Small molecule inhibitors of Bcl-2 are a novel class of anticancer drugs that target anti-apoptotic proteins. In recent years,small molecule inhibitors such as ABT-737 ,ABT-263, gossypol, apogossypol,TW-37,obatoclax, HAl4-1 have attracted much reseach attention. Preclinical trials have shown that the inhibitors have cancer killing effect on some tumors when used alone and exhibit striking synergistic effect when combined with radiotherapy and/or chemotherapy.

Autophagy is an evolutionarily conserved lysosomal pathway for the degradation of cytoplasmic proteins,macromolecules,and organelles.Now,autophagic cell death is considered as programmed cell death type Ⅱ.In multiple studies,inhibition of autophagy will result in contrasting outcomes-survival or death.Thus,whether autophagy in cancer cells causes death or protects cells is controversial.Taken together,the manipulation of autophagy may lead to development of new cancer therapies.This article focuses on recent progresses of autophagy research related to human cancers therapy.

Apigenin is a plant flavonoid which has various biological activities and pharmacological effects including anti-tumor, antioxidant, anti-inflammatory, sedative and so on, particularly in the anti-tumor areas. It can inhibit proliferation, invasion, metastasis and angiogenesis of tumor cells. In addition, it can also induce apoptosis and enhance chemotherapy sensitivity.

Objecitve To investigate the changes of chronotropic response before and after percutaneous coronary intervention ( PCI)in patients with coronary disease .Methods A total of 339 patients with coronary disease was included in this study .All sub-jects underwent treadmill exercise test and coronary angiogram , and some patients underwent PCI if necessary .The parameters of chro-notropic response were recorded and analyzed , including ratio of the highest to predicted heart rates ( rHR) ,chronotropic response in-dex ( CRI) , and heart rate reserve ( HRR) .After coronary angiogram , the score of gensin was recorded and analyzed .Results There was significant difference in the parameter of CRI between unstable angina pectoris and silent myocardial ischemia groups ( P <0.05 ) , CRI were 0.80 ±0.11 and 0.89 ±0.07 , respectively .After coronary angiogram and PCI , there were significant differences in the parameters of rHR, CRI, and HRR between pre-therapy and post-treatment ( t =2.440, 1.977, 2.529, all P <0.05).A nega-tive correlation was found between the parameters of rHR , CRI, and HRR and the score of Gensin ( r =-0.686 , -0.673 , and-0.672, all P <0.05).The significant difference in rHR, CRI, and HRR existed between the groups of <20 and >40 ( t =2.567, 2.223, 2.062, all P <0.05).Conclusions Parameters (rHR, CRI, and HRR) had important clinical values in evaluating the changes of chronotropic response before and after PCI in patients with coronary disease with a negative correlation with the score of Gensin.

Objective To investigate the effects of a new c-Met inhibitor SU11274 on apoptosis and motility of c-Met-positive basal-like breast cancer cells MDA-MB-231. Methods The concentrations of SUl1274 were set to 0,0.1,1,10 and 20 μmol/L.Morphological change of apoptotic cells was analyzed by Hoechst33342,MitroTrackerRed and Yo-pro-1 staining.The apoptotic rate of MDA-MB-231 cells were determined by Annexin V/PI double-staining. The expression of apoptosis related proteins (Bcl-XL,Caspase-3 and PARP) and phosphorylation levels of c-Met and Akt were analyzed by Western blot.The capability of motility were measured by wound-healing assay and chemotaxis assay. Results After treatment by SU11274( 10 μmol/L) for 48 h,shrinking apoptotic cells of MDA-MB-231 was observed by flurescent microscope and nuclear fragmentation was seen.Annexin V/PI double-staining showed SU11274induced apoptosis of MDA-MB-231 cells (P ＜ 0.05 ),and the apoptotic rates were (7.3 ± 0.9) ％,( 14.1 ±0.6) ％,(35.5 ± 4.4) ％ and (48.2 ± 5.3 ) ％,respectively.SU11274 downregulated the expression of Bcl-XL and promoted the dissection of Caspase-3 and PARP in a dose dependent relationship.SU11274 prolongs the wound-healing time,decreases the migration cell count (P ＜ 0.05 ) and effectively inhibits the phosphorylation of c-Met and its downstream key proteins Akt in a dose-dependent manner.Conclusions C-Met inhibitor SU11274 induces apoptosis and inhibits the motility of c-Met-positive basallike breast cancer cell line MDA-MB-231,probably through inhibiting phosphorylation of c-Met/PI3K/Akt.

Objective To discuss the effect and safety about large dosage of tilofiban injection into coronary artery in patients with ST-segment elevated myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods A prospective study was conducted. Two hundred and eighteen patients with STEMI admitted into Cardiology Department of Taizhou Central Hospital were enrolled. According to the difference in dosage, they were divided into a large dosage tilofiban group (102 cases) and a routine dosage tilofiban group (116 cases). In both groups, they received the injection of load dosage of tilofiban into coronary artery during they underwent primary PCI, the load dosage being 25μg/kg in the large dosage group, and 10μg/kg in the routine dosage group. Afterwards, the dosage was kept on 0.15μg·kg-1·min-1 in both groups lasting for 18-24 hours. The flow of thrombolysis in myocardial infarction (TIMI) immediately after PCI, the return of ST-segment after operation for 2 hours, the rate of bleeding events, the rate of major adverse cardiac event [MACE, including death, re-infarction and target vessel revascularization (TVR)] and prognosis after operation for 30 days were observed. Results The ratios of the immediate reflow of TIMI 3 grade after operation and the return of ST-segment after operation for 2 hours in the large dosage tirofiban group were higher than those in the routine dosage tirofiban group [the ratio of the reflow of TIMI 3 grade:92.16%(94/102) vs. 81.90%(95/116), the ratio of the return of ST-segment after operation for 2 hours:89.22%(91/102) vs. 73.28%(85/116), both P < 0.05]. The ratios of re-infarction, TVR and the total MACE in 30 days after operation in large dosage tirofiban group were lower than those in the routine dosage tirofiban group [re-infarction: 0.98% (1/102) vs. 2.59% (3/116), TVR: 0.98% (1/102) vs. 2.59% (3/116), total MACE: 1.96% (2/102) vs. 6.03% (7/116), all P < 0.05]. There were no statistically significant differences in mortality and the bleeding events between the large dosage tirofiban group and routine dosage tirofiban group [mortality:0 (0/102) vs. 0.86%(1/116), bleeding events:1.96%(2/102) vs. 0.86%(1/116), both P>0.05]. Conclusion The injection of a large dosage of tilofiban into a coronary artery in patients with STEMI undergoing primary PCI is an effective and safe method to allow them to get more clinical benefits.

Objective: To analyze the feasibility of axillary lymph node staging through sentinel lymph node biopsy (SLNB) after neoad-juvant chemotherapy (NAC) in patients with node-positive breast cancer and to explore the follow-up treatment of these patients. Methods: Clinical data of 82 patients with node-positive breast cancer before NAC in Tianjin Medical University Cancer Institute and Hospital from January 2016 to January 2018 were analyzed retrospectively. All these patients accepted SLNB after NAC. The detection rate, accuracy, false negative rate (FNR), and influencing factors were analyzed. Results: A nodal pathological complete response (PCR) was achieved in 43 of 82 patients. The PCR rate was 52.4%. The detection rate, accuracy, and FNR were 97.56% (80/82), 88.75% (71/80), and 23.08% (9/39), respectively. The accuracy of 1, 2, and≥3 SLNs detected were 90.9% (20/22), 66.7% (10/15), and 95.3% (41/43), respectively. The FNRs were 20.0% (2/10), 71.4% (5/7), and 9.1% (2/22), respectively (both P<0.05). Conclusions: Due to its overall high FNR, without clinically acceptable limits, post-NAC SLNB cannot completely replace axillary lymph node dissection (ALND) in node-positive patients. However, with no less than 3 SLNs detected, SLNB can accurately evaluate the status of axillary lymph nodes.

Objective: To analyze the clinicopathological features and prognosis of breast invasive ductal carcinoma patients receiving radical mastectomy according to the primary tumor location. Methods: From January 2008 to December 2008, 993 patients with breast invasive ductal carcinoma received radical mastectomy in Tianjin Medical University Cancer Institute and Hospital. Patients were grouped according to the primary tumor location when breast cancer was diagnosed. The clinicopathological characteristics and follow-up information of them was collected and analyzed retrospectively. Results: Of the 993 patients, primary tumor located in the upper-outer quadrant (UOQ) in 556 patients (56.0%), the lower-outer quadrant (LOQ) in 97 (9.8%), the central portion in 99 (10.0%), the upper-inner quadrant (UIQ) in 186 (18.7%), and the lower-inner quadrant (LIQ) in 55 (5.5%). Patients in the central portion tended to have larger tumors, and more patients in the upper-inner quadrant received endocrine therapy. The estimated 5-year disease-free survival (DFS) rates of patients with primary lesion in the UOQ, LOQ, central portion, UIQ and LIQ were 90.3%, 88.7%, 79.8%, 86.0% and 72.7%, respectively, with significant differences (P<0.001). The 5-year overall survival (OS) rates were 97.5%, 96.9%, 90.9%, 94.1% and 87.3%, respectively, with significant differences (P<0.001). Multivariate analysis showed that 5-year recurrence and metastasis risks were significantly increased in patients with primary lesion in the central portion, UIQ and LIQ compared to other groups (P<0.001), and 5-year mortality risks were increased in these three groups (P=0.002). Conclusion Primary lesion located in central portion and inner quadrant is an independent adverse prognostic factor for patients with breast invasive ductal carcinoma patients receiving radical mastectomy.

Objective:To investigate the effect of peripheral blood methylation hyaluronoglucosaminidase 2 (HYAL2) before initial chemotherapy in Ⅱ to Ⅲ rectal cancer patients undergoing adjuvant chemotherapy after surgery.Methods:The clinical data of 98 patients with Ⅱ to Ⅲ rectal cancer from May 2019 to May 2021 in Sinopharm Dongfeng General Hospital, Hubei University of Medicine were retrospectively analyzed. All patients underwent adjuvant chemotherapy after radical surgery. The clinical characteristics of patients were record. The peripheral blood level of methylation HYAL2 before initial chemotherapy was detected by real-time fluorescence quantitative polymerase chain reaction. The cut-off value of peripheral blood methylation HYAL2 level was determined by X-tile 3.6.1 software. Multivariate Cox regression was used to analyze the independent risk factors of overall survival (OS) and disease-free survival (DFS) in patients with Ⅱ to Ⅲ rectal cancer. Kaplan-Meier survival curve was drawn to analyze the survival status in Ⅱ to Ⅲ rectal cancer patients with different peripheral blood level of methylation HYAL2. The efficacy of peripheral blood level of methylation HYAL2 in predicting the DFD and OS in patients with Ⅱ to Ⅲ rectal cancer was evaluated by the receiver operating characteristics (ROC) curve.Results:The peripheral blood level of methylation HYAL2 in 98 patients with Ⅱ to Ⅲ rectal cancer before initial chemotherapy was (45.13 ± 12.13)%, and the cut-off for evaluating OS was 43.18% by X-tile 3.6.1 software. Among them, 66 cases were high expression (peripheral blood level of methylation HYAL2 ≥43.18%), and 32 cases were low expression (<43.18%). The tumor diameter and TNM stage were the affect factors of peripheral blood level of methylation HYAL2 in patients with Ⅱ to Ⅲ rectal cancer ( P<0.05); the peripheral blood level of methylation HYAL2 was not related to gender, age, differentiation degree, lymph node metastasis and depth of invasion ( P>0.05). Multivariate Cox regression analysis result showed that TNM stage and peripheral blood level of methylation HYAL2 were the independent risk factors of OS in patients with Ⅱ to Ⅲ rectal cancer ( HR = 0.451 and 1.697, 95% CI 0.204 to 1.001 and 0.309 to 2.787, P<0.05); the peripheral blood level of methylation HYAL2 was an independent risk factor of DFS in patients with Ⅱ to Ⅲ rectal cancer ( HR = 1.027, 95% CI 0.146 to 1.943, P<0.05). Kaplan-Meier survival curve analysis result showed that the median OS and DFS in patients with low peripheral blood level of methylation HYAL2 were significantly longer than those in patients with high peripheral blood level of methylation HYAL2 (29 months vs. 21 months and 26 months vs. 21 months), and there were statistical differences (log-rank χ2 = 12.57 and 8.66, P<0.05). ROC curve analysis result showed that the area under curve (AUC) of peripheral blood level of methylation HYAL2 to predict the OS in patients with Ⅱ to Ⅲ rectal cancer was 0.882 (95% CI 0.801 to 0.938), with the specificity of 65.67% and the sensitivity of 99.45%; the AUC of peripheral blood level of methylation HYAL2 to predict the DFS in patients with Ⅱ to Ⅲ rectal cancer was 0.847 (95% CI 0.760 to 0.913), with the specificity of 62.90% and the sensitivity of 97.22%. Conclusions:The peripheral blood level of methylation HYAL2 before initial chemotherapy is an independent risk factor of prognosis in Ⅱ to Ⅲ rectal cancer patients undergoing adjuvant chemotherapy after surgery, and it can serve as an index for prognostic evaluation.

Objective To analyze the clinicopathological features and prognosis of breast invasive ductal carcinoma patients receiving radical mastectomy according to the primary tumor location. Methods From January 2008 to December 2008, 993 patients with breast invasive ductal carcinoma received radical mastectomy in Tianjin Medical University Cancer Institute and Hospital. Patients were grouped according to the primary tumor location when breast cancer was diagnosed. The clinicopathological characteristics and follow?up information of them was collected and analyzed retrospectively. Results Of the 993 patients, primary tumor located in the upper?outer quadrant ( UOQ) in 556 patients ( 56.0%), the lower?outer quadrant (LOQ) in 97 (9.8%), the central portion in 99 (10.0%), the upper?inner quadrant (UIQ) in 186 (18.7%), and the lower?inner quadrant (LIQ) in 55 (5.5%). Patients in the central portion tended to have larger tumors, and more patients in the upper?inner quadrant received endocrine therapy. The estimated 5?year disease?free survival (DFS) rates of patients with primary lesion in the UOQ, LOQ, central portion, UIQ and LIQ were 90.3%, 88.7%, 79.8%, 86.0% and 72.7%, respectively, with significant differences (P＜0.001). The 5?year overall survival (OS) rates were 97.5%, 96.9%, 90.9%, 94.1% and 87.3%, respectively, with significant differences ( P＜0.001). Multivariate analysis showed that 5?year recurrence and metastasis risks were significantly increased in patients with primary lesion in the central portion, UIQ and LIQ compared to other groups ( P＜0.001), and 5?year mortality risks were increased in these three groups (P＝ 0.002). Conclusion Primary lesion located in central portion and inner quadrant is an independent adverse prognostic factor for patients with breast invasive ductal carcinoma patients receiving radical mastectomy.