Chemotherapeutic Effects (chemotherapeutic + effects)

Distribution by Scientific Domains


Selected Abstracts


Histologic survey of neuroblastomas after intensive induction chemotherapy,

PEDIATRIC BLOOD & CANCER, Issue 5 2005
Yoshiaki Tsuchida MD
Abstract Background Histology after intensive induction chemotherapy is expected to become a beacon indicating when and how extensively radical surgery and lymph node dissection should be performed in advanced neuroblastoma. A thorough histologic review of surgical specimens was undertaken. Procedure All specimens from 34 patients who were pretreated intensively (,3 cycles) with recent chemotherapy were reviewed. Thirty patients were >12 months of age with stage 3/4 disease, and 4 were <12 months of age but with MYCN -amplified stage 4 diseases. After 3 to 7 cycles (mean, 4.3 cycles) of induction chemotherapy, patients underwent radical surgery of the primary tumor and lymph nodes in all retroperitoneal sections. A single pathologist reviewed all of the specimens, and histologic chemotherapeutic effects were graded as: (+++), <1% viable tumor; (++), 1%,10% viable tumor; (+), 11%,50% viable tumor; (±), 51%,90% viable tumor; and (,), >91% viable tumor. Results Grade (+++) effects were observed in 56% of patients treated with the new regimens, whereas grade (+++) was seen in only 20% treated with regimens before 1991. Operation time and blood loss were 7 hr and 6 min (P,=,0.087) and 646 ml (P,=,0.064), respectively, in patients with >5 cycles (mean, 5.3 cycles) of chemotherapy, while they were 7 hr and 50 min and 1,168 ml, respectively, in those with approximately 3 cycles (mean, 3.2 cycles). Histologically, metastases were found in the contralateral nodes beyond the aorta in 92% of those whose tumor originated on the left, and in 80% of those with tumors occurring on the right. Conclusions Five cycles of induction chemotherapy did not improve histologic chemotherapeutic effects, but helped to facilitate a shorter operation time and less blood loss than 3 cycles of chemotherapy. Surgery after 5 cycles of 98A3 also appears to be easier to perform than that after 3 cycles of A1/new A1. Only 14% of the children treated before 1985 with the St. Jude protocols experienced grade (+++) chemotherapeutic effects, and 22% of the patients treated before 1991 with regimen A1, or new A1 of the Study Group of Japan showed grade (+++) effects, whereas 56% of the patients treated after 1991 with either regimen A3 or 98A3 exhibited grade (+++) chemotherapeutic effects. Histologic chemotherapeutic effects were roughly parallel with a good prognosis. Pediatr Blood Cancer © 2005 Wiley-Liss, Inc. [source]


Preclinical evaluation of antisense bcl -2 as a chemosensitizer for patients with gastric carcinoma

CANCER, Issue 10 2004
Ph.D., Ryungsa Kim M.D.
Abstract BACKGROUND Because bcl -2 is a critical factor for anticancer drug-induced apoptosis, the authors conducted a preclinical evaluation of antisense (AS) bcl -2 as an enhancer of the chemotherapeutic effect in the treatment of patietns with gastric carcinoma. METHODS AS bcl -2 was used with 18-mer phosphorothiated oligonucleotides in the MKN-45 gastric carcinoma cell line. Drug sensitivity in vitro was evaluated using the methyl-thiazoldiphenyl tetrazolium assay, and antitumor effects in vivo were evaluated using the nude mouse xenograft. Apoptosis was determined with the terminal deoxyuridine triphosphate nick-end labeling assay. AS bcl -2 in vitro was treated with lipofectin, whereas it was administered intraperitoneally for 6 consecutive days twice every 2 weeks in vivo. Anticancer drugs were administered intraperitoneally four times per week. RESULTS bcl -2 was down-regulated to 60% of its initial value after treatment with 1.0 ,M AS bcl -2 compared with the controls of random and mismatched oligonucleotides. Drug sensitivity to doxorubicin, cisplatin, and paclitaxel (TXL) was increased 3,4-fold when used in combination with AS bcl -2, which was determined with 50% inhibitory concentration values, compared with the control group. Increased drug sensitivity was associated with apoptosis, which increased in Bax and poly-adenosine diphosphate (ADP-ribose) polymerase and decreased in phosphorylated Akt (pAkt). The antitumor effect of cisplatin and TXL in vivo was enhanced significantly in combination with AS bcl -2. Down-regulation of bcl -2 was observed on Day 4 after the treatment with AS bcl -2. CONCLUSIONS Combination treatment with AS bcl -2 and anticancer drugs, including cisplatin and TXL, may be a new strategy for enhancing chemotherapeutic effects in the treatment of gastric carcinoma. Cancer 2004. © 2004 American Cancer Society. [source]


Establishment of six new human biliary tract carcinoma cell lines and identification of MAGEH1 as a candidate biomarker for predicting the efficacy of gemcitabine treatment

CANCER SCIENCE, Issue 4 2010
Hidenori Ojima
The aim of this study was to establish new biliary tract carcinoma (BTC) cell lines and identify predictive biomarkers for the potential effectiveness of gemcitabine therapy. Surgical specimens of BTC were transplanted directly into immunodeficient mice to establish xenografts, then subjected to in vitro cell culture. The gemcitabine sensitivity of each cell line was determined and compared with the genome-wide gene expression profile. A new predictive biomarker candidate was validated using an additional cohort of gemcitabine-treated BTC cases. From 55 BTC cases, we established 19 xenografts and six new cell lines. Based on their gemcitabine sensitivity, 10 BTC cell lines (including six new and four publicly available ones) were clearly categorized into two groups, and MAGEH1 mRNA expression in the tumor cells showed a significant negative correlation with their sensitivity to gemcitabine. Immunohistochemically, MAGEH1 protein was detected in three (50%) out of six sensitive cell lines, and four (100%) out of four resistant cell lines. In the validation cohort of gemcitabine-treated recurrence cases, patients were categorized into "effective" and "non-effective" groups according to the RECIST guidelines for assessment of chemotherapeutic effects. MAGEH1 protein expression was detected in two (40%) out of five "effective" cases and all four (100%) "non-effective" cases. We have established a new BTC bioresource that covers a wide range of biological features, including drug sensitivity, and is linked with clinical information. Negative expression of MAGEH1 protein serves as a potential predictive marker for the effectiveness of gemcitabine therapy in BTC. (Cancer Sci 2010; 101: 882,888) [source]