MicroRNA-298 determines the radio-resistance of colorectal cancer cells by directly targeting human dual-specificity tyrosine(Y)-regulated kinase 1A.

BACKGROUND: Radiotherapy stands as a promising therapeutic modality for colorectal cancer (CRC); yet, the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission. AIM: To elucidate the role played by microRNA-298 (miR-298) in CRC radio-resistance. METHODS: To establish a radio-resistant CRC cell line, HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period. The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR, and protein expression determination was realized through Western blotting. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay. Radio-induced apoptosis was discerned through flow cytometry analysis. RESULTS: We observed a marked upregulation of miR-298 in radio-resistant CRC cells. MiR-298 emerged as a key determinant of cell survival following radiation exposure, as its overexpression led to a notable reduction in radiation-induced apoptosis. Intriguingly, miR-298 expression exhibited a strong correlation with CRC cell viability. Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A (DYRK1A) as miR-298's direct target. CONCLUSION: Taken together, our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation, thereby positioning miR-298 as a promising candidate for mitigating radio-resistance in CRC.

[Correlations of c-erb-B2, EGFR, and TGF-alpha expression to recurrence of Dukes'A and B colorectal carcinoma].

BACKGROUND & OBJECTIVE: Currently, pathologic stage is the main prognostic indicator of colorectal carcinoma, but the current staging system is insufficient to predict the risk of recurrence or the need for adjuvant treatment for the patients with Dukes'A and B disease. Biologic prognostic markers may supplement the staging system and provide a basis for the decision of therapeutic strategies according to individual tumor biology. This study was to investigate the correlations of c-erbB-2, epithelial growth factor receptor (EGFR), and transforming growth factor-alpha (TGF-alpha) expression to recurrence of Dukes'A and B colorectal carcinoma. METHODS: The expression of c-erbB-2, EGFR and TGF-alpha in 26 specimens of Dukes'A and 62 specimens of Dukes'B colorectal adenocarcinoma was detected by SP immunohistochemistry. Of the 88 patients underwent curative resection between 1989 and 1999, 44 had recurrence, and 44 had not. The patients were followed up for at least 5 years or till recurrence. The tumor location, Dukes staging, age, sex, and depth of bowel wall invasion matched as closely as possible between the 2 groups. RESULTS: The overexpression rate of c-erbB-2 was higher in recurrence group than in non-recurrence group (43.2% vs. 25.0%, P=0.072); the overexpression rates of EGFR and TGF-alpha were significantly higher in recurrence group than in non-recurrence group (63.6% vs. 27.3%, P=0.001; 65.9% vs. 43.2%, P=0.032). The co-overexpression rate of EGFR and TGF was significantly higher in recurrence group than in non-recurrence group (36.4% vs. 11.4%, P=0.006). Multivariate analysis showed that the overexpression of EGFR was associated with postoperative recurrence of colorectal carcinoma. CONCLUSION: The expression of EGFR may be associated with postoperative recurrence of Dukes'A and B colorectal carcinoma.

Outcome of surgical management of the bladder in advanced colorectal cancer.

BACKGROUND: To evaluate morbidity, mortality, and long-term survival in patients undergoing partial or total cystectomy during en bloc resection for locally advanced colorectal cancer. METHODS: This study retrospectively evaluated the outcome of combined bladder resection for colorectal cancer in our department. RESULTS: Patients (n=33) with colorectal tumors adherent to the bladder were followed. Overall morbidity was 11/33 (33.3%). Histological staging demonstrated inflammatory adhesion in 54.5% (18/33) and invasion in 45.6% (15/33). Morbidity was significantly higher in those that had undergone total cystectomy than in those that had undergone partial cystectomy (4/5 vs 7/28, P=0.033). The local recurrence has no difference the between total cystectomy group and the partial cystectomy group (1/5 vs 8/28, P=1.000). Overall 5-year survival rate was 39.4% (13/33). Mean survival time was 46.6875 month. There was no difference in 5-year survival between patients with inflammatory adhesion vs those with tumorous infiltration between colorectal tumor and bladder (P=0.7389). CONCLUSION: Survival after surgery for colorectal cancer is not influenced by the need to excise part or all of the urinary bladder in case it is contiguous to a colorectal tumor. Experienced surgeons in urology and colon and rectal surgery should be left to decide on the surgical options to be employed.

[Experimental study on antitumor effects of Shen Qi Jin Kang (SQJK)].

BACKGROUND & OBJECTIVE: SHEN QI JIN KANG (SQJK) capsule is a complex preparation, consisting of effective components extracted from radix astragali, ginseng, curcuma, etc. It has been demonstrated to be able to decrease tumor volume, increase life quality and prolong survival time in clinic application. The study was to investigate the antitumor effects of SQJK capsule in vivo and in vitro, and further explore the possible mechanisms. METHODS: The proliferation of cancer cells treated with SQJK was measured by MTT assay in twelve cell lines; cell apoptosis was observed under an electric microscopic and detected by flow cytometry in MCF-7 and MA891 cells; altered telomerase activity in A549 cells was examined by a telomerase activity detection kit. Furthermore, the inhibitory effect of SQJK on tumors was also surveyed in vivo by using mice and nude mice models bearing transplanted tumors. RESULTS: Inhibitory concentration 50% (IC(50)) of SQJK on A549, U251, MCF-7, Ketr-3, EJ, and A2780 cells was 30.954 microg/ml, 31.746 microg/ml, 37.220 microg/ml, 40.366 microg/ml, 41.398 microg/ml, and 45.083 microg/ml, respectively. Typical sub-G1 peaks, indicating the occurrence of apoptosis, were revealed in MA891and MCF-7 cells treated with SQJK. Morphological changes including cell shrinkage and condensation of chromosomes were observed. The telomerase activity of A549 was inhibited after 48 h of SQJK treatment. SQJK 1.8 g/kg inhibited the weights of transplanted tumors (MA891, H22, S180 in mice and PC-3 (M), MCF-7 and Ketr-3 in nude mice) by 50.84%, 48.91%, 40.88%, 62.50%, 47.83% and 30.06%, while SQJK 3.6 g/kg inhibited the weights by 56.49%, 59.62%, 55.70%, 70.76%, 58.66% and 50.18%, respectively. CONCLUSION: SQJK has demonstrated antitumor bioactivity both in vitro and in vivo, which may be related to its effects of inducing apoptosis and decreasing telomerase activity.

[Expression of P33ING1, P53 and their relationship with apoptosis in anal canal carcinoma].

OBJECTIVE: To explore the expressions of P33ING1, P53 and their relationships with apoptosis in anal canal carcinoma (ACC). METHODS: The expressions of P33ING1, P53 proteins were measured by immunohistochemistry method (SP method), and apoptosis was detected in 42 cases with ACC, 36 cases with anal canal adenoma (ACA) or anal canal papilloma (ACP), and 40 cases with paraanal inflammatory mass(PAIM). RESULTS: The positive expression rates of P33ING1 and P53 proteins were 40.5% (17/42), 97.2% (35/36) and 97.5% (39/40), 50.0% (21/42), 22.2% (8/36) and 27.5% (11/40) respectively, and the average apoptosis indexes(AI) were (10.27+/- 1.23) per thousand, (42.75+/- 0.98) per thousand and (42.67+/- 1.04) per thousand respectively in ACC, ACA or ACP and PAIM. There were significant differences in the positive expression rates of P33ING1, P53 and apoptosis index between ACC and the other two groups respectively (P< 0.05). Among 21 cases of ACC with positive expression of P53 protein,there were 18 cases with P33ING1 negative expression. CONCLUSIONS: P33ING1 expression decrease in ACC, which may play an important role in the carcinogenesis and progression of ACC. P33ING1 and P53 may have an synergistic effect of suppressing cell growth and accelerating cell apoptosis.

Genetic alterations and expression of inhibitor of growth 1 in human sporadic colorectal cancer.

AIM: To explore the effect and significance of inhibitor of growth 1 (ING1) gene in carcinogenesis and progression of human sporadic colorectal cancer. METHODS: mRNA expression, mutation, and loss of heterozygosity (LOH) of ING1 gene in 35 specimens of sporadic colorectal cancer tissues and the matched normal mucous membrane tissues were detected by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), PCR-single strain conformation polymorphism (PCR-SSCP) and PCR-simple sequence length polymorphism (PCR-SSLP) using microsatellite markers, respectively. RESULTS: The average ratios of light intensities of p33(ING1b) and p47(ING1a) mRNA expression in the cancerous tissues were significantly lower than those in normal tissues. The difference between the two mRNA splices was not significant in the matched tissues. In addition, the ratios of light intensities of p33(ING1b) and p47(ING1a) mRNA expression in the cancerous tissues of Dukes' stages C and D were significantly lower than those in cancerous tissues of Dukes' stages A and B. However, no mutation of ING1 gene was detected in all 35 cases; only 4 cases of LOH (11.4%) were found. CONCLUSION: p33(ING1b) and p47(ING1a) mRNA expressions are closely related with the carcinogenesis and progression of human sporadic colorectal cancer. No mutation of ING1 gene is found, and there are only few LOH in sporadic colorectal cancers. These might not be the main reasons for the down regulation of ING1 expression. Its low expression may happen in transcription or post-transcription.

[Clinical analysis of anorectal malignant melanoma].

OBJECTIVE: To summarize the clinicopathological characteristics of primary anorectal malignant melanoma (AMM). METHODS: Clinical data of nine patients with AMM were reviewed retrospectively from January 1999 to March 2005. RESULTS: Anorectal malignant melanoma had a female predominance. The average age was 56 years old and average course of disease was 5.8 months. The onset of symptom was hematochezia, then anus prolapses. 94.7% of patients had AMM within 5 cm from anus margin; the average tumor size was (3.3+/- 2.1) cm. The polyp and ulcer were most common types. More than a half (54.5%) of the tumor was movable, 19.1% smooth surfaced, 6.6% soft textured. Synchronous metastasis was found in 14.0% of the patients, the first common metastasis was found in liver, the secondary was superficial inguinal lymph node metastasis. Half of the patients were misdiagnosed,and over 50% of patients were misdiagnosed as benign disease. Mile's operation was performed in most of patients (63%), while anal resection was performed in 30% of the patients. CONCLUSIONS: Anorectal malignant melanoma is often misdiagnosed,surgical procedure is the first choice for patients with AMM.

[Multivariate regression analysis of recurrence following curative surgery for colorectal cancer].

BACKGROUND & OBJECTIVE: Recurrence is a very important prognostic factor for colorectal cancer patients after operation. The selection of patients for individualized follow-up and adjuvant therapy after curative resection of colorectal carcinoma depends on prognostic factors for recurrence. The objective of this study was to investigate the clinicopathologic factors related to recurrence following curative surgery for colorectal cancer. METHODS: The clinicopathologic factors and follow-up data of 692 cases of colorectal cancers after surgical treatment from 1991 to 1999 were retrospectively analyzed by univariate and multivariate methods. RESULTS: The overall 3-year and 5-year survival rates were 33.1% and 19.7% in recurrent group, and 92.8% and 86.1% in nonrecurrent group, respectively. Univariate analysis showed that Dukes' stage, lymph node metastasis, tumor location, histological differentiation, gross findings and depth of bowel wall invasion were significantly associated with recurrence after operation. Multivariate analysis showed that lymph node metastasis and tumor location were prognostic factors for recurrence after operation. In separate analysis of distant metastasis and local recurrence with multivariate method, lymph node metastasis was an prognostic variable for both distant metastasis and local recurrence. Depth of bowel wall invasion was associated with distant metastasis, and tumor location was associated with local recurrence. CONCLUSION: Lymph node metastasis is the most important prognostic factor for recurrence or distant metastasis and local recurrence after operation for the patients with colorectal carcinoma. Depth of bowel wall invasion is an important prognostic factor for distant metastasis. Rectal cancer patients should be considered to have additional risks for local recurrence.