α-Mangostin, a Dietary Xanthone, Exerts Protective Effects on Cisplatin-Induced Renal Injury via PI3K/Akt and JNK Signaling Pathways in HEK293 Cells.

Previous report has confirmed the beneficial effects of α-mangostin (α-MG), a major and representative xanthone distributed in mangosteen (Garcinia mangostana) on the cisplatin-induced rat model. However, the molecular mechanisms related to its renoprotection have not been elucidated exhaustively. The present study investigated the protective effect of α-MG against cisplatin-induced cytotoxicity in the human embryonic kidney (HEK293) cell model. In this study, α-MG prevented cisplatin-induced cell death, accompanied with the decreased levels of malondialdehyde and increased glutathione content. Particularly, α-MG significantly suppressed the overproduction of reactive oxygen species (ROS), restored the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and downregulated the c-JUN N-terminal kinase (JNK) pathways following cisplatin challenge. Subsequently, the cleavage of caspases and poly-ADP-ribose polymerase (PARP) implicating ROS-mediated apoptosis pathways induced by cisplatin was effectively inhibited by α-MG. In conclusion, our findings provided a rationale for the development of α-MG to attenuate cisplatin-induced nephrotoxicity.

Cullin7 enhances resistance to trastuzumab therapy in Her2 positive breast cancer via degrading IRS-1 and downregulating IGFBP-3 to activate the PI3K/AKT pathway.

Patients with Her2-positive breast cancer exhibit de novo resistance or develop acquired resistance in less than one year after Her2 targeting treatment, but the mechanism is not fully elucidated. Compensatory pathways such as the IGF-1R/IRS-1 pathway, are activated, leading to aberrant enhanced PI3K/Akt/mTOR pathway activity to attenuate the efficacy of trastuzumab. Cullin7 could participate in the degradation of IRS-1 in a mTOR/S6K dependent manner. Whether Cullin7 participates in trastuzumab resistance needs to be further investigated. Here, we reveals that Cullin7 is overexpressed in trastuzumab-resistant Her2 positive breast cancer cells. Knockdown of Cullin7 reduces degradation of Ser phosphorylation of IRS-1, attenuates activation of the PI3K/AKT pathway, and partly restores trastuzumab sensitivity in trastuzumab-resistant Her2 positive breast cancer cells. IGFBP-3 expression is decreased in trastuzumab-resistant Her2 positive breast cancer cells, which leads to release of the Wnt signaling pathway inhibition and an increase in Cullin7 expression, as mediated by TCF7L2. Overexpression of Cullin7 in Her2-amplified breast cancer tissues has clinical implications because it positively correlates with shorter disease-free survival (DFS) and inadequate response to trastuzumab. Thus, our results suggest a critical role for Cullin7 in response to trastuzumab, which has significant implications for selection of the optimal therapeutic strategy for Her2 positive breast cancers.

MODIFIED STOPPA APPROACH FOR PELVIC AND ACETABULAR FRACTURE TREATMENT.

OBJECTIVE: A retrospective review aims to investigate the operative methods and therapeutic effects of the modified Stoppa approach for treating pelvic and acetabular fractures. METHODS: 18 patients with acetabular fracture of the anterior column and pelvic anterior ring fracture underwent surgical treatment using the modified Stoppa approach. Some of the treatment was combined with the iliac fossa approach or rear K-L approach. Fracture reduction and postoperative function were evaluated using the Matta scoring standard and the Majeed scoring system. The Oxford Centre for Evidence-Based Medicine system was used to grade the literature review and create graded B recommendations. RESULTS: Incision length was 6-12 cm (mean, 10 cm), operative duration was 50-150 minutes (mean, 85 minutes), and intraoperative blood loss volume was 400-1,000 ml (mean, 500 ml). 18 patients were followed up for 12-36 months post-operation. In the results of X-ray films, 12 cases were anatomical reductions and the remaining cases were satisfactory reductions. According to Majeed standard, 13 patients were excellent and five patients were good. CONCLUSIONS: Treatment using the modified Stoppa approach was suitable for anterior approaches, in which pelvic and acetabular fractures were sufficiently exposed, the fracture was conveniently reduced, less complications occurred, and curative effect was satisfactory. Level of evidence III, Retrospective comparative study.

OBJETIVO: Uma revisão retrospectiva tem como objetivo investigar os métodos operatórios e efeitos terapêuticos da abordagem modificada de Stoppa para o tratamento de fraturas pélvicas e acetabulares. MÉTODOS: 18 pacientes com fratura acetabular da coluna anterior e fratura do anel anterior pélvico foram submetidos a tratamento cirúrgico utilizando a abordagem de Stoppa modificada. Parte do tratamento foi feita em conjunto com a abordagem da fossa ilíaca ou com a abordagem pelo acesso posterior de K-L. A redução da fratura e a função pós-operatória foram avaliadas pelo padrão de pontuação de Matta e o sistema de pontuação de Majeed. O sistema do Oxford Centre for Evidence-Based Medicine foi usado para classificar a revisão de literatura e criar as recomendações de grau B. RESULTADOS: O comprimento da incisão foi de 6 a 12 cm (média de 10 cm), a duração da cirurgia foi de 50 a 150 minutos (média de 85 minutos) e o volume de perda sanguínea intraoperatória foi de 400 a 1.000 ml (média de 500 ml). 18 pacientes foram acompanhados por 12-36 meses após a operação. Nos resultados dos filmes radiográficos, 12 casos foram de reduções anatômicas e os demais casos foram de reduções satisfatórias. De acordo com o padrão de Majeed, 13 pacientes foram considerados excelentes e cinco pacientes foram considerados bons. CONCLUSÕES: O tratamento que utilizou a abordagem de Stoppa modificada foi adequado para abordagens anteriores, nas quais as fraturas pélvicas e acetabulares estavam suficientemente expostas, a fratura foi convenientemente reduzida, ocorreram menos complicações e o efeito curativo foi satisfatório. Nível de evidencia III, Estudo retrospectivo comparativo.

Modified stoppa approach for pelvic and acetabular fracture treatment / Stoppa modificada para tratamento de fraturas pélvicas e acetabulares

ABSTRACT Objective: A retrospective review aims to investigate the operative methods and therapeutic effects of the modified Stoppa approach for treating pelvic and acetabular fractures. Methods: 18 patients with acetabular fracture of the anterior column and pelvic anterior ring fracture underwent surgical treatment using the modified Stoppa approach. Some of the treatment was combined with the iliac fossa approach or rear K-L approach. Fracture reduction and postoperative function were evaluated using the Matta scoring standard and the Majeed scoring system. The Oxford Centre for Evidence-Based Medicine system was used to grade the literature review and create graded B recommendations. Results: Incision length was 6-12 cm (mean, 10 cm), operative duration was 50-150 minutes (mean, 85 minutes), and intraoperative blood loss volume was 400-1,000 ml (mean, 500 ml). 18 patients were followed up for 12-36 months post-operation. In the results of X-ray films, 12 cases were anatomical reductions and the remaining cases were satisfactory reductions. According to Majeed standard, 13 patients were excellent and five patients were good. Conclusions: Treatment using the modified Stoppa approach was suitable for anterior approaches, in which pelvic and acetabular fractures were sufficiently exposed, the fracture was conveniently reduced, less complications occurred, and curative effect was satisfactory. Level of evidence III, Retrospective comparative study.

RESUMO Objetivo: Uma revisão retrospectiva tem como objetivo investigar os métodos operatórios e efeitos terapêuticos da abordagem modificada de Stoppa para o tratamento de fraturas pélvicas e acetabulares. Métodos: 18 pacientes com fratura acetabular da coluna anterior e fratura do anel anterior pélvico foram submetidos a tratamento cirúrgico utilizando a abordagem de Stoppa modificada. Parte do tratamento foi feita em conjunto com a abordagem da fossa ilíaca ou com a abordagem pelo acesso posterior de K-L. A redução da fratura e a função pós-operatória foram avaliadas pelo padrão de pontuação de Matta e o sistema de pontuação de Majeed. O sistema do Oxford Centre for Evidence-Based Medicine foi usado para classificar a revisão de literatura e criar as recomendações de grau B. Resultados: O comprimento da incisão foi de 6 a 12 cm (média de 10 cm), a duração da cirurgia foi de 50 a 150 minutos (média de 85 minutos) e o volume de perda sanguínea intraoperatória foi de 400 a 1.000 ml (média de 500 ml). 18 pacientes foram acompanhados por 12-36 meses após a operação. Nos resultados dos filmes radiográficos, 12 casos foram de reduções anatômicas e os demais casos foram de reduções satisfatórias. De acordo com o padrão de Majeed, 13 pacientes foram considerados excelentes e cinco pacientes foram considerados bons. Conclusões: O tratamento que utilizou a abordagem de Stoppa modificada foi adequado para abordagens anteriores, nas quais as fraturas pélvicas e acetabulares estavam suficientemente expostas, a fratura foi convenientemente reduzida, ocorreram menos complicações e o efeito curativo foi satisfatório. Nível de evidencia III, Estudo retrospectivo comparativo.

Rotundic acid induces Cas3-MCF-7 cell apoptosis through the p53 pathway.

In the present study, the functions and mechanisms of rotundic acid (RA) underlying its induction of apoptosis in caspase-3-transfected MCF-7 human breast cancer cells (Cas3-MCF-7 cells) were investigated. RA induced apoptosis in Cas3-MCF-7 cells more efficiently compared with that in MCF-7 cells transfected with control plasmid. The results from an MTT assay demonstrated that RA effectively inhibited Cas3-MCF-7 cell viability in a dose-dependent manner and induced cell apoptosis via caspase-3 activity within 12 to 48 h. Western blotting and fluorescence-activated cell sorting demonstrated that RA initiated Cas3-MCF-7 cell apoptosis via p53 activation. The silencing of the p53 gene in the Cas3-MCF-7 cell line led to decreased RA-induced Cas3-MCF-7 cell caspase-3 activity and cell apoptosis. Collectively, the results of the present study indicate that caspase-3 serves a critical function in rotundic acid-induced apoptosis, and suggest that caspase-3 deficiency may contribute to the chemotherapy-resistance of breast cancer. Reconstitution of caspase-3 sensitizes MCF-7 breast cancer cells to chemotherapy. RA has the potential for development as a novel drug combined with reconstitution of caspase-3 gene therapy for the treatment of human breast cancer with caspase-3 deficiency.

Platycodin D protects acetaminophen-induced hepatotoxicity by inhibiting hepatocyte MAPK pathway and apoptosis in C57BL/6J mice.

The root of Platycodon grandiflorus (Jacq.) A. DC. (P. grandiflorus), Platycodonis Radix, has been commonly applied to prevent and treat human diseases including bronchitis, asthma and excessive phlegm. Platycodin D (PD), one of the most important therapeutic components of P. grandiflorus, has been reported to possess protective effect against alcohol and carbon tetrachloride induced hepatotoxicity. In this study, we examined the protective efficacy of PD on acetaminophen (APAP)-induced liver injury and possible underlying mechanisms in C57BL/6J mice. Administration of PD prior to APAP intoxication significantly ameliorated the increase in serum transferases, interleukin 1ß (IL-1ß), IL-6, tumor necrosis factor alpha (TNF-α), and hepatic malondialdehyde (MDA) and the depletion of glutathione (GSH) in mice. PD pretreatment decreased the expression of heme oxygenase-1 (HO-1), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) in presence of APAP. Moreover, PD treatment noticeably reduced APAP-induced hepatocyte necrosis and apoptosis evidenced by evaluating physiological and histological hepatocyte changes in mice. Finally, PD pretreatment significantly diminished c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and p38 phosphorylation induced by APAP. Collectively, PD pretreatment effectively protects hepatocytes against APAP-induced hepatotoxicity in mice through ameliorating oxidative stress, inflammatory response, and hepatocyte apoptosis.

Rotundic acid enhances the impact of radiological toxicity on MCF-7 cells through the ATM/p53 pathway.

Although radiation therapy is a powerful anticancer modality, radiation- induced stress response and gene expression with adaptive resistance may severely compromise the effectiveness of radiation. The function of rotundic acid (RA) on inducing apoptosis in the human breast cancer cell line MCF-7 has been investigated in a previous study. In the present study, the combined effect of chemotherapy and radiotherapy on reducing side effects was examined. The results of an MTT assay revealed that radiation (0.5, 2 and 10 Gy) effectively inhibit MCF-7 cell viability in a dose-dependent manner, consistent with the effects of RA (2, 5 and 12.5 µM). Interestingly, a lower dose of radiation (1 Gy) combined with RA (5 µM) exhibited a greater inhibition efficiency compared with a high dose of radiation alone. Flow cytometry revealed that radiation combined with RA induced the apoptosis of MCF-7 cells. Using western blotting, it was demonstrated that radiation induced the expression of ataxia-telangiectasia mutated (ATM) and p53 protein, and that RA enhanced this effect. On examining the potential underlying mechanism, it was revealed that radiation and RA combined induce Bcl-2-associated X protein expression and cell apoptosis in MCF-7 cells. An ATM inhibitor was able to restore the effect of radiation and RA on inducing MCF-7 cell apoptosis. These results suggest that the ATM/p53 pathway directly participates in radiation and RA-induced apoptosis in MCF-7 cells. RA has the potential for development as a novel drug for the treatment of human breast cancer combined with radiation therapy, given that the combined side effects are reduced.

The Liver Protection Effects of Maltol, a Flavoring Agent, on Carbon Tetrachloride-Induced Acute Liver Injury in Mice via Inhibiting Apoptosis and Inflammatory Response.

The purpose of this research was to evaluate whether maltol could protect from hepatic injury induced by carbon tetrachloride (CCl4) in vivo by inhibition of apoptosis and inflammatory responses. In this work, maltol was administered at a level of 100 mg/kg for 15 days prior to exposure to a single injection of CCl4 (0.25%, i.p.). The results clearly indicated that the intrapulmonary injection of CCl4 resulted in a sharp increase in serum aspartate transaminase (AST) and alanine transaminase (ALT) activities, tumor necrosis factor-α (TNF-α), irreducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB) and interleukin-1ß (IL-1ß) levels. Histopathological examination demonstrated severe hepatocyte necrosis and the destruction of architecture in liver lesions. Immunohistochemical staining and western blot analysis suggested an accumulation of iNOS, NF-κB, IL-1ß and TNF-α expression. Maltol, when administered to mice for 15 days, can significantly improve these deleterious changes. In addition, TUNEL and Hoechst 33258 staining showed that a liver cell nucleus of a model group diffused uniform fluorescence following CCl4 injection. Maltol pretreatment groups did not show significant cell nuclear condensation and fragmentation, indicating that maltol inhibited CCl4-induced cell apoptosis. By evaluating the liver catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) activity, and further using a single agent to evaluate the oxidative stress in CCl4-induced hepatotoxicity by immunofluorescence staining, maltol dramatically attenuated the reduction levels of hepatic CAT, GSH and SOD, and the over-expression levels of CYP2E1 and HO-1. In the mouse model of CCl4-induced liver injury, we have demonstrated that the inflammatory responses were inhibited, the serum levels of ALT and AST were reduced, cell apoptosis was suppressed, and liver injury caused by CCl4 was alleviated by maltol, demonstrating that maltol may be an efficient hepatoprotective agent.

Therapeutic effect of chitosan on CCl4­induced hepatic fibrosis in rats.

Chitosan is a linear polysaccharide that is made by treating the chitin shells of shrimp and crustaceans with an alkaline substance, for example sodium hydroxide. Due to its unique physical and chemical properties, chitosan has a wide range of applications in the medical field. Currently, there are no effective treatments for liver fibrosis; therefore, the aim of the present study was to investigate the therapeutic effect of chitosan in a CCl4­induced hepatic fibrosis (HF) rat model. The serum levels of aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were measured by ELISA. Collagen (COL) 3 and α­smooth muscle actin (SMA) expression levels in the rat liver were detected by reverse transcription­semiquantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that treatment with chitosan significantly improved HF, by decreasing the serum levels of AST, ALT, and ALP; improving liver histology; and decreasing the expression levels of COL3 and α­SMA. Chitosan may offer an alternative approach for the clinical treatment of HF.

Role of S100A3 in human hepatocellular carcinoma and the anticancer effect of sodium cantharidinate.

The fifth most common cancer worldwide is hepatocellular carcinoma (HCC), which has an annual mortality rate of ~800,000. Although surgical procedures for HCC, such as hepatic resection and liver transplantation, have progressed and the outcomes of patients have improved, HCC is still characterized by frequent recurrence, even after liver transplantation. In the present study the expression of the protein coding gene, S100 calcium binding protein A3 (S100A3), was observed in 62 HCC tissues and tumor-surrounding tissues. The present study indicated that S100A3 activation was involved in tumorigenesis and tumor aggressiveness. The protein and mRNA expression levels of S100A3 in the human HCC cell line (HepG2) were investigated using western blotting and reverse transcription-quantitative polymerase chain reaction analysis, respectively. The function of sodium cantharidinate in inducing HCC cell apoptosis was also investigated. Sodium cantharidinate inhibited the protein and gene expression of S100A3 in HepG2 cells in vitro. These data suggested that S100A3 has an important role in human HCC. The present study indicates that the functional properties of sodium cantharidinate are promising for the development of a novel drug that may control the expression of S100A3 and improve the treatment of human HCC in the near future.

Saponins (Ginsenosides) from the Leaves of Panax quinquefolius Ameliorated Acetaminophen-Induced Hepatotoxicity in Mice.

Acetaminophen (APAP) overdose is one of the most common inducements of drug-induced liver injury (DILI) in the world. The main purpose of this paper was to investigate the liver protection activity of saponins (ginsenosides) from the leaves of Panax quinquefolius (PQS) against APAP-induced hepatotoxicity, and the involved mechanisms were demonstrated for the first time. Mice were pretreated with PQS (150 and 300 mg/kg) by oral gavage for 7 days before being treated with 250 mg/kg APAP. Severe liver injury was exerted at 24 h post-APAP, and hepatotoxicity was assessed. Our results showed that pretreatment with PQS significantly decreased the serum alanine aminotransferase (ALT), aspartate transaminase (AST), tumor necrosis factor (TNF-α), and interleukin-1ß (IL-1ß) levels in a dose-dependent manner as compared to the APAP administration. Meanwhile, compared with that in the APAP group, PQS decreased hepatic malondialdehyde (MDA) contents and 4-hydroxynonenal (4-HNE) expression and restored reduced glutathione (GSH) content and superoxide dismutase (SOD) activity in livers of mice. PQS inhibited the overexpression of pro-inflammatory factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the liver tissues. Furthermore, Western blotting analysis revealed that PQS pretreatment inhibited the activation of apoptotic signaling pathways via increase of Bcl-2 and decrease of Bax and caspase-3 protein expression levels. Liver histopathological observation provided further evidence that PQS pretreatment significantly inhibited APAP-induced hepatocyte necrosis, inflammatory cell infiltration, and congestion. Biological indicators of nitrative stress such as 3-nitrotyrosine (3-NT) were inhibited after PQS pretreatment, compared to the APAP group. The present study clearly demonstrates that PQS exerts a protective effect against APAP-induced hepatic injury because of its antioxidant, anti-apoptotic, and anti-inflammatory activities. The findings from the present investigation show that PQS might be a promising candidate treatment agent against drug-induced ALI.

Design, synthesis and evaluation of antitumor activity of new rotundic acid acylhydrazone derivatives.

In light of the important antitumor activity of acylhydrazone compounds and based on our previous study, 18 new rotundic acid (RA) acylhydrazone derivatives were synthesized. All of the compounds were characterized by their spectroscopic data. The antiproliferative activity of the compounds was evaluated in vitro via the MTT method in three tumor cell lines, including A-375 (human malignant melanoma cells), SPC-A1 (human lung adenocarcinoma) and NCI-H446 (small cell lung cancer). The results showed that the antiproliferative activity of all of the compounds on the NCI-H446 cell line did not increase compared to RA, however, most of the derivatives exhibited higher activity against the A375 and SPC-A1 cell lines as compared to RA. Importantly, the antiproliferative activities of compounds 5a and 5b were the highest among the compounds, with IC(50) values <10 µM. Collectively, compounds 5a and 5b may act as potential anti-tumor agents in the future.

[HPLC Fingerprint and Determination in the Root of Amorpha fruticosa].

Objective: To establish HPLC fingerprint in the root of Amorpha fruticosa, and simultaneously to determine the content of calycosin-7-O-ß-D-glucopyranoside, ononin, calycosin, formononetin. Methods: The analytical column was Diamonsil C18( 250 mm ×4. 6 mm,5 µm). The mobile phase was acetonitrile( A)-water( B)( containing 0. 2% phosphoric acid) in gradient elution, and the detection wavelength was set at 260 nm. "Chromatographic fingerprint similarity evaluation software "version( 2004A) was used to evaluate similarity for the ten batches medicinal materials,and SPSS software was used for cluster analysis. Results: The HPLC fingerprint of the root of Amorpha fruticosa was established with good separation, and four chemical compositions were determinated. 16 common peaks were defined in the HPLC fingerprint among the 10 batches of the root of Amorpa fruticosa. The similarity among them was more than0. 90. Conclusion: This analytical method has strong features,with a good repeatability and the method is simple, which can be used efficiently in the quality control in the root of Amorpha fruticosa.

Anti-Tumor Effect of Steamed Codonopsis lanceolata in H22 Tumor-Bearing Mice and Its Possible Mechanism.

Although previous studies confirmed that steaming and the fermentation process could significantly improve the cognitive-enhancement and neuroprotective effects of Codonopsis lanceolata, the anti-tumor efficacy of steamed C. lanceolata (SCL) and what mechanisms are involved remain largely unknown. The present study was designed to evaluate the anti-tumor effect in vivo of SCL in H22 tumor-bearing mice. The results clearly indicated that SCL could not only inhibit the tumor growth, but also prolong the survival time of H22 tumor-bearing mice. Besides, the serum levels of cytokines, such as interferon gamma (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-2 (IL-2), were enhanced by SCL administration. The observations of Hoechst 33258 staining demonstrated that SCL was able to induce tumor cell apoptosis. Finally, immunohistochemical analysis revealed that SCL treatment significantly increased Bax expression and decreased Bcl-2 and vascular endothelial growth factor (VEGF) expression of H22 tumor tissues in a dose-dependent manner. Moreover, LC/MS analysis of SCL indicated that it mainly contained lobetyolin and six saponins. Taken all together, the findings in the present study clearly demonstrated that SCL inhibited the H22 tumor growth in vivo at least partly via improving the immune functions, inducing apoptosis and inhibiting angiogenesis.

Design, synthesis and cytotoxicity of cell death mechanism of rotundic acid derivatives.

In the present investigation, 16 new rotundic acid (RA) derivatives modified at the C-3, C-23 and C-28 positions were synthesized. The cytotoxicities of the derivatives were evaluated against HeLa, A375, HepG2, SPC-A1 and NCI-H446 human tumor cell lines by MTT assay. Among these derivatives, compounds 4-7 exhibited stronger cell growth inhibitory than RA and compound 4 was found to be the best inhibition activity on five human tumor cell lines with IC50 <10 µM. The apoptosis mechanism of compound 4 in HeLa cells was investigated by western blot analysis. The results indicated that compound 4 could induce apoptosis through increasing protein expression of cleaved caspase-3 and Bax, and decreasing protein expression of Bcl-2. In summary, the present work suggests that compound 4 might serve as an effective chemotherapeutic candidate.

Novel rotundic acid derivatives: synthesis, structural characterization and in vitro antitumor activity.

Six novel rotundic acid (RA, 1) derivatives 4a-4f modified at the 28-COOH position were synthesized, and their structures were confirmed by IR, MS, 1H NMR and 13C NMR. The derivatives were evaluated for cytotoxic properties on the following three tumor cell lines: HeLa, HepG2 and SGC-7901. Compound 4f showed better cytotoxic activity compared with RA treatment and lower IC50 (4.16 µM) on HepG2 cells than on HeLa (8.54 µM) and SGC-7901 cells (11.32 µM). The anticancer mechanism of compound 4f was studied through cell cycle progression and apoptosis. Notably, compound 4f was able to induce apoptosis and G0/G1 cell cycle arrest of HepG2 at a concentration of 4.16 µM. In summary, RA was modified to obtain six novel derivatives. Compound 4f exhibited better cytotoxicity and may be developed as a potential agent against hepatocellular carcinoma.

Synthesis, characterization and cytotoxicity of new rotundic acid derivatives.

Rotundic acid (RA, 1), a natural compound, exhibits potent tumor cell growth inhibiting properties. To date there are no reports on derivatives of RA. Furthermore, the 28-COOH position of RA might make it unstable and induced serious gastrointestinal side effects when it was applied in vivo. Therefore, in order to explore and make use of this compound, eight new amino acid derivatives of RA at the 28-COOH position were synthesized and evaluated for their cytotoxicities in vitro on three tumor cell lines including A375, HepG2 and NCI-H446. As a result, a few of these new amino acid derivatives showed stronger cytotoxicity. Compound 5a was found to have the best inhibition activity on the three tested human tumor cell lines with IC(50) values of less than 10 µM compared with RA treatment. Meanwhile, the cytotoxicity of compound 6b was significantly higher than that of RA on the A375 cell line and almost the same as RA on the HepG2 and NCI-H446 cell lines. Hence, compounds 5a and 6b may serve as potential lead compounds for the development of new anti-tumor drugs.

[Primary evaluation of a mass screening program for colorectal tumor in China].

OBJECTIVE: To evaluate a colorectal cancer screening program by tumor detection rate and discussing its application values. METHOD: In total, 43 713 subjects were recruited in the screening program who were the registered people aged 40 - 74 in Xiacheng and Jiashan during year 2007 - 2009. The first screening involved questionnaire survey of colorectal cancer related risk factors and fecal occult blood test (FOBT), colonoscopy was performed when a positive result was observed in the first screening. If polyps were found during colonoscopy, biopsy and pathological diagnosis were carried out. The screening data were analyzed and the tumor detection rate was calculated according to age or sex. RESULTS: 6489 subjects (14.85%) belonged to the high risk group of colorectal cancer in the first screening, in which 4701 subjects finished complete colonoscopy. Finally, 569 colorectal neoplasm were diagnosed, the detection rate was 12.10% (95%CI: 11.17% - 13.04%). It included 52 colorectal cancer (1.11%, 95%CI: 0.81% - 1.41%), 183 advanced adenoma (3.89%, 95%CI: 3.34% - 4.45%), 334 non-advanced adenoma (7.10%, 95%CI: 6.37% - 7.84%). The highest detective rate was observed in male group that aged 70 - 74 (22.81%, 95%CI: 16.98% - 28.70%), the lowest detective rate was observed in female group aged 40 - 44 (2.49%, 95%CI: 0.79% - 4.20%). CONCLUSION: The current colorectal cancer screening program in China works well, but the revision of the program is necessary.

Fast and sensitive LC-DAD-ESI/MS method for analysis of saikosaponins c, a, and d from the roots of Bupleurum Falcatum (Sandaochaihu).

In the present study, we developed a liquid chromatography-diode array detector-electrospray ionization/mass spectrometric (LC-DAD-ESI/MS) method for analysis of saikosaponins in Bupleurum falcatum. The LC method employed a ZORBAX SB-Aq analytical column (150 x 4.6 mm i.d., 5 µm) at a flow rate of 0.8 mL/min coupled with a diode array detector at 204 nm. A step gradient of acetonitrile-water (v/v) containing 0.5% formic acid from 30 to 70% was applied, leading to a sample analysis time of 30 min. The ESI-MS was carried out in positive and negative modes from 500 to 1,500 m/z. Saikosaponins c, a, and d gave strong sodium adducts at m/z 949.6, 803.5 and 803.6, respectively, in positive mode. The data indicate that the present LC-DAD-ESI/MS assay is an effective method for the determination of saikosaponins c, a and d from the roots of Bupleurum falcatum.