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.

Neoadjuvant Chemotherapy With Oxaliplatin and Fluoropyrimidine Versus Upfront Surgery for Locally Advanced Colon Cancer: The Randomized, Phase III OPTICAL Trial.

PURPOSE: The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery. PATIENTS AND METHODS: OPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat ≥5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population. RESULTS: Between January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% v 94%), lymph node metastasis (pN1-2: 31% v 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]). CONCLUSION: NAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.

Efficacy of Laparoscopic Primary Repair in the Treatment of Colonic Perforation After Colonoscopy: A Review of 40,127 Patients.

BACKGROUND: In recent years, increasing colonoscopy use increases the incidence of colonic perforation. Colonic perforation during colonoscopy is a rare but extremely serious complication. Traditionally, the management of colonic perforation is explorative laparotomy with bowel resection. Treatment using laparoscopic approach is a novel approach, and has been reported in some recent literatures. Nowadays, the using of laparoscopic primary repair in treatment of colonoscopic perforations has not been confirmed. This study retrospectively reviewed our experiences in treating colonoscopic perforations by laparoscopic primary repair. OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of the laparoscopic primary repair in the treatment of colonic perforations during colonoscopy. METHODS: Between January 2003 and December 2014, data were collected retrospectively on all patients who underwent colonoscopy and compared the recovery parameters and morbidity of patients who underwent laparoscopic primary repair versus those who had open surgery. RESULTS: A total of 40,127 colonoscopies were performed during the study period. There were 24 patients who underwent primary repair [13 underwent laparoscopic surgery (LS) and 8 underwent open surgery (OS)]. There were no demographic differences between the LS and OS groups (P>0.05). Compared with OS group, patients who underwent laparoscopic repair had a significantly shorter incision length (LS: 3.15±0.35 mm vs. OS: 12.60±2.87 mm, P=0.000), fewer blood loss (LS: 28.54±10.82 mL vs. OS: 159.25±46.90 mL, P=0.000), shorter postoperative hospital stay (LS: 8.31±1.93 d vs. OS: 12.38±1.41 d, P=0.000), and shorter postoperative fasting time (LS: 3.38±0.7 d vs. OS: 5.25±0.71 d, P=0.000). The operative time of LS group was a little longer than OS group, but there were no significant differences (LS: 86.31±22.22 min vs. OS: 75.125 ±14.24 min, P=NS). CONCLUSIONS: Laparoscopic primary repair is safe and effective in resolving colonic perforation due to colonoscopy, and it might offer benefits over the open approach.

Near-infrared Hong-Ou-Mandel interference on a silicon quantum photonic chip.

Near-infrared Hong-Ou-Mandel quantum interference is observed in silicon nanophotonic directional couplers with raw visibilities on-chip at 90.5%. Spectrally-bright 1557-nm two-photon states are generated in a periodically-poled KTiOPO4 waveguide chip, serving as the entangled photon source and pumped with a self-injection locked laser, for the photon statistical measurements. Efficient four-port coupling in the communications C-band and in the high-index-contrast silicon photonics platform is demonstrated, with matching theoretical predictions of the quantum interference visibility. Constituents for the residual quantum visibility imperfection are examined, supported with theoretical analysis of the sequentially-triggered multipair biphoton, towards scalable high-bitrate quantum information processing and communications. The on-chip HOM interference is useful towards scalable high-bitrate quantum information processing and communications.

[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.

Estimation of the optimal electrophoretic temperature of DNA single-strand conformation polymorphism by DNA base composition.

To explore the relation between DNA base composition and the optimal single-strand conformation polymorphism (SSCP) electrophoretic temperature (T(s)), we analyzed DNA base composition and T(s) of 24 DNA fragments from different genes and found that T(s) was positively correlative with the ratio of base C/base A. T(s) could be estimated by the formula T(s) = [80 x C/(A+1)]/[2.71 + [C/(A+1)]]. T(s) could be increased dramatically by the complementary sequences in both 5'-and 3'-ends of a DNA single-strand.