Lung cancer is one of the common malignant tumors that impair human health. With the development of epigenetics, the researchers found that enhancer of Zeste homolog 2 (EZH2) is highly expressed in lung cancer tissue and its expression is closely related to the prognosis. EZH2 inhibitor can also enhance the sensitivity of tumor cells to a variety of anti-tumor drugs. The purpose of this study is to investigate the effect of combination of EZH2 inhibitor and gefitinib on the proliferation, apoptosis and migration of Gefitinib-resistant lung cancer cells.

Membrane anatomy is in broad sense the anatomy of the mesentery and its bed, both of which are consisted of fascia membrane or/and serous membrane. Although the traditional mesentery has the definition of mesentery, people unconsciously identify them according to their "fan-shaped" and "free" characteristics. The "generalized mesentery" we propose refers to the fascia and/or serosa, envelope-like organs and their blood vessels, suspending to the posterior wall of the body, regardless of its shape, free or not. So the main points of the anatomy are as follows.(1) Organs or tissues with their feeding structures are enveloped by the fascia membrane or/and serous membrane, suspending to posterior wall of the body, to form different shapes of the mesentery in broad sense, and most of them are buried in the mesentery bed. (2) Cancer metastasis type V of in the gut moves in the envelop of the mesentery in broad sense.(3) Intraoperative breach of the envelop membrane not only results in intraoperative bleeding, but also cancer cell leakage from the mesentery. (4) The cancer of gut can be divided into cancer in the mesentery, cancer out of the mesentery and cancer at edge of the mesentery based on this anatomy. Radical tumor resection is effective for cancer in the mesentery, which should not be artificially breached into those of cancer out of the mesentery. The essence of neoadjuvant chemoradiation is to push cancer at edge of the mesentery back inside the mesentery.(5) Based on such anatomy, radical gut tumor operations are divided into D2/D3 procedure, without emphasizing the integrity of the mesentery during lymphatic dissection; CME procedure, which emphasizes the integrity of the mesentery but does not strictly define the extent of lymphatic dissection; D2/D3 + CME procedure, which strictly defines the integrity of the mesentery and the extent of lymphatic dissection.(6)For gastrointestinal tumors of the same T stage, shorter mesentery indicates worse prognosis.(7) For gastrointestinal tumors with the same T stage and the same length of mesentery, the more mesentery buried in the mesentery bed, the worse prognosis. (8) The above seven principles are universal in the organs of the body cavity (and even all internal organs).Membrane anatomy, unlike traditional "plane surgery" , is completely different from the "anatomy of the membrane..." described by Japanese scholars, but mainly bases on generalized mesentery and mesentery bed, meanwhile inherent life events can be accurately defined and confirmed.

The research of anti-hepatocellular carcinoma(HCC) drug has attracted more and more attention. Natural products are the important source of active compounds for cancer treatment. A biflavonoid HIS-4 was isolated from Resina draconis in our previous study. MTT assay, hoechst staining, and flow cytometry analysis were used to investigate the effects of HIS-4 on the proliferation and apoptosis of human hepatoma HepG2 and SK-HEP-1 cells. Moreover, the effects of HIS-4 on the migration and invasion ability of HepG2 and SK-HEP-1 cells were evaluated by wound healing assay and Transwell assay. In addition, MTT assay, flow cytometry analyses, Hoechst staining, wound healing assay, Transwell assay, and tube formation assay were used to explore the anti-angiogenic activity of HIS-4 in human umbilical vein endothelial cells(HUVECs). Mechanistically, the HIS-4 regulatory of signal pathways in H9 epG2 and SK-HEP-1 cells were analyzed by Western blot. This results showed that HIS-4 suppressed the proliferation of human hepatoma HepG2 and SK-HEP-1 cells. Moreover HIS-4 induced their apoptosis of HepG2 and SK-HEP-1 cells. HIS-4 inhibited the migration and invasion of HepG2 and SK-HEP-1 cells. Additionally, HIS-4 exhibited angiogenesis effects. Mechanistically, up-regulation of MAPK signaling pathway and down-regulation of mTOR signaling pathway may be responsible for anti-hepatoma activity of HIS-4. Therefore, HIS-4 may be a promising candidate drug for HCC treatment.

To investigate the effects of salinomycin on proliferative, migratory and invasive properties of tongue squamous cell carcinoma cells, and to explore its possible mechanism.

Objective To assess the efficacy and safety of apatinib in the treatment of advanced colorectal cancer(CRC). Methods The clinical data of 16 CRC patients treated with apatinib after failure of prior lines of treatment were retrospectively analyzed in terms of objective response rate,disease control rate,progression-free survival,overall survival,adverse events,and prognostic factors. Results The efficacy was evaluable in 14 patients,among whom the objective response rate was 7.1% and the disease control rate was 50%.The median progression-free survival was 3 months(95%CI=1.57-4.42),and the median overall survival was 6.5 months(95%CI=4.10-8.89).The safety was evaluable in 16 patients,among whom the most common grade 3 adverse events were hypertensinon(37.5%)and proteinuria(25%).No grade 4 adverse event was observed.Multivariate analysis did not show any factor directly related to survival.Conclusion Apatinib may be effective in treating advanced CRC,with tolerable side effects.

Perioperative treatment combined with radical resection is the major approach to cure non-metastatic colon cancer. A precise evaluation and perioperative treatment would probably improve the R0 resection rate, recurrence-free survival and overall survival of colon cancer patients. Recently, individualized treatment is the mainstream due to the development of molecular pathology and multi-disciplinary therapy. The indications and course of perioperative treatment and preoperative neoadjuvant therapy of colon cancer are still in intense discussion. The present review will mainly discuss three topics. Firstly, the various reaction of adjuvant therapy to stage II colon cancer is caused by patients' heterogeneity. Choosing stratified treatment for these patients according to clinical and molecular pathological features is the future. Secondly, we discuss the adjuvant chemotherapy course for stage III colon cancer according to the Chinese Society of Clinical Oncology (CSCO) guideline and the progress of this field. Lastly, we summarize the status and significance of colon cancer neoadjuvant therapy.

Objective: To investigate the in vitro and in vivo effects of apatinib in esophageal squamous cell carcinoma and the underlying mechanisms. Methods: The esophageal cancer cells, KYSE-150 and ECA-109, were divided into control group and apatinib treatment group at the concentrations of 2.5, 5, 10, 20 and 40 μmol/L respectively. All of experiments were performed in triplicate. MTT and colony formation assays were used to measure cell proliferation. Transwell assay was used to determine the migration capacity. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression of VEGF and VEGFR-2 was measured by real-time quantitative PCR (qRT-PCR). The concentration of VEGF in the cell supernatant was assessed by enzyme-linked immunosorbent assay (ELISA). The expression levels of MEK, ERK, p-MEK, p-ERK, JAK2, STAT3 and p-STAT3 after VEGF stimulation were detected by Western blot. Furthermore, the nude mice xenograft model was established. The tumor-bearing mice were randomly divided into control group, apatinib low dose treatment group (250 mg) and apatinib high dose treatment group (500 mg), respectively. Tumor inhibition rates of different groups were calculated. And then the expressions of VEGF and VEGFR2 were detected in xenograft tissues by immunohistochemical staining. Results: In the presence of 20 μmol/L and 40 μmol/L of apatinib for 24 hours, the migration cell numbers of KYSE-150 and ECA-109 were 428.67±4.16 and 286.67±1.53 as well as 1 123.67±70.00 and 477.33±26.84, respectively, that were significantly lower than control group (P<0.05 for all). In addition, after treatment with 10 μmol/L, 20 μmol/L and 40 μmol/L of apatinib for 7 days on KYSE-150 and ECA-109, the colony formation rates were (65.12±25.48)%, (58.19±24.73)% and (29.10±22.40)% as well as (70.61±15.14)%, (61.12±17.21)% and (43.09±11.13)%, respectively. The colony formation rates of 20 μmol/L and 40 μmol/L of apatinib treatment groups were significantly lower than control group (100.00±0.00, P<0.05). The cell cycle ratio of G(2)/M phase and apoptosis rate of control group and 20 μmol/L apatinib group in KYSE-150 cells were (12.14±2.13)% and (3.49±0.74)% as well as (26.27±3.30)% and (15.65±1.54)%, respectively. The corresponding ratios in ECA-109 cells were (3.44±0.57)% and (6.31±1.43)% as well as (22.64±2.36)% and (49.26±1.62)%, respectively. The results show that apatinib suppressed cell cycle progression at G(2)/M phase and induced cell apoptosis in both KYSE-150 and ECA-109 cells (P<0.05 for all). In the presence of 20 μmol/L and 40 μmol/L of apatinib in KYSE-150 cells, the relative levels of VEGF mRNA were (42.57±10.43)% and (25.69±1.24)%, and those of VEGF-2 mRNA were (36.09±10.82)% and (13.99±6.54)%, which were all significantly decreased compared to control group (100.00±0.00, P<0.05 for all). For ECA-109 cells, the relative expression of VEGF and VEGFR2 showed similar tendency (P<0.05 for all). Moreover, after treatment with 20 μmol/L and 40 μmol/L of apatinib in KYSE-150 cells, the VEGF concentrations were (766.48±114.27) pg/ml and (497.40±102.18)pg/ml, which were significantly decreased compared to control group [(967.41±57.75) pg/ml, P<0.05)]. The results in ECA-109 were consistent (P<0.05). Furthermore, after treatment with 40 μmol/L of apatinib in KYSE-150 and ECA-109, the relative expression of p-MEK and p-ERK were 0.49±0.05 and 0.28±0.03 as well as 0.63±0.03 and 1.22±0.15, which were significantly lower than control group (1.23±0.19 and 0.66±0.07 as well as 1.03±0.20 and 1.76±0.20; P<0.05). The relative expression of STAT3, p-STAT3 in control group and experimental group were 0.96±0.15 and 0.85±0.16 as well as 0.62±0.09 and 0.36±0.13, respectively. The results showed that the protein levels of STAT3 and p-STAT3 were significantly lower than the control group (P<0.05 for all). The inhibition rates of apatinib in xenograft nude mice were 29.25% and 19.96% for 250 mg and 500 mg treatment groups. The concentration of VEGF were (25.11±4.12) pg/ml, (16.40±2.81) pg/ml and (15.04±4.88)pg/ml for control, 250 mg and 500 mg treatment groups, respectively. Conclusions: Apatinib can inhibit cell proliferation, induce apoptosis and suppress migration of esophageal cancer cells in vitro and in vivo. This effect was mainly mediated via the alterations of Ras/Raf/MEK/ERK pathway and JAK2/STAT3 pathway.

Objective To investigate the effect of hederagenin on the activity and apoptosis of cervical cancer cells and its mechanism. Methods Cervical cancer CaSki cells were cultured and treated with 0, 10, 20, 40, 80 μg/mL hederagenin. Cell viability was determined by MTT assay. The 50% inhibitory concentration (IC50) was determined to be about 40 μg/mL. The cervical cancer cells were treated with 40 μg/mL hederagenin. The apoptosis of cervical cancer cells was measured by flow cytometry, and the levels of cleaved caspase-3 (c-caspase-3), c-caspase-9, and STAT3 and p-STAT3 proteins were determined by Western blot analysis. STAT3 signaling pathway inhibitor AG490 and hederagenin were used to treat cervical cancer cells, and then the activity and apoptotic level of cervical cancer cells were detected by the above methods. Results Compared with the control cells, the proliferation activity of the cervical cancer cells treated with 40 μg/mL hederagenin decreased, the apoptotic level increased, the levels of c-caspase-3 and c-caspase-9 increased, and the level of p-STAT3 protein decreased. Compared with the cells treated with hederagenin, the activity of cervical cancer cells treated with AG490 and hederagenin decreased further, the apoptotic rate increased, and the protein levels of c-caspase-3 and c-caspase-9 increased. Conclusion Hederagenin inhibits the proliferation and promotes the apoptosis of cervical cancer cells, which is related to the inhibition of STAT3 signaling pathway.

Objective To explore the relationship between the drug resistance gene ATP binding cassette sub-family B member 4 (abcb4) in zebrafish and Wnt/β-catenin signaling pathway. Methods Wild-type zebrafish and transgenic zebrafish were set in the blank control group, doxorubicin treatment group, vinblastine treatment group, gefitinib treatment group, doxorubicin combined with gefitinib treatment group, and vinblastine combined with gefitinib treatment group. The 100 embryos of each group were treated with drugs until the 5th day, and 50 zebrafish juveniles were tested on the 5th day in each group. The drug resistance of wild-type zebrafish was tested by rhodamine 123 experiment. The fluorescence intensity of transgenic zebrafish was tested by microplate reader, and the fluorescence distribution was tested by living cell workstation. The protein levels of transgenic zebrafish β-catenin, GSK-3β, ABCB4 and enhanced green fluorescent protein (EGFP) were tested by Western blot analysis. Results Rhodamine 123 experiments proved that there was drug resistance in zebrafish when treated with doxorubicin and vinblastine. Compared with the blank group, the EGFP fluorescence intensity increased in the transgenic zebrafish when treated with doxorubicin and vinblastine. Western blot assay showed the accumulation of β-catenin accompanied by the increase of EGFP and ABCB4 proteins in the transgenic zebrafish exposed to adriamycin and vincristine. Conclusion The Wnt/β-catenin signaling pathway in zebrafish is involved in the activation and drug resistance of zebrafish abcb4 gene.

To investigate the antitumor activity of Jiawei Sijunzi decoction and study its liver and kidney toxicity and its effect on the immune system in a tumor-bearing mouse model.

To investigate the effects of methanol-ethyl acetate partitioned fractions from Descurainia sophia (MEDS) on the proliferation and apoptosis of human non-small cell lung cancer H1975 cells.

Human health has been severely threatened by malignant tumors continuously.Rational and effective drug use provides an effective means for the treatment of malignant tumors,and is expected to become an important way to solve the problem of tumor treatment in the future.In recent years,with the escalation of new cancer theories and the emergence of clinical drug resistance,innovative research and development of anti-cancer drugs has always been a hot spot and focus in cancer research.Among them,the discovery of novel anti-cancer drugs from natural compound is of top priority due to its strong anti-cancer efficacy and the abundant drug resources.Therefore,it is imperative to systematically summarize the cutting-edge advancements of the natural products and their potential pharmacological mechanisms according to the characteristics of tumor progression,and put forward the new directions and trends for further development of anti-cancer natural products in the future.Specifically,the research advancements on anti-cancer effect of natural products were reviewed,focusing on both the traditional and innovative application.We hope this review could bring the light on the research path of the natural anti-cancer products clearly and comprehensively,and also provide inspirations for innovative,safer and more effective anti-cancer drug development and exploration.

Objective: To explore the role and mechanism of 2-deoxyglucose (2-dg) in reversing osimertinib- acquired resistance of non-small cell lung cancer(NSCLC)cell line. Methods: The NSCLC line H1975 (purchased from the American Type Culture Collection) was conducted by induction method in vitro to construct the osimertinib-resistance NSCLC cell line H1975-OR. The osimertinib-resistance of H1975-OR cell line was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony-formation assay, Ki67 incorporation assay and the expression of apoptosis-related protein. The glycolysis level was assayed by the lactic acid production measured in the culture medium supernatant of H1975 and H1975-OR. The expression of glycolysis key enzymes (HK2, GLUT1, P-PKM2) and apoptosis-related protein (BIM, Bcl-2) were detected by Western blot. The cells were divided into control group, 2-deoxyglucose (4 mmol/L) monotherapy group, osimertinib (3 μmol/L) monotherapy group and 2-deoxyglucose (4 mmol/L)+ osimertinib (3 μmol/L) combination therapy group, then the apoptosis rate of cells was measured by flow cytometry to evaluate the pro-apoptotic ability of drugs. Date were analyzed by Independent-Samples t-test using SPSS 16.0 statistical software. Results: The glycolysis level of osimertinib-sensitive cell line H1975 was lower than that of osimertinib-resistance cell line H1975-OR [the yield of lactic acid, respectively, was (21.0±0.9) and (26.5±2.8) mmol·L(-1)·10(4)cells(-1), P<0.05]. The osimertinib- acquired resistance of H1975-OR could be reversed by 4 mmol/L 2-deoxyglucose(the IC(50) value of osimertinib in H1975-OR cell line decreased from (7.0±1.9) μmol/L to (1.4±0.1) μmol/L, which was close to the IC(50) value of osimertinib in H1975 cell line (1.0±0.2) μmol/L. The apoptosis rate of H1975-OR was significantly higher in 2-deoxyglucose + osimertinib combination therapy group (26.7±2.4)%, compared to control group (5.1±0.7)%, 2-deoxyglucose monotherapy group (6.1±2.5)% and osimertinib monotherapy group (11.4±2.7)%(all P<0.05). The expression of pro-apoptotic protein BIM in H1975-OR was significantly higher in 2-deoxyglucose+ osimertinib combination therapy group (177.8±28.1)% and the expression of anti-apoptotic protein Bcl-2 in H1975-OR was significantly lower in 2-deoxyglucose+ osimertinib combination therapy group (24.6±5.2)%, compared to control group (100±0)%, all P<0.05. Conclusion: 2-deoxyglucose can reverse the acquired resistance of NSCLC cell line to osimertinib, which may be related to the inhibition of cell glycolysis and the induction of apoptosis.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated some dramatic efficacy in advanced non-small-cell lung cancer (NSCLC) patients with activating EGFR mutation. However, progression-free survivals (PFS) among those patients who were treated with first line EGFR TKIs were inconsistent. The aim of this study is to explore the association of clinical prognostic factors with EGFR-TKI efficacy in advanced NSCLC patients.

The aim of this study is to systematically evaluate the efficacy and adverse effects of Lobaplatin and Cisplatin in the treatment of malignant pleural effusion.

ErbB receptor tyrosine kinase inhibitors (EGFR-TKI), gefitinib, erlotinib, icotinib and aftinib, which are approved as a frontline treatment for patients with non-small cell lung cancer (NSCLC) who have tumors harboring EGFR mutations in China. And osimertinib was approved in second line setting for patients with EGFRT 790M-positive NSCLC. Rash, paronychia, diarrhea, stomatitis, liver dysfunction and (interstitial lung disease, ILD) are frequently observed in patients treated with EGFR-TKI. Chinese Society of Lung Cancer, Chinese Anti-Cancer Association, organized Chinese experts to develop the Chinese expert consensus on EGFR-TKI adverse event (AE) management based on domestic diagnosis and treatment of ADR and also incorporating international updated theory and recommendations.
.

Six patients with POEMS syndrome who received autologous peripheral blood stem cell transplantation (auto-PBSCT) were retrospectively analyzed. Conditioning regimen was high dose melphalan. Peripheral blood stem cells were collected after mobilization with cyclophosphamide (CTX) and growth factors. One patient presenting hydrothorax and ascites was treated with 3 cycles of lenalidomide and dexamethasone before mobilization. Auto-PBSCT was fairly tolerable. Hematopoietic reconstitution was successful in all patients without transplantation-related mortality. A decrease or normalization of serum vascular epithelial growth factor (VEGF) was observed in all patients at 3 months after transplantation. The neurological remission was seen in 5/6 patients.

Downstaging of breast cancer primary lesions and metastatic axillary lymph nodes among patients who underwent neoadjuvant chemotherapy (NAC) has raised the new challenges and opportunities on individualized breast cancer surgical treatment. Downstaging of the primary lesion has given patients that were previously deemed inoperable or not suitable for surgery a second chance. While downstaging of the lymph nodes has made it possible for sentinel lymph node biopsy (SLNB) to safely replace axillary lymph node dissection. However, the detection rate and false negative rate of early breast cancer SLNB technique in post-NAC patients barely meet the standard of clinical practice. Therefore, it is required that SLNB in post-NAC patients to be carried out by a medical team with advanced imaging equipments and extensive experiences in SLNB. Furthermore, they should be able to precisely evaluate axillary lymph node status before and after NAC as well as mark metastatic lymph node before NAC. Indications of SLNB should be restricted to patients that are downstaged from cN0 to ycN0 or from cN1 to ycN0. Particularly, it is only safe for patients whose axillary lymph node status become negative after NAC to receive SLNB when dual tracer (blue dye and radionuclide), removing more than 2 sentinel lymph nodes and targeted axillary dissection technique are used.

To investigate the value of neoadjuvant chemoradiotherapy (nCRT) combined with total pelvic exenteration (TPE) in the treatment of primary T4b rectal cancer.

In recent years, a large number of studies have achieved tumor targeting by mesenchymal stem cells (MSC)-based delivery system attributed to the tumor tropism of MSCs. Biomacromolecules and antineoplastic drugs loaded on MSC via internalization or cell membrane anchoring can be released or expressed at tumor site to perform their antitumor effects. The genetically modified MSC are extensively studied, however, the applications of MSCs in targeted delivery of antineoplastic drug with small molecules are not well summarized. In this review, MSCs homing mechanism and the distribution of injected MSCs in vivo is introduced; the examples of antitumor drug-primed MSCs and drug loaded MSCs are presented; the drug loading and releasing process from MSCs is also illustrated; finally, challenges and future perspectives of MSCs-based drug delivery system on realizing its full potential are prospected.