G2 Cancer Research Articles

Photoactivated cytotoxicity of ferrocenyl-terpyridine oxovanadium(IV) complexes of curcuminoids

Oxovanadium(IV) complexes, viz. [VO(Fc-tpy)(Curc)](ClO4) (1), [VO(Fc-tpy)(bDHC)](ClO4) (2), [VO(Fc-tpy)(bDMC)](ClO4) (3) and [VO(Ph-tpy)(Curc)](ClO4) (4), of 4′-ferrocenyl-2,2′:6′,2″-terpyridine (Fc-tpy) and 4′-phenyl-2,2′:6′,2″-terpyridine (Ph-tpy) and monoanionic curcumin (Curc), bis-dehydroxycurcmin (bDHC) and bis-demethoxycurcumin (bDMC) were prepared, characterized and their photo-induced DNA cleavage activity and photocytotoxicity in visible light studied. The ferrocenyl complexes 1–3 showed an intense metal-to-ligand charge transfer band near 585 nm in DMF and displayed Fc+/Fc and V(IV)/V(III) redox couples near 0.65 V and −1.05 V vs. SCE in DMF–0.1 M TBAP. The complexes as avid binders to calf thymus DNA showed significant photocleavage of plasmid DNA in red light of 647 nm forming OH radicals. The complexes showed photocytotoxicity in HeLa and Hep G2 cancer cells in visible light of 400–700 nm with low dark toxicity. ICP-MS and fluorescence microscopic studies exhibited significant cellular uptake of the complexes within 4 h of treatment with complexes. The treatment with complex 1 resulted in the formation of reactive oxygen species inside the HeLa cells which was evidenced from the DCFDA assay.

Tumor targeting by pH-sensitive, biodegradable, cross-linked N-(2-hydroxypropyl) methacrylamide copolymer micelles

Increasing the molecular weight of N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers by using micellar structures could result in more pronounced enhanced permeability and retention effect, thus increase the tumor accumulation of drug. However, most micellar formulations are relatively unstable and release their drug non-specifically. To improve on these disadvantages, we developed a micellar drug delivery system based on self-assembly of HPMA copolymers. Amphiphilic conjugates were synthesized by conjugating the hydrophobic drug doxorubicin and hydrophobic β-sitosterol to the hydrophilic HPMA polymer backbone via pH-sensitive hydrazone linkages. This linkage is quite stable at physiological pH but hydrolyzes easily at acidic pH. After conjugates self-assembly into micelles, HPMA copolymer side chains were cross-linked through the hydrazone linkages to ensure micelle stability in the blood. Using this approach, cross-linked micelles were obtained with molecular weight of 1030 KD and diameter of 10–20 nm. These micelles remained stable with undetectable doxorubicin release at pH 7.4 or mouse plasma, whereas collapsed quickly with 80% of the drug released at pH 5 which corresponds to the pH of lyso/endosome compartments of tumor cells. Both cross-linked and non-cross-linked micelles displayed similar in vitro anti-tumor activity as linear copolymer conjugates in Hep G2 and A549 cancer cell lines with internalization mechanism by caveolin, clathrin, and giant macropinocytosis. In vivo studies in an H22 mouse xenograft model of hepatocarcinoma showed the tumor accumulation (1633 μCi/L*h) and anti-tumor rate (71.8%) of cross-linked micelles were significantly higher than non-cross-linked ones (698 μCi/L*h, 64.3%). Neither type of micelle showed significant toxicity in heart, lung, liver, spleen or kidney. These results suggest that cross-linked HPMA copolymer micelles with pH-sensitivity and biodegradability show excellent potential as carriers of anti-cancer drugs.

Phytochemical investigation of sesquiterpenes from the fruits of Schisandra chinensis and their cytotoxic activity

Phytochemical investigation of ethanolic extract from the fruits of Schisandra chinensis led to the isolation of four new sesquiterpenes (1–4); their structures were determined by a combination of NMR (1D and 2D) and MS spectroscopic techniques. In addition, all these isolates were screened for their cytotoxic activities against MCF-7, Caco-2, Hela, Lncap, Hep G2 and MDA-MB231 cancer cell lines. Results indicated that compounds 2 and 3 displayed potent cytotoxic activity against Caco2 cell lines with IC50 values of 17.10μg/mM and 16.46μg/mM, respectively.

Suppression of E-cadherin mediates gallotannin induced apoptosis in Hep G2 hepatocelluar carcinoma cells.

Though gallotannin was known to have anti-oxidant and antitumor activity, the underlying antitumor mechanism of gallotannin still remains unclear. Thus, in the present study, antitumor mechanism of gallotannin was elucidated in hepatocellular carcinoma cells. Gallotannin significantly exerted cytotoxicity against Hep G2 and Chang hepatocellular carcinoma cells with the accumulation of the sub-G1 population and increase of terminal deoxynucleotidyltransferasedUTP nick end labeling (TUNEL) positive cells as an apoptotic feature. Also, gallotannin attenuated the expression of pro-caspase9, pro-caspase3, Bcl2 and integrin β1 and cleaved poly(ADP)-ribose polymerase (PARP) in Hep G2 and Chang cancer cells. Furthermore, gallotannin suppressed cell repair motility by wound healing assay and also inhibited cell adhesion in Hep G2 cells. Of note, gallotannin attenuated the expression of epithelial cadherin (E-cadherin) to form cell-cell adhesion from the early stage, and also beta-catenin at late phase in Hep G2 cells. Consistently, Immunofluorescence assay showed that E-cadherin or β-catenin expression was suppressed in a time dependent manner by gallotannin. Furthermore, silencing of E-cadherin by siRNA transfection method enhanced PAPR cleavage, caspase 3 activation and sub G1 population and attenuated the cell adhesion induced by gallotannin in Hep G2 cells. Overall, our findings demonstrate that the disruption of cell adhesion junction by suppression of E-cadherin mediates gallotannin enhanced apoptosis in Hep G2 liver cancer cells.

English

Naturally isolated cyclic pentapeptide Longicalycinin A, which showed cytotoxicity to Hep G2 cancer cell line with an IC50 value 13.52 μg/mL, has been successfully synthesized by solid-phase methodology with Fmoc/t-Bu protecting schemes via solution-phase macrocyclization. 2-chlorotrityl chloride resin was used as solid support. Solution phase macrocyclization of linear pentapeptide precursor was carried out by two different routes with mild and severe acidic conditions correspondingly and found that percentage yield of Longicalycinin A under mild acidic condition (33%) was better than severe acidic conditions (13.7%). In addition, the cytotoxicity against Dalton’s lymphoma ascites (DLA) and Ehrlich’s ascites carcinoma (EAC) cell lines with CTC50 values were found to be 2.62 and 6.17 µM respectively.   Key words: Longicalycinin A, solid phase synthesis, 2-chlorotrityl chloride, solution-phase macrocyclization, cytotoxicity.

Abundant in vitro expression of the oncofetal ED-B-containing fibronectin translates into selective pharmacodelivery of 131I-L19SIP in a prostate cancer patient

The extradomain B of fibronectin (ED-B) is a promising vascular target for selective pharmacodelivery in cancer patients. We analyzed a large series of prostatectomies from patients with prostate cancer, hyperplastic prostate disease, and normal prostates to study extent and tumor-selectivity of ED-B expression. Using immunohistology, 68 adenocarcinomas of the prostate or prostate cancer-inflicted lymph nodes, 4 samples of benign prostatic hyperplasia, and 6 normal prostate glands were studied for ED-B expressing newly formed blood vessels. Further, we treated an advanced prostate cancer patient with the anti-ED-B antibody (131)I-L19SIP to study in vivo target accessibility. ED-B-positive blood vessels were found significantly more frequent in prostate cancers as compared with peritumoral prostate tissues or normal prostate glands, independent of tumor differentiation. The ED-B-positive blood vessels' density was 97 (±23), 65 (±9), and 59 (±9)/mm(2) in G3, G2, and G1 prostate cancers, respectively, and 7 (±5)/mm(2) in normal prostate glands. In high-grade (G3) prostate cancers, also the peritumoral tissue showed a higher density of ED-B vessels than normal prostate glands. Similar results were obtained when ED-B-positive vessel density was expressed as a fraction of CD34-positive vessel density. Finally, selective uptake of ED-B-binding (131)I-L19SIP to tumor lesions was found in an advanced prostate cancer patient by whole-body planar scintigraphy. ED-B-positive blood vessels were found to a large extent in prostate cancer tissues, but only rarely in normal prostates or benign prostatic hyperplasia. Whole-body planar scintigraphy in a prostate cancer patient confirmed selective uptake of (131)I-L19SIP in the prostate cancer tissues, qualifying ED-B as a promising target for selective pharmacodelivery of anticancer agents in prostate cancer.

A stable and practical etoposide-containing intravenous long-/medium-chain triglycerides-based lipid emulsion formulation: pharmacokinetics, biodistribution, toxicity, and antitumor efficacy

Objectives: This work aimed to evaluate pharmacokinetics, biodistribution, toxicity, and antitumor activities of a highly stable long-/medium-chain triglycerides (LCT/MCT)-based etoposide parenteral emulsion (EPE) in comparison to etoposide parenteral solution (EPS).Methods: Using high-pressure homogenization method, EPE was prepared and sterilized at 121°C for 10 min by autoclaving. The biological samples were analyzed using the UPLC-ESI-MS/MS method.Results: Superior stability of EPE was verified with no significant changes in physicochemical properties in the accelerating and long-term stability tests. Similar pharmacokinetic behavior in beagle dogs was obtained and the AUC0 – 12h values were 1196.73 ± 320.85 and 1505.56 ± 617.93 µg·h/L for EPE and EPS (p > 0.5), respectively. Likewise, no remarkable difference in biodistribution profiles in mice was found for both formulations. Safety assessment studies including hemolysis test, rabbit ear vein test and injection anaphylaxis were undertaken and the EPE was proven to be safe for intravenous administration. Specifically, after consecutive 12 weeks administration in rats, systematic and local toxicity induced by EPE were alleviated relative to that of EPS. Furthermore, significant and comparable antitumor activities to EPS were also demonstrated by EPE with tumor suppression rate (TSR) of 66.63, 55.94, and 60.16% against H460, Hep G2, and BCAP-37 human cancer cell lines in nude mice at the dose of 15 mg/kg, respectively.Conclusion: These results suggest that this LCT/MCT-based lipid emulsion is a promising alternative intravenous carrier for etoposide with high stability, improved convenience, alleviated toxicity, and noncompromised antitumor efficacy.

Investigating the Antiproliferative Activity of High Affinity DNA Aptamer on Cancer Cells

Vascular endothelial growth factor (VEGF) is an angiogenic mitogen involved in promoting tumor angiogenesis inside the body. VEGF is a key protein required for progression of tumor from benign to malignant phenotype. In this study, we investigated the binding affinity of a previously selected 26-mer DNA aptamer sequence (SL2-B) against heparin binding domain (HBD) of VEGF165 protein. The SL2-B was first chemically modified by introduction of phosphorothioate linkages (PS-linkages). Subsequently, surface plasmon resonance (SPR) spectroscopy and circular dichroism (CD) were used to determine the binding affinity, specificity and to deduce the conformation of PS-modified SL2-B sequence. Finally, antiproliferative activity of the modified SL2-B sequence on Hep G2 cancer cells was investigated. Our results demonstrate a marked enhancement in the biostability of the SL2-B sequence after PS modification. The modified SL2-B sequence also exhibits enhanced antiproliferative activity against Hep G2 cancer cells in hypoxia conditions. In addition, modified SL2-B sequence inhibits the expression of Jagged-1 protein, which is one of the ligands to VEGF linked delta/jagged-notch signaling pathway.

Determination of Cancer Antigen CA15-3 and Carcino Embryonic Antigen CEA concentration as Tumor Markers in Patients with Stomach and Colorectal cancers.

Background: Tumor markers are often requested as part of a diagnostic workup, and increased concentrations in serum may suggest malignancy of a particular organ. However, definitive diagnosis is based on histological evaluation of the involved tissue.Objective: The aim of present study is to evaluated CEA and CA15-3 in order to clarify at least in part their possible use as an early diagnosis tools in sera of patients with stomach, colon and rectum cancers.Patients and methods: The study was carried out on 61 subjects comprising of 16 patients with colon cancer group (G1), 10 patients with rectum cancer group (G2), 10 patients with stomach cancer group (G3) and 25 normal healthy control The patients were selected, during the period from (February 2010 to January 2011) with age range of (40-55) years. The patients were admitted to Al khadmiya Teaching Hospital, Iraq for treatment. Serum CA15-3 and CEA were measured by enzyme linked immunosorbent assay (ELISA).Results: The serum value of CA15-3, was highly significant increase (p≤0.001) in G1 and G2 cancer groups compared to normal healthy subjects. while the serum value of CEA of G1 and G2 was a significant increase (p≤0.05)compared to control but CA15-3 and CEA in serum of G3 showed no significant difference(p>0.05) compared to control.Conclusions: In this study CA15-3 and CEA could not be of valuable use as diagnostic markers in serum of stomach cancer while in colon and rectal cancers are of useful value.

Cytotoxic Dehydromonacolins from Red Yeast Rice

Two new dehydromonacolins (1 and 3), together with nine known monacolins (4-12), were isolated from red yeast rice. Compounds 4-6 were isolated from a natural resource for the first time. Their structures were elucidated by means of NMR and mass spectroscopic analyses. The structure of dehydromonacolin N (1) was further confirmed by its semisynthesis from monacolin K (lovastatin) (11). Dehydromonacolin J (2), an intermediate in the semisynthesis of 1, was obtained as a new dehydromonacolin. The structure of dehydromonacolin L (3) was also confirmed by an elimination reaction of monacolin L (12). Compound 1, possessing a C2 side chain, is unprecedented in the natural monacolin family and exhibited moderate cytotoxic activity against Hep G2, Caco-2, and MCF-7 cancer cell lines. Dehydromonacolin K (8) demonstrated the most potent cytotoxicity to all three of these cell lines. The structure-activity relationship of natural and synthesized monacolins was discussed. This is the first report on the cytotoxic effects of dehydromonacolins.

Identification of 3- deoxyanthocyanins from red sorghum (Sorghum bicolor) bran and its biological properties

Anthocyanins known as potent antioxidant provides attractive colours and used as an ingredient in food systems. This study aims to evaluate a potential anthocyanin extraction method from red sorghum bran and to investigate its antioxidant and cytotoxic properties. The anthocyanin content was found to be higher in acidified methanol and on separation was identified as apigeninidin and leuteolinidin, which obviously could attribute to its antioxidant properties and cytotoxic activity. Anthocyanins are natural pigments used as food additives and known for its potent antioxidant and antiproliferative property. In addition to their potential as food colorants, anthocyanins are nowadays regarded as an important nutraceuticals mainly due to their possible antioxidant effects and they have been given a potential therapeutic role related to some cardiovascular diseases, cancer treatment, inhibition of certain types of virus including Human Immunodeficiency Virus type 1 (HIV-1) and improvement of visual acuity (Stintzing et al., 2002; Talavera et al., 2006; Sandvik et al., 2004; Beattie et al., 2005; Jang et al., 2005; Cooke et al., 2005; Andersen et al., 1997; Nakaishi et al., 2000). This study aims to evaluate anthocyanin content, to analyze antioxidant and antipropliferative activity from red sorghum bran. When acidified methanol was used as a solvent for extraction, maximum amount of anthocyanin was obtained as compared to methanol alone. On separation by Thin Layer Chromatography and High Pressure Liquid Chromatography, the compounds were identified as apigenindin and luteolindin. The antioxidant activity was found to be higher in red sorghum bran. Anthocyanin from red sorghum bran also showed moderate cytotoxic activity against HT 29 and HEP G2 cell lines. Is assumed that the antioxidant and antiproliferative activity of the extract from red sorghum bran was due to apigenindin and luteolindin. So the anthocyanins extracted from easily available red sorghum bran would be a valuable source for antioxidant and antiproliferative activity in food industry. Key words: Bran, sorghum, anthocyanins, antioxidant activity, high pressure liquid chromatography, DPPH, HT 29 cancer cell line, HEP G2 cancer cell line.

Paraminabeolides A−F, Cytotoxic and Anti-inflammatory Marine Withanolides from the Soft Coral Paraminabea acronocephala

Six new withanolides, paraminabeolides A-F (1-6), along with five known compounds, minabeolides-1, -2, -4, -5, and -8 (7-11), were isolated from a Formosan soft coral, Paraminabea acronocephala. The structures of these compounds were elucidated by extensive spectroscopic analysis and chemical transformation. The absolute configuration of 4 was determined by the application of Mosher's method. Compounds 1 and 7 were cytotoxic toward Hep G2 cancer cells. Compounds 1-4 and 7-10 were found to significantly inhibit the accumulation of the pro-inflammatory iNOS protein. Compounds 7-10 also could effectively reduce the expression of COX-2 protein.

Evaluation of the efficacy, toxicity and safety of vinorelbine incorporated in a lipid emulsion

To reduce the severe adverse effects of vinorelbine (VRB) with the aim of improving patient compliance, a parenteral vinorelbine-loaded lipid emulsion (VLE) has been developed. The objective of the present study was to get insight into the preclinical antitumor efficacy, toxicity and safety of VLE, and compare this with that of the commercial product, Navelbine ® i.v. (VS). Comparable antitumor efficacy of VLE and VS was observed in tumor-bearing nude mouse models inoculated with A549 human lung cancer, hepatoma solidity (Heps) G2 cancer and BCAP-37 human breast cancer cells. The median lethal dose (LD 50) in mice was 29.3 mg/kg (male) and 32.1 mg/kg (female) for VLE, while the corresponding value was 30.5 mg/kg (male and female) for VS. In the long-term toxicity study, VLE significantly reduced the decreases in RBC, HC, WBC and WBC differential count (DC) levels. Lesions in spleen, thymus, lymph nodes, bone marrow, testis, ovary and injection site induced by VS were much more severe compared with VLE. VLE also exhibited less local venous irritation than VS, as well as no hemolysis or hypersensitivity. Consequently, these observations clearly indicate that the lipid emulsion could be a useful potential parenteral carrier for VRB with equivalent efficacy and lower toxicity.

Preparations of Anthraquinone and Naphthoquinone Derivatives and Their Cytotoxic Effects

Chrysophanol and 1,8-di-O-hexylchrysophanol derivatives having nucleic acid bases at position 5 were synthesized. Furthermore, derivatives of menadione substituted at position 11 (type A naphthoquinone derivatives) or methylmenadione substituted at position 7 (type B naphthoquinone derivatives) modified with nucleic acid bases, amines and thiocyano, selenocyano or thioacetyl groups were synthesized. The cytotoxic effects of these derivatives on HCT 116 cells, which poorly express P-glycoprotein (P-gp), and Hep G2 cells, which stably express P-gp, were evaluated by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results were compared with those obtained using 5-fluorouracil (5-FU), which has been used clinically. Several of these derivatives exhibited markedly higher potent cytotoxic effects not only on HCT cancer cells but also Hep G2 cancer cells as compared with 5-FU.

Synthesis and biological evaluation of 3′,4′,5′-trimethoxychalcone analogues as inhibitors of nitric oxide production and tumor cell proliferation

A series of 23 3′,4′,5′-trimethoxychalcone analogues was synthesized and their inhibitory effects on nitric oxide (NO) production in LPS/IFN-γ-treated macrophages, and tumor cell proliferation has been investigated. 4-Hydroxy-3,3′,4′,5′-tetramethoxychalcone ( 7), 3,4-dihydroxy-3′,4′,5′-trimethoxychalcone ( 11), 3-hydroxy-3′,4,4′,5′-tetramethoxychalcone ( 14), and 3,3′,4′,5′-tetramethoxychalcone ( 15) were the most potent growth inhibitory agents on NO production, with an IC 50 value of 0.3, 1.5, 1.3 and 0.3 μM, respectively. The tumor cells proliferation assay results revealed that several compounds exhibited potent inhibition activity against different cancer cell lines. The chalcone 15 was the most potent anti-proliferative compound in the series with IC 50 values of 1.8 and 2.2 μM toward liver cancer Hep G2 and colon cancer Colon 205 cell lines, respectively. 2,3,3′,4′,5′-Pentamethoxychalcone ( 1), 3,3′,4,4′,5,5′-hexamethoxychalcone ( 3), 2,3′,4,4′,5,5′-hexamethoxychalcone ( 5), 2-hydroxy-3,3′,4′,5′-tetramethoxychalcone ( 10), 11 and 14 showed significant anti-proliferation actions in Hep G2 and Colon 205 cells with an IC 50 values ranging between 10 and 20 μM. Among the tested agents, compound 7 showed selective NO production inhibition (IC 50 = 0.3 μM), while has no effect on tumor cell proliferation (IC 50 >100 μM). 3,3′,4,4′,5′-Pentamethoxychalcone ( 2) showed selective anti-proliferation effect in Hep G2 cells, in addition to its potent NO inhibition, however has no such response in Colon 205 cells. In contrast, 3-formyl-3′,4′,5′-trimethoxychalcone ( 22) showed moderate growth inhibition in Colon 205 cells, while has no such effect on NO production and Hep G2 cells proliferation. These results provide insight into the correlation between some structural properties of 3′,4′,5′-trimethoxychalcones and their in vitro anti-inflammatory and anti-cancer differentiation activity.

Ent-Kaurane Diterpenoids fromRabdosia rubescensand Their Cytotoxic Effects on Human Cancer Cell Lines

Two new ent-kaurane diterpenoids, 16,17-exo-epoxide-oridonin ( 1) and 11,15- O,O-diacetyl-rabdoternins D ( 2), together with thirteen known ones, were isolated from the aerial parts of Rabdosia rubescens. Their structures were established on the basis of high-field 1D and 2D NMR methods supported by HRMS. All diterpenoids were tested for cytotoxicity against human Hep G2, COLO 205, MCF-7, and HL-60 cancer cells. The compounds oridonin ( 3), 14- O-acetyl-oridonin ( 4), 1,14- O,O-diacetyl-oridonin ( 5), rosthorin ( 6), effusanin E ( 7), and ponicidin ( 8), as well as six alpha-methylene gamma-ketone bearing diterpenoids, were modestly active in these assays.

Fluorescent in situ hybridization as a screening test for HER2 amplification in G2 and G3 breast cancers of lobular and ductal histotype and metastases

The aim of the present study was to evaluate the effectiveness of fluorescence in situ hybridisation (FISH), as a screening test, in moderately- (G2) or poorly- (G3) differentiated breast cancers of the ductal (IDC) and lobular (ILC) histotypes and distant metastases. HER2 FISH was performed on 486 G2 and 477 G3 both of IDC and ILC histotypes and in 241 metastases. A significant difference in the HER2 amplification was observed between G2 (14.8%) and G3 (31.9%), with no difference according to the histotype. However, the rate of amplification increased to 36% in the G2/hormone receptor-negative cases as compared to 10.6% in the G2/receptor-positive cases (p<0.0001). HER2 was amplified in 17% of metastases with some differences depending on the location. These data suggest that the HER2 FISH analysis may be an effective screening test in breast cancer metastases and G3 tumors, irrespective of the hormone receptor status or presence of lymphovascular invasion.

Cytotoxic Hydrolyzable Tannins from Balanophora japonica

Four hydrolyzable tannins named balanophotannins D-G ( 1- 4) were isolated from the aerial parts of the parasitic plant Balanophora japonica. Their structures were characterized on the basis of spectroscopic and chemical evidence. Balanophotannins D-G contain an oxidized hexahydroxydiphenoyl (HHDP) group. The absolute configurations of balanophotannins D ( 1) and F ( 3) were determined via the PGME method. Balanophotannin E ( 2) showed cytotoxicity to Hep G2 cancer cells with an IC 50 value of 4.22 microM.

Preparation of 1,8-Di-O-alkylaloe-emodins and 15-Amino-, 15-Thiocyano-, and 15-Selenocyanochrysophanol Derivatives from Aloe-Emodin and Studying Their Cytotoxic Effects

1,8-di-O-alkylaloe-emodin derivatives (namely, methyl-, propyl-, hexyl-, dodecyl-, and octadecyl) were synthesized from naturally occurring aloe-emodin. Further, derivatives having various substituents such as diethylamino, pyrrolidinyl, piperidinyl, methylpiperazinyl, imidazolyl, thiocyano and selenocyano groups at the 15 position of chrysophanol and 1,8-di-O-hexylchrysophanol from aloe-emodin were synthesized. The cytotoxic effects of these derivatives on less P-glycoprotein (P-gp)-expressing HCT 116 cells and stably P-gp-expressing Hep G2 cells were evaluated by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among these products, several of them exhibited markedly higher potent cytotoxic effects not only on HCT116 cells but also Hep G2 cancer cells as compared to aloe-emodin.

Histologic evaluation of resection specimens obtained at 293 endoscopic resections in Barrett's esophagus

Evidence-based selection criteria for endoscopic resection (ER) of Barrett's neoplasia are scarce. To study the histopathology of ER specimens of Barrett's neoplasia and correlate this with endoscopic characteristics to make recommendations for patient management. DESIGN, SETTING, INTERVENTIONS: Histology and correlating endoscopy reports of specimens obtained at 293 consecutive ERs performed at a Dutch tertiary referral center between 2000 and 2006 were reviewed. Histologic findings in ER specimens and their relation with endoscopic characteristics. A total of 150 ERs were performed for focal lesions: 16% type 0-I, 23% 0-IIa, 7% 0-IIb, 3% 0-IIc, 9% 0-IIa-IIb, and 42% 0-IIa-IIc; and 143 for flat mucosa. Histology revealed no dysplasia in 57 ERs, low-grade intraepithelial neoplasia in 52, high-grade intraepithelial neoplasia in 104, T1m in 61, and T1sm in 17; in two cancers, infiltration depth was not assessable because of artifacts. Type 0-I and 0-IIc lesions significantly more often penetrated the submucosa (P = .009): 60% were G1 cancers, 23% were G2 cancers, and 18% were G3 cancers. G2-G3 cancers significantly more often invaded the submucosa (P < .001) or had positive vertical margins (P = .015). Histology of ER specimens led to a change in diagnosis in 49% of the focal lesions and a relevant change in treatment policy in 30%. A retrospective study. ER is a valuable diagnostic tool that frequently leads to a change in treatment policy. Most endoscopically resected early Barrett's neoplasia are 0-II type, G1 mucosal neoplasia. Submucosal infiltration is more often encountered in type 0-I and 0-IIc lesions and in G2-G3 cancers.