Aged ; Antitubercular Agents ; therapeutic use ; Cholangiocarcinoma ; diagnosis ; pathology ; Diagnosis, Differential ; Humans ; Magnetic Resonance Imaging ; Male ; Tuberculosis, Hepatic ; diagnosis ; drug therapy ; pathology

OBJECTIVETo investigate the effect of photodynamic therapy (PDT) mediated by hematoporphyrin derivative (HPD) on apoptosis and invasion of cholangiocarcinoma QBC939 cell lines.

METHODSIn vitro cultured cholangiocarcinoma QBC939 cell line was exposed to 2, 4, 6, 8, 10, 12, and 14 μg/ml HPD with 5, 10, and 15 J/cm2 light intensity, respectively. The optical density at 450 nm of the QBC939 cells was measured by CCK8 assay and its growth inhibition ratio was calculated. Flow cytometry and transwell migration assay were applied to detect cell apoptosis and invasion respectively. RT-PCR and immunocytochemistry analyses were used to detect expressions of vascular endothelial growth factor-C (VEGF-C), cyclooxygenase-2 (COX-2), and proliferating cell nuclear antigen (PCNA). Enzyme-linked immunosorbent assay (ELISA) was carried out to examine the secretion of VEGF-C and COX-2 in QBC939 cells.

RESULTSExposure to HPD-PDT can significantly suppress the growth of QBC939 cells (all P<0.05). HPD-PDT can promote apoptosis of QBC939 cells at the early stage. When the concentration of HPD was 2 μg/ml and light irradiation was 5 J/cm2, HPD-PDT had no obvious inhibitory effect on QBC939 cell growth, but can obviously inhibit cell invasion, and significant difference was observed between the HPD-PDT and control groups (P<0.01). The HPD-PDT can reduce the mRNA and protein expressions of VEGF-C, COX-2, and PCNA, and decrease the secretion of VEGF-C and COX-2 in QBC939 cells.

CONCLUSIONPDT could promote apoptosis and inhibit growth and invasion of cholangiocarcinoma cells QBC939 in vitro.

Apoptosis ; drug effects ; Bile Duct Neoplasms ; drug therapy ; pathology ; Bile Ducts, Intrahepatic ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cholangiocarcinoma ; drug therapy ; pathology ; Humans ; Neoplasm Invasiveness ; Photochemotherapy ; Proliferating Cell Nuclear Antigen ; analysis

OBJECTIVETo investigate and compare the biological characteristics and sensitivity to chemotherapy and radiotherapy of intrahepatic and extrahepatic cholangiocarcinoma cells in vitro.

METHODSThe intrahepatic and extrahepatic cholangiocarcinoma cell lines were established, and cells with steady passage were chosen to study the biological characteristics including morphology, growth dynamics, chromosome, and levels of cancer antigen (CA) 125, CA19-9, alpha-fetoprotein (AFP), and carcino-embryonic antigen (CEA). Meanwhile, MTT assay was used to determine the sensitivity of both kinds of cells to 6 chemotherapeutic drugs, including cisplatin, paclitaxel, harringtonine, 5-fluorouracil, vincristine, and aclacimomycin, and the inhibitory rate of cells under the irradiation of 10 Gy ray was also measured.

RESULTSThe intrahepatic cholangiocarcinoma cells were mostly fusiform in shape, and extrahepatic cholangiocarcinoma cells were mostly round or polygon in shape. Their doubling time was 26. 3 hours and 23. 1 hours, respectively. Their average number of chromosomes was 59 (range, 38-84) and 67 (range, 49-103), respectively. The chromosome karyotypes of most intrahepatic cholangiocarcinoma cells were hyperdiploid and hypotriploid, while hypertriploid was predominant in extrahepatic cholangiocarcinoma cells. The level of CA 125 in supernatant of extrahepatic cholangiocarcinoma cells increased obviously, while levels of other determined tumor markers in both kinds of cells were all within normal range. The intrahepatic cholangiocarcinoma cells were low sensitive to cisplatin and paclitaxel, but not sensitive to the other 4 chemotherapeutic drugs. The extrahepatic cholangiocarcinoma cells were high sensitive to cisplatin, but not sensitive to the other 5 drugs. Both kinds of cells had poor sensitivity to radiotherapy.

CONCLUSIONSIntrahepatic and extrahepatic cholangiocarcinoma cells show differences in shape, doubling time, chromosome karyotype, tumor marker level, and chemosensitivity, whereas they both have poor radiosensitivity. Though they are similar in histopathology, they have different growth characteristics and have discrepancy in treatment and prognosis.

Antineoplastic Agents ; therapeutic use ; Bile Duct Neoplasms ; drug therapy ; genetics ; pathology ; radiotherapy ; Bile Ducts, Intrahepatic ; pathology ; Biomarkers, Tumor ; Cell Line, Tumor ; Cholangiocarcinoma ; drug therapy ; genetics ; pathology ; radiotherapy ; Enzyme-Linked Immunosorbent Assay ; Humans ; Karyotyping ; Radiation Tolerance

A 54-year-old female with postprandial dyspepsia and abdominal pain was diagnosed as locally advanced unresectable intrahepatic cholangiocarcinoma by radiologic imaging studies resulting in invasion to bilateral main bile duct and right portal vein. The patient underwent extended right hepatectomy and portal vein resection after gemcitabine and cisplatin combined chemotherapy for a total of 40 cycles after the diagnosis. Final pathology showed, followed by pathological complete remission, without any residual cancer cell. The patient has survived for over 6 years without any evidence of recurrence. This case suggests that locally advanced intrahepatic cholangiocarcinoma, which can't be resected, was also proved to be capable of pathological complete remission with active chemotherapy, and long-term survival could be achieved. Therefore, active multidisciplinary approach and patient-oriented treatments using various methods should be considered for locally advanced unresectable intrahepatic cholangiocarcinoma.
Abdominal Pain ; Bile Duct Neoplasms ; Bile Ducts ; Cholangiocarcinoma* ; Cisplatin ; Diagnosis ; Drug Therapy* ; Dyspepsia ; Female ; Hepatectomy ; Humans ; Middle Aged ; Neoplasm, Residual ; Pathology ; Portal Vein ; Recurrence

Hepatoblastoma usually occurs in children under the age of 2 years, with very few cases reported in adults. We experienced a case of adult hepatoblastoma in a 36-year-old female with chronic hepatitis B . She had experienced sudden onset abdominal pain. Her serum alpha-fetoprotein level was markedly elevated, and abdominal CT showed a 9-cm mass with internal hemorrhage in the right hepatic lobe with hemoperitoneum, so an emergency hepatic central bisectionectomy was performed. The initial histologic examination revealed that the mass mimicked combined hepatocellular carcinoma and cholangiocarcinoma with spindle-cell metaplasia of the cholangiocarcinoma element. Follow-up abdominal CT performed 3 months later showed a 5.5-cm metastatic mass in the left subphrenic area. Laparoscopic splenectomy with mass excision was performed, and hepatoblastoma was confirmed histologically. A histologic re-examination of previously obtained surgical specimens also confirmed the presence of hepatoblastoma. Metastatic hepatoblastoma was found at multiple sites of the abdomen during follow-up, and so chemotherapy with cisplatin, 5-fluorouracil (5-FU), and vincristine was applied, followed by carboplatin and doxorubicin . Despite surgery and postoperative chemotherapy, she died 12 months after symptom onset.
Adult ; Carcinoma, Hepatocellular/pathology ; Cholangiocarcinoma/pathology ; Cisplatin/therapeutic use ; Diagnostic Errors ; Doxorubicin/therapeutic use ; Drug Therapy, Combination ; Female ; Fluorouracil/therapeutic use ; Hepatitis B, Chronic/complications/diagnosis ; Hepatoblastoma/drug therapy/*pathology/radiography ; Humans ; Liver Neoplasms/drug therapy/*pathology/radiography ; Tomography, X-Ray Computed ; Vincristine/therapeutic use

Opisthorchis viverrini (O. viverrini) is a well-known causative agent of cholangiocarcinoma (CCA) in humans. CCA is very resistant to chemotherapy and is frequently fatal. To understand the pathogenesis of CCA in humans, a rodent model was developed. However, the development of CCA in rodents is time-consuming and the xenograft-transplantation model of human CCA in immunodeficient mice is costly. Therefore, the establishment of an in vivo screening model for O. viverrini-associated CCA treatment was of interest. We developed a hamster CCA cell line, Ham-1, derived from the CCA tissue of O. viverrini-infected and N-nitrosodimethylamine-treated Syrian golden hamsters. Ham-1 has been maintained in Dulbecco's Modified Essential Medium supplemented with 10% fetal bovine serum for more than 30 subcultures. These cells are mostly diploid (2n=44) with some being polyploid. Tumorigenic properties of Ham-1 were demonstrated by allograft transplantation in hamsters. The transplanted tissues were highly proliferative and exhibited a glandular-like structure retaining a bile duct marker, cytokeratin 19. The usefulness of this for in vivo model was demonstrated by berberine treatment, a traditional medicine that is active against various cancers. Growth inhibitory effects of berberine, mainly by an induction of G1 cell cycle arrest, were observed in vitro and in vivo. In summary, we developed the allo-transplantable hamster CCA cell line, which can be used for chemotherapeutic drug testing in vitro and in vivo.
Allografts ; Animals ; Antineoplastic Agents/*isolation & purification/therapeutic use ; Berberine/therapeutic use ; Cell Culture Techniques ; *Cell Line, Tumor ; Cell Transplantation/methods ; Cholangiocarcinoma/*drug therapy/pathology ; Cricetinae ; Culture Media/chemistry ; Disease Models, Animal ; Drug Evaluation, Preclinical/*methods ; Male ; Mesocricetus

Intrahepatic cholangiocarcinoma (ICC), a malignant tumor derived from the intrahepatic bile duct epithelium, has a poor prognosis and is refractory to conventional chemotherapy and radiation therapy. Thus, there is an urgent need to develop new effective therapeutic strategies for this disease. We previously found that L1 cell adhesion molecule (L1CAM) plays an important role in tumor progression of ICC, and we generated a murine mAb, A10-A3 (IgG1), that binds to the Ig1 domain of L1CAM. In the present study, we further characterized A10-A3, constructed a chimeric A10-A3 antibody (cA10-A3) containing the constant regions of human IgG1, and evaluated the therapeutic potential in a human ICC xenograft nude mice model. The affinities (K D) of A10-A3 and cA10-A3 for soluble L1CAM were 1.8 nM and 1.9 nM, respectively, as determined by competition ELISA. A10-A3 inhibited L1CAM homophilic binding and was slowly internalized into the tumor cells, but it did not significantly inhibit proliferation of ICC cells in vitro. cA10-A3 mediated antibody-dependent cell-mediated cytotoxicity in vitro and displayed anti-tumor activity in the ICC animal model. These results suggest that the humanized A10-A3 antibody may have potential as an anticancer agent for the treatment of ICC.
Animals ; Antibodies, Monoclonal/genetics/*immunology ; Antibody-Dependent Cell Cytotoxicity ; Bile Ducts, Intrahepatic/drug effects/immunology/pathology ; CHO Cells ; Cell Adhesion/drug effects ; Cell Proliferation/drug effects ; Cholangiocarcinoma/*drug therapy/immunology/pathology ; Cricetinae ; Disease Models, Animal ; Endocytosis/drug effects ; Humans ; Immunoglobulin G/genetics/*immunology ; Liver Neoplasms/*drug therapy/immunology/pathology ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neural Cell Adhesion Molecule L1/genetics/*immunology/metabolism ; Protein Binding ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/immunology/metabolism/*therapeutic use

OBJECTIVETo investigate the efficacy of the combination of gemcitabine with capecitabine in the chemotherapy for patients with relapsed or metastatic biliary tract carcinoma.

METHODSForty-one patients with unresectable relapsed or metastatic carcinoma of the biliary tract were treated from March 2000 to December 2004. The regimen consisted of intravenous administration of gemcitabine plus oral intake of capecitabine every 3 weeks for more than 2 cycles. The parameters including tumor response, clinical benefit rate,survival and safety were observed.

RESULTSThirty-six patients were valuable and 5 patients were excluded from this series due to various reasons. Eleven patients (30.1%) had a partial response and another 11 patients (30.1%) experieced stable disease with a clinical benefit rates of 61.1%. The median overall survival time and time to progression were 10 months and 6 months, respectively. The one-year survival rate was 40.0%. The adverse events including nausea, diarrhea and hand-foot syndrome, fatigue, neutropenia, thrombocytopenia were frequently observed, which were usually in grade I or II, rarely in grade III and none in grade IV (NCI-CTC).

CONCLUSIONOur results show that the regimen of gemcitabine combined with capecitabine is effective and well tolerated in patients with unresectable relapsed or metastatic carcinoma of the biliary tract.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Bile Duct Neoplasms ; drug therapy ; pathology ; Bile Ducts, Intrahepatic ; Capecitabine ; Cholangiocarcinoma ; drug therapy ; pathology ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Diarrhea ; chemically induced ; Female ; Fluorouracil ; administration & dosage ; analogs & derivatives ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neutropenia ; chemically induced ; Remission Induction ; Survival Rate

An 80-year-old woman with hilar cholangiocarcinoma was hospitalized due to sudden-onset abdominal pain. Computed tomography revealed hepatic necrosis accompanied with emphysematous change in the superior segment of the right liver (S7/S8), implying spontaneous rupture, based on the presence of perihepatic free air. Although urgent percutaneous drainage was performed, neither pus nor fluids were drained. These findings suggest emphysematous hepatitis with a hepatic mass. Despite the application of intensive care, the patient's condition deteriorated rapidly, and she died 3 days after admission to hospital. Liver gas has been reported in some clinical diseases (e.g., liver abscess) to be caused by gas-forming organisms; however, emphysematous hepatitis simulating emphysematous pyelonephritis is very rare. The case reported here was of fatal emphysematous hepatitis in a patient with hilar cholangiocarcinoma.
Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Bile Duct Neoplasms/complications/diagnosis ; Bile Ducts, Intrahepatic/pathology ; Cefotaxime/therapeutic use ; *Cholangiocarcinoma/complications/diagnosis ; Clostridium Infections/drug therapy/microbiology ; Clostridium perfringens/isolation & purification ; Emphysema/complications/*diagnosis ; Escherichia coli/isolation & purification ; Escherichia coli Infections/drug therapy/microbiology ; Female ; Hepatitis/complications/*diagnosis ; Humans ; Metronidazole/therapeutic use ; *Pneumoperitoneum/complications/diagnosis ; Tomography, X-Ray Computed

Cholangiocarcinoma (CC) is a chemoresistant intrahepatic bile duct carcinoma with a poor prognosis. The aims of this study were to identify molecular pathways that enhance sesquiterpene lactone parthenolide (PTL)-induced anticancer effects on CC cells. The effects of PTL on apoptosis and hemoxygenase-1 (HO-1) induction were examined in CC cell lines. The enhancement of PTL-mediated apoptosis by modulation of HO-1 expression and the mechanisms involved were also examined in an in vitro cell system. Low PTL concentrations (5 to 10 micrometer) led to Nrf2-dependent HO-1 induction, which attenuated the apoptogenic effect of PTL in Choi-CK and SCK cells. PTL-mediated apoptosis was enhanced by the protein kinase C-alpha inhibitor Ro317549 (Ro) through inhibition of expression and nuclear translocation of Nrf2, resulting in blockage of HO-1 expression. Finally, HO-1 silencing resulted in enhancement of apoptotic cell death in CC cells. The combination of PTL and Ro efficiently improved tumor growth inhibition compared to treatment with either agent alone in an in vivo subcutaneous tumor model. In conclusion, the modulation of HO-1 expression substantially improved the anticancer effect of PTL. The combination of PTL and Ro could prove to be a valuable chemotherapeutic strategy for CC.
Active Transport, Cell Nucleus/drug effects ; Antineoplastic Agents/chemistry/*pharmacology ; Apoptosis/drug effects/genetics ; Cell Line, Tumor ; Cell Nucleus/*metabolism ; Cholangiocarcinoma/drug therapy/*metabolism/pathology ; Drug Resistance, Neoplasm/drug effects/genetics ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Heme Oxygenase-1/genetics/*metabolism ; Humans ; Lactones/chemistry ; NF-E2-Related Factor 2/genetics/*metabolism ; Protein Kinase C-alpha/antagonists & inhibitors ; RNA, Small Interfering/genetics ; Sesquiterpenes/chemistry/*pharmacology ; Signal Transduction/drug effects