Adjuvant Chemotherapy Seemed Not to Have Survival Benefit in Rectal Cancer Patients with ypTis-2N0 After Preoperative Radiotherapy and Surgery from a Population-Based Propensity Score Analysis.

BACKGROUND: Adjuvant chemotherapy is currently offered routinely, as standard, after radical resection for patients with rectal cancer receiving neo-adjuvant chemoradiation. However, the efficacy of adjuvant chemotherapy in patients with ypTis-2N0M0 has not been documented to the same extent, and the survival benefit remained controversial. The purpose of this work was to determine the role of chemotherapy in patients with ypTis-2N0M0 classification. MATERIALS AND METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results database (n = 4,217). A propensity score model was utilized to balance baseline covariates. RESULTS: Of the 4,217 included patients, 335 with ypTis-2N0M0 did not receive adjuvant chemotherapy. There were comparable cancer-specific survivals (CSS) between those undergoing adjuvant chemotherapy or not (log-rank test = 0.136, p = .712) in the overall sample. After propensity score matching, the cancer-specific survival did not differ between the chemotherapy and observation groups (log-rank test = 0.089, p = .765). Additionally, the Cox model did not demonstrate adjuvant chemotherapy as the prognostic factor, with hazard ratio = 0.95 (95% confidence interval 0.69-1.32) for CSS. Furthermore, the 10-year cumulative CSS was 78.7% and 79.4% between the chemotherapy and observation groups, indicating no significance, and no impact of adjuvant chemotherapy on survival was observed in different subgroups stratified by T stage, histological grade, histology, lymph nodes, and tumor size. CONCLUSION: Patients with ypTis-2N0 rectal cancer did not benefit from adjuvant chemotherapy after preoperative radiology and radical surgery in this cohort study. These results provided new insight into the routine use of adjuvant chemotherapy for patients with rectal cancer with completed neo-adjuvant radiotherapy and curative surgery. IMPLICATIONS FOR PRACTICE: Inconsistent recommendations for patients with rectal cancer receiving neo-adjuvant chemoradiation are offered by clinical guidelines. Adjuvant chemotherapy had no cancer-specific survival benefit, not only in the whole cohort, but also in the propensity score-matched cohort. A Cox model also confirmed adjuvant chemotherapy was not a significant prognostic factor in ypTis-2N0 rectal cancer. No survival benefit conferred by adjuvant chemotherapy was observed, regardless of whether T stage, histological type, grade, lymph nodes and tumor size varied.

Mucinous Adenocarcinomas Histotype Can Also be a High-Risk Factor for Stage II Colorectal Cancer Patients.

BACKGROUND/AIMS: Colorectal mucinous adenocarcinoma (MA) has been associated with a worse prognosis than adenocarcinoma (AD) in advanced stages. Little is known about the prognostic impact of a mucinous histotype on the early stages of colorectal cancer with negative lymph node (LN) metastasis. In contrast to the established prognostic factors such as T stage and grading, the histological subtype is not thought to contribute to the therapeutic outcome, although different subtypes can potentially represent different entities. In this study, we aimed to define the prognostic value of mucinous histology in colorectal cancer with negative LNs. METHODS: Between 2006 and 2017, a total of 4893 consecutive patients without LN metastasis underwent radical surgery for primary colorectal cancer (MA and AD) in Fudan University Shanghai Cancer Center (FUSCC). Clinical, histopathological, and survival data were analyzed. RESULTS: The incidence of MA was 11% in 4893 colorectal cancer patients without LN metastasis. The MA patients had a higher T category, a greater percentage of LN harvested, larger tumor size and worse grading than the AD patients (p < 0.001 for each). We found that MA histology was correlated with a poor prognosis in terms of relapse in node-negative patients, and MA histology combined with TNM staging may be a feasible method for predicting the relapse rate. Additionally, MA presented as a high-risk factor in patients with negative perineural or vascular invasion and well/moderate-differentiation and showed a more dismal prognosis for stage II patients. Meanwhile, the disease-free survival was identical in MA and AD patients after neo- and adjuvant chemotherapy. CONCLUSION: MA histology is an independent predictor of poor prognosis due to relapse in LN-negative colorectal cancer patients. Mucinous histology can suggest a possible high risk in early-stage colorectal carcinoma.

Novel γ-lactone derivatives from Trigonostemon heterophyllus with their potential antiproliferative activities.

Two novel γ-lactone derivatives, trigoheterophines A (1) and B (2), together with four known furan derivatives (3-6), were isolated from the stems and leaves of Trigonostemon heterophyllus. The structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparing with the data reported in literature. Among them, trigoheterophines A (1) and B (2) represent an unusual type of γ-lactone derivatives, possessing 21 carbon atoms on the carbon skeleton, and known compouds (3-6) are rare furan derivatives in the plant kingdom with diverse long-chain hydrocarbyl groups as substituents at C-4. All isolated compounds were evaluated for their antiproliferative activities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1-6 showed significant antiproliferative effects against various human cancer cell lines with IC50 values ranging from 0.28 to 12.06 µM. These findings suggest that the discoveries of these novel γ-lactone derivatives and furan derivatives with significant antiproliferative activities isolated from T. heterophyllus could be of great importance to the development of new anticancer agents.

Carbazole alkaloids from Clausena hainanensis with their potential antiproliferative activities.

Five new carbazole alkaloids, clausehainanines A-E (1-5), together with seven known analogues (6-12) were isolated from the stems and leaves of C. hainanensis. Their structures were elucidated by extensive spectroscopic methods. Among them, compounds 1-5 were an unusual type of carbazole alkaloids, possessing diverse isopentenyl derivatives as substituents at C-2. All isolated compounds were evaluated for their antiproliferative activities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Alkaloids 1-12 showed significant antiproliferative effects against various human cancer cell lines with IC50 values ranging from 0.12 to 15.56 µM. These findings suggest that the discoveries of these carbazole alkaloids with significant cytotoxic activities isolated from C. hainanensis could be of great importance to the development of new anticancer agents.

[Effect of salvianolic acid A on anesthetized canine experimental myocardial infarction].

Salvianolic acid A (SAA), one of the major active water-soluble salvianolic acids of traditional Chinese medicine Salvia miltiorrhiza Bunge, has been reported to be effective on anti-myocardial ischemia, anti-oxidation and anti-thrombus. This study aimed to investigate appropriate administration route on dogs with acute myocardial ischemia(AMI). Twenty-four dogs were randomized into four groups (n=6), model, oral administration of SAA (8 mg•kg⁻¹), intravenous administration of SAA (4 mg•kg⁻¹), intravenous administration of Herbesser(0.5 mg•kg⁻¹) as positive drug group. AMI model was established by ligating left anterior descending coronary arteries(LAD) of dogs. Changes of ST segment were determined by epicardial electrocardiogram(ECG), coronary blood flow (CBF) and myocardial oxygen consumption were measured by ultrasonic Doppler flow meter, serum creatine kinase (CK) and lactate dehydrogenase (LDH) were observed by fully automatic biochemical analyser. Myocardial infarct size was assessed by nitro blue tetrazolium (NBT) staining. Both oral and intravenous administration of SAA reduced the myocardial infarct area/left ventricle area significantly [(16.73±6.52)% and (13.19±2.38)%, compared with (24.35±4.89)% in model group, P<0.01). Oral administration of SAA improved the ECG performance of Σ-ST from 30-190 min after ischemia (P<0.05-0.01), while intravenous SAA had a rapid onset (10-190 min after ischemia, P<0.05-0.01). Compared with model group, oral and intravenous SAA both decreased serum CK and LDH significantly (P<0.05-0.01), while the difference of intravenous administration is more significant. SAA protects myocardium in canine experimental myocardial infarction models. Intravenous administration of SAA alleviates myocardial infarction with greater significance than oral route.

SP1 mediates the link between methylation of the tumour suppressor miR-149 and outcome in colorectal cancer.

Although recent studies indicate that DNA methylation contributes to the down-regulation of microRNAs (miRNAs) in colorectal cancer (CRC), this field remains largely unexplored. To identify methylation-silenced miRNAs and clarify their role in CRC, we performed a microarray analysis and screened for miRNAs that were induced in CRC cells by 5-aza-2'-deoxycytidine treatment or by the knockdown of DNA methyltransferases. The DNA methylation status of the candidate miRNA was analysed by bisulphite sequencing PCR and methylation-specific PCR. We found that miRNA-149 (miR-149) was epigenetically silenced in CRC and down-regulation of miR-149 was associated with hypermethylation of the neighbouring CpG island (CGI). Quantitative RT-PCR analysis demonstrated that the miR-149 level was markedly reduced in 51.6% of the CRC tissues compared with matched non-cancerous tissues. In addition, low expression of miR-149 was associated with a greater depth of invasion (p = 0.012), lower 5-year survival rate (p = 0.025), and was found to be an independent prognostic factor for overall survival (p = 0.016) in a multivariate analysis. Moreover, transfection of miR-149 inhibited cell growth and invasion of CRC cells in vitro. We also identified mRNA for Specificity Protein 1 (SP1, Sp1), a potential oncogenic protein, as a target of miR-149. Our data suggest that, as a methylation-sensitive miRNA, miR-149 may play an important role as a tumour suppressor in CRC, which has prognostic and therapeutic implications.

[Effect of formula of removing both phlegm and blood stasis in improving cardiac function of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome].

OBJECTIVE: To evaluate that the effect of formula of removing both phlegm and blood stasis in improving cardiac function of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome. METHOD: Totally 36 Chinese mini-swine were randomly divided to six groups: the normal control group, the model group, the Danlou tablet group, and Tanyu Tonzhi Fang(TYTZ) groups with doses of 2. 0, 1. 0 and 0. 5 g kg-1, with six in each group. Except for the normal control group, all of other groups were fed with high-fat diet for 2 weeks. Interventional balloons are adopted to injure their left anterior descending artery endothelium. After the operation, they were fed with high-fat diet for 8 weeks to prepare the coronary heart disease model of phlegm-stasis cementation syndrome. After the operation, they were administered with drugs for 8 weeks. The changes in the myocardial ischemia were observed. The changes in the cardiac function and structure were detected by cardiac ultrasound and noninvasive hemodynamic method. RESULT: Compared with the normal control group, the model group showed significant increase in myocardial ischemia and SVR and obvious decrease in CO, SV and LCW in noninvasive hemodynamic parameters (P <0.05 or P <0.01). The ultrasonic cardiogram indicated notable decrease in IVSd, LVPWs, EF and FS, and remarkable increase in LVIDs (P<0. 05 orP<0.01). Compared with the model group, TYTZ could reduce the myocardial ischemia, strengthen cardiac function, and improve the abnormal cardiac structure and function induced by ischemia (P <0. 05 or P <0. 01). CONCLUSION: TYTZ shows a significant effect in improving cardiac function of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome. The clinical cardiac function detection method could be adopted to correctly evaluate the changes in the post-myocardial ischemia cardiac function, and narrow the gap between clinical application and basic experimental studies.

A genetic variant in microRNA-196a2 is associated with increased cancer risk: a meta-analysis.

MicroRNAs (miRNAs) are small non-coding RNA molecules that function as negative regulators of gene expression. Common genetic variants (single nucleotide polymorphisms, SNPs) in miRNA genes may alter their expression or maturation resulting in varied functional consequences. Until now, several studies had evaluated the association between the polymorphisms in the hsa-miR-196a2 rs11614913 and cancer risk in diverse populations and in multiple types of cancer, with contradictory outcomes. Therefore, here we performed a meta-analysis to address the association between this polymorphism and cancer risk. A total of nine studies involving 6,540 cases and 7,562 controls were retrieved based on PubMed. Our analysis demonstrated that hsa-miR-196a2 rs11614913 CC genotype significantly increased the cancer risk in homozygote comparison model compared to TT genotype (OR=1.18; 95% CI, 1.01-1.68). Moreover, significant association of this polymorphism with breast cancer was found based on homozygote comparison model (OR=1.30; 95% CI, 1.01-1.26) and dominant model (OR=1.11; 95% CI, 1.01-1.23). In addition, hsa-miR-196a2 rs11614913 CC genotype was significantly associated with cancer risk in Chinese and Indian (OR=1.21; 95% CI, 1.05-1.40), but not in Caucasians (OR=1.03; 95% CI, 0.89-1.19). Taken together, our results indicate that the polymorphism of hsa-miR-196a2 rs11614913 is associated with cancer susceptibility, especially with breast cancer and in Chinese and Indian populations.

Human embryonic stem cells and metastatic colorectal cancer cells shared the common endogenous human microRNA-26b.

The increase in proliferation and the lack of differentiation of cancer cells resemble what occur in the embryonic stem cells during physiological process of embryogenesis. There are also striking similarities in the behaviour between the invasive placental cells and invasive cancer cells. In the present study, microarrays were used to analyse the global expression of microRNAs in a human embryonic stem cell line (i.e. HUES-17) and four colorectal cancer (CRC) cell lines (i.e. LoVo, SW480, HT29 and Caco-2) with different metastatic potentialities. Only the expression of miR-26b was significant decreased in HUES-17s and LoVo cells, compared with other three cell lines (P < 0.01). The quantitative real-time PCR analysis confirmed the results of the microarray analysis. Overexpression of miR-26b expression by miR-26 mimics transfection and led to the significant suppression of the cell growth and the induction of apoptosis in LoVo cells in vitro, and the inhibition of tumour growth in vivo. Moreover, the potential targets of miR-26b was predicted by using bioinformatics, and then the predicted target genes were further validated by comparing gene expression profiles between LoVo and NCM460 cell lines. Four genes (TAF12, PTP4A1, CHFR and ALS2CR2) with intersection were found to be the targets of miR-26b. MetaCore network analysis further showed that the regulatory pathways of miR-26b were significantly associated with the invasiveness and metastasis of CRC cells. These data suggest that miR-26b might serve as a novel prognostic factor and a potential therapeutic target for CRC.

Histidine decarboxylase is identified as a potential biomarker of intestinal mucosal injury in patients with acute intestinal obstruction.

Various biomarkers currently used for the diagnosis of intestinal mucosal injury (IMI) in patients with acute intestinal obstruction have low sensitivity and specificity. In the present study, IMI, as indicated by the impaired expression of tight junction proteins, including zonula occludens-1, occludin and claudin-1, and inflammation were determined in colonic tissues of patients with 45 strangulated intestinal obstruction (STR-IO) and the adjacent "normal" colonic tissues of 35 patients with colon cancers by quantitative real-time polymerase chain reaction (QRT-PCR), Western blotting, immunohistochemistry and histological examination, respectively. Then, two-dimensional fluorescent difference gel electrophoresis coupled with linear trap quadrupole mass spectrometry was used to screen for potential biomarkers of IMI in the serum samples of 10 STR-IO, 10 simple intestinal obstruction (SIM-IO) and 10 normal healthy controls. A total of 35 protein spots were differentially expressed among the serum samples, and six of the proteins were identified as potential biomarkers. Among the six proteins, histidine decarboxylase (HDC) and ceruloplasmin (CP) were elevated significantly in patients with STR-IO, compared with patients with SIM-IO and healthy controls. Thus, HDC and CP were further validated by QRT-PCR, Western blotting, immunohistochemistry and enzyme-linked immunosorbent assay, respectively, in colonic tissues, serum and urine samples. Finally, the receiver operating characteristic curves were used to show the area under the curves of HDC, CP and several established biomarkers, followed by the determination of the appropriate cutoff values and their sensitivities and specificities. It was shown that for serum and urine, HDC levels achieved sensitivities and specificities compatible to or even greater than those of established biomarkers for the diagnosis of IMI in patients with acute intestinal obstruction, although further validation in a larger cohort is required.

Tamoxifen reverses the multi-drug-resistance of an established human cholangiocarcinoma cell line in combined chemotherapeutics.

Our previous study established the human multi-drug-resistant cholangiocarcinoma cell line QBC939/ADM. In this study, we investigate further the ability of tamoxifen (TAM) to reverse drug-resistance to chemotherapeutics using QBC939/ADM cells. Cell growth inhibition was determined by the MTT assay, while cell cycle progression, apoptosis and the intra-cellular concentration of adriamycin (ADM) were all determined by flow cytometry. P-glycoprotein (P-gp) protein and mRNA expression was determined by Western blotting and real-time PCR. Growth inhibition and apoptosis induced by ADM, mitomycin (MMC), or vindesine (VDS) were enhanced after pre-treatment with 5 or 10 µM TAM, while only VDS increased cell numbers in the G(2)/M phase. The intra-cellular concentration of ADM rose after pre-treatment with 10 µM TAM, but not 5 µM TAM. Furthermore, real-time PCR and western blot analysis revealed down-regulation of P-gp expression in QBC939/ADM cells after TAM pre-treatment. The enhanced effects of TAM on growth inhibition, apoptosis, and intra-cellular concentration and the down-regulation of P-gp expression were blocked by an anti-P-gp antibody. TAM (10 µM) may reverse the multi-drug-resistance (MDR) of QBC939/ADM and enhance the chemotherapeutic effects on cholangiocarcinoma, by competitively inhibiting over-expressed P-gp.

HnRNP K and PDI marked response to chemotherapy to human colorectal cancer cells.

UNLABELLED: 5-Fluorouracil has been the chemotherapy agent of first-choice for colorectal cancer for many years, but since there are no proven predictors of a patient's response to therapy, all patients receive similar treatment. Consequently, identification of biomarkers for therapeutic effect is crucial for the development of novel therapeutic strategies. Two human colorectal cancer cell lines of different metastatic potential (LoVo and SW480) were studied. IC50 of 5-FU for both cell lines were measured by 3-(4,5-dimethy-lthiazol-2-yl)-2,5-diphenyltetrazolium assay and validated by cell cycle analysis. Then the cell lines were treated with 5-FU at IC50 concentration and protein was extracted for 2-DE. Differential protein spots were examined by MALDI-TOF/TOF MS. The expression levels of the different proteins were further confirmed by Western blot and immunofluorescence analyses. Eleven proteins were identified. Expression of heterogeneous nuclear ribonucleoprotein K (hnRNP K) in LoVo cells was higher than in SW480 cells, while protein disulfide isomerase (PDI) displayed the opposite trend. After treatment with 5-FU, the expression of hnRNP K in LoVo decreased more significantly than in SW480, while PDI in SW480 increased more significantly than in LoVo cells. CONCLUSION: hnRNP K and PDI in the two cell lines have different expression characteristics. The sensitivity to 5-FU is not consistent in tumor progression. It may assist in development of novel treatment strategies for colorectal cancer metastasis.

Effects of oral Lactobacillus plantarum on hepatocyte tight junction structure and function in rats with obstructive jaundice.

Surgery and infection are prominent risk factors for the development of obstructive cholestasis which in turn is associated with failure of the liver barrier. We studied the effects of oral Lactobacillus plantarum (LP) supplementation on endotoxemia, oxidative stress, apoptosis, and tight junctions of hepatocytes in an experimental model of obstructive jaundice. Fifty male Wistar rats were randomly divided into five groups of 10 each: group I, sham-operated; group II, ligation and division of the common bile duct (BDL); group III, BLD followed by oral LP treatment; group IV, BDL followed by internal biliary drainage (IBD); group V, BDL followed by IBD and oral LP treatment. Hepatocyte apoptosis, plasma reduced glutathione (GSH) and oxidized glutathione (GSSG) levels, and portal blood endotoxin levels were measured and changes in tight junction-associated proteins occludin, claudin-1, claudin-4, and ZO-1 were observed. Compared to the sham-operated group I, significant increases in endotoxemia, apoptosis, and GSSG were observed in group II and significant decreases were observed in group V. Tight junctions were destroyed in group II animals but were not in animals treated with oral LP (groups III and V). An increase in occludin, claudin-1, claudin-4, and ZO-1 mRNA and protein levels were detected in livers in LP-treated animals (group V) compared with group II levels. Oral LP treatment of rats with obstructive jaundice assisted in the return of active hepatic barrier function. These results may lead to treatments to prevent the deleterious effects of obstructive jaundice.

Lactobacillus plantarum prevents the upregulation of adhesion molecule expression in an experimental colitis model.

BACKGROUND: Lactobacillus consumption has been shown to attenuate the severity of experimental colitis. Whether the effects of Lactobacillus on colitis are related to modulation of leukocyte recruitment into the inflamed intestine is unclear. AIMS: To investigate the effect of Lactobacillus plantarum daily intragastric administration on lymphocyte homing and intestinal inflammation in interleukin 10 (IL-10) knockout mice, an experimental model of colitis. METHODS: Two groups of ten IL-10 knockout mice were fed phosphate buffered saline containing Lactobacillus plantarum 1258 or unmodified vehicle for 4 weeks. Two groups of ten wild-type mice were used as controls. At killing, the bowels were histologically scored and evaluated by transmission electron microscopy. Mucosal addressin cell adhesion molecule 1 (MAdCAM-1) and intercellular adhesion molecule 1 (ICAM-1) expression were determined by immunohistochemistry. The levels of proinflammatory cytokines, tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma) were determined by ELISA. In addition, levels of CD3, alpha4beta7, ICAM-1, and MAdCAM-1 were determined by reverse-transcription polymerase chain reaction and Western blot. RESULTS: L. plantarum treatment improved the histological damage score in KO mice compared to untreated KO mice. L. plantarum significantly attenuated the expression of MAdCAM-1, ICAM-1, CD3, and alpha4beta7, but did not affect the levels of TNF-alpha and IFN-gamma when treated KO mice were compared to untreated KO mice. CONCLUSIONS: L. plantarum interfered with the upregulation of adhesion molecules observed in IL-10 knockout mice compared to wild-type mice, attenuating the symptoms of colitis.

Bisabolane sesquiterpenes from Clausena sanki with their potential anti-inflammatory activities.

The investigation on the stems and leaves of Clausena sanki led to the isolation of a previously undescribed bisabolane sesquiterpene, clausemargic A (1), together with six known analogues (2-7). The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with data reported in the literature. All known compounds (2-7) were isolated from C. sanki for the first time. All isolated compounds were evaluated for their anti-inflammatory activities via examining the inhibitory activity on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro. Compounds 1-7 showed significant inhibitory activities with IC50 values comparable to that of hydrocortisone.

Heterogeneous nuclear ribonucleoprotein A1 is identified as a potential biomarker for colorectal cancer based on differential proteomics technology.

Colorectal cancer (CRC) is the third most common cancer worldwide and has poor prognosis. To identify the proteins involved in colorectal carcinogenesis, we employed 2-DE and MALDI-TOF/TOF-based proteomics approach to study the differentially expressed proteins in tumor and adjacent nontumor tissue samples. Samples from 10 colorectal patients were analyzed. Of the 7 significantly and consistently altered proteins identified, hnRNP A1 was one of the most significantly altered proteins and its overexpression was confirmed using RT-PCR and Western blot analyses. Immunohistochemical examination showed that the enhanced expression of hnRNP A1 was correlated with the increasing severity of colorectal tissue and the progression of the colorectal cancer, as well as UICC (International Union against Cancer) staging, histo-differentiation, recurrence and decreased survival. By developing a highly sensitive immunoassay, hnRNP A1 could be detected in human serum and was significantly elevated in CRC patients compared with healthy volunteers. We proposed that hnRNP A1 could be considered as a novel serum tumor marker for CRC that may have significance in the detection and in the management of patients with this disease. Knockdown of hnRNP A1 expression by RNA interference led to the significant suppression of the cell growth in colorectal cancer SW480 cells in vitro. These data suggested that hnRNP A1 may be a potential biomarker for early diagnosis, prognosis, and monitoring in the therapy of colorectal cancer. Further studies are needed to fully assess the potential clinical value of this biomarker candidate.

Ultra-high performance liquid chromatography-mass spectrometry for the metabolomic analysis of urine in colorectal cancer.

We report here the results of a pilot study in which ultra-high performance liquid chromatography/time-of- flight-mass spectrometry (UPLC/TOF-MS) and multivariate statistical analysis (supervised partial least squares discriminant analysis, PLS-DA) were applied for urinary metabolite profiling and data interpretation. The results of the PLS-DA indicated that the metabolic pattern as a whole was significantly different between the groups of preoperative colorectal cancer (CRC) patients, postoperative CRC patients, and healthy volunteers, respectively. The preoperative group of patients showed significantly increased levels of low-molecular weight compounds (LMC) MW 283 and MW 234 in comparison to the group of healthy volunteers group. After the operation, the levels of these two LMC significantly decreased. These preliminary results suggest that the UPLC-MS-based method coupled with pattern recognition will likely lead to procedures with the potential to be clinically applicable for the diagnosis of CRC and, consequently, to an improvement in patient prognosis.

Structurally diverse diterpenoids from Trigonostemon howii.

Phytochemical investigation on the stems and leaves of Trigonostemon howii resulted in the isolation of a new abietane diterpenoid, trigohowimine A (1), along with seven known structurally diverse diterpenoids (2-8). The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparison with data reported in the literature. New compound 1 was evaluated for its cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480. Compound 1 showed significant inhibitory effects against various human cancer cell lines with IC50 values ranging from 0.82 to 8.53 µM.

Furanocoumarins with potential antiproliferative activities from Clausena lenis.

A phytochemical investigation on the stems and leaves of Clausena lenis led to the isolation of a new furanocoumarin, clauselenisin A (1), together with five known analogues (2-6). The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with data reported in the literature. All known compounds (2-6) were isolated from C. lenis for the first time. All isolated compounds were evaluated for their their antiproliferative activities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1-6 showed significant antiproliferative effects with IC50 values ranging from 0.36 to 16.48 µM.