Treating patients undergoing chemotherapy who display findings of liver toxicity, requires a solid understanding of these medications. It is important for any clinician to have an index of suspicion for liver toxicity and be able to recognize it, even on imaging. Cancer chemotherapy has evolved, and newer medications that target cell biology have a different pattern of liver toxicity and may differ from the more traditional cytotoxic agents. There are several hepatic conditions that can result and keen clinical as well as radiographic recognition are paramount. Conditions such as sinusoidal obstructive syndrome, steatosis, and pseudocirrhosis are more commonly associated with chemotherapy. These conditions can display clinical signs of acute hepatitis, liver cirrhosis, and even liver failure. It is important to anticipate and recognize these adverse reactions and thus appropriate clinical action can be taken. Often times, patients with these liver manifestations can be managed with supportive therapies, and liver toxicity may resolve after discontinuation of chemotherapy.
Adult ; Aged ; Antibiotics, Antineoplastic/adverse effects/therapeutic use ; Antimetabolites, Antineoplastic/adverse effects/therapeutic use ; Antineoplastic Agents/*adverse effects/therapeutic use ; Antineoplastic Agents, Alkylating/adverse effects/therapeutic use ; Drug-Induced Liver Injury/etiology/radiography ; Enzyme Inhibitors/adverse effects/therapeutic use ; Fatty Liver/etiology/radiography ; Female ; Humans ; Immunotherapy ; Liver Cirrhosis/etiology/radiography ; Liver Diseases/etiology/*radiography ; Male ; Middle Aged ; Neoplasms/therapy ; Tomography, X-Ray Computed

This study investigated the effect of TNP-470 in combination with carmustine (BCNU) on the growth of subcutaneously implanted human glioblastoma xenografts in nude mice. Human glioblastoma U-251 cells (1×10(7)) were injected into 24 nude mice subcutaneously. The tumor-bearing mice were randomly divided into 4 groups on the seventh day following tumor implantation: TNP-470 group, in which TNP-470 was given 30 mg/kg subcutaneously every other day 7 times; BCNU group, in which 20 mg/kg BCNU were injected into peritoneal cavity per 4 days 3 times; TNP-470 plus BCNU group, in which TNP-470 and BCNU were coadministered in the same manner as in the TNP-470 group and the BCNU group; control group, in which the mice were given 0.2 mL of the mixture including 3% ethanol, 5% acacia and 0.9% saline subcutaneously every other day 7 times. The tumor size and weights were measured. The tumor microvessel density (MVD) was determined by immunostaining by using goat-anti-mouse polyclonal antibody CD105. The results showed that on the 21th day following treatment, the volume of xenografts in the TNP-470 plus BCNU group was (108.93±17.63)mm(3), markedly lower than that in the TNP-470 group [(576.10±114.29)mm(3)] and the BCNU group [(473.01±48.04)mm(3)] (both P<0.01). And the xenograft volume in these 3 treatment groups was even much lower than that in the control group [(1512.61±470.25) mm(3)] (all P<0.01). There was no significant difference in the volume of xenografts between the TNP-470 group and the BCNU group (P>0.05). The inhibition rate of the tumor growth in the TNP-470 plus BCNU group was (92.80±11.37)%, notably higher than that in the TNP-470 group [(61.91±6.29)%] and the BCNU group [(68.73±9.65)%] (both P<0.01) on the 21th day following treatment. There was no significant difference in the inhibition rate of tumor growth between the TNP-470 group and the BCNU group (P>0.05). The MVD of xenografts in the TNP-470 plus BCNU group was decreased significantly as compared with that in the TNP-470 group or the BCNU group (both P<0.05). The MVD of xenografts in the 3 treatment groups was markedly reduced as compared with that in the control group (all P<0.05). No significant changes in weights were observed before and after the treatment in each group (all P>0.05). It was concluded that the combination of TNP-470 and BCNU can significantly inhibit the growth of human glioblastoma xenografts in nude mice without evident side effects.
Angiogenesis Inhibitors ; administration & dosage ; Animals ; Antibiotics, Antineoplastic ; administration & dosage ; Antineoplastic Agents, Alkylating ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Brain Neoplasms ; drug therapy ; Carmustine ; administration & dosage ; Cell Line, Tumor ; Cyclohexanes ; administration & dosage ; Female ; Glioblastoma ; drug therapy ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Sesquiterpenes ; administration & dosage ; Xenograft Model Antitumor Assays

Antineoplastic Agents, Alkylating ; pharmacology ; Apoptosis ; drug effects ; Benzimidazoles ; pharmacology ; DNA Repair ; Dacarbazine ; analogs & derivatives ; pharmacology ; Drug Resistance, Neoplasm ; drug effects ; physiology ; Humans ; Membrane Proteins ; metabolism ; O(6)-Methylguanine-DNA Methyltransferase ; antagonists & inhibitors ; metabolism ; Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases ; metabolism ; Proto-Oncogene Proteins ; metabolism ; Purines ; pharmacology ; Pyrimidines ; pharmacology ; Tumor Suppressor Protein p53 ; metabolism

BACKGROUND/AIMS: The clinical efficacy and safety of a three-drug combination of melphalan, prednisone, and thalidomide were assessed in patients with multiple myeloma who were not candidates for high-dose therapy as a first-line treatment. Because the side effects of thalidomide at a dose of > or = 100 mg daily can be a barrier to effective treatment for these patients, we evaluated the efficacy and safety of a reduced dose of thalidomide, 50 mg, for non-transplant candidates. METHODS: Twenty-one patients were treated in 4-week cycles, receiving 4 mg/m2 melphalan and 40 mg/m2 prednisone on days 1-7 and 50 mg thalidomide daily. The primary efficacy outcome was the overall response rate. Aspirin (100 mg daily) was also provided as prophylactic treatment for thromboembolism. RESULTS: The overall response rate was 57.1%; a complete response was seen in 23.8% of patients, a partial response in 33.3%, and stable disease in 9.5%. After a median follow-up time of 16.1 months, the median time to progression was 11.4 months (95% confidence interval, 2.1 to 20.6); the median overall survival was not reached. Grades 3 and 4 adverse events included infection (10%), peripheral neuropathy (5%), diarrhea (5%), thrombosis (10%), and loss of consciousness (10%). Two patients discontinued treatment due to loss of consciousness and neuropathy. CONCLUSIONS: Low-dose thalidomide (50 mg) plus melphalan and prednisone is an effective combination drug therapy option for newly diagnosed myeloma patients who are ineligible for high-dose chemotherapy.
Aged ; Angiogenesis Inhibitors/*therapeutic use ; Antineoplastic Agents, Alkylating/*therapeutic use ; Antineoplastic Agents, Hormonal/*therapeutic use ; Confidence Intervals ; Disease Progression ; Drug Therapy, Combination ; Female ; Humans ; Kaplan-Meier Estimate ; Korea ; Male ; Melphalan/*therapeutic use ; Middle Aged ; Multiple Myeloma/*drug therapy/mortality ; Prednisone/*therapeutic use ; Risk ; Thalidomide/*therapeutic use ; Time Factors ; Treatment Outcome

OBJECTIVETo evaluate in vitro antitumor effects of chemotherapeutic drugs, and investgate the relationship with expression of hTERT mRNA in human gastric cancer tissues.

METHODSFresh samples of gastric cancer obtained from operation room were prepared to single-cell suspension (3 x 10(5) to 5 x 10(5) cells ml(-1)) and were separately exposed to taxol (TAX), cisplatin (CDDP), 5-fluorouracil (5-Fu), adriamycin (ADM), mitomycin (MMC) for 48 hours. Metabolic activity and inhibitory rate of the cells were determined by trypan blue exclusion and MTT assay. Expression of hTERT mRNA was detected by in situ hybridization (ISH).

RESULTSThe inhibition rate of cancer cells exposed to chemotherapeutic drugs was different, and that of TAX, CDDP, 5-Fu was significantly higher than that of ADM and MMC. The positive rate of hTERT mRNA expression was 90.0% (54/60) and positive cells showed resistance to 5-Fu and ADM.

CONCLUSIONOverexpression of hTERT mRNA may contribute to primary drug-resistance of tumors. Chemosensitivity tests by MTT assay may contribute to prediction of effectness in applying chemotherapeutic drugs and identify drug-resistant cases.

Adenocarcinoma, Mucinous ; metabolism ; pathology ; Adenocarcinoma, Papillary ; metabolism ; pathology ; Adult ; Aged ; Antibiotics, Antineoplastic ; pharmacology ; Antimetabolites, Antineoplastic ; pharmacology ; Antineoplastic Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Carcinoma, Signet Ring Cell ; metabolism ; pathology ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; Female ; Fluorouracil ; pharmacology ; Humans ; Male ; Middle Aged ; Mitomycin ; pharmacology ; Paclitaxel ; pharmacology ; RNA, Messenger ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Telomerase ; genetics ; metabolism

BACKGROUND AND OBJECTIVEmiRNA-200c can not only inhibit the aggressiveness of cancer cells but also increase the sensitivity of cells to antitumor drugs. However, some mechanisms are still unclear. Recent researches revealed that E-cadherin is more than an inhibitor of metastasis, and it also plays important roles in reversing drug resistance. We had previously found that miRNA-200c could not only induce the expression of E-cadherin but also increase the sensitivity of gastric cancer SGC7901/DDP cells to cisplatin (DDP). This study aimed to explore the effects of miRNA-200c on biological characteristics of SGC7901/DDP cells and the roles of E-cadherin in the regulatory pathway of miRNA-200c.

METHODSSGC7901/DDP cells and its parental cell line SGC7901 cells were transfected with miRNA-200c precursor (Pre-200c) and E-cadherin siRNA, respectively. Real-time RT-PCR was used to detect miRNA-200c expression after transfection with Pre-200c in SGC7901/DDP cell line. Drug sensitivities to DDP, 5-fluorouracil (5-FU), paclitaxel, and adriamycin (ADR) after transfection were tested using MTT assay. The proliferation of SGC7901/DDP cells was also detected after transfection. The protein changes of E-cadherin, Bax, and Bcl-2 after transfection were detected by Western blot.

RESULTSThe miRNA-200c expression in SGC7901/DDP cells after transfection of Pre-200c was 7.128 ± 0.159 times of that in negative control (P < 0.05). The IC50 of DDP, 5-FU, paclitaxel, and ADR in Pre-200c-transfected group were significantly lower than that in negative control group (P < 0.05). Compared to the control group, cell proliferation was significantly decreased (P < 0.05). The relative protein expressions of E-cadherin and Bax in Pre-200c-transfected group were significantly higher than those in negative control group (P < 0.05), whereas Bcl-2 was significantly lower than that in control (P < 0.05). Additionally, E-cadherin protein expression was significantly inhibited after transfected with E-cadherin siRNA in SGC7901 cells. The Bax protein expression was significantly down-regulated by E-cadherin siRNA (P < 0.05), whereas the Bcl-2 expression was significantly up-regulated (P < 0.05).

CONCLUSIONmiRNA-200c can indirectly regulate apoptosis through E-cadherin in SGC7901/DDP cells, which may be a possible mechanism of miRNA-200c in reversing drug resistance and inhibiting proliferation.

Antibiotics, Antineoplastic ; pharmacology ; Antimetabolites, Antineoplastic ; pharmacology ; Antineoplastic Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Cadherins ; genetics ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Cisplatin ; pharmacology ; Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Fluorouracil ; pharmacology ; Humans ; MicroRNAs ; genetics ; metabolism ; physiology ; Paclitaxel ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA, Small Interfering ; genetics ; Sensitivity and Specificity ; Stomach Neoplasms ; metabolism ; pathology ; Transfection ; bcl-2-Associated X Protein ; metabolism

Antibiotics, Antineoplastic ; therapeutic use ; Antineoplastic Agents, Alkylating ; therapeutic use ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; surgery ; Cyclophosphamide ; therapeutic use ; Epirubicin ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; metabolism ; pathology ; surgery ; Lymph Node Excision ; Lymphatic Metastasis ; Middle Aged ; Neoplasms, Multiple Primary ; drug therapy ; metabolism ; pathology ; surgery ; Paclitaxel ; therapeutic use

PURPOSE: To evaluate the visual outcomes of retinoblastoma in the posterior pole (RBPP) treated with chemotherapy plus local treatments and to address the prognostic factors that influence such outcomes. METHODS: The medical records of patients with RBPP diagnosed at the Department of Pediatric Ophthalmology, Seoul National University Children's Hospital between August 1987 and September 2007 were reviewed retrospectively. Only those patients treated via primary chemotherapy plus local treatments were included. The presence of foveal involvement and tumors in the posterior pole before and after treatment, the type of regression pattern and the best corrected visual acuity (BCVA) of each patient were evaluated. RESULTS: A total of 13 eyes in 12 patients were included. The mean final BCVA for treated RBPP was 20/210 (range, hand motion to 20/16). However, eight eyes (61.5%) had an acuity of 20/200 or better and seven eyes (53.8%) had an acuity of 20/50 or better. The mean final BCVA was significantly better in cases with negative foveal involvement; however, four eyes (37.5%) with positive foveal involvement had an acuity of 20/200 or better. Tumors area in the posterior pole and the type of regression pattern were not significantly related to final BCVA. CONCLUSIONS: Over one half of the studied RBPP patients had working vision. Although the eyes had RBPP with positive foveal involvement, about one-third of the patients had working vision. Vision preservation should be considered when deciding on RBPP treatment.
Antibiotics, Antineoplastic/administration & dosage ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents, Alkylating/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cisplatin/administration & dosage ; Cyclophosphamide/administration & dosage ; Doxorubicin/administration & dosage ; Etoposide/administration & dosage ; Eyeglasses ; Female ; Follow-Up Studies ; Fovea Centralis/pathology ; Humans ; Infant ; Male ; Prognosis ; Retinal Neoplasms/*drug therapy/pathology/*physiopathology ; Retinoblastoma/*drug therapy/pathology/*physiopathology ; Retrospective Studies ; Treatment Outcome ; Visual Acuity

OBJECTIVETo investigate the changes of biological characteristics of breast cancer cell line by cyclin E expression.

METHODSHuman breast cancer cell line MCF-7 was transfected with cyclin E siRNA vector pEGFP/CCNE2. siRNA-induced silencing of cyclin E was determined by RT-PCR at RNA level and Western blot at protein level. The proliferation of MCF-7 cells and their sensitivity to chemotherapy was measured by CCK-8 assay. The cells were examined by FCM. The cell line was injected into nude mice and the tumor size was measured.

RESULTSThe expression of cyclin E was inhibited in the MCF-7 cells. The relative expression level of cyclin E mRNA was 0.23 +/- 0.05, and that of cyclin E protein was 0.24 +/- 0.05. The cell growth was inhibited by 68.56% +/- 0.08%, and their sensitivity to chemotherapy was increased. Most cells were blocked at G(1) (77.38%), their tumorigenic ability in nude mice was reduced, and the size of tumor formed in mice of the experimental group was decreased than that of controls.

CONCLUSIONInhibition of cyclin E expression in breast cancer cells can block their cell cycle at G(1) phase, reduce their cell growth, differentiation and proliferation, and increase their sensitivity to chemotherapy.

Animals ; Antibiotics, Antineoplastic ; pharmacology ; Antimetabolites, Antineoplastic ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Breast Neoplasms ; metabolism ; pathology ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin E ; genetics ; metabolism ; Doxorubicin ; pharmacology ; Female ; Fluorouracil ; pharmacology ; Genetic Vectors ; Humans ; Male ; Mice ; Mice, Inbred ICR ; Mice, Nude ; Neoplasm Transplantation ; Paclitaxel ; pharmacology ; Plasmids ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Transfection ; Tumor Burden

BACKGROUND AND OBJECTIVEChemotherapy is the main treatment for colon cancer, while multidrug-resistance is the main reason for chemotherapy failure and tumor relapse. This study was to establish two oxaliplatin-resistant colon cancer cell lines and evaluate their biological characteristics.

METHODSOxaliplatin-resistant colon cancer cell lines SW620/L-OHP and lovo/L-OHP were established in vitro by continuous exposure to oxaliplatin (L-OHP) of low and gradually increased concentration. Growth curve, cross-resistance and resistance index of the oxaliplatin-resistant cell lines to various anti-cancer agents were determined by CCK8 assay. The expressions of P-glycoprotein (P-gp), multidrug-resistance protein 1 (MRP1) and MRP2 were detected by Western blot. Cell cycle distribution as well as the expression of CD133 and CD44 were measured by flow cytometry.

RESULTSIt took 10 months to establish the SW620/L-OHP and LoVo/L-OHP cell lines with stable resistance to oxaliplatin. Cross-resistance to 5-fluorouracil, etoposide, cisplatin, vincristine and epirubicin but not to paclitaxel was observed. Longer doubling time, higher proportion of cells in G(0)/G(1) phase and lower proportion in G(2)/M phase were observed in the two oxaliplatin-resistant cell lines compared with their parental cell lines. The expression of MRP2 in the oxaliplatin-resistant cells was up-regulated, while those of P-gp and MRP1 had no significant change. CD133 was overexpressed while CD44 level remained unchanged in SW620/L-OHP and LoVo/L-OHP cells.

CONCLUSIONSSW620/L-OHP and LoVo/L-OHP cell lines show a typical and stably resistant phenotype and may be used as research models.

AC133 Antigen ; ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Antibiotics, Antineoplastic ; pharmacology ; Antigens, CD ; metabolism ; Antimetabolites, Antineoplastic ; pharmacology ; Antineoplastic Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Cycle ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Colonic Neoplasms ; metabolism ; pathology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Epirubicin ; pharmacology ; Etoposide ; pharmacology ; Fluorouracil ; pharmacology ; Glycoproteins ; metabolism ; Humans ; Hyaluronan Receptors ; metabolism ; Multidrug Resistance-Associated Proteins ; metabolism ; Organoplatinum Compounds ; pharmacology ; Peptides ; metabolism ; Vincristine ; pharmacology