To investigate the effect of chloroxoquinoline on cytoskeleton of breast cancer cells and its relation with Rho/Rho kinase signaling pathway.

Aromatase inhibitors (AIs) directly applies to postmenopausal breast cancer patients. Patients underwent bilateral ovariectomy or ≥60 years were acknowledged as postmenopausal.Alternatively, for <60 years breast cancer patients, sex hormone detection to evaluate menopause is recommended by National Comprehensive Cancer Network (NCCN) guideline, textbooks, and AIs clinical trials.However, series of clinical trial found that, a broad overlap region of follicle stimulating hormone and estradiol appeared between premenopausal and postmenopausal patients, which unable to determine the menopause even with sensitivity promotion of detection equipment or manners.We have abandon this detection in clinical treatment, and decision making was only according to the relapse risk and disease status. We recommend bilateral ovariectomy resection accompanied with AIs for breast cancer patients with high recurrence risk (e.g. T3-4 or LNM≥4) or patients with advanced metastatic disease.However, patients with low or moderate recurrence risk can be treated with tamoxifen.

Hyperthermic intraperitoneal chemotherapy (HIPEC) has a unique effect on the prevention and treatment of peritoneal metastasis from malignancies. Recently, the first prospective, multicenter, randomized controlled clinical trial of HIPEC to prevent the development of peritoneal metastasis after curative surgery for patients with locally advanced colon cancer was published in the "Lancet Gastroenterol Hepatol" (COLOPEC). Regrettably, no significant difference was observed in 18-month peritoneal metastasis-free survival between postoperative adjuvant HIPEC and standard systemic chemotherapy for patients with T4 stage or perforated colon cancer. However, we wonder whether we might achieve better outcomes by further optimizing the following issues: (1) We propose that the inclusion criteria for that trial may not be entirely reasonable, which included pT4N0-2M0 and perforation. Additionally, we found that 91% of patients underwent HIPEC 5-8 weeks after primary tumor resection. (2) The imbalance in starting time of postoperative systemic chemotherapy between the two groups may have a negative impact.(3) Nine patients with peritoneal metastasis preceding HIPEC might weaken the potential efficacy of HIPEC. (4) We wonder whether HIPEC using high-dese oxaliplatin (460 mg/m(2)) perfusing 30 minutes for one cycle is the optimal regimen. Therefore, we are planning to conduct a randomized controlled trial (HIPEC-06) in accordcance with the characteristics of Chinese patients, to explore the clinical efficacy of curative surgery combined with HIPEC in the treatment of cT4 colorectal cancer.

Objective: To study influencing factors which cause the endometrial diseases in patients with breast cancer after operation. Methods: A retrospective study was performed on 212 breast cancer post-operation patients with endometrial diseases between June 2006 and January 2018 in Women's Hospital School of Medicine Zhejiang University to analyse the factors which influenced the endometrial diseases. Results: The abnormal uterine bleeding and endometrial thickness were related to the severity of endometrial disease in patients with breast cancer, and they were independent risk factors for breast cancer patients to have endometrial cancer (P<0.05) . When the diagnostic cut off value of endometrial thickness was ≥0.49 cm, the sensitivity and specificity to endometrial cancer were 78% and 25%, respectively. The average endometrial thickness was (0.56±0.39) cm in patients who were treated by selective estrogen receptor modulator (SERM) after gynecological surgery, which was significantly thicker than that of aromatase inhibitor (AI) group [ (0.33±0.23) cm] and no treatment group [ (0.44±0.28) cm, P<0.05]. The endometrial disease recurrent rate and reoperation rate in SERM group were (26.2%, 14.3%) slightly higher than that of AI group (9.5%, 4.8%) and no treatment group (21.6%, 4.9%), but there were not significant differences (all P>0.05). Conclusions: The clinical symptom of abnormal uterine bleeding and thickening endometrium are risk factors for breast cancer patients to have endometrial cancer. The endometrial thickness has high predictive value for breast cancer patients to diagnose endometrial cancer. The SERM treatment increases the endometrial thickness, recurrent rate and reoperation rate in post-operation patients.

According to drug design flattening principle and using podophyllotoxin or 4'-demethylepipodophyllotoxin and aldehydes as starting material,a series of podophyllotoxin derivatives containing an imine structure with low toxicity were highly effective synthesized. Nine target compounds were successfully synthesized,and their structures were confirmed by ~1H-NMR,HR-ESI-MS and melting point data analysis. Using etoposide as positive control drug,nine target compounds were screened for cytotoxicity against He La cells in vitro by MTT method. The antitumor activity screening results showed that compound 6 b,6 d,6 e,6 f,6 g,6 i exhibited higher inhibitory rate against He La cells than those of control drug VP-16. It provides some practical reference value for the further development on the structure modification of podophyllotoxin and study on anti-tumor activity.

To explore the effect of the composition ratio on substitution of sulfate group in sulfated exopolysaccharide (EPS) from Rhizopus nigricans and how sulfate modification affects the anti-tumor activity of EPS.

Objective: To describe the status of non-steroidal anti-inflammatory drugs (NSAIDs) use in areas with a high incidence of upper gastrointestinal cancer in China. Methods: This study was based on the National Key Research and Development Program of "National Precision Medicine Cohort of Esophageal Cancer" and "Study on Identification and Prevention of High-risk Populations of Gastrointestinal Malignancies (Esophageal cancer, Gastric cancer and Colorectal cancer)" . From January 2017 to August 2018, 212 villages or communities with a high incidence of esophageal cancer or gastric cancer were selected from 12 regions in 6 provinces. A total of 35 910 residents aged between 40 and 69 years old who met the inclusion criteria and signed the informed consent were investigated and enrolled in this study. The use of NSAIDs, demographic characteristics, health-related habits, height, weight, and blood pressure were collected by the questionnaire and physical examination. The status of main NSAIDs (aspirin, acetaminophen and ibuprofen) use with the difference varying in genders, age groups and regions were analyzed by using χ(2) test and Cochran-Armitage trend analysis method. Results: Of 35 910 subjects, the mean age was (54.6±7.1) years old and males accounted for 43.42% (15 591). The overall prevalence of NSAIDs intake was 4.56% (1 638), but it significantly varied in different provinces (P<0.001). The overall prevalence of NSAIDs intake was 4.87% (1 750) in females, which was significantly higher than that in males 4.24% (1 524) (P<0.001). The prevalence of NSAIDs intake increased with age (P for trend <0.001). As the frequency of NSAIDs intake increased, the incidence of gastrointestinal symptoms, gastrointestinal ulcers and black stools increased (P for trend <0.05 for all). Conclusion: The use of NSAIDs is prevalent in some areas with a high incidence of upper gastrointestinal cancer in China. The increased use of NSAIDs may lead to more adverse effects related to the gastrointestinal tract.

Objective: To evaluate the efficacy and safety of apatinib combined with chemotherapy in the first-line treatment of advanced non-small cell lung cancer (NSCLC) with negative driving genes. Methods: From January 2016 to March 2018, 62 advanced NSCLC patients with negative driving genes diagnosed at Xuzhou Cancer Hospital were randomly divided into study group (30 cases) and control group (32 cases), respectively. The patients in the study group were treated with standard first-line chemotherapy combined with apatinib, while those in control group were treated with chemotherapy alone. Results: The disease control rate (DCR) and objective remission rate (ORR) in the study group were 60.0% and 16.7%, respectively, higher than 46.9% and 9.3% in the control group, but without statistical difference (P>0.05). The median progression-free survival (PFS) of study group and control group were 6.4 months and 4.9 months, respectively (P=0.004), and the median overall survival (OS) were 11.3 months and 9.2 months, respectively (P=0.006). Multivariate survival analysis indicated that treatment regimen (P=0.001) was the independent prognostic factor of PFS, and PS score (P=0.002), clinical stage (P=0.02) and treatment regimen (P<0.001) were the independent prognostic factors of OS. After treatment, the incidence of hypertension and hand-foot syndrome in the study group were 46.7% and 53.3%, respectively, significantly higher than 3.3% and 0 in the control group, respectively (P<0.05). The incidence of grade 3-4 adverse drug reactions (ADRs) in the study group was 26.7% (8/30), mainly including hypertension, hand-foot syndrome and bone marrow suppression. The incidence of grade 3-4 ADRs in the control group was 15.6% (5/32), all of which were bone marrow suppression, without significant difference (P=0.286). There was no difference in serum levels of VEGF and CEA between the two groups before treatment. After treatment, the serum level of VEGF in the study group was (169.3±10.1) pg/ml, lower than (211.8±16.7) pg/ml of the control group (P<0.05). Conclusion: Apatinib combined with first-line chemotherapy for advanced NSCLC patients with negative driving genes is safe and beneficial for survival. This therapeutic strategy can significantly prolong the PFS and OS, and further improvement and application can be considered as a choice in the clinical treatment.

Microsatellite instability (MSI) which resulted from the deficiency of DNA mismatch repair (MMR), is an important clinical significance in the related solid tumors, such as colorectal cancer and endometrial cancer. There are several methods to detect MSI status, including immunohistochemistry for MMR protein, multiplex fluorescent polymerase chain reaction (PCR) for microsatellite site and MSI algorithm based on next generation sequencing (NGS). The consensus elaborates the definition and clinical significance of MSI as well as the advantages and disadvantages of the three detection methods. Through this expert consensus, we hope to promote the screening which based on MSI status in malignant tumors and improve the acknowledge of clinicians about various testing methods. Thereby, they could interpret the results more accurately and provide better clinical services to patients.

The incidence of retroperitoneal tumor is low, and treatment is difficult.According to the recent updates of evidence-based medical evidence at home and abroad, the consensus on the standardized treatment of retroperitoneal tumors were discussed including examination and diagnosis , surgical treatment comprehensive treatment, nutrition, rehabilitation, and review and follow-up, etc.

Pathological myopia refers to high myopia with fundus pathological changes. Choroidal neovascularization is one of its serious complications, and also the main cause of visual loss. Currently, the first-line treatment is anti-VEGF treatment, with good efficacy, high safety, good prognosis, and other advantages of vision. Commonly used anti-VEGF drugs include bevacizumab, ranibizumab, aflibercept, and conbercept. The main treatment strategies include 1+pro re nata and 3+pro re nata, and the standard of REPAIR test is often used to evaluate the re-injection. This article reviews the advantages of anti-VEGF therapy, drug selection, treatment strategy, and re-injection criteria. (Chin J Ophthalmol, 2019, 55:791-795).

To observe the effect of Tripterygium Glycosides Tablets on angiogenesis of rats with type Ⅱ collagen-induced arthritis( CIA) and on the tube formation of human umbilical vein endothelial cells( HUVEC) in vitro. The HUVEC were induced by 20 μg·L-1 vascular endothelial growth factor( VEGF) in vitro,and were treated with 0. 1,1,10 mg·L-1 Tripterygium Glycosides Tablets continuously for 7 hours. The numbers of branches of tube formation were measured. SD rats were immunized to establish CIA. CIA rats were treated with 9,18,36 mg·kg-1·d-1 Tripterygium Glycosides Tablets for 42 days. Histopathological examination( HE) was performed to observe the vascular morphology and vascular density in the synovial membrane of the inflamed joints. Immunohistochemistry and immunofluorescence were performed to observe the expression of platelets-endothelial cell adhesion molecule( CD31) and αsmooth muscle actin( αSMA) in synovial membrane. Immunohistochemistry and Western blot were performed to observe the expression of hypoxia-inducible factors 1α( HIF1α) and angiotensin 1( Ang1) in the synovial tissue. The results showed that the numbers of branches of tube formation of HUVEC induced by VEGF were improved,and declined significantly after treated by Tripterygium Glycosides Tablets. Compared with the normal group,the vascular density,CD31 positive expression,CD31 +/αSMA-immature and total vascular positive expression in the synovial membrane of the model group were significantly increased,and so as HIF1α and Ang1 in the synovium. Tripterygium Glycosides Tablets reduced the synovial vascular density and inhibited the positive expression of CD31,CD31+/αSMA-immature blood vessels and total vascular,but has no effect on CD31+/αSMA+mature blood vessels. Tripterygium Glycosides Tablets also inhibited the expression of HIF1α and Ang1 in synovial membrane of inflammatory joints. Our results demonstrated that Tripterygium Glycosides Tablets could inhibit the angiogenesis of synovial tissue in CIA rats and the tube formation of HUVEC,which is related to the down-regulation of HIF1α/Ang1 signal axis.

Tumors are major chronic diseases and seriously threaten human health all over the world. How to effectively control and cure tumors is one of the most pivotal problems in the medical field. At present,surgery,radiotherapy and chemotherapy are still the main treatment methods. However,the side effects of radiotherapy and chemotherapy cannot be underestimated. Therefore,it is of great practical significance to find new anti-cancer drugs with low toxicity,high efficiency and targeting to cancer cells. With the increasing incidence of tumor,the anti-tumor effect of traditional Chinese medicine has increasingly become a research hotspot. Triptolide,which is a natural diterpenoid active ingredient derived from of Tripterygium wilfordii,as one of the highly active components,has anti-inflammatory,immunosuppressive,anti-tumor and other multiple effects. A large number of studies have confirmed that it has good anti-tumor activity against various tumors in vivo and in vitro. It can play an anti-tumor role by inhibiting the proliferation of cancer cells,inducing apoptosis of cancer cells,inducing autophagy of cancer cells,blocking the cell cycle,inhibiting the migration,invasion and metastasis of cancer cells,reversing multidrug resistance,mediating tumor immunity and inhibiting angiogenesis. On the basis of literatures,this paper reviews the anti-tumor effect and mechanism of triptolide,and analyzes the current situation of triptolide combined with other chemotherapy drugs,in order to promote deep research and better clinical application about triptolide.

Objective: To evaluate the efficacy of the Chinese Children's Leukemia Group (CCLG) acute lymphoblastic leukemia (ALL) 2008 protocol (CCLG-ALL 2008) in the treatment of children's T-cell acute lymphoblastic leukemia (T-ALL). Methods: Clinical characteristics and outcomes of 84 newly diagnosed T-ALL children (63 males and 21 females) treated with CCLG-ALL 2008 protocol from April 2008 to April 2015 in the Department of Pediatric Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences were analyzed retrospectively. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and event free survival (EFS), and COX regression was used to evaluate the influencing factors of OS and EFS. Results: (1) Baseline data: 84 children were included, 56 cases (67%) of children were younger than 10 years old. Patients whose white blood cell count≥50×10(9)/L ranked 70% (59/84). Karyotype: 58% (49/84) with normal karyotype, 10% (8/84) with abnormality of chromosome 11, 8%(7/84) with abnormality of chromosome 9, 2%(2/84) with abnormality in both chromosome 11 and chromosome 9, 8% (7/84) with other complex karyotypes. Fusion gene: 33%(28/84) were SIL-TAL1 positive. The patients were grouped by CCLG-ALL 2008 risk score, 40% (34/84) were in the intermediate risk group and 60% (50/84) in the high risk group. (2) Treatment efficacy: 84 cases were followed up until May 30, 2018. The follow-up time was 42.0 (0.3-120.0) months. The sensitivity rate of prednisone treatment was 56% (47/84); the complete response (CR) rate after the induction therapy of vincristine+daunoblastina+L-asparaginase+dexamethasone (VDLD)(d 33) was 88% (74/84); the total CR rate after VDLD induction combined with cyclophosphamide+cytarabine+6-mercaptopurine (CAM) treatment (d80) was 94% (79/84); the recurrence rate was 24% (20/84). Among the 20 recurrent cases, there were 13 cases (65%) with ultra-early recurrence (within 18 months after diagnosis), 6 cases (30%) with early recurrence (18 to 36 months after diagnosis); 1 patient (5%) with late recurrence (over 36 months after diagnosis). During the follow-up period, twenty-eight children (33%) died (22 cases with recurrence or suspending treatment without remission, 2 cases with infection, 1 case of sudden death in chemotherapy, 1 patient failed in transplantation, 1 patient with severe cirrhosis, and 1 patient with unknown cause). (3) Kaplan-Meier analysis: the 5-year OS and EFS of the 84 children were (63±6)% and (60±6)% respectively. (4) Efficacy in different risk groups: prednisone sensitivity rates in the two different risk groups were 100% (34/34) and 26% (13/50), respectively (χ(2)=3.237, P<0.05). The CR rates at the end of VDLD induction therapy (d 33) were 100% (34/34) and 80% (40/50), respectively (χ(2)=2.767, P<0.05). The recurrence rate of children in the two groups was 12% (4/34) and 32% (16/50), respectively (χ(2)=4.245, P<0.05).The mortality rates of the two groups were 21% (7/34) and 42% (21/50), respectively (χ(2)=3.198, P<0.05). Kaplan-Meier analysis showed that the 5-year OS of the two groups were (77±7)% and (53±8)%; and the 5-year EFS of the two groups were (75±8)% and (49±8)% (χ(2)=4.235, 3.875, both P<0.05) . (5) COX multivariate regression analysis showed that the classification of risk according to CCLG-ALL 2008 was an important factor influencing the prognosis of children with T-ALL (OR=3.313, 95% CI 1.165-9.422, P=0.025). Conclusions: The results of the risk group treatment according to the CCLG-ALL 2008 protocol showed that the long-term survival of children with middle risk was significantly better than that of children at high risk.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumors in the gastrointestinal tract. Though surgical resection is the only radical treatment, postoperative recurrence and metastasis often occur. The first-line therapy for the treatment of recurrent, metastatic and unresectable GIST is imatinib. More than 80% of patients can benefit from imatinib treatment, but half of patients will still have recurrence or metastasis within 2 years after treatment initiation, and secondary drug resistance is a major cause of disease progression. Therefore, adeep understanding of the mechanisms of secondary drug resistance will guide us to develop personalized therapeutic schedule in the future. This article describes the mechanism of IM secondary resistance from the aspects of gene alteration, abnormal activation of signal transduction pathway, autophagy, apoptosis and drug concentration. It is found that single drug therapy has certain limitations in patients with secondary resistance to IM. Using IM combined with downstream signaling molecule inhibitors, autophagy inhibitors, insulin-like growth factor 1 receptor (IGF-1R) inhibitors, heat shock protein 90 (HSP90) inhibitors, cytotoxic T lymphocyte - associated antigen - 4 (CTLA - 4) antibodies and mitochondrial inhibitors provide us new therapeutic ideas. However, these combination treatments are still in the research phase, and further trials are needed to confirm the safety and efficacy. With the gradual deepening of research on drug resistance mechanisms, it will provide more solutions to the current serious drug resistance problem.