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.

A case of ichthyosis follicularis,alopecia and photophobia syndrome caused by a novel mutation c.1165C＞T in the membrane-bound transcription factor protease site 2 (MBTPS2) gene was firstly reported.The proband presented with dry skin,congenital hairlessness,follicular keratotic papules,photophobia,epilepsy,and mental and motor retardation.Next-generation and Sanger sequencing analysis confirmed that the proband and his mother both had a c.1165C＞T (p.pro389Ser) mutation in exon 9 of the MBTPS2 gene.According to the clinical manifestations of the patient and genetic characteristics of the MBTPS2 gene mutation,the patient was diagnosed with ichthyosis follicularis,alopecia and photophobia syndrome.

A male patient, who was aged 3 months and 12 days, presented with well-circumscribed erythema and scales on the scrotum, perineum, buttocks and perianal region at 1 month after birth. The lesions gradually involved the perioral and axillary regions, flexor aspect of the elbow, popliteal fossa and neck. Shortness of breath, crying, dysphoria and vomiting occurred without fever and cough 3 days before hospitalization. Laboratory examinations at admission showed metabolic acidosis, hyperlactacidemia, hyperammonemia and organic aciduria. Second-generation sequencing and Sanger sequencing of the holocarboxylase synthetase gene revealed a known mutation c.1522C>T in exon 9 and a novel mutation c.1796_1814del in exon 11. According to a guideline from the American College of Medical Genetics and Genomics, this novel mutation was ranked as a pathogenic mutation. The patient was diagnosed as multiple carboxylase deficiency. His clinical symptoms were improved after oral biotin treatment, no neurological symptoms or signs were observed.

Objective To investigate the clinical effects and safety of bevacizumab combined with S-1 as the second-line treatment of recurrent and/or metastatic esophageal cancer after chemoradiation. Methods Patients with recurrent or metastatic esophageal cancer after chemoradiation were treated with bevacizumab and S-1. Bevacizumab was used by intravenous infusion, 7.5mg/kg body weight on day 1; S-1 was used by oral at 80mg/m·d on day 1-14, 21 days as a cycle of treatment and repeated until either pro- gressive disease or intolerable toxicity occurred. Chest CT were performed and RECIST 1.1 was used for response evaluation. Kaplan-Meier method was used for survival analysis. Side effects were recorded and analyzed. Results Totally 78 patients were enrolled in the study, including 67 squamous cell carcinoma and 11 adenocarcinoma histologically. The overall response (CR+PR) rate was 22.4% (17/76) and disease control (CR+PR+SD) rate was 61.8% (47/76) respectively. The median follow-up time was 20 months (range from 9 to 44 months). The median progression-free survival (PFS) was 4.9 months (95% CI 4.4-5.5) and the median overall survival (OS) was 8.1 months (95% CI 7.6-9.2). The median PFS and OS of patients with metastasis diseases were 6.2 months (95% CI 3.3 to 6.3) and 8.5 months (95% CI 5.8 to 11.2), where PFS was longer than that of patients with local regional recurrence (median 5.0 months, 95% CI 3.0 to 5.5, P=0.017) and OS was longer than that of patients with regional disease and metastasis (median 8.0 months, 95% CI 4.6 to 9.5, P=0.010). The common adverse effects were mild to moderate neutropenia (84.2%), grade I-II hand and foot syndrome (51.3%), grade I-II nausea (48.7%), mild epistaxis (30.1%) and mild vomiting (14.5%). Esophageal bleeding occurred in 7.9% of patients. One patient (1.3%) died from massive bleeding which was caused by esophageal perforation. Conclusion Bevacizumab combined with S-1 was effective and safe for esophageal cancer patients who had recurrent or metastatic diseases after chemoradiation.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bevacizumab ; administration & dosage ; adverse effects ; Drug Combinations ; Esophageal Neoplasms ; drug therapy ; mortality ; pathology ; Female ; Humans ; Male ; Middle Aged ; Oxonic Acid ; administration & dosage ; adverse effects ; Tegafur ; administration & dosage ; adverse effects

OBJECTIVETo 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.

METHODSLentivirus-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.

RESULTSLentivirus-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).

CONCLUSIONSLentivirus-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.

Animals ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Colorectal Neoplasms ; pathology ; therapy ; Gene Expression ; HMGB1 Protein ; genetics ; metabolism ; Humans ; In Vitro Techniques ; Lentivirus ; Mice ; Mice, Nude ; Neoplasm Invasiveness ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; therapeutic use ; Transfection ; Tumor Burden

OBJECTIVETo 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.

METHODSImmunohistochemical 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.

RESULTSHMGB1 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).

CONCLUSIONSHMGB1 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.

Cell Nucleus ; Colorectal Neoplasms ; HMGB1 Protein ; Humans ; Lymphatic Metastasis ; Prognosis ; Survival Analysis ; Survival Rate

OBJECTIVETo compare the clinical short-term safety and efficacy between robotic right colectomy (RRC) and laparoscopic right colectomy(LRC) with meta-analysis.

METHODSA 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.

RESULTSSix 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).

CONCLUSIONCompared to LRC, RRC is associated with less estimated blood loss, faster postoperative intestinal peristalsis recovery, lower postoperative overall complications, and longer operative time.

Colectomy ; Humans ; Laparoscopy ; Length of Stay ; Operative Time ; Postoperative Complications ; Postoperative Period ; Robotic Surgical Procedures

Objective 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. Methods 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. Results 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). Conclusions 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.

Objective To compare the clinical short-term safety and efficacy between robotic right colectomy (RRC) and laparoscopic right colectomy (LRC) with meta-analysis. Methods 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. Results 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). Conclusion Compared to LRC, RRC is associated with less estimated blood loss, faster postoperative intestinal peristalsis recovery , lower postoperative overall complications , and longer operative time.

Objective 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. Methods 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. Results 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). Conclusions 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.