Triple-negative breast cancer (TNBC) is a special type of breast cancer, accounting for 15%-20% of all diagnosed breast cancer cases. Its estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) expression is negative, with unique biological characteristics, clinicopathological features and tumor heterogeneity. Its clinical features include high incidence of relapse, early metastasis and poor prognosis. Currently, it lacks effective treatment. This review described the clinicopathological features of TNBC, its molecular subtypes, several important pathways and targets, as well as presented the progress in clinical studies of targeted drugs in the hope of generating new ideas for the treatment of TNBC in the future.

Background and purpose:Checkpiont targeted immunotherapy in the field of solid tumor therapy has huge potential, triggering a boom in the study of immune targeted drugs. A study has provided a basis for the follow-up study of ipilimumab combined with chemotherapy in the treatment of non-small cell lung cancer(NSCLC) patients. This study counted the adverse event statistics that ipilimumab or placebo combined with paclitaxel and carboplatin as first-line therapy for the treatment of stage Ⅳ or recurrent squamous cell carcinoma to evaluate the safety of ipilimumab combined with chemotherapy in the treatment of advanced squamous cell carcinoma.Methods:This study selected 13 patients with ECOG scores≤1 and stage ⅣA or ⅣB squamous cell carcinoma in the Shanghai Chest Hospital, Shanghai Jiao Tong Uni-versity. Randomized controlled double blind trial was used in this study. The patients of experimental group were treated with ipilimumab combined with paclitaxel and carboplatin, while the patients of control group were treated with the placebo combined with paclitaxel and carboplatin. Adverse events (AEs) were counted in the process of treatment.Results:The most common AEs were the 1/2 grade AEs. Immune-related AEs (irAEs) reported in the ipilimumab group included level Ⅰ of diarrhea and pruritus, level Ⅱ of rash and pruritus and level Ⅲ of hypophysitis.Conclusion:The side effects of ipilimumab were mild, tolerable and manageable.

Background and purpose:Lymph node metastasis commonly occurs in papillary thyroid carcino-ma (PTC). The object of this study was to investigate the relationship between the rate of involved lymph nodes (LR) and distant metastasis (DM) in PTC, and its potential value in predicting the risk of DM.Methods:PTC patients were divided into two groups as M0 (121 cases) and M1 (41 cases) according to the presence of distant metastases or not. The t-text andχ2 test were used to evaluate the statistical differences in basic clinicopathological features between the two groups. Multivariate analysis was used to quantify LR as an independent factor of DM. The receiver operating charac-teristic (ROC) curve was employed to evaluate the clinical value of LR and the number of involved lymph node (LNs) for predicting DM and optimal cut-off point respectively. The cumulative risk of distant metastasis curves according to the LR and LNs status were constructed with the Kaplan-Meier method, and the Log-rank test was used to compare these curves.Results:There were no statistical differences in age and multifocality between two groups (P>0.05), while signiifcant differences in gender, extrathyroidal invasion and tumor size were observed. LR is an independent indicator for predicting DM (OR=1.133,P=0.000). An increase in LR was signiifcantly associated with DM. Patients with more than 15 involved LNs had the steepest increasing pattern in the cumulative risk of DM compared with those who had less than 15 involved LN (P=0.002).Conclusion:LR may be an independent predictive marker for distant metastases in PTC, and its combination with LNs might better predict the risk of DM.

Background and purpose:It has been demonstrated that radical prostatectomy for patients with oligometastatic prostate cancer may contribute to improving local control of prostate cancer and overall survival by several retrospective studies. Perioperative complications play an important role in determining whether radical prostatectomy is appropriate for patients with oligometastatic prostate cancer. This study aimed to discuss the recurrence rate and the sever-ity of perioperative complications, and the primary curative effect of radical prostatectomy on oligometastatic prostate can-cer patients.Methods:A total number of 247 patients who received radical prostatectomy were recruited in the study from Jul. 2015 to Jan. 2016, including 25 patients with oligometastatic prostate cancer and 222 patients with localized prostate cancer. Patients with perioperative complications in both groups were graded with the Clavien-Dindo grading system. The proportion of PSA decline and the rates and severity of perioperative complications were analyzed in both groups.Results:The cases of prostate specific antigen (PSA) decline in the oligometastatic group were 21 (84.0%), lower than the localized group with 212 cases (95.5%). There were 6 cases (24.0%) with postoperative complications in the oligometastatic group, including serious complications (Ⅲ or above) 1 case (4.0%), and 49 cases (22.1%) with postoperative complications in the localized group, including serious complications (Ⅲ or above) 7 cases (3.2%). The differences between the groups reached no statistical significance (P>0.05).Conclusion:Radical prostatectomy for patients with oligometastatic prostate cancer could be safe, effective, and appropriate, the risk of perioperative complications should not be one of the limiting factors.

Background and purpose:Lung cancer is the leading cause of morbidity and cancer-related mortality worldwide. A variety of driver genes were detected in lung cancer. Studies have shown that different gene mutations of lung cancer were found between different races. Most of Uyghurs live in Xinjiang, accompanied by a high morbidity of lung cancer. This study aimed to investigate the expression of driver genes in Uyghur patients with lung cancer in Xinjiang, China.Methods:This study collected the tissue specimens of 43 Uyghur patients with lung cancer, with a very different method to detectEGFR gene expression. real-time fluorescent quantitative polymerase chain reaction(RTFQ-PCR) was used to detectK-ras,ALK,ROS1, mutatedBRAF andPIK3CA gene expression. Analysis of the correlation between lung cancer gene mutations in Uyghur and clinical features of patients with lung cancer were performed.Results:Among 43 cases of specimens,EGFR mutation rate was 11.63%, while theEGFR gene mutation rates in adenocarcinoma and squamous cell carcinoma were 26.67% and 4.76%, respectively.EGFR gene mutation was not detected in large cell carcinoma, adenosquamous carcinoma and small cell lung cancer.EGFR gene mutation rate in patients with adenocarcinoma (26.67%) was signiifcantly higher than that in other types of lung cancer (3.57%). The difference was statistically signiifcant (P=0.024). There were 6 patients withK-ras12/13 heterozygous mutation, and the mutation detection rate was 16.28% (6/43). There were 2 patients withPIK3CA heterozygous mutation, and the mu-tation detection rate was 4.65% (2/43).EGFR andK-ras mutations occurred simultaneously in 1 case. No relationship was found betweenEGFR mutations and age, gender, smoking status, TNM staging, ECOG score among Uyghur lung cancer patients. This study did not ifnd mutation inALK,ROS1 fusion gene andBRAF gene among the 43 specimens. Conclusion:Compared with Asian populations, Xinjiang Uyghur patients with lung cancer have a lower rate ofEGFR mutations and a higher rate ofK-ras mutations, which is similar to the characteristics of European Caucasians.

Background and purpose:Promoter methylation ofPCDH10, a gene encoding protocadherin 10, has been found to be correlated to poor prognosis in gastric cancer (GC) patients. However, the relationship between the expression of PCDH10 and prognosis in GC remained unknown. This study aimed to explore the relationship be-tween the expression of PCDH10 and clinicopathological features and prognosis of GC, and to identify biomarker for predictions of recurrence and survival of GC.Methods:mRNA expressions of PCDH10 in 115 pairs of GC tissues and adjacent normal tissues were detected by real-time lfuorescence quantitative polymerase chain reaction (RTFQ-PCR). The correlation between PCDH10 expression level and clinicopathological features and prognosis of GC was analyzed. Prediction models for 5-year recurrence and 5-year survival were established using logistic regression method.Results:Progression-free survival (PFS) and overall survival (OS) were signiifcantly prolonged in patients with PCDH10 low expression compared to patients without PCDH10 low expression (P=0.046 andP=0.033 respectively). PCDH10 low expression signiifcantly correlated with less lymph node metastasis (P=0.001) and earlier TNM staging (P=0.001), and was more common in female than in male (P=0.040). The mRNA expression of PCDH10 did not correlate with age, Lauren classiifcation, T stage, neural invasion or vascular invasion. Univariate Cox analysis showed Lauren classiifca-tion, T stage, N stage, M stage and PCDH10 expression signiifcantly correlated with PFS and OS. Logistic regression models for the prediction of 5-year recurrence or 5-year survival based on clinicopathological features included Lauren classiifcation, T stage, N stage and M stage as variables. Logistic regression models for the prediction of 5-year recur-rence or 5-year survival based on PCDH10 expression included Lauren classiifcation, T stage, M stage and PCDH10 expression level but not N stage as variables. The models based on PCDH10 expression had the same effciencies as models based on clinical parameters in predicting 5-year recurrence or 5-year survival for GC patients.Conclusion:PCDH10 low expression correlated with better prognosis, less lymph node metastasis and earlier TNM stage in GC patients. Low expression of PCDH10 may be a biomarker of better survival for GC patients. Logistic regression model based on PCDH10 mRNA expression may serve as a prediction model when patients have unknown lymph node metas-tasis status.

Background and purpose:Cyclooxygenase-2 (COX-2) participates in angiogenesis and lymph node metastasis of lung cancer. COX-2 inhibitors could inhibit invasion and metastasis of lung cancer. This study aimed to investigate the inhibition of invasion and metastasis by COX-2 inhibitor imrecoxib in xenograft tumor of lung adenocar-cinoma A549 cell in nude mice and to explore its possible mechanisms, in addition, to observe the efficacy of imrecoxib combined with lobaplatin.Methods:Thirty male BALB/c nude mice were injected subcutaneously with A549 cells into the right axillary region to establish xenograft models. Twenty-nine successfully modeled mice were randomly divided into four groups: control group (n=7), imrecoxib group (n=8), lobaplatin group (n=7), imrecoxib combined with lobaplatin group (n=7). The control group was treated with the same amount of sterile distilled water and injected with the same amount of 0.9% sodium chloride solution via caudal vein. The treatment group was treated with imrecoxib tablets 40 mg/kg per day through gavage and injected with lobaplatin 7.5 mg/kg per week via caudal vein respectively. The diet, physical activity and other normal conditions of nude mice were observed everyday. After 6 weeks, 29 mice were sacrificed and transplanted tumor tissues were cut off. The expression of PTEN, cortactin protein and mRNA were detected by immunohistochemistry and real-time PCR. The data were analyzed with one-way anova and non-parametric test.Results:In the last week, the diet and physical activity of all nude mice were less than before, and they became thinner, which were more obvious among the mice in lobaplatin group and imrecoxib combined with lobaplatin group. Compared with the control group, the expression of PTEN protein and mRNA were significantly increased in imrecoxib group and imrecoxib combined with lobaplatin group (P<0.001, respectively). Compared with the control group, the expression of cortactin protein and mRNA were significantly decreased in imrecoxib group and imrecoxib combined with lobaplatin group (P<0.001, respectively). PTEN and cortactin protein, PTEN and cortactin mRNA had significantly negative correlation (r=-0.660, -0.983,P<0.001, respectively). Conclusion:Imrecoxib can inhibit non-small cell lung cancer invasion and metastasis which may be involved in upregu-lating PTEN protein and reducing cortactin protein. Imrecoxib could enhance the effect of lobaplatin chemotherapy.

Background and purpose:As a member of the catenin family, Delta-catenin protein could promote proliferation and invasion of tumor cells, but the accurate mechanism of Delta-catenin promoting cell proliferation is not clear. In the present study, we illustrated that Delta-catenin’s effect on cell apoptosis and their relationship with mitogen-activated protein kinase (MAPK) signaling pathway, and the possible mechanism was also explored for Delta-catenin promoting invasion and proliferation of tumor cells. Methods:The alterations of p38 and c-jun N-terminal rinasel JNK protein activity were detected in SPC and SK lung cancer cell lines with Delta-catenin overexpression or not, by Western blot method. At the same time, the apoptotic number of tumor cells was also examined by FCM method. Furthermore, the number of invasive tumor cells was examined by Matrigel invasive experiment. Results:Compared with untreated group and empty vector group, the activity of p38 protein was unchanged in lung cancer cell lines with Delta-catenin overexpressed (P>0.05), but the activity of JNK protein was decreased signiifcantly (P<0.05),meanwhile, apoptotic proportion of tumor cells were also reduced (P<0.05), and invasive ability of tumor cells was enhanced signiifcantly (P<0.05). Conclusion:Delta-catenin probably decreases apoptosis number of lung cancer cells via inhibiting the activity of JNK pathway, and then promotes invasive ability of tumor cells.

Background and purpose:The mutation of BRCA1 gene is widely acknowledged to be related to the incidence of triple-negative breast cancer (TNBC). The aim of this study was to investigate the association between TNBC and single nucleotide polymorphisms (SNPs) of BRCA1-associated genes. Methods:This study investigated the associations between the BRCA1-A complex genes and risk of developing TNBC in a case-control study of Chinese Han Women population including 414 patients with TNBC and 354 cancer-free controls diagnosed in the Fudan University Shanghai Cancer Center during 2008-2011. This study also detected 37 common variants in Abraxas, BRE, Rap80, NBA1 and BRCC36 genes encoding the BRCA1-A complex and evaluated their genetic susceptibility to the risk of TNBC. An additional cohort with 652 other types of breast cancer (non-TNBC) cases and 890 controls were used to investigate the associations between TNBC-speciifc SNPs genotype and non-TNBCs susceptibility. Results:This study found that rs7250266 in the promoter region of NBA1 confers a decreased risk to TNBC (P<0.01). Compared with CC genotype, women with the GC genotype (OR=0.70, 95%CI:0.51-0.97) and GG genotype (OR=0.48, 95%CI:0.21-1.07) had a lower risk of developing TNBC (P=0.03). In addition, the haplotypes containing two polymorphisms rs7250266 and rs2278256 were associated with a lower chance of TNBC development. In the second part of the study, the result showed that there was no difference in rs7250266 expression between non-TNBC and normal people (0.19 vs 0.18, P=0.85).Conclusion:Genetic variants in NBA1 may be an important genetic determinant of TNBC susceptibility in Chinese women.

Background and purpose:The effect of TPF (docetaxel, cisplatin and 5-lfuorouracil) induction chemotherapy plus concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. This study aimed to compare the outcomes and tolerance of neoadjuvant chemotherapy with TPF versus cisplatin and 5-lfuorouracil (PF) followed by concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma patients.Methods:Patients with locoregionally advanced nasopharyngeal carcinoma were randomly divided into 2 groups: Group TPF and Group PF. Group TPF: One hundred and sixteen nasopharyngeal carcinoma patients received TPF consisting of docetaxel at 60 mg/m2 on day 1, cisplatin at 60 mg/m2 on day 1, and 5-lfuorouracil at a dose of 750 mg/m2by 24 h continuous infusion for 5 days for 3 cycles with a 21 day interval; Group PF: One hundred and sixteen nasopharyngeal carcinoma patients received PF consisting of cisplatin at 80 mg/m2 on day 1, and 5-lfuorouracil at a dose of 750 mg/m2by 24 h continuous infusion for 5 days for 3 cycles with a 21 day interval. After the completion of neoadjuvant chemotherapy, all the patients received intensity modulated radiation therapy (IMRT) with concomitant chemotherapy consisting of 2 cycles of cisplatin at 80 mg/m2 on day 1 and day 22. The prescribed doses were 6 810 cGy at 2.27 Gy/fraction to the gross tumor volume (GTV) with 5 daily fractions per week for 6 weeks. The acute toxicity and tumor response rate (RR), including complete response (CR) and partial response (PR), were evaluated. Addition-ally, the 5-year progress-free survival (PFS) rates and overall survival (OS) rates were further evaluated.Results:RR of Group TPF was higher than that of group PF at the end of neoadjuvant chemotherapy and within 13 weeks of the completion of concurrent chemoradiotherapy. The median recurrence time of TPF group was 2.98 years, and the 5-year PFS was 84.48%. The median recurrence time of PF group was 2.32 years, and the 5-year PFS was 82.75%. There was no statistically signiifcant difference between the 2 groups (P=0.458). The 5-year OS of TPF group was 87.06%, and for the PF group was 85.34%. There was no statistically signiifcant difference between the 2 groups (P=0.274). The incidence of leukopenia, thrombocyte penia, liver and kidney damage, diarrhea and mucosa necrosis in TPF group were signiifcantly higher than those in PF group (P<0.001). TheⅢ andⅣ degrees adverse reactions in TPF group were sig-niifcantly higher than those in PF group (P<0.001).Conclusion:TPF induction chemotherapy was not superior to the PF regimen for locoregionally advanced nasopharyngeal carcinoma patients. It should not be recommended in terms of more acute toxicity.