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Objective:To study the expressions of heat shock protein (HSP) 90α and HSP90β in colorectal cancer and paracancer tissues, and to investigate the relationships between HSP90α, HSP90β and clinicopathological features of colorectal cancer patients, and to analyze their correlation.Methods:The tumor tissues and paracancer tissues of 117 patients with colorectal cancer were selected from the Department of Gastrointestinal Surgery, Third Affiliated Hospital of Shandong First Medical University from January 2016 to December 2020. The expression levels of HSP90α and HSP90β were detected by immunohistochemistry, and the relationships between the two proteins and clinicopathological features and the correlation of their expressions were analyzed.Results:The positive expression rates of HSP90α in colorectal cancer tissues and paracancer tissues were 74.4% (87/117) and 12.0% (14/117) , and there was a statistically significant difference ( χ2=92.83, P<0.001) . The positive expression rate of HSP90β in colorectal cancer tissues and paracancer tissues was 61.5% (72/117) and 10.3% (12/117) , and there was a statistically significant difference ( χ2=66.86, P<0.001) . The expression of HSP90α was correlated with tumor location ( χ2=8.67, P=0.003) , vascular invasion ( χ2=8.68, P=0.003) , lymph node metastasis ( χ2=8.52, P=0.004) , T stage ( χ2=21.07, P<0.001) , N stage ( χ2=11.94, P=0.003) , M stage ( χ2=5.37, P=0.020) , pathological stage ( χ2=25.64, P<0.001) . The expression of HSP90β was correlated with lymph node metastasis ( χ2=4.03, P=0.045) , T stage ( χ2=11.09, P=0.007) , N stage ( χ2=6.56, P=0.038) , M stage ( χ2=12.43, P<0.001) , pathological stage ( χ2=17.34, P=0.001) . There was a positive correlation between the expressions of the two proteins in colorectal cancer tissues ( r=0.42, P<0.001) . Conclusion:The expressions of HSP90α and HSP90β in colorectal cancer tissues are significantly higher than those in paracancer tissues, and they are related to lymph node metastasis and pathological stage. There is a positive correlation between the two proteins, which may be involved in the occurrence and development of colorectal cancer and are expected to become new tumor markers.
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Objective:To investigate therapeutic efficacy and mechanisms of action of oncolytic agent derived from herpes simplex virus type 2 (oHSV2) in a xenograft mouse model bearing CT26 colorectal cancer. Methods:BALB/c mice were subcutaneously inoculated with CT26 cells to establish a xenograft mouse model of colorectal cancer. 1) After intratumoral administration of oHSV2, enzyme-linked im-munosorbent assay was used to determine granulocyte-macrophage colony-stimulating factor (GM-CSF) expression levels in the blood. 2) Model mice were divided into three groups:PBS group (negative control), oHSV2 group, and 5-fluorouracil (5-FU) group (positive control). After drug administration, drug effectiveness was evaluated on the basis of weight, tumor volume, general state, and survival time. 3) Cells from the draining lymph nodes (TDLN) and tumor were surgical y removed and used to quantify mature dendritic cel s (DCs) and T lym-phocytes by flow cytometry. Result:1) In the CT26 xenograft model, level of GM-CSF continuously elevated. At day 8, peak value was attained in the blood at concentration of 3150±327.1 pg/mL. Then, GM-CSF expression gradually reduced as time progressed. 2) In in vivo study, both oHSV2 and 5-FU exerted antitumor effects relative to PBS group (50 days vs. 36 days, P0.05). Skin of virus injection region did not present necrosis and ulceration. 3) In the TDLN, the frequency of DC was increased when treated with oHSV2 compared with the control group (6.49%vs. 3.73%, P<0.01). Similarly, the percentage of CD4+and CD8+T-cel s from the oHSV2-treated group was signifcantly higher than mock-treated tumors (15%vs. 8.57%, P<0.01;8.19%vs. 5.15%, P<0.01). However, number of cells in the 5-FU group were significantly reduced with respect to that of the negative group (al P<0.01). Conclusion:oHSV2 exerted potent antitumor effects in a murine colorectal cancer model. Compared with 5-FU, oHSV2 treatment caused fewer side effects. Such antitumor effect may be induced by stimulation of immune activity by GM-CSF production.
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Objective To compare the short-term efficacies of laparoscopic intersphincteric resection (ISR) and laparotomy for ultra-low rectal cancers by Meta-analysis.Methods We searched case-control trials that compared clinical outcomes of laparoscopic ISR and laparotomy from PubMed, EMBase, Ovid, CNKI and Wanfang database.Relevant published and unpublished data and conference papers were also retrieved.Two reviewers independently assessed the qualities of the included studies.Meta-analysis was performed by using of RevMan5.2 software.Results A total of 5 trials with 552 cases were included.The results of Meta-analysis showed that in terms of blood loss of the operation [mean difference (MD) =-65.42, 95％ CI:-93.45--37.38, Z=4.57, P＜0.000 01], flatus passage time (MD=-0.96, 95％CI:-1.45--0.47, Z=3.83, P=0.000 1) and hospital stays (MD=-1.69,95％CI:-2.19--1.19, Z=6.63, P＜0.00001),laparoscopic ISR were significantly superior than those of laparotomy, with significant differences.In terms of operation time (MD =6.61,95 ％ CI:-21.29-34.51, Z =0.46, P =0.64), the positive rate of circumferential resection margin (OR =1.01, 95％ CI: 0.37-2.80, Z =0.02, P =0.98) and postoperative morbidity (0R=0.73, 95％ CI: 0.45-1.20, Z =1.23, P =0.22), there were no significant differences in the two groups.However, laparotomy may clean more numbers of lymph nodes than those of laparoscopic ISR (MD =-1.16, 95％CI:-2.14--0.18, Z =2.31, P =0.02), with significant difference.Conclusion The shortterm efficacy of laparoscopic ISR is superior than that of laparotomy in the treatment of ultra-low rectal cancer.
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Virus-based anti-tumor therapies are novel biological treatments. Viral vectors can infect tumors to kill cancers directly (on-colysis), act as cancer vaccines to activate the immune system, and deliver genes with anti-tumor activity to the cancer cells. Genetic engineering has been applied to viruses to achieve more specific and efficient cancer treatment. Simultaneously, a reasonable combi-nation of viral vectors and existing anti-tumor therapy can improve the therapeutic effect. Consequently, virus-based therapy is expect-ed to serve as an effective anti-tumor strategy. We reviewed recent studies on the anti-tumor viral therapy of colorectal carcinoma.
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At present,the main treatment methods of the patients with advanced colorectal cancer include surgery,chemotherapy,radiotherapy,targeted therapy,physical ablation and immunotherapy,but the chemotherapy is still the main treatment.The emergence of new chemotherapy drugs and the combination of radiotherapy,chemotherapy and targeted therapy in clinical have improved curative effect for the patients with advanced colorectal cancer.In order to better improve the quality of life,reduce side effects and obtain the best effect,now the individual multidisciplinary treatment has become an inevitable trend in the treatment of advanced colorectal cancer in clinical.
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<p><b>OBJECTIVE</b>To compare the short-term efficacy of laparoscope-assisted transanal total mesorectal excision (LA-taTME) and conventional laparoscopic TME (LTME) for rectal cancer by meta-analysis.</p><p><b>METHODS</b>Clinical studies that compared clinical outcomes of LA-taTME and LTME were searched from form PubMed, Embase, Ovid, CNKI and Wanfang database before January 2016. Two reviewers independently screened the articles and assessed the quality of the included studies by using the MINORS standard which involves 12 items. The score is 0-2 for each item and the maximum score is 24, and the ideal global score should be above16. RevMan 5.3 software was used for meta-analysis and outcome measures included operation time, hospital stay, number of harvested lymph node, rate of conversion, positive rate of circumferential resection margin and the rate of incomplete mesorectum.</p><p><b>RESULTS</b>Seven studies were included in the analysis, and the score of all the studies was more than 16 points. A total of 479 patients (208 in LA-taTME, 271 in LTME) were enrolled. There were no significant differences in terms of age, sex, tumor location and clinical stage between two groups (all P>0.05). Results of meta-analysis showed that LA-taTME had lower rate of incomplete mesorectum (OR=0.29, 95% CI:0.10 to 0.84, P=0.02), lower rate of complications (OR=0.59, 95% CI:0.35 to 0.97, P=0.04) and shorter hospital stay (MD=-1.66, 95% CI:-3.22 to -0.11, P=0.04) than those of LTME, with significant differences. In terms of operation time (MD=-14.49, 95% CI:-37.87 to 8.90, P=0.22), number of harvested lymph node (MD=-0.45, 95% CI:-1.98 to 1.08, P=0.56), the rate of conversion (OR=0.31, 95% CI:0.08 to 1.24, P=0.10) and positive rate of circumferential resection margin (OR=0.43, 95% CI:0.17 to 1.04, P=0.06), there were no significant differences between two groups.</p><p><b>CONCLUSION</b>Compared to LTME, LA-taTME has similar short-term efficacy for rectal cancer, but it can reduce the rate of complications and rate of incomplete mesorectum.</p>
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Humans , Abdomen , Digestive System Surgical Procedures , Methods , Laparoscopes , Laparoscopy , Length of Stay , Operative Time , Rectal Neoplasms , General SurgeryABSTRACT
<p><b>OBJECTIVE</b>To compare the clinical short-term safety and efficacy between robotic right colectomy (RRC) and laparoscopic right colectomy(LRC) with meta-analysis.</p><p><b>METHODS</b>A search of the Medline, Embase, Ovid, CNKI and WANFANG databases was performed for studies comparing clinical or oncologic outcomes of RRC with LRC before July 2014. The RevMan 5.2 software was used for meta-analysis. The operative time, estimated blood loss, length of hospital stay, conversion rate to open surgery, postoperative complications and related outcomes were evaluated.</p><p><b>RESULTS</b>Six studies including 217 RRC cases and 400 conventional LRC cases were enrolled and analyzed. The meta-analysis showed that RRC had longer operative time (MD=48.05, 95% CI: 26.52 to 69.57, P<0.01), less estimated blood loss (MD=-17.74, 95% CI: -28.32 to -7.16, P=0.01), faster postoperative intestinal peristalsis recovery (MD=-0.79, 95% CI: -1.10 to -0.48, P<0.01), lower postoperative overall complications (OR=0.63, 95% CI: 0.42 to 0.93, P=0.02). Conversion rate and postoperative hospital stay between the two groups were not significantly different (all P>0.05).</p><p><b>CONCLUSION</b>Compared to LRC, RRC is associated with less estimated blood loss, faster postoperative intestinal peristalsis recovery, lower postoperative overall complications, and longer operative time.</p>
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Humans , Colectomy , Laparoscopy , Length of Stay , Operative Time , Postoperative Complications , Postoperative Period , Robotic Surgical ProceduresABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression level of high mobility group box-1 (HMGB1) in human colorectal cancer and its relation with different clinicopathological characteristics and prognosis of colorectal cancer patients.</p><p><b>METHODS</b>Immunohistochemical method was used to detect the HMGB1 expression in tissue samples of 86 colorectal cancer patients and 32 normal colorectal tissue samples. Positive rates of HMGB1 expression were compared among different clinicopathological characteristics. Relation of HMGB1 expression with survival was analyzed.</p><p><b>RESULTS</b>HMGB1 expression was mainly in colorectal cancer cell nucleus, with a few appearance of co-expression in nucleus and cytoplasm. Positive rate of HMGB1 expression in normal tissues was significantly lower than that in colorectal cancers [9.4% (3/32) vs. 66.3% (57/86), P=0.000], and it was much higher in large cancers, lower differentiation, invasion to outside serosa, advanced clinical stage and lymph node metastasis (all P<0.05), but was similar in terms of age and gender (P>0.05). Survival analysis showed that 3-year survival rate of patients with positive HMGB1 expression was significantly lower as compared to those with negative HMGB1 expression (56.1% vs. 85.7%, P=0.021), meanwhile it was significantly lower in patients with co-expression in nucleus and cytoplasm as compared to those with simple nuclear expression (41.4% vs. 75.0%, P=0.013).</p><p><b>CONCLUSIONS</b>HMGB1 expression in colorectal cancer is high, and its positive rate increases with the low differentiation, invasion and metastasis. HMGB1 co-expression in nucleus and cytoplasm indicates poor prognosis of colorectal cancer patients.</p>
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Humans , Cell Nucleus , Colorectal Neoplasms , HMGB1 Protein , Lymphatic Metastasis , Prognosis , Survival Analysis , Survival RateABSTRACT
Objective To explore the clinical efficacy of image-guided 125I radioactive seed interstitial implantation therapy for unresectable pancreatic cancer.Methods 25 patients with unresectable pancreatic cancer evaluated by retrospective follow-up were enrolled in this study,13 patients received radioactive seeds implantation while 12 patients were given non-surgical treatment.We observe and compare the clinical benefits,objective curative effect,complications,adverse reaction,survival between the two groups of patients.Results Compared with the non-surgical treatment group,the clinical benefit rate in the radiotherapy seed implantation group was 92％ (12/13) while that of the non-surgical group was 42％ (5/12),the difference was of statistically significance.The numbers of cases evaluated as effective were 6 (46％) and 4 (33 ％) respectively,the difference was not statistical significant (x2 =0.427,P ＞ 0.05);The radioactive seed implantation group had no serious postoperative complications;3 cases who received subsequent chemotherapy in radioactive seed implantation group(23％,3/13) and 3 cases in non-surgical treatment group(25％,3/12)suffered from serious adverse reactions,the difference was of no statistical significance(x2 =0.013,P ＞0.05);Comparing the survival rate between the two groups,x2 =0.001,P =0.969,the difference was of no statistical significance.Conclusions The therapy of 125I radioactive seed implantation for unresectable pancreatic cancer significantly relieves cancer caused pain and improves quality of life.
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<p><b>OBJECTIVE</b>To inquire into the influence of silencing HMGB1 expression by small interfering RNA (siRNA) on cell growth, proliferation, invasion and metastasis of colorectal cancer LoVo cells both in vitro and in vivo.</p><p><b>METHODS</b>Lentivirus-mediated HMGB1 siRNA was transfected into LoVo cells to silence the HMGB1 expression. The HMGB1 mRNA and protein expression after siRNA transfection was detected by RT-PCR and Western blot. MTT assay was used to observe the cell proliferation and to draw a growth curve. Cell cycle was measured by flow cytometry. The ability of invasion and speed of cell migration were evaluated by transwell chamber invasion and cell scratch assay. The influence of HMGB1 silencing on the proliferation of LoVo cells in vivo was observed in LoVo tumor-bearing nude mice.</p><p><b>RESULTS</b>Lentivirus-mediated siRNA was successfully transfected into colorectal cancer cell line LoVo. The expression of HMGB1 mRNA and protein in the HMGB1-siRNA group were 0.24±0.04 and 0.21±0.03, respectively. Compared with the HMGB1-siRNA-Neg group (0.82±0.13, 1.15±0.18) and control group (0.93±0.15, 1.21±0.20), the difference was significant (P<0.05). MTT assay showed that the cell proliferation in the HMGB1-siRNA group was significantly inhibited when compared with that in the HMGB1-siRNA-Neg group and control group (P<0.05). Flow cytometry showed that the proliferation index (PI) of HMGB1-siRNA group was 38.27±1.32, significantly lower than 54.66±1.74 in the HMGB1-siRNA-Neg group and 57.43±1.29 in the control group (P<0.05). The transwell assay showed that the number of penetrated cells in the HMGB1-siRNA group was 14.0±3.5, significantly lower than 51.0±6.7 in the HMGB1-siRNA-Neg group and 68.0±5.3 in the control group (P<0.05). Similarly, the scrape wound recovered significantly slower in the HMGB1-siRNA group (83.61±23.21) µm than that in the other two groups (202.86±46.46) µm and (214.58±57.38) µm(P<0.05). The nude mouse xenograft tumor experiment showed that the final tumor volume was (521±34) mm3 in the HMGB1-siRNA group, significantly smaller than that in the HMGB1-siRNA-Neg group of (763±46) mm3 and control group of (802±51) mm3 (P<0.05).</p><p><b>CONCLUSIONS</b>Lentivirus-mediated HMGBl-siRNA can effectively inhibit the HMGB1 expression in colorectal cancer LoVo cells both in vitro and in vivo. HMGB1 gene silencing can slow the growth of colorectal cancer cells, extend the cell proliferation cycle, decrease their invasion and migration, and significantly inhibit the growth of xenograft tumor in nude mice.</p>
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Animals , Humans , Mice , Cell Cycle , Cell Line, Tumor , Cell Movement , Cell Proliferation , Colorectal Neoplasms , Pathology , Therapeutics , Gene Expression , HMGB1 Protein , Genetics , Metabolism , In Vitro Techniques , Lentivirus , Mice, Nude , Neoplasm Invasiveness , RNA Interference , RNA, Messenger , Metabolism , RNA, Small Interfering , Therapeutic Uses , Transfection , Tumor BurdenABSTRACT
<p><b>OBJECTIVE</b>To investigate the association between expression of hepatocyte growth factor(HGF) and its receptor c-Met and primary colorectal cancers with synchronous liver metastases.</p><p><b>METHODS</b>A total of 30 colorectal cancer patients with synchronous liver metastasis underwent radical resection of primary cancer and liver cancer in our hospital from June 2001 to June 2010. According to lymphatic metastasis, patients were divided into group A(T1~T4N1~N2M1, n=21) and group B(T1~T4N0M1, n=9). Twenty-one matched T1~T4N1~N2M0 and 21 T1~T4N0M0 patients were used as the controls of group A. Nine matched T1~T4N0M0 patients were used as the controls of group B. Expressions of HGF and c-Met in tissues of primary loci, liver loci and metastatic loci were detected by immunohistochemistry.</p><p><b>RESULTS</b>In primary loci of group A, the positive rate of HGF was significantly higher than that of T1~T4N1~N2M0 and T1~T4N0M0 controls [71%(15/21) vs. 43%(9/21), 19%(4/21), all P<0.05]. The positive rate of c-MET[90%(19/21)] was significantly higher compared to T1~T4N0M0 control[43%(9/21), P<0.05], while not significantly different compared to T1~T4N1~N2M0 control[86%(18/21)]. In primary loci of group B, positive rates of HGF and c-MET were not significantly different as compared to T1~T4N0M0 control[6/9 vs. 5/9, P>0.05; 8/9 vs. 6/9, P>0.05]. Concordance of HGF and c-MET expression in group A among primary loci, lymphatic metastatic loci and hepatic metastatic loci was 81%(17/21) and 76%(16/21).</p><p><b>CONCLUSION</b>HGF-c-Met may play a role in colorectal cancer patients with synchronous liver metastasis who have regional lymphatic metastasis, and may have few effect on colorectal cancer with synchronous liver metastasis without corresponding lymphatic metastasis.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Colorectal Neoplasms , Metabolism , Pathology , Hepatocyte Growth Factor , Metabolism , Liver Neoplasms , Lymphatic Metastasis , Proto-Oncogene Proteins c-met , MetabolismABSTRACT
After lower rectal anterior resection, patients often experience defecation disorders such as increased stool frequency and fecal incontinence. Researches have shown that these disorders may be resulted from pathophysiological consequences such as impaired neorectal compliance, decreased internal anal sphincter function, direct damage or injury of the nervous supply and the loss of rectal sensation.
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Objective:To explore the clinical and pathological features of familial gastric cancer, and to get the early discovery and early treatment of it.Methods:Two kindreds of familial gastric cancer were followed up and their clinical and pathological features were analyzed.Results:Six patients with gastric cancer were found in the 2 kindreds.Autosomal dominant inheritance was observed in these cases.clinical and pathological features of familial gastric cancer were showed according to the document analysis:early onset;poor prognosis;patients suffer simultaneous or metachronous carcinoma;CDH1 germline mutation carriers had higher penetrance;pathologically, tumors are mostly diffuse infiltrative type with lower differentiated degree and earlier metastasis to lymphnodes;in one kindred,the sites of the lesions were relatively consistent.Conclusion:Familial gastric cancer has particular clinical and pathological features:early onset;poor prognosis;patients suffer simultaneous or metachronous carcinoma;CDH1 germline mutation carriers have higher penetrance; pathologically,tumors are mostly diffuse infiltrative type with lower differentiated degree and earlier metastasis to lymphnodes.
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Objective To investigate the characteristic,diagnosis,clinical staging, treatment and clinical prognosis of occult breast carcinoma (OBC). Method Forty-six cases of OBC were analyzed retrospectively with the clinical and follow-up information that were confirmed by postoperative pathologic diagnosis from November 1981 to November 2005. Results All patients showed axillary node enlargement as the first sign and were operated.The operation included axillary node excision in 2 patients,radical mastec-tomy or modified radical mastectomy in 44 patients. Forty-five cases got follow-up for 1-22 years,33 cases had existed 3 years,18 cases had existed 5 years,8 cases had existed 10 years. Conclusions For axillary mass which causes are uncertain ,the possibility of OBC should be considered .Meanwhile excision and pathological examination is necessary.The metastatic histological structure and immunohistochemical index of the axillary nodes usually provide important clue for the source of this tumor.Radical or modified mastectomy is the best method, and pest-operative chemotherapy and/or radiotherapy should be done. It has been showed that targeted therapy is very important to breast cancer with C-erbB-2 positive recently.To the cases that neck lymphatic metastasis is M4G3 positive by immunohistochemical examination and no primary focus clinically, the diagnosis of OBC should be considered. The cases without primary focus have better prognosis than those with primary focus.