Search

Purpose: Colorectal cancer is becoming an increasing concern in the middle-aged population of Iran. This study aimed to compare the preliminary results of short-course and long-course neoadjuvant chemoradiotherapy treatment for rectal cancer patients. Materials and Methods: In this clinical trial we recruited patients with rectal adenocarcinoma located from 5 cm to 15 cm above the anal verge. Patients in group I (short-course) received three-dimensional conformational radiotherapy with a dose of 25 Gy/5 fractions in 1 week plus concurrent XELOX regimen (capecitabine 625 mg/m² from day 1-5 twice daily and oxaliplatin 50 mg/m² on day 1 once daily). Patients in group II (long-course) received a total dose of 50-50.4 Gy/25-28 fractions for 5 to 5.5 weeks plus capecitabine 825 mg/m² twice daily. Both groups underwent consolidation chemotherapy followed by delayed surgery at least 8 weeks after radiotherapy completion. The pathological response was assessed with tumor regression grade. Results: In this preliminary report on complications and pathological response, 66 patients were randomized into two study groups. Mean duration of radiotherapy in the group II (long-course) was 5 ± 1 days (range, 5 to 8 days) and 38 ± 6 days (range, 30 to 58 days). The median follow-up was 18 months. Pathological complete response was achieved in 32.3% and 23.1% of patients in the shortcourse and long-course groups, respectively (p = 0.558). Overall, acute grade 3 or higher treatment- related toxicities occurred in 24.2% and 22.2% of patients in group I and II, respectively (p = 0.551). No acute grade 4 or 5 adverse events were observed in either group except one grade 4 hematologic toxicity that was seen in group II. Within one month of surgery, no significant difference was seen regarding grade =3 postoperative complications (p = 0.333). Conclusion: For patients with rectal cancer located at least 5 cm above the anal verge, short-course radiotherapy with concurrent and consolidation chemotherapy and delayed surgery is not different in terms of acute toxicity, postoperative morbidity, complete resection, and pathological response compared to long-course chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Purpose. Insulin like growth factor receptor 1 (IGF-1R) is well-documented to play a key role in radiation response and tumor radiosensitivity, thus offering an attractive clinic drug target to enhance tumor sensitivity to anti-cancer radiotherapy. Material and methods. Human colon carcinoma SW480 cells were transfected with the specific small interference RNA (siRNA) expression vector (pkD-shRNA-IGF-1R-V2) designed to target IGF-1R mRNA. The expression of IGF-1R mRNA and its protein among the transfected and untransfected cells were detected by semi-quantitative RT-PCR and ELISA assay. The changes in cell radiosensitivity were examined by MTT assay. Results. Transfection of mammalian expression vector pkD containing IGF-1R siRNA was shown to reduce IGF-1R mRNA levels by up to 95%. ELISA assay detected a similar inhibition of IGF-1R protein levels in cells transfected with IGF-1R siRNA. SW480 cells transfected with the expression vector for siRNA significantly rendered cells more sensitive to radiation and the highest radiation enhancement ratio was 2.02 ± 0.08. Conclusion. These data provide the first evidence that specific siRNA fragment (pkD-shRNA-IGF-1R-V2) targeting human IGF-1R mRNA is able to enhance colon cancer radiosensitivity. Also results indicated that, combining IGF-1R siRNA and radiation significantly enhances antitumor efficacy compared with either modality alone. [ABSTRACT FROM AUTHOR]

Background and Aims: Colon cancer is the second leading cause of death due to cancer worldwide. Elevated expression of IGF-IR is a frequent genetic abnormality seen in this malignancy. The aim of the study was to examine the anti-growth effects elicited by a decrease in the protein level of IGF-IR by RNA interference (RNAi) in SW480 cells. Methods: A plasmid-based polymerase III promoter system was used to deliver and express short interfering RNA (siRNA) targeting IGF-IR to reduce its expression in SW480 cells. The expression of IGF-1R protein was detected by Western blot. We assessed the effects of IGF-IR silencing on cancer cell growth by a growth curve. Results: We prepared a type of IGF-IR short hairpin RNA (shRNA) expression vector that could efficiently inhibit the expression of IGF-IR in SW480 cells. At 48 h after transfection, the expression inhibition rate was 92 ± 2% at mRNA level detected by RT-PCR analysis. Western blotting detected a similar inhibition of IGF-IR protein levels in cells transfected with pkD-shRNA-IGF-IR-V2. Downregulation of IGF-IR resulted in significant inhibition of cancer cell growth in vitro. The cell growth inhibition rates at 24, 48, and 72 h after pkD-shRNA-IGF-IR-V2 transfection were 32.06, 47.61, and 35.36%, respectively. Conclusions: Our data show that decreasing the IGF-IR protein level in SW480 cells by RNAi could significantly inhibit tumor growth in vitro, implying the therapeutic potential of RNAi on the treatment of colon cancer by targeting overexpression oncogenes such as IGF-IR. IGF-IR may be a potential therapeutic target for human colon cancer. [Copyright &y& Elsevier]