To observe the effectiveness of grain-moxibustion in resisting oxidative stress in doxorubicin (DOX)-induced cardiomyopathy rats.

To investigate the inhibitory effect of decitabine (DAC) in various dosages on the proliferention of MDS-RAEB cell line MDS-L and its mechanism.

To explore the effects of mTOR inhibitor rapamycin on proliferation, cell cycle and apoptosis of Burkitt's lymphoma cell line Raji and CA46 cells and its mechanism, so as to provide the experimental evidence for a therapeutic target of Burkitt's lymphoma.

To explore the molecular mechanism of resistance to imatinib in K562 cells(K562-R) and the anti-proliferative effect of oridonin (OR), as well as its mechanism in imatinib-sensitive and imatinib-resistant K562 cells (K562-S and K562-R cells).

To investigate the effects of rigosertib on the apoptosis, proliferation and cell cycle of HEL and K562 cells.

To investigate the synergistic antiproliferative and inducing-apoptotic effect of EPZ-5676 combined with chemotherapeutic drugs on acute lymploblastic leukemia(ALL).

Objective: To explore the influence of the 4th revised treatment recommendations in childhood acute lymphoblastic leukemia (ALL) on high dose methotrexate(HD-MTX)-induced nephrotoxicity and MTX blood concentrations. Method: The clinical data from 330 ALL children who received 1 242 courses of HD-MTX therapies from September 2012 to November 2016 was collected. The courses were divided into two groups based on the chemotherapies: original scheme group was treated with the 3rd revised regimen, and new scheme group was treated with the 4th revised regimen. The two groups in acute kidney injury (AKI) and MTX blood concentrations were compared. Result: The incidences of AKI with low risk (LR) and intermediate risk (IR) in new scheme group were significantly lower than those in original scheme group (1.3%(3/229) vs. 7.9%(24/303), 4.9%(10/204) vs. 12.8%(26/203), χ(2)=11.831 and 7.888 respectively, both P<0.05). There was no significant difference in the incidence of AKI with high risk (HR) in the two groups (15.2%(10/66) vs. 10.5%(25/237), χ(2)=1.071, P>0.05). The 48h MTX blood concentrations and the interphase from onste to MTX concentrations decreased to the safe level with LR and IR children in new scheme group were significantly lower than those in original scheme group (0.36(0.08-4.00) vs. 0.44(0.06-32.00) μmol/L, 0.49(0.22-33.00) vs. 0.60(0.18-83.00) μmol/L, 3(2-6) vs. 3(2-11) d, 3(2-11) vs. 3(2-19) d, Z=-5.953, -2.658, -4.490 and -4.729 respectively, all P<0.05). The differences with HR were not observed between the two groups (0.61(0.14-36.00) vs. 0.71(0.11-68.00) μmol/L, 3(2-15) vs. 3(2-13) d, Z=-1.465 and -1.179 respectively, both P>0.05). Conclusion: Decreased renal toxicity and acceleration of MTX excretion may occur when childhood ALL with LR and IR were treated with the 4th revised regimen. However, nephrotoxicity and MTX blood concentrations have no significant differences with HR in the two regimens, and close monitoring are necessary.

Seven lanostane-type triterpenes including fomitopsin C(1),3-keto-dehydrosulfurenic acid(2),dehydroeburiconic acid(3),3-acetyloxylanosta-8, 24-dien-21-oic acid(4),pinicolic acid A(5),trametenolic acid B(6),and eburicoic acid(7),were isolated from the fruitbodies of Fomitopsis pinicola and F. officinalis. In vitro assay, all compounds were evaluated against MCF-7, HeLa, HepG2 and A549 cells lines using the MTT assay and the structure-activity relationship of antitumor activity was discussed. The results showed that the seven compounds were more sensitive to MCF-7 cells.The IC₅₀ value for MCF-7 was 2<5<4<1<3<6<7. H22 tumor mouse model was used to assay compounds 2, 3, 4 and 5 in vivo. Compounds 2 and 4 had obvious effect and the necrosis area and measurement were positively correlated. The results showed that compounds 2, 4 and 5 had significant antitumor activities at a dose of 20 mg•L⁻¹ with 65.31%, 56.71%, 58.72% suppression, respectively, approaching to CTX group with 69.19% suppression in subcutaneous H22-implanted mice.The results showed that these compounds had significant against the expression of VEGF, cytokines IL-4 and IFN-γ tumor, additionally, the structure-activity relationship of lanostane-type triterpenes indicated that the acetoxyl or carbonyl at C-3 and hydroxy at C-15 can enhance the antitumor activity.

In this study, the tanshinone ⅡA loaded albumin nanoparticles were prepared by high pressure homogenization method. The formulation was optimized by central composite design-response surface method (CCD-RSM), with the particle size, encapsulation efficiency, and drug loading as indexes to investigate their in vitro anti-tumor effect. The results showed that the prepared nanoparticles had uniformly spherical morphology and uniform particle size distribution. The average particle size, encapsulation efficiency and drug loading of nanoparticles were about (175.7± 3.07) nm, 90.8%±1.47% and 5.52%±0.09%, respectively. Tanshinone ⅡA loaded albumin nanoparticles showed a more powerful antitumor effect than free tanshinone ⅡA for human promyelocytic leukemia NB4 cells. The preparation method of the drug-loaded albumin nanoparticles was simple and easy, and can significantly improve the solubility of tanshinone ⅡA, so it was helpful to extend its application in therapies against hematological malignancies.

It has reported that Ganoderma lucidum triterpenoids had anti-tumor activity. However, the anti-tumor target is still unclear. The present study was designed to investigate the anti-tumor activity of G. lucidum triterpenoids on different tumor cells, and predict their potential targets by virtual screening. In this experiment, molecular docking was used to simulate the interactions of 26 triterpenoids isolated from G. lucidum and 11 target proteins by LibDock module of Discovery Studio2016 software, then the anti-tumor targets of triterpenoids were predicted. In addition, the in vitro anti-tumor effects of triterpenoids were evaluated by MTT assay by determining the inhibition of proliferation in 5 tumor cell lines. The docking results showed that the poses were greater than five, and Libdock Scores higher than 100, which can be used to determine whether compounds were activity. Eight triterpenoids might have anti-tumor activity as a result of good docking, five of which had multiple targets. MTT experiments demonstrated that the ganoderic acid Y had a certain inhibitory activity on lung cancer cell H460, with IC₅₀ of 22.4 μmol•L ⁻¹, followed by 7-oxo-ganoderic acid Z2, with IC₅₀ of 43.1 μmol•L ⁻¹. However, the other triterpenoids had no anti-tumor activity in the detected tumor cell lines. Taking together, molecular docking approach established here can be used for preliminary screening of anti-tumor activity of G.lucidum ingredients. Through this screening method, combined with the MTT assay, we can conclude that ganoderic acid Y had antitumor activity, especially anti-lung cancer, and 7-oxo-ganoderic acid Z2 as well as ganoderon B, to a certain extent, had anti-tumor activity. These findings can provide basis for the development of anti-tumor drugs. However, the anti-tumor mechanisms need to be further studied.

Objective: To investigate the relationship of heterogeneity of esophageal squamous cell carcinoma (ESCC) and chemotherapy sensitivity. Methods: Five different region specimens isolated from primary tumor(R1~R5)and 1 specimen(R6)isolated from adjacent non-neoplastic tissue from 10 ESCC patients who underwent surgical treatment were cultured in vitro. The inhibitory effect of cisplatin on proliferation of ESCC cells from different regions was determined by methyl thiazolyl tetrazolium (MTT). The cell cycle and apoptosis induced by cisplatin was determined by flow cytometry (FCM) analysis. The mRNA levels of ATP7A and ATP7B were determined by quantitive RT-PCR (qRT-PCR). Results: The result showed that different regions of each specimen exhibited different chemotherapy sensitivity to cisplatin, and the cell survival rates of region R6 of each specimen were higher than other regions from the same specimen. The cell survival rate of region R3 from the tenth specimen was (81.42±8.84)%, which is significantly higher than (11.90±2.75)% of region R5 (P<0.01). FCM analysis showed that significant differences of early apoptosis and later apoptosis were observed in six specimens induced by cisplatin (P<0.05), and significant differences of cell cycle and G(1) period were observed in seven specimens (P<0.05). The qRT-PCR results showed that the mRNA level of ATP7A in region R1, R2, R3, R4 and R5 was (100.00±3.42)%, (118.10±2.21)%, (75.40±4.15)%, (95.40±3.32)% and (41.70±2.57)%, respectively, with significant differences (P<0.05). The mRNA level of ATP7A in region R6 was (175.20±5.32)%, significantly higher than those of regions from R1 to R5 (P<0.05). The mRNA level of ATP7B in region R1, R2, R3, R4 and R5 was (100.00±4.89)%, (73.60±2.65)%, (175.60±6.12)%, (46.10±4.62)% and (363.70±8.67)%, respectively, with significant differences (P<0.05). The mRNA level of ATP7B in region R6 was (1 165.40±7.25)%, significantly higher than those of regions from R1 to R5 (P<0.05). Conclusion: The intratumor heterogeneity of ESCC results in the heterogeneity of resistance to cisplatin, which affects the chemotherapeutic effect.

Objective: To explore the synergistic effect of silibinin combined with crizotinib on anaplastic lymphoma kinase positive (ALK+ ) non-small cell lung cancer (NSCLC) cells and its mechanism. Methods: H2228 and H3122 cells were treated with silibinin, crizotinib alone or in combination. Cell proliferation was measured by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and colony formation assay. Migration or invasion ability was tested by wound healing assay or transwell assay, respectively. Expressions of E-Cadherin and vimentin protein were examined by immunofluorescence staining. The protein expressions of ALK, p-ALK, E-Cadherin and Vimentin were detected by western blotting.The anti-cancer effect of silibinin combined with crizotinib in vivo was determined by subcutaneously injecting 2×10(6) H2228 cells into immunodeficient nude mice. Results: The result of MTT assay showed that the cell viability of H2228 or H3122 treated with 100 μmol/L silibinin was (88.38±4.10)% or (72.27±3.62)%, respectively, marginally decreased compared with that of the control. The 50% inhibitory concentration (IC(50)) of H2228 cells treated with crizotinib alone or combined with 100 μmol/L silibinin was (917.10±7.75) nmol/L or (238.73±7.67) nmol/L, respectively. The IC(50) of H3122 cells treated with crizotinib alone or combined with 100 μmol/L silibinin was (472.50±15.70) nmol/L or (206.10±12.01) nmol/L, respectively. The IC(50s) of H2228 and H3122 cells were significantly decreased by combined treatment of crizotinib and silibinin compared to crizotinib treatment alone (P<0.01). When compared with the control group, colony forming ratios of H2228 cells were (83.34±2.72)% in 100 μmol/L silibinin treatment group, (69.42±3.06)% in 400 nmol/L crizotinib treatment group and (27.32±1.42)% in combined treatment group. When compared with the control group, colony forming ratios of H3122 cells were (84.45±5.67)% in 100 μmol/L silibinin treatment group, (45.02±5.83)% in 400 nmol/L crizotinib treatment group and (17.43±3.83)% in combined treatment group. Silibinin combined with crizotinib treatment significantly inhibited the colony formation ability of H2228 and H3122 cells (P<0.01). Migration and invasion results showed that combined treatment of crizotinib and silibinin markedly inhibited the migration and invasion ability of H2228 cells (P<0.01). Western blot results indicated that treated with silibinin alone or in combination of crozitinib for 48 hours, the protein level of E-cadherin in H2228 cells was upregulated, while the expressions of p-ALK and vimentin were downregulated, without obvious alteration of ALK protein expression. In the xenograft model, the mean tumor weight was (9.40±2.58)g in crizotinib treatment group and (4.58±1.07)g in the combined treatment group. The inhibitory effect of tumor growth in vivo of combined treatment was significantly superior to that of crizotinib treatment alone (P<0.05). Conclusion: Silibinin enhances the inhibitory effect of crizotinib on ALK positive NSCLC cells, which may be associated with suppression of ALK activity and mesenchymal-epithelial transition.

A target cell extraction-chemical profiling method based on human alveolar adenocarcinoma cell line (A549 cells) and UHPLC/LTQ Orbitrap MS for screening the anti-lung cancer bioactive compounds from Curcuma longa has been developed in this paper. According to the hypothesis that when cells are incubated together with the extract of Curcuma longa, the potential bioactive compounds in the extract should selectively combine with the cells, then the cell-binding compounds could be separated and analyzed by LC-MS. The bioactive compounds in C. longa are lipophilic components. They intend to be absorbed on the inner wall of cell culture flask when they were incubated with A549 cells, which will produce interference in the blank solution. In this paper, by using cells digestion and multi-step centrifugation and transfer strategy, the interference problem has been solved. Finally, using the developed method, three cell-binding compounds were screened out and were identified as bisdemethoxycurcumin, demethoxycurcumin, and curcumin. These compounds are the main bioactive compounds with anti-lung cancer bioactivity in C. longa. The improved method developed in this paper could avoid the false positive results due to the absorption of lipophilic compounds on the inner wall of cell culture flask, which will to be an effective complementary method for current target cell extraction-chemical profiling technology.

To investigate the influence of metabolic enzymes polymorphisms on variations of imatinib (IM) pharmacokinetics in gastrointestinal stromal tumors (GIST) patients.

To summarize the treatment status of gastric gastrointestinal stromal tumor (GIST) in Shandong province,by analyzing the clinicopathological features and prognostic factors.

New immunotherapy represented by immune checkpoint inhibitor therapy and chimeric antigen receptor T-Cell immunotherapy (CAR-T) has already become hot trend in the treatment of malignant tumors. In gastrointestinal stromal tumor (GIST), with notable tumor-infiltrating immune cells existing in GIST tissues and immunological effects reported in imatinib mesylate (IM) treatment, the clinicians and researchers started to realize the possibilities of immunotherapy in GIST. Recent studies reported that PD-1/PD-L1 or CTLA-4 blockade may enhance the T-cell activity and anti-tumor effect of targeted therapy, which can be applied in advanced GIST, and anti-KIT CAR T-cells indicated a new immunotherapeutic targeted strategy for GIST patients with TKI resistance. All the immunotherapies in GIST mentioned above are frontline researches but their efficacies still need more evidence from clinical trials to verify.

Surgery remains the primary treatment for patients with localized gastrointestinal stromal tumor (GIST), however, even after complete resection of the tumor, there is still a part of patients with tumor recurrence and metastasis. Imatinib, as adjuvant therapy in GIST patients with intermediate and high risk of recurrence, can significantly improve the disease-free survival, but whether it can prolong the overall survival is still unknown. It has reached a consensus that the intermediate and high risk patients should receive adjuvant therapy, but the duration for adjuvant therapy is still under investigation, especially for high-risk patients. Adjuvant therapy is recommended for at least 3 years, while in the end of adjuvant therapy, some patients still develop recurrence and metastasis. In 2017, results from PERSIST-5 study reported by the ASCO conference indicated that 5-year adjuvant therapy may further prolong disease-free survival of intermediate and high risk patients. In addition, adjuvant therapy is still not individualized based on the combination with different genotypes, and present adjuvant therapy is recommended for GIST patients with positive CD117 and intermediate-high risk of recurrence. It remains controversial whether different genotypes are associated with alternative adjuvant treatment options. Results of more researches are expected to provide better guidance for clinical treatment in the future.

Objective: To analyze the efficacy of branches portal vein embolization (TBPVE) combined with transcatheter arterial chemoembolization (TACE) on liver neoplasms. Methods: From August 2016 to May 2017, there were 13 patients including 11 males and 2 females with primary hepatocellular carcinoma who underwent TBPVE+ TACE , among whom there were 11 cases with a history of HBV infection.Average age of the 13 patients was (60.8±6.2)years. The live function of all patients were Child-Pugh A classification.The CT or MRI images of each patient was reconstructed and the standard liver volume(SLV) before TBPVE+ TACE was (1 181.2±49.3)ml, estimated future liver remnant(FLR) was (326.1±72.1)ml and FLR/SLV was (27.6±6.0)%.The puncture site for TBPVE was determined by the three-dimensional reconstruction of portal vein.CT scan or MRI, AFP and liver function test were repeated after one and two weeks after TBPVE+ TACE.FLR and FLR/SLV were calculated respectively.Hepatectomy would be performed if the patients agreed.The postoperative complications were analyzed. Results: On the 7thday after TBPVE+ TACE, the FLR/SLV was(42.6±8.0)% and the FLR increasement was(56.0±24.6)%.The level of AFP decreased from(87.9±81.8)μg/L to (29.7±20.9)μg/L.On the 14thday after TBPVE+ TACE, the FLR/SLV was(45.8±6.2)% and the FLR increasement was(71.8±29.0)%.Four patients underwent surgery which including 2 right hepatectomies and 2 right trisegmentectomies in 2 weeks after TBPVE+ TACE.Nine patients were performed with targeting intratumoral lactic acidosis TACE (TILA-TACE). No severe complication occurred in all patients. Conclusions: TBPVE could induce a rapid growth of the liver remnant but still with the concern of inducing the growth of neoplasms at the same time.To combine TACE in TBPVE therapy not also can the growth of neoplasms be prevented but also inducing its shrinking.This method might be a new mode for the treatment of hepatocellular carcinoma.

Objective: To evaluate the efficacy and safety of intravitreal chemotherapy for refractory vitreous seeding from retinoblastoma. Methods: Retrospective series of case studies. Nine patients (13 eyes) with the diagnosis of refractory vitreous seeding were enrolled in Department of Ophthalmology of Eye& ENT Hospital of Fudan University from March 2014 to October 2015.There were 6 males and 3 females. Children aged 8 to 40 months, median age of 18 months. In the 13 eyes, 3 eyes were E period, 9 eyes were D period, and 1 eyes were C period. The fundus was examined by indirect ophthalmoscope and recorded by RetcamIII. Systemic chemotherapy was performed using the VEC protocol, that is vincristine, etoposide, and carboplatin. Local treatment also involves cryotherapy and/or thermotherapy. All patients were treated with intravitreal injection of melphalan. They underwent intravitreal melphalan, once every 4 weeks, with an average of 3 times of injections. The treatment dose of melphalan is 20 to 40 μg per dose. Observe the vitreous seed control and complications of therapy. Results: Vitreous seeds control was attained in all cases. There was no case of orbital extension or remote metastasis. Complications included retinal pigment epithelial and choroidal atrophy in 7 eyes, pupillary synechia and iris atrophy in 2 eyes,retinal vasculitis and vascular occlusion in 2 eyes, optic atrophy in 2 eyes, vitreous hemorrhage in 1 eye, and temporary hypotony in 3 eyes. Conclusions: Intravitreal melphalan is an effective treatment for refractory vitreous seeding from retinoblastoma. High dose may lead to local adverse reactions. (Chin J Ophthalmol, 2017, 53: 570-574).

Intravenous chemotherapy and intra-arterial chemotherapy (IAC) both are the first-line treatment for retinoblastoma (RB) in clinical. There is a controversy on if intra-arterial chemotherapy can substitute the intravenous chemotherapy due to its high eye salvage rate in retinoblastoma therapy. The advantages and disadvantages of these two therapies were retrospectively reviewed here to suggest an individualized and comprehensive regimen for getting the proximal results for retinoblastoma afflicted children. (Chin J Ophthalmol, 2017, 53: 566-569).