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BACKGROUND: Colorectal adenoma is benign glandular tumor of colon, the precursor of colorectal cancer. But no pharmaceutical medication is currently available to treat and prevent adenomas. PURPOSE: To evaluate efficacy of Shenbai Granules, an herbal medicine formula, in reducing the recurrence of adenomas. STUDY DESIGN: This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted by eight hospitals in China. METHODS: Patients who had received complete polypectomy and were diagnosed with adenomas within the recent 6 months were randomly assigned (1:1) to receive either Shenbai granules or placebo twice a day for 6 months. An annual colonoscopy was performed during the 2-year follow-up period. The primary outcome was the proportion of patients with at least one adenoma detected in the modified intention-to-treat (mITT) population during follow-up for 2 years. The secondary outcomes were the proportion of patients with sessile serrated lesions and other specified polypoid lesions. The data were analyzed using logistic regression. RESULTS: Among 400 randomized patients, 336 were included in the mITT population. We found significant differences between treatment and placebo groups in the proportion of patients with at least one recurrent adenoma (42.5 % vs. 58.6 %; OR, 0.47; 95 % CI, 0.29-0.74; p = 0.001) and sessile serrated lesion (1.8 % vs. 8.3 %; OR, 0.20; 95 % CI, 0.06-0.72; p = 0.01). There was no significant difference in the proportion of patients developing polypoid lesions (70.7 % vs. 77.5 %; OR, 1.43; 95 % CI, 0.88-2.34; p = 0.15) or high-risk adenomas (9.0 % vs. 13.6 %; OR, 0.63; 95 % CI, 0.32-1.25; p = 0.18). CONCLUSION: Shenbai Granules significantly reduced the recurrence of adenomas, indicating that they could be an effective option for adenomas. Future studies should investigate its effects in larger patient populations and explore its mechanism of action to provide more comprehensive evidence for the use of Shenbai Granules in adenoma treatment.
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Adenoma , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Colonoscopia , Método Duplo-Cego , Adenoma/tratamento farmacológico , Adenoma/cirurgia , Adenoma/diagnóstico , ChinaRESUMO
Bioinspired structure adhesives have received increasing interest for many applications, such as climbing robots and medical devices. Inspired by the closely packed keratin nanopillars on the toe pads of tree frogs, tightly arranged polycaprolactone nanorod arrays are prepared by mold process and chemical modification. Nanorod arrays show enhanced adhesion and friction on both smooth and rough surfaces compared to the arrays with hexagonal micropillars. The bonding of nanorods results in a larger stiffness of the nanorod surface, contributing mainly to friction rather than adhesion. The results suggest the function of closely packed keratin nanopillars on the toe pad of tree frogs and offer a guiding principle for the designing of new structured adhesives with strong attaching abilities.
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Anuros/fisiologia , Nanopartículas/química , Adesivos , Óxido de Alumínio/química , Animais , Eletrodos , Fricção , Nanopartículas/ultraestrutura , Propriedades de SuperfícieRESUMO
BACKGROUND: Bismuth-containing quadruple therapy achieves higher eradication rate of Helicobacter pylori. High level of bismuth in blood may result in damage of many organs. Wei Bi Mei is a new bismuth-containing drug combining chemicals and Chinese medicine portions. The present research is to study the pharmacokinetics of bismuth to evaluate the safety and rational use of Wei Bi Mei granules. Material and Methods. Seven healthy Chinese adult subjects were enrolled in this research, which included a single-dose study and a multiple-dose study. Wei Bi Mei granules were administered orally to the subjects at corresponding time. Blood and urine were collected. All samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: For single-dose Wei Bi Mei granules administration, the mean time to peak concentration (t max) of bismuth was 2.29 ± 0.76 h, and the mean peak concentration (C max) of bismuth was 0.85 ± 0.55 ng/mL. For multiple-dose Wei Bi Mei granules administration, the C max was 2.25 ± 1.18 ng/mL at day two, and the volume of distribution (V d ) was (22.97 ± 9.82) × 103 L. The urinary excretion of bismuth was the fastest during the first two days, with a mean excretion rate of 3.84 ± 1.23 ng/h. The bismuth concentration in urine was significantly reduced at day 16. CONCLUSION: Bismuth has a washout period of approximately two months. The concentration of bismuth in blood was far less than the "safe level." Thus, Wei Bi Mei is a highly safe therapeutic medicine, with a good clinical application value. Wei Bi Mei should be recommended more widely for use in bismuth-containing quadruple therapy for the treatment of Helicobacter pylori infection.
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BACKGROUND: Colorectal Adenomatous Polyp (CAP) was one precursor of colorectal cancer (CRC) and having a high chance of developing into CRC. There was a lack of conclusive chemoprevention evidences to prevention new CAP occurrence in post-polypectomy. Xiaoai Jiedu Decoction, Chinese National Medical Professor (Zhou Zhongying)'s experience formula, has been used to treat new CAP occurrence in post-polypectomy from the 20th century in China. However, clinical research of Xiaoai Jiedu Decoction in the treatment of CAP recurrence was lack. We design this study to evaluate the efficacy and safety of Xiaoai Jiedu Decoction in the treatment of new CAP occurrence in post-polypectomy on colonoscopy. METHODS/DESIGN: A randomized, controlled, blind and multicenter trial to evaluate the efficacy and safety of Xiaoai Jiedu Decoction is proposed. CAP patients (after complete polypectomy under colonoscopy) will be randomly assigned into Xiaoai Jiedu Decoction group and Xiaoai Jiedu Decoction mimetic agent group. Patients will receive 6-course treatments and a 2-year follow-up. Follow-up colonoscopy will be anticipated to perform in 1 and 2 years after the baseline examinations. The primary outcome measure is the new CAP occurrence in 1 and 2 years. The secondary outcome measure is the occurrence of advanced adenoma in 1 and 2 years. DISCUSSION: This study will provide objective evidences to evaluate the efficacy and safety of Xiaoai Jiedu Decoction as an adjuvant treatment for new CAP occurrence in post-polypectomy. TRIAL REGISTRATION: NCT03616444.
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Pólipos Adenomatosos/prevenção & controle , Neoplasias Colorretais/prevenção & controle , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Lesões Pré-Cancerosas/prevenção & controle , Método Duplo-Cego , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Bismuth-containing quadruple therapy has been recommended as the first line of treatment in areas of high clarithromycin or metronidazole resistance. However, safety concerns of bismuth agents have long been raised. We first assessed the efficacy and safety of Wei Bi Mei granules, which are bismuth compounds consisting of three synthetic drugs and five medicinal herbs, compared to bismuth aluminate and colloidal bismuth subcitrate (CBS) in H. pylori-infected mouse model. We then used atomic fluorescence spectroscopy and autometallography to measure the accumulation of three bismuth agents in the brain, heart, liver, and kidneys in adult Sprague-Dawley rats. We also evaluated the safety of bismuth agents by conducting clinical biochemistry tests in blood samples of experimental animals. Wei Bi Mei granules exhibited the highest efficacy of anti-H. pylori activity and yielded the lowest bismuth accumulation when compared to CBS and bismuth aluminate. Our findings show that Wei Bi Mei granules are a safe Chinese medicinal herb with potent anti-H. pylori activity and can be considered as an alternative to current bismuth compounds. Thus, Wei Bi Mei granules merit further evaluation, particularly with regard to efficacy and safety when they are combined with other H. pylori eradication medications in the clinical setting.
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BACKGROUND: Gastric cancer is the second leading cause of cancer related deaths after lung cancer globally. Among natural products, natural triterpenes represent a structurally diverse group of organic compounds with potent antitumor activity. PURPOSE: The objective of the present research work demonstrated the antiproliferative and apoptotic activity of rosamultic acid, a natural triterpenoid, in human gastric cancer (SGC-7901) cells. Its effect on cellular morphology, cell cycle arrest, DNA fragmentation and expression levels of caspase-3, caspase-8 and caspase-9 were also determined. METHODS: Antiproliferative activity of rosamultic acid was evaluated by MTT assay. Phase contrast, fluorescence microscopy as well as flow cytometry using Hoechst 33342, acridine orange/ethidium bromide and Annexin V-FITC as cellular probes were used to evaluate the induction of apoptosis by rosamultic acid. Protein level expressions were analyzed by western blot analysis. RESULTS: The results revealed that rosamultic acid induced dose-dependent as well as time dependent cytotoxic effects in SGC-7901 gastric cancer cells. It also led to a reduction in clonogenic activity along with inhibiting the cell migration. Characteristic features of apoptosis induced by rosamultic acid were observed and quantified. Cell cycle arrest at sub-G1 phase was induced by rosamultic acid along with downregulation of expression levels of CDK4, CDK6 and cyclin D1. Rosamultic acid also significantly led to the activation of caspase-3, -8 and -9 during the 48 h treatment along with cleaving PARP in a dose-dependent manner. DNA fragmentation following rosamultic acid treatment was also observed in these cells. CONCLUSION: The current study strongly reveals that rosamultic acid inhibits gastric cancer proliferation by inducing apoptosis mediated through cell cycle arrest, downregulation of cell cycle related protein expressions, inhibition of cell migration, DNA damage, and activation of caspases.
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Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias Gástricas/patologia , Triterpenos/farmacologia , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Movimento Celular , Dano ao DNA , Relação Dose-Resposta a Droga , Humanos , Raízes de Plantas/química , Rosa/químicaRESUMO
Bufalin, a digoxin-like active component of the traditional Chinese medicine Chan Su, exhibits potent antitumor activities in many human cancers. Bufalin induces mitochondria-dependent apoptosis in cancer cells, but the detailed molecular mechanisms are largely unknown. hTERT, the catalytic subunit of telomerase, protects against mitochondrial damage by binding to mitochondrial DNA and reducing mitochondrial ROS production. In the present study, we investigated the effects of bufalin on the cell viability, ROS production, DNA damage, and apoptosis of CAPAN-2 human pancreatic and CAL-27 human oral cancer cells. Bufalin reduced CAPAN-2 and CAL-27 cell viability with IC50 values of 159.2 nM and 122.6 nM, respectively. The reduced cell viability was accompanied by increased ROS production, DNA damage, and apoptosis and decreased expression of hTERT. hTERT silencing in CAPAN-2 and CAL-27 cells by siRNA resulted in increased caspase-9/-3 cleavage and DNA damage and decreased cell viability. Collectively, these data suggest that bufalin downregulates hTERT to induce mitochondria-dependent apoptosis in CAPAN-2 and CAL-27 cells. Moreover, bufalin increased the phosphorylation of JNK and p38-MAPK in CAPAN-2 and CAL-27 cells, and blocking the JNK/p38-MAPK pathway using the JNK inhibitor SP600125 or the p38-MAPK inhibitor SB203580 reversed bufalin-induced hTERT downregulation. Thus, the JNK/p38 pathway is involved in bufalin-induced hTERT downregulation and subsequent induction of apoptosis by the mitochondrial pathway.
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Bufalin is a traditional oriental medicine which is known to induce apoptosis in many tumor cells, and it is thus considered as a new anticancer therapeutic. By now, most of the studies of bufalin are in vitro, however in vivo evaluations of its therapeutic efficacy are less and are in great demand for its development toward anticancer drug. One of the problems probably hampering the development of bufalin is the lack of tumor selectivity, which may reduce the therapeutic effect as well as showing side effects. To overcome this drawback, in this study, we designed a tumor-targeted drug delivery system of bufalin based on enhanced permeability and retention (EPR) effect, by using biotinylated chitosan, resulting in bufalin encapsulating nanoparticles (Bu-BCS-NPs) with mean hydrodynamic size of 171.6 nm, as evidenced by dynamic light scattering and transmission electron microscope. Bu-BCS-NPs showed a relative slow and almost linear release of bufalin, and about 36.8% of bufalin was released in 24 h when dissolved in sodium phosphate buffer. Compared to native bufalin, Bu-BCS-NPs exhibited a stronger cytotoxicity against breast cancer MCF-7 cells (IC50 of 0.582 µg/ml vs 1.896 µg/ml of native bufalin). Similar results were also obtained in intracellular reactive oxygen species production, apoptosis induction, and decrease in mitochondria membrane potential. These results may contribute to the rapid intracellular uptake of nanoparticles, partly benefiting from the highly expressed biotin receptors in tumor cells. In vivo studies using MCF-7 tumor models in nude mice confirmed the remarkable therapeutic effect of Bu-BCS-NPs. These findings suggest the potential of Bu-BCS-NPs as an anticancer drug with tumor targeting property.
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Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Bufanolídeos/administração & dosagem , Quitosana/administração & dosagem , Nanopartículas/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Células MCF-7 , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Permeabilidade , Espécies Reativas de Oxigênio/metabolismo , Receptores de Fatores de Crescimento/metabolismoRESUMO
AIM: To investigate the prophylactic and therapeutic efficacy of intraperitoneal IL-2 immunotherapy following intraperitoneal thermochemotherapy in the metastasis and recurrence of gastric and colorectal cancer after operation. METHODS: Forty-two gastric cancer patients at T(3)II-T(4)III( B) stages and 96 patients with colorectal cancer at B to D stages admitted from January 1996 to October 1998 were randomly divided into control group (group I, 65 cases) receiving intraperitoneal thermochemotherapy, and group II (73 cases) receiving both intraperitoneal thermochemotherapy and intraperitoneal IL-2 immunotherapy. Distilled water at 43-45 degrees containing 5-Fu 0.5 g/L and MMC 8 mg/L was perfused into peritoneal cavity before closure at the end of operation for 1 h, and from the third day, IL-2 10 million IU in 500 ml 0.9 % sodium chloride was intraperitoneally administrated daily for 10 times. One month after operation, all the patients underwent regular intravenous chemotherapy. Before and after the IL-2 immunotherapy, some Th1 type cytokines in the peripheral blood of the patients in the two groups were detected by ELISA, and the intraperitoneal recurrence and liver metastasis rates and the 3-year survival rate were statistically evaluated after intensive follow-up. RESULTS: IL-2 intraperitoneal immunotherapy significantly elevated the level of some Th1 type cytokines (P<0.01 compared with that of control group), and the 3-year survival rate of group II was 18.1 % higher and the rates of intraperitoneal recurrence and liver metastasis were 16.9 % and 6.0 % lower than those of group I significantly (P<0.05-0.01). CONCLUSION: The combination of intraperitoneal IL-2 immunotherapy and thermochemotherapy could promote Th1 immune paradigm and enforce anti-tumor activity of bodies, which plays a positive role in preventing gastric and colorectal cancer from intraperitoneal recurrence and development.