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2018  Vol. 45  No. 6

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EXPERT FORUM
Comment on Prospect of Optical Molecular Imaging in Oncological Surgery
Abstract:

With the development of optical molecular imaging technology and target optical molecular, the guided surgery by optical molecular imaging will be the third generation surgery after open surgery and minimally invasive surgery. In this paper, fluorochrorne and fluorescence diagnosis, fluorescence imaging and optical molecular imaging, optical molecular imaging and optical molecular imaging equipment are discussed in concept. It is clearly pointed out that optical molecular imaging surgery will be a new cutting edge of precision surgery. Optical molecular imaging surgery is composed of target optical molecular agent, optical molecular imaging equipment, and clinical diagnosis and treatment technology.

BASIC RESEARCH
Berberine Inhibits Proliferation and Induces Apoptosis of Esophageal Cancer Cells via Inactivation of IGF-1R Signaling Pathway
Abstract:
Objective 

To investigate the effects of berberine on the proliferation, cell cycle progression and apoptosis of esophageal cancer cells and related mechanism.

Methods 

MTT assay was used to evaluate the effects of berberine on cell viability. Propidium iodide staining was used to detect cell cycle progression. Annexin V-FITC/PI staining assay was used to measure cell apoptosis, and Western blot analysis was performed to determine the phosphorylation of insulin-like growth factor 1 receptor (IGF-1R) as well as the two major downstream signaling molecules AKT and p42/44MAPK(ERK).

Results 

In vitro, berberine inhibited the proliferation of four esophageal cancer cell lines in a concentration-dependent manner. Moreover, the IC50 values of berberine against different esophageal cancer cells were negatively correlated with the expression level of IGF-1R. The distribution of KYSE450 cells cycle was arrested in G2/M phase. Berberine dose-dependently induced the cell apoptosis, and the apoptosis ratio of KYSE450 cells with high IGF-1R level was significantly higher than that of KYSE150 cells with low IGF-1R level after berberine treatment at the same concentration. Berberine dose-dependently inhibited the phosphorylation of IGF-1R and blocked AKT and ERK activation.

Conclusion 

Berberine could inhibit cell proliferation, cell cycle arrest and induce cell apoptosis of esophageal cancer via inactivation of IGF-1R as well as the downstream molecules AKT and ERK.

Mechanism About How Piceatannol Enhances Anti-tumor Effect of Cisplatin on Laryngeal Cancer Hep-2 Cells
Abstract:
Objective 

To investigate how piceatannol enhances the anti-tumor effect of cisplatin on laryngeal cancer cells and related molecular mechanism.

Methods 

Laryngeal carcinoma Hep-2 cells were cultured in vitro and then treated with piceatannol and cisplatin. Cell proliferation apoptosis, karyopyknosis ratio and proteins expression of BCL-2 family were detected by CCK8, flow cytometry, Hoechst staining and Western blot, respectively.

Results 

No effect of 50 μmol/L piceatannol was found on the Hep-2 cell apoptosis or proliferation. Compared with cisplatin, cisplatin combined with piceatannol could significantly decrease the cell proliferation; after 48h, the absorbance of cells treated with cisplatin and piceatannol was decreased for 60%, and the apoptosis ratio was significantly increased (P < 0.05). Hoechst staining revealed the karyopyknosis ratio of Hep-2 cells treated with cisplatin and piceatannol was significantly increased. Western blot showed piceatannol could down-regulate BCL-2 expression and up-regulate BAX expression.

Conclusion 

The anti-tumor effect of cisplatin on laryngeal cancer cells could be enhanced by piceatannol, and its molecular mechanism is related to the regulatory effect of piceatannol on the key proteins of BCL-2 family.

Combination of SAHA and Paclitaxel Induce Apoptosis of Human Cervical Cancer HeLa Cells
Abstract:
Objective 

To investigate the inhibition effect of paclitaxel combined with SAHA on the proliferation of human cervical cancer HeLa cells in vitro and related mechanism.

Methods 

Human cervical cancer HeLa cells were treated with paclitaxel (10 nmol/L), SAHA (10 μmol/L), and paclitaxel (10 nmol/L)+SAHA (10 μmol/L) separately for 24h or 48h. The inhibitory rate of tumor cells was determined by MTT assay. Flow cytometry was used to detect HeLa cells apoptosis and cell cycles.

Results 

MTT assay showed that the proliferation inhibitory rates of the combination group after 24h or 48h treatment were significantly higher than those of paclitaxel and SAHA groups, moreover, paclitaxel and SAHA had overlapping effects (Q=0.861, Q=1.25). SAHA combined with paclitaxel could significantly increase the apoptotic rate of HeLa cells than SAHA or paclitaxel alone. HeLa cells were randomly in G0/G1 phase after SAHA and paclitaxel treatment for 24h, which suggested that SAHA combined with paclitaxel could significantly inhibit DNA synthesis and replication during HeLa cell mitosis.

Conclusion 

The combination of SAHA and paclitaxel could significantly induce cervical cancer HeLa cells apoptosis, inhibit cell proliferation, block cell cycle and enhance their anti-tumor ability.

CLINICAL RESEARCH
Influence of Different Radio-chemotherapy Modes for Incidence of Radiation Pneumonitis in Patients with Lung Cancer
Abstract:
Objective 

To compare the difference of different radio-chemotherapy modes and clinical characters for more than grade 2 radiation pneumonitis (RP) incidence in patients with lung cancer.

Methods 

We retrospectively analyzed the 136 patients with lung cancer who were treated with radio-chemotherapy in our hospital from January 2014 to January 2016. Following-up was undergone regularly after treatment. RTOG standard of acute radiation pneumonia was applied to evaluate lung injury grade. We also analyzed the effect of clinical character and treatment modes on RP.

Results 

There were 36 cases diagnosed as ≥grade 2 RP, and the occurrence rate was 26.5%. The patients with dust exposure history(P=0.048) and NSCLC pathology type (P=0.047) had a higher RP incidence, while other characters had no statistical difference. Comparing between concomitant chemoradiation group and sequential chemoradiation group, there was statistical difference in the incidence of ≥grade 4 RP (6.7% vs. 0, P=0.05), however, no statistical difference in overall RP, grade 2 or grade 3 RP. There was no statistical difference among different chemotherapy regimens to ≥grade 2 RP. There was significantly positive correlation of RP severity with the total chemotherapy cycles or induction chemotherapy cycles(P=0.000).

Conclusion 

Dust exposure history and pathology type are two clinical character factors to influence the incidence of RP. RP is closely related to the chemotherapy cycles, especially in total chemotherapy cycles or induction chemotherapy cycles.

Gab2 Promotes Invasion and Metastasis of Gastric Cancer via Regulating EMT
Abstract:
Objective 

To investigate the expression of Grb2 binding protein-2(Gab2) in gastric cancers and its significance and mechanism in the invasiveness and metastasis of gastric cancer.

Methods 

Immunohistochemical method was used to detect the expression of Gab2, E-cadherin, N-cadherin and MMP-9 in gastric cancer tissues. The relationship between Gab2 expression and lymphatic metastasis was analysed. SiRNA plasmid targeting Gab2 and empty vector plasmid were transfected into SGC7901 cells and named siGab2/SGC7901 and NC/SGC7901 cells respectively. RT-PCR method was applied to analyze mRNA expression of Gab2 in siGab2/SGC7901 and NC/SGC7901 cells. In vitro matrigel invasion assay was used to detect the invasiveness of siGab2/SGC7901 and SGC7901 cells. Western blot was applied to analyze protein expression.

Results 

Gab2 expression in gastric cancer tissues was related with lymphatic metastasis significantly(P=0.002), E-cadherin expression level negatively (r=-0.693, P=0.000), and N-cadherin and MMP-9 levels positively (r=0.407, P=0.021; r=0.335, P=0.017). After microRNA interference, the mRNA and protein expressions of Gab2 in siGab2/SGC7901 cells were decreased obviously, moreover, the quantity of gastric cancer cells which invaded and penetrated matrigel membrane was decreased. Western blot showed that the expressions of N-cadherin and MMP-9 were decreased and E-cadherin expression was increased in siGab2/SGC7901 cells.

Conclusion 

Gab2 plays a key role in the invasiveness and metastasis of gastric cancer by regulating EMT.

Established of Serum Diagnostic Model for Colorectal Cancer Patients Using MB-WCX and MALDI-TOF MS
Abstract:
Objective 

Serum protein expression profiling was examined using magnetic bead-based matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF-MS) to establish a serum proteomic diagnostic model for colorectal cancer.

Methods 

Serum samples of normal control (CRTL, n=72), colorectal cancer (pre-operation CRC, n=72, and post-operation CRC, n=72) were collected from 2014-9-1 to 2016-9-1. Peptidome of all samples were extracted by magnetic-bead-based weak cation-exchange chromatography (MB-WCX) and detected by calibrated Autoflex Ⅲ MALDI-TOF-MS. Peptide mass fingerprinting were analyzed by ClinProtTools 2.0 software, and the differentially-expressioned peptides were further identified using LC-ESI-MS/MS.

Results 

MALDI-TOF-MS identified 80 peaks (m/z), in which 12 peaks showed significant differences among CRTL, pre-operation and post-operation CRC patients (P < 0.01). 9 peaks were up-regulated and 3 peaks were down-regulated in CRC compared with CRTL, and these peaks showed a tendency to CRTL after operation. Based on the GA model, CRC patients could be discriminated from CRTL with 99.31% sensitivity and 96.49% specificity. Moreover, 3 peaks (m/z: 2663.36, m/z: 4793.17 and m/z: 5343.48) of the GA model were identified as protein FGA, SETD7 and MUC5AC respectively.

Conclusion 

The serum proteomic diagnostic model could accurately distinguish between CRTL and CRC, but it needs further research.

Risk Factor of Intestinal Obstruction After Radical Surgery of Cervical Cancer
Abstract:
Objective 

To investigate the risk factors of intestinal obstruction after radical surgery of cervical cancer.

Methods 

We retrospectively analyze the clinical data of 2585 cervical cancer patients underwent radical surgery in Tumor Hospital of Yunnan Province from June 2012 to June 2017. Among them, 149 patients had intestinal obstruction. We comparatively analyzed the risk factors for intestinal obstruction.

Results 

The incidence of intestinal obstruction was related to age, duration of operation, postoperative serum potassium level, postoperative fasting time, the history of preoperative pelvic operation, BMI, operation method, postoperative infection and postoperative peritoneal effusion (P < 0.05). The history of pelvic operation, long postoperative fasting time, low postoperative blood potassium level and long operation time were independent risk factors. However, there was no statistically significant difference between the two groups in blood loss, hemoglobin level or intraoperative blood transfusion(P > 0.05).

Conclusion 

Shortening the operation time, encouraging patients to eat early and maintaining the postoperative blood potassium level after operation are the effective measures to prevent the intestinal obstruction after radical surgery of cervical cancer.

CLINICAL DIAGNOSIS
Clinical Value of Abnormal Prothrombin Combined with CEA, CA72-4 and CA199 on Patients with Gastric Cancer
Abstract:
Objective 

To evaluate the clinical value of abnormal prothrombin (PIVKA-Ⅱ) combined with CEA, CA199 and CA72-4 on the diagnosis, treatment, recurrence and metastasis of patients with gastric cancer.

Methods 

Serum PIVKA-Ⅱ, CEA, CA72-4, CA199 levels in 123 gastric cancer patients, 80 healthy controls and 30 benign gastric diseases patients were performed by chemiluminescent immunoassay(CLIA), electrochemiluminescence immunoassay (ECLIA), respectively. And random 20 patients with gastric cancer were followed up.

Results 

The level of PIVKA-Ⅱ was significantly higher in gastric cancer group than those in benign gastric disease group and healthy control group (all P < 0.001). ROC analysis showed the cut-off value to discriminate cancer from control was established at 32.14U/L for PIVKA-Ⅱ (sensitivity (39.84%), specificity (95%)). The sensitivity of PIVKA-Ⅱ was not significantly higher than CEA, CA199 or CA72-4, while the specificity was slightly lower. With the rising of gastric carcinoma stage, the levels of PIVKA-Ⅱ as well as the positive rate were increased (all P < 0.05). Elevated levels of PIVKA-Ⅱ were found in the recurrent or metastasis disease patients, and the levels were decreased in 20 patients who were sensitive to therapy. The sensitivity and effectiveness of the group of four tumor markers were the highest in all combination groups.

Conclusion 

There is specifically clinical application value of PIVKA-Ⅱ, CEA, CA199 and CA72-4 in the diagnosis, curative effect and prognosis monitoring of gastric cancer.

CLINICAL APPLICATION
Efficacy and Safety of Paclitaxel, Ifosfamide and Cisplatin as First-line Treatment on Patients with Intermediate- or Poor-risk Advanced Testicular Cancer
Abstract:
Objective 

To assess the efficacy and safety of paclitaxel, ifosfamide and cisplatin (TIP) as the first-line treatment for the patients with intermediate- or poor-risk testicular cancer retrospectively.

Methods 

Patients with intermediate- or poor-risk testicular cancer in our center received TIP as the first-line treatment. Objective response rate, 2-year progression free survival(PFS) and overall survival(OS) were evaluated.

Results 

The mean treatment of 20 patients was 4.25cycles. Six patients achieved CR(30%), seven patients had partial response(35%) and overall response rate was 65%. The median follow-up time was 25 months. Three patients died of tumor progression. Hematologic toxicity was most common(95%), with 30% of grade 3-4 neutropenia. Estimated 2-year PFS was 72.9% and OS was 89.1%.

Conclusion 

Paclitaxel, ifosfamide and cisplatin(TIP) are safe and effective as the first-line treatment on patients with intermediate- or poor-risk testicular cancer. Compared with previous studies, 2-year PFS and OS have been improved. Adverse effect could be controlled. Further researches are still needed.

Prognosis of Stage ⅡB-Ⅲ Thoracic Esophageal Carcinoma Patients Treated with Prophylactic After Radical Esophagectomy
Abstract:
Objective 

To investigate the effect of prophylactic radiotherapy after radical surgery on the long-term survival of patients with stage ⅡB-Ⅲ thoracic esophageal carcinoma.

Methods 

We enrolled 336 stage ⅡB (n=65) and Ⅲ(n=271) thoracic esophageal carcinoma patients who underwent radical resection with (S+R, n=116) or without (S, n=220) postoperative prophylactic radiotherapy from 2007 to 2010. The median dose of postoperative radiotherapy was 50 Gy. The Kaplan-Meier method, Log rank test and Cox model were used for survival rate calculation, univariate analysis and multivariate analysis, respectively.

Results 

The 5-year overall survival (OS) and disease-free survival rates were 29.3% and 25.6%, respectively. The 5-year OS of stage ⅡB patients in S and S+R groups were 30.1% and 48.6%, respectively (χ2=2.279, P=0.131). The 5-year OS of stage Ⅲ patients in S and S+R groups were 24.9% and 32.8%, respectively (χ2=5.865, P=0.015). The 5-year OS of lymph node-positive patients in S and S+R groups were 25.9% and 35.8%, respectively (χ2=7.663, P=0.006). Postoperative prophylactic radiotherapy resulted in significantly decreased intrathoracic and supraclavicular recurrence, and obviously delayed median local recurrence time in S and S+R groups (10.6 vs. 16.3 months; χ2=6.043, P=0.014).

Conclusion 

Postoperative prophylactic radiotherapy reduces local recurrence and improves the survival of stage Ⅲ or lymph node-positive thoracic esophageal carcinoma patients.

Comparison of Efficacy and Safety Between Liposome-paclitaxel plus Carboplatin and Paclitaxel plus Carboplatin on Epithelial Ovarian Cancer
Abstract:
Objective 

To compare the efficacy and safety between liposome-paclitaxel plus carboplatin and paclitaxel plus carboplatin on epithelial ovarian cancer.

Methods 

We randomly divided 198 cases of epithelial ovarian cancer who had undertook at least six chemotherapy circles after operation into two groups: the experimental group were treated with liposome-paclitaxel (175mg/m2)+carboplatin AUC5 and the control group were treated with paclitaxel (175mg/m2)+carboplatin AUC5. One cycle of chemotherapy was 21 days. A strict observation in the efficacy and adverse reactions of two groups was started from the second chemotherapy cycle.

Results 

The total effective rates (CR+PR) in the experimental group and control group were 50.50% vs. 53.60% (P=0.738). There were 22(11.11%) recurrent cases after chemotherapy, among which six patients 6(27.27%) patients in the experimental group and 16(72.72%) patients in the control group (P=0.029). The incidences of allergic reactions, alopecia, nausea, vomiting, diarrhea, leukopenia, thrombocytopenia, hepatic dysfunction in the experimental group were significantly lower than those in the control group (P < 0.05), while there was no significant difference in terms of other adverse reactions (P > 0.05).

Conclusion 

Compared with paclitaxel plus carboplatin group, the efficacy of liposome-paclitaxel plus carboplatin group is equivalent, the recurrence rate is lower in follow-up period, and the incidence of adverse events is significantly lower, including allergic reactions, bone marrow suppression, gastrointestinal reactions and liver dysfunction.

EPIDEMIC RESEARCH
Cancer Incidence and Mortality in Hubei Cancer Registries, 2013
Abstract:
Objective 

To analyze the cancer incidence and mortality in cancer registration areas in Hubei Province in 2013.

Methods 

The incidence, mortality and population data were collected and evaluated from nine cancer registries of Hubei Province, 2013. All quality indicators were evaluated according to national standards.

Results 

The total estimates of new cancer cases and deaths were 29 738 and 17 986 in 2013. The crude incidence, age-standardized incidence rates by Chinese standard population (ASR China 2000) and world standard population(ASR World 2000) were 284.85/105, 188.08/105 and 203.59/105, respectively. The crude mortality, age-standardized mortality rates by ASR China 2000 and ASR World 2000 were 172.28/105, 107.97/105 and 122.54/105, respectively. Lung cancer was the most common cancer and the leading cause of cancer deaths. The incidence rate and mortality of male were higher than those of female. And the incidence rate and mortality in urban areas were higher than those in rural areas.

Conclusion 

Age-standardized incidence rate by ASR China 2000 is slightly lower than that in 2012 in cancer registration areas in Hubei Province, and the mortality is slightly lower than national rate. Lung cancer, digestive system malignancies and breast cancer are the main cancers that should be focused on the prevention and control, in terms of health education in general population.

REVIEWS
Application Status of C-phycocyanin in Anti-tumor
Abstract:

In recent years, the search for anti-tumor drugs with high efficiency, low toxicity and little side effects in marine organisms has attracted the attention of scholars. C-phycocyanin (C-PC) has toxic and side effects on a variety of tumor cells, which can inhibit the growth of tumor cells and promote the apoptosis of tumor cells. Phycocyanin combined with other drugs can improve its anti-tumor activity. This review discusses the therapeutic use of phycocyanin and focuses on the latest advances of phycocyanin as a promising natural anti-cancer drug.

Progress in Fluorescence-guided Resection of High-grade Glioma Using Fluorescein Sodium
Abstract:

The invasive growth nature of the high-grade gliomas results in unclear margin between glioma and normal brain tissues, making it difficult to achieve total removal of the tumors. Recent studies have demonstrated that intraoperative real-time fluorescence imaging by intravenous injection of fluorescein sodium can facilitate the identification of tumor margin with relatively high specificity and sensitivity, holding promising prospects in improving the gross total resection rate and progression free survival.

Progress and Controversy of Endoscopic Thyroid Cancer Surgery
Abstract:

With the rapid development of endoscopic techniques, endoscopic thyroid surgery has gradually become a new research focus due to the tiny neck scar, invisible surgical incision, etc.. However, because of the unclear indications of endoscopic thyroid surgery, difficult lymph node dissection in lateral neck, etc., there are different opinions about whether endoscopic thyroid surgery can cure thyroid cancer or not. After reviewing the related literatures, this paper discusses the indications and disputations of endoscopic thyroid cancer surgery, puts forward the countermeasures to avoid the risk and provides rationalization proposals for their future trends.

CASE REPORT
Postoperative Vesicovaginal Fistula in Cervical Cancer Patient Diagnosed by Ultrasound: A Case Report
TUMOR INFORMATION
Would New Epigenetic Therapy on Tumor Affect the Female Germline Epigenome