Lnc-HUR1 is an HBV-related long non-coding RNA, which can promote the proliferation of hepatoma cells and the occurrence and development of liver cancer. In this study we explored the effect of lnc-HUR1 on the apoptosis of hepatocellular carcinoma cells by taking the approach of immunoblotting, quantitative real time PCR, luciferase reporter assay, chromatin immunoprecipitation (ChIP) and flow cytometry. We found that overexpression of lnc-HUR1 significantly reduced the activity of caspase3/7 and the cleavage of PARP-1, while knocking down of lnc-HUR1 significantly increased the activity of caspase3/7 and promoted the cleavage of PARP-1 in HepG2 cells treated with TGF-β, pentafluorouracil or staurosporine. Consistently, the data from Annexin-V/PI staining showed that overexpression of lnc-HUR1 inhibited apoptosis, while knockdown of lnc-HUR1 promoted apoptosis. Moreover, overexpression of lnc-HUR1 up-regulated the apoptosis inhibitor Bcl-2 and down-regulated the pro-apoptotic factor BAX at both RNA and protein levels. In the CCL4-induced acute liver injury mice model, the expression of Bcl-2 in the liver tissue of lnc-HUR1 transgenic mice was higher than that of the control mice. The data from ChIP assay indicated that lnc-HUR1 reduced the enrichment of p53 on Bcl-2 and BAX promoters. All these results indicated that lnc-HUR1 inhibited the apoptosis by promoting the expression of apoptosis inhibitor Bcl-2 and inhibiting the expression of apoptosis promoting factor BAX. Further studies showed that lnc-HUR1 regulated the transcription of Bcl-2 and BAX in HCT116 cells, but had no effect on the expression of Bcl-2 and BAX in HCT116 p53^-/- cells, indicating that lnc-HUR1 regulates the transcription of Bcl-2 and BAX dependent upon the activity of p53. In conclusion, HBV upregulated lnc-HUR1 can inhibit the apoptosis of hepatoma cells. Lnc-HUR1 inhibits apoptosis by inhibiting the transcriptional activity of p53. These results suggest that lnc-HUR1 plays an important role in the occurrence and development of HBV-related hepatocellular carcinoma.
Animals ; Annexins/pharmacology* ; Apoptosis ; Carcinoma, Hepatocellular/genetics* ; Cell Proliferation ; Hep G2 Cells ; Hepatitis B virus/metabolism* ; Humans ; Liver Neoplasms/genetics* ; Mice ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology* ; Proto-Oncogene Proteins c-bcl-2/pharmacology* ; RNA, Long Noncoding/metabolism* ; Staurosporine/pharmacology* ; Transforming Growth Factor beta/pharmacology* ; Tumor Suppressor Protein p53/pharmacology* ; bcl-2-Associated X Protein/pharmacology*

The mutation rate of anaplastic lymphoma kinase (ALK) in patients with non-small cell lung cancer is 3% to 7%. Due to its low mutation rate and better long-term survival compared with epidermal growth factor receptor-positive non-small cell lung cancer patients, therefore, it's called "diamond mutation". At present, there are three generations of ALK tyrosine kinase inhibitor (TKI) drugs in the world. The first-generation ALK-TKI drug approved in China is crizotinib, and the second-generation drugs are alectinib, ceritinib and ensartinib. Among them, ensartinib is an ALK-TKI domestically developed, and its efficacy is similar to that of alectinib. The main adverse event is transient rash, and compliance to ensartinib is better from the perspective of long-term survival of patients. The manifestation of rash caused by ensartinib is different from that of other ALK-TKI drugs. In order to facilitate clinical application and provide patients with more treatment options, under the guidance of the Committee of Cancer Rehabilitation and Palliative Care of China Anti-Cancer Association, this article collects and summarizes the common adverse reactions of ensartinib. Based on the clinical practice, a clear adverse classification and specific treatment plan are formulated, in order to provide a corresponding reference for clinicians to make more comprehensive clinical decisions.
Anaplastic Lymphoma Kinase ; Carbazoles/adverse effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Consensus ; Exanthema/drug therapy* ; Humans ; Lung Neoplasms/pathology* ; Piperazines ; Protein Kinase Inhibitors/adverse effects* ; Pyridazines

OBJECTIVE: To explore the effects and mechanisms of PKC412 inhibitor on proliferation and apoptosis of HL-60 cell line. METHODS: CCK-8 assay was used to detect the effect of PKC412 on the proliferation of HL-60 cells at different concentrations; Wright-Giemsa staining was used to estimated the effect of PKC412 on the apoptosis of HL-60 cells; the mRNA expression of BCL-2 and P53 genes was detected by qRT-PCR, the expression of BCL-2 and P53 proteins was detected by Western blot. HL-60 cells were injected into mouse caudal vein to construct acute myeloid leukemia model, PKC412 was administered to tail vein for 31.25 nmol/kg, normal saline was injected into the same site of the mice as control group, and the inhibitory effect of PKC412 on HL-60 cells in mice was observed. ELISA assay was used to detect the effect of PKC412 on the inflammatory factors of TNF-α and TGF-β in tumor mice. RESULTS: PKC412 could inhibit the proliferation of HL-60 cell, which was in a dose dependent manner(r=0.9973) (IC50 was 0.31 μmol/L), and induce apoptosis of HL-60 cells. After HL-60 cell was treated by PKC412 for 48 h the expression of BCL-2 gene was down regulated(0.417±0.044 vs 0.933±0.033, t=9.347, P<0.001), the expression of P53 gene was up regulated(1.533±0.145 vs 1.050±0.161, t=2.231, P>0.05) as compared with control group. And the expression of BCL-2 protein was decreased, while the expression of P53 protein was increased. PKC412 could inhibited the growth of HL-60 tumor cells in vivo, the survival rate of mice after administration was 50% and the weight was increased as compared with that in control group(18.02±0.403 g vs 16.44±0.562 g, t=2.272, P=0.0356). The secretion of TNF-α and TGF-β cytokine in serum and spleen cells in PKC412 group was significantly lower than that in control group (P<0.05). CONCLUSION PKC412 can induce apoptosis of HL-60 cells by inhibiting the expression level of BCL-2 gene, PKC412 administration in vivo can inhibit the growth of the tumors.
Animals ; Apoptosis ; Cell Proliferation ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute ; Mice ; Proto-Oncogene Proteins c-bcl-2 ; Staurosporine/analogs & derivatives*

Lung cancer is a malignant tumor with high incidence rate and mortality rate in China and even the whole world, of which non-small cell lung cancer accounts for about 80%. Anaplastic lymphoma kinase (ALK) gene mutation accounts for about 5%. Alectinib, ALK-tyrosine kinase inhibitor (ALK-TKI), has great performance in clinical. The early detection and treatment of adverse drug reactions can greatly improve clinical benefits. This paper reports a patient of ALK positive non-small cell lung cancer was admited to Baotou Central Hospital in April 2020. The diagnosis and treatment was retrospectively analyzed, and the literature was reviewed.
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Anaplastic Lymphoma Kinase/genetics* ; Antineoplastic Agents/therapeutic use* ; Carbazoles/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/secondary* ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Piperidines/therapeutic use* ; Pleural Neoplasms/secondary* ; Protein Kinase Inhibitors/therapeutic use* ; Retrospective Studies ; Tomography, X-Ray Computed

OBJECTIVE: To investigate the effect of GÖ6976 on the proliferation of chronic myeloid leukemia cells and its toxic effect on normal cells and mice, so as to provide experimental basis for the effectiveness and safety of its clinical application. METHODS: Different concentrations of GÖ6976 were applied to the K562 cells, human peripheral blood mononuclear cells (PBMNC) and normal BaF3 cells, MTT assay was used to detect the effect on cell proliferation. BALB/C mice were used to investigate the toxicity in vivo. The general situation, body weight and the number of white blood cells in peripheral blood were monitored during administration, the blood collected from eyeballs before and after administration was used for biochemical examination, at the same time, the liver, kidney and femurs were examined pathologically. RESULTS: GÖ6976 could significantly inhibit the proliferation of K562 cells, inhibition effect increased with increasing dose (r=0.9623). However, there was no significant change in the inhibitory effect on PBMNC and BaF3 cells. The pathological examination of organs in each group showed no abnormal manifestations such as inflammatory infiltration, while the change rate of leukocyte count in peripheral blood of high dose group fluctuated greatly (P＜0.05), which might be related to the inhibition of intracellular protein kinase C, and no abnormality was observed in blood biochemical indexes. In the low dose group, there was no significant difference in peripheral blood leukocyte count, blood biochemical index and histopathology during administration drug as compared with the control group. CONCLUSION GÖ6976 possesses a significant inhibitory effect on the proliferation of K562 cells, and the inhibitory effect increases with increasing dose. Long-term application of 5.0 μmol/L and below concentrations of GÖ6976 shows no obvious inhibitory effect on PBMNC, BaF3 cells. Long-term application of 10 mg/kg and below concentrations of GÖ6976 shows no obvious toxic effect on BALB/c mice.
Animals ; Apoptosis ; Carbazoles ; Cell Proliferation ; Humans ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukocytes, Mononuclear ; Mice ; Mice, Inbred BALB C

OBJECTIVE: The effects of the staurosporine on contraction of self-assembled constructs and extracellular matrix syntheses of goat temporomandibular joint discs were investigated. METHODS: Goat temporomandibular joint disc cells were isolated and cultured to P3, and 5.5×10⁶ cells were combined with different concentrations of staurosporine (0, 0.1, 1, 10, 100 nmol·L⁻¹) in agarose wells and cultured for one week. The samples were frozen and sectioned. Safranin-O,  Picro-sirius red and immunohistochemical staining were performed to observe the distributions of the extracellular matrix and the expression of alpha-smooth muscle actin (α-SMA). Enzyme linked immunosorbent assay (ELISA) and Blyscan kits were utilized to quan--titatively detect the contents of type Ⅰ collagen (ColⅠ) and glycosaminoglycans (GAGs). RESULTS: Each group of goat temporo-mandibular joint disc cells in the agarose wells were gathered to self-assemble into a disc-shaped base for 4 hours and then to gradually contract into a round shape. The Picro-sirius red staining was strong and indicated collagen distribution. The Safranin-O staining observed GAGs throughout the entire construct. The expression of ColⅠ was strongly posi-tive in the staurosporine groups; however, the expression of α-SMA was weak. ColⅠ and GAGs contents in the stau-rosporine groups were greater than that of the control group, especially in the 10 nmol·L⁻¹ group (P<0.01). CONCLUSIONS Staurosporine has a certain effect on the shrinkage of self-assembled constructs; however, such effect is not prominent. Staurosporine contributes to the construction synthesis of extracellular matrix.
Animals ; Collagen Type I ; Glycosaminoglycans ; Goats ; Staurosporine ; pharmacology ; Temporomandibular Joint ; Temporomandibular Joint Disc ; cytology ; drug effects

PURPOSE: Oral ondansetron is a safe and effective antiemetic drug to facilitate oral rehydration therapy in acute gastroenteritis (AGE) with mild dehydration. We investigated the effect of oral ondansetron therapy on intravenous (IV) hydration frequency and emergency department length of stay (EDLOS) in dehydrated children with AGE. METHODS: We reviewed 15,813 children aged 12-60 months with primary diagnosis of AGE who visited a tertiary care university-affiliated hospital emergency department. The enrolled children were divided into the pre- (from January 2009 to June 2011) and post- (from January 2016 to June 2018) ondansetron groups according to the implementation of oral ondansetron therapy in the emergency department. As primary outcomes, IV hydration frequency, EDLOS, and hospitalization rate were compared between the 2 groups. As secondary outcomes, EDLOS and hospitalization rate were compared between the children in the post-ondansetron group who underwent the therapy, and those who did not. RESULTS: Of 7,990 enrolled children, 3,300 (41.3%) were designated as the post-ondansetron group, and among them 1,093 (33.1%) underwent oral ondansetron therapy. This group showed a lower IV hydration frequency, a shorter median EDLOS compared to the other group (55.8% vs. 61.9%, P < 0.001; 175.0 vs. 223.0 minutes, P < 0.001, respectively), and a higher hospitalization rate (9.9% vs. 7.9%, P < 0.001). The children in the post-ondansetron group who underwent the therapy showed a shorter median EDLOS and a lower hospitalization rate compared to those who did not (142.0 vs. 205.0 minutes, P < 0.001; 2.9% vs. 13.4%, P < 0.001, respectively). CONCLUSION: Oral ondansetron therapy may reduce IV hydration frequency and EDLOS in dehydrated children with AGE, and can be considered in those having severe vomiting.
Child ; Dehydration ; Diagnosis ; Emergencies ; Emergency Service, Hospital ; Fluid Therapy ; Gastroenteritis ; Hospitalization ; Humans ; Length of Stay ; Ondansetron ; Tertiary Healthcare ; Vomiting

BACKGROUND: Aprepitant is effective in prevention of chemotherapy-induced nausea and vomiting, when administrated with other antiemetics. We compared the effectiveness of aprepitant to ondansetron for prevention of post-operative nausea and vomiting (PONV) in patients who received a patient-controlled analgesia (PCA) containing opioids. METHODS: 198 patients were randomized into two groups. The treatment group was received an aprepitant, 80 mg, and the control group received a placebo. General anesthesia with inhalational anesthetics–N2O was performed, and PCA was supplied, which contained opioids-NSAIDs-ondansetron. The primary end-point was the incidence of PONV for postoperative 48 hours, and the secondary end-point was the changes in the relationship between PONV incidence and risk factors. RESULTS: PONV incidence in the treatment group was lower than in the control group (18.6% [95% CI: 10.8–26.3], 33.3% [95% CI: 23.6–43.1], respectively, P = 0.021). Relative risk of PONV in the control group was 1.80 (95% CI: 1.08–3.00, P = 0.010). PONV scores peaked at around postoperative 6 hours, then gradually decreased in the control group but not in the treatment group, which showed lower values than the control group (P = 0.001), and no changing patterns were observed (P < 0.001). Risk factors analyzed were sex, surgery type, history of motion sickness or PONV, and smoking habits. Their effects of all risk factors except sex were abolished in the treatment group. CONCLUSIONS: Prophylactic aprepitant with ondansetron was more effective than ondansetron-only regimen in preventing PONV after volatile anesthesia with opioid-containing PCA. Aprepitant abolished the effects of most of risk factors, so it could be efficacious in a high-risk PONV group.
Analgesia, Patient-Controlled* ; Analgesics, Opioid ; Anesthesia ; Anesthesia, General ; Antiemetics ; Humans ; Incidence ; Motion Sickness ; Nausea ; Ondansetron ; Passive Cutaneous Anaphylaxis ; Postoperative Nausea and Vomiting* ; Pre-Exposure Prophylaxis ; Risk Factors ; Smoke ; Smoking ; Vomiting

No abstract available.
Ondansetron* ; Postoperative Nausea and Vomiting*

The present study carried out a phytochemical investigation of the methanol extract of the branches and leaves of Clausena lansium and afforded nine carbazole alkaloids (compounds 1-9) including two new carbazole alkaloids, claulansiums A and B (compounds 1 and 2). The new compounds were elucidated on the basis of extensive spectroscopic data (MS, NMR, IR, and UV) and the known compounds were identified by comparing spectroscopic data with those reported in literature. All the isolated compounds were tested for their cytotoxic activity against A549 and Hela cancer cell lines. Our results showed that compounds 2-6 exhibited varying degrees of cytotoxicity to cancer cells, with IC values ranging from 8.67 to 98.89 μmol·L.
A549 Cells ; Alkaloids ; chemistry ; isolation & purification ; toxicity ; Antineoplastic Agents ; chemistry ; isolation & purification ; toxicity ; Carbazoles ; chemistry ; isolation & purification ; toxicity ; Cell Line, Tumor ; Cell Survival ; drug effects ; Clausena ; chemistry ; HeLa Cells ; Humans ; Molecular Structure ; Plant Extracts ; chemistry ; toxicity ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry