Oncology reports
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The IEV schedule consisted of epirubicin 100 mg/m2 on day 1, etoposide 150 mg/m2 on days 1-3, and ifosfamide 2.5 g/m2 on days 1-3. Patients who proceeded to haematopoietic stem cell transplants (HDTs) received conditioning therapy with BEAM [for the Hodgkin's Lymphoma (HL) and non-Hodgkin's Lymphoma (NHL) groups], or melphalan 100 mg/m2 and mitoxantrone [for the multiple myeloma (MM) patients]. The study consisted of 65 patients with a median age of 53 years: 27 had aggressive NHL, 20 had HL, 7 had indolent NHL, and 11 had MM. ⋯ The median overall survival rate in HL, aggressive NHL, and indolent NHL is 32 (5-60), 16 (2-46), and 14 (4-42) months, respectively. Median EFS is 31 (5-60), 7 (2-46), and 7.5 (4-42) months, respectively. In conclusion, our study confirms that IEV +/- HDT is a well-tolerated and effective salvage treatment for lymphoid malignancies, and that IEV acts as an excellent stem cell mobiliser.
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Comparative Study
Genetic susceptibility of catechol-O-methyltransferase polymorphism in Japanese patients with breast cancer.
Polymorphic catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens. It has been reported that COMT polymorphism is a representative genetic trait related to the susceptibility of an individual to breast cancer. However, there is no consensus concerning the association between breast cancer in Japanese patients and COMT polymorphism. ⋯ Furthermore, the distribution of genotypes in post-menopausal patients with breast cancer showed a significant difference with that of healthy subjects of the same menopausal status (p=0.01). No significant difference was found between the distribution of genotypes and clinicopathological features of the cancer. These results suggest that COMT polymorphism may thus be implicated as a genetic trait affecting the susceptibility of an individual to breast cancer in a Japanese population and be an important genetic risk factor in the development of breast cancer in post-menopausal women.
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Estrogen receptor (ER) and human epidermal growth factor 2 (HER2) are well-investigated molecules and the focus of many breast cancer therapies. There is a group of breast cancers lacking ER and HER2, but it is not fully understood. Treatment for these patients is limited to cytotoxic chemotherapy. ⋯ Overall, the ER(-)/HER2(-) breast cancer showed the highest Ki-67 LI, the most frequent expression of EGFR, p53 and vimentin, as well as the lowest expression of cyclinD1. It is unlikely that gene amplification contributes to EGFR expression. ER(-)/HER2(-) breast cancers have potential in the development of novel therapeutics, including targeted medicines.
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Clusterin has been shown to be implicated in the acquisition of resistant phenotype to various kinds of apoptotic stimuli, including radiation. In bladder cancer, our previous study demonstrated that overexpression of clusterin is closely associated with disease progression and recurrence. The objective of this study was to investigate whether radiation sensitivity was enhanced by suppressing clusterin gene expression with antisense (AS) oligodeoxynucleotide (ODN) in the human bladder cancer KoTCC-1 model. ⋯ In vivo systemic administration of AS clusterin ODN enhanced radiation sensitivity, significantly reducing subcutaneous KoTCC-1 tumor volume in nude mice, compared with that of mismatch control ODN. Moreover, additional administration of cisplatin to this combined regimen further achieved potential antitumor effects on subcutaneous KoTCC-1 tumor growth in nude mice. Collectively, these findings suggest that clusterin acts as a cell survival protein mediating radioresistance through the inhibition of apoptosis, and that inactivation of clusterin using AS technology might offer a novel strategy to improve the outcome of radiation therapy for patients with bladder cancer.
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Randomized Controlled Trial Clinical Trial
Irinotecan combined or alternated with bolus 5-fluorouracil and folinic acid versus the Mayo Clinic regimen in the first-line therapy of advanced colorectal cancer.
The objective of this study was to assess the efficacy and safety of two regimens of irinotecan, combined or alternated with bolus 5-fluorouracil (5-FU) and folinic acid (FA), and the Mayo Clinic regimen as first-line therapy for colorectal cancer (CRC). A total of 152 patients with advanced CRC were randomised, and 149 patients were treated intravenously by irinotecan 125 mg/m2, FA 20 mg/m2 followed by 5-FU 500 mg/m2 bolus, weekly for 4 weeks (arm A, Saltz regimen; n=46), or irinotecan 350 mg/m2 alternating with FA 20 mg/m2/day followed by 5-FU bolus 425 mg/m2/day for 5 days (arm B; n=53), or FA 20 mg/m2/ day followed by 5-FU bolus 425 mg/m2/day over 5 days every 4 weeks (arm C, Mayo Clinic regimen; n=50). Patients were analyzed for tumor response, time to progression, overall survival, safety and quality of life. ⋯ Median times to progression were 7.9, 7.0 and 6.9 months and median survival times were 22.2, 17.0 and 18.2 months for arms A, B and C, respectively, in the intention-to-treat population. The main grade 3-4 adverse events were neutropenia (7%, 39% and 12%) and diarrhea (6%, 21% and 18%). In conclusion, both regimens containing irinotecan were active and well tolerated in patients with advanced CRC.