blood ; pathology ; therapy ; Chemoembolization, Therapeutic ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Female ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Liver Neoplasms ; blood ; pathology ; therapy ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Quality of Life ; Remission Induction ; Survival Rate ; Young Adult