Pharmacokinetics and disposition of anlotinib, an oral tyrosine kinase inhibitor, in experimental animal species.

Anlotinib is a new oral tyrosine kinase inhibitor; this study was designed to characterize its pharmacokinetics and disposition. Anlotinib was evaluated in rats, tumor-bearing mice, and dogs and also assessed in vitro to characterize its pharmacokinetics and disposition and drug interaction potential. Samples were analyzed by liquid chromatography/mass spectrometry. Anlotinib, having good membrane permeability, was rapidly absorbed with oral bioavailability of 28%-58% in rats and 41%-77% in dogs. Terminal half-life of anlotinib in dogs (22.8±11.0 h) was longer than that in rats (5.1±1.6 h). This difference appeared to be mainly associated with an interspecies difference in total plasma clearance (rats, 5.35±1.31 L·h-1·kg-1; dogs, 0.40±0.06 L·h-1/kg-1). Cytochrome P450-mediated metabolism was probably the major elimination pathway. Human CYP3A had the greatest metabolic capability with other human P450s playing minor roles. Anlotinib exhibited large apparent volumes of distribution in rats (27.6±3.1 L/kg) and dogs (6.6±2.5 L/kg) and was highly bound in rat (97%), dog (96%), and human plasma (93%). In human plasma, anlotinib was predominantly bound to albumin and lipoproteins, rather than to α1-acid glycoprotein or γ-globulins. Concentrations of anlotinib in various tissue homogenates of rat and in those of tumor-bearing mouse were significantly higher than the associated plasma concentrations. Anlotinib exhibited limited in vitro potency to inhibit many human P450s, UDP-glucuronosyltransferases, and transporters, except for CYP3A4 and CYP2C9 (in vitro half maximum inhibitory concentrations, <1 µmol/L). Based on early reported human pharmacokinetics, drug interaction indices were 0.16 for CYP3A4 and 0.02 for CYP2C9, suggesting that anlotinib had a low propensity to precipitate drug interactions on these enzymes. Anlotinib exhibits many pharmacokinetic characteristics similar to other tyrosine kinase inhibitors, except for terminal half-life, interactions with drug metabolizing enzymes and transporters, and plasma protein binding.

Trace determination of mutagenic alkyl toluenesulfonate impurities via derivatization headspace-GC/MS in an active pharmaceutical ingredient of a candidate drug.

This study aims to optimize sodium iodide (NaI) derivatization headspace-GC/MS described in European Pharmacopoeia by using vitamin C as an alternative antioxidant for the determination of mutagenic alkyl toluenesulfonate impurities in an active pharmaceutical ingredient (API) of a candidate drug with an artemisinin derivative. Alkyl toluenesulfonates are transformed into their corresponding alkyl iodides (methyl iodide, ethyl iodide, propyl iodide, and isopropyl iodide) by utilizing the derivatization reagent NaI. Results show that the MS response of methyl iodide is a critical indicator of method robustness because of the deteriorating effects of methyl iodide on stability when sodium thiosulfate is used as an antioxidant originally described in the pharmacopoeia. With vitamin C as a newly developed antioxidant, the robustness of this method is improved significantly. The optimized method is further validated and applied successfully for the quality control and safety of the API of an artemisinin derivative.

Crystal structures and physicochemical properties of amisulpride polymorphs.

The purpose of this work was to investigate the crystal structures and physicochemical properties of amisulpride polymorphs. Except of the previously reported polymorph (named as Form I), a new polymorphic form (named as Form II) was discovered through comprehensive solid-state screening experiments. Both polymorphic forms were characterized by single crystal X-ray structure analysis (SXRD), powder X-ray diffraction (PXRD), dynamic vapor sorption (DVS) and thermal analysis (TGA and DSC) as well. It has been found that the Forms I and II are of conformational polymorph with the main conformational difference around ethylsulfonyl group. Form II possesses lower hygroscopicity and better solubility compared with that of Form I, indicating Form II could be an alternate solid form for formulation development.

[Study of the Detecting System of CH4 and SO2 Based on Spectral Absorption Method and UV Fluorescence Method].

According to the spectral absorption characteristics of polluting gases and fluorescence characteristics, a time-division multiplexing detection system is designed. Through this system we can detect Methane (CH4) and sulfur dioxide (SO2) by using spectral absorption method and the SO2 can be detected by using UV fluorescence method. The system consists of four parts: a combination of a light source which could be switched, the common optical path, the air chamber and the signal processing section. The spectral absorption characteristics and fluorescence characteristics are measured first. Then the experiment of detecting CH4 and SO2 through spectral absorption method and the experiment of detecting SO2 through UV fluorescence method are conducted, respectively. Through measuring characteristics of spectral absorption and fluorescence, we get excitation wavelengths of SO2 and CH4 measured by spectral absorption method at the absorption peak are 280 nm and 1.64 µm, respectively, and the optimal excitation wavelength of SO2 measured by UV fluorescence method is 220 nm. we acquire the linear relation between the concentration of CH4 and relative intensity and the linear relation between the concentration of SO2 and output voltage after conducting the experiment of spectral absorption method, and the linearity are 98.7%, 99.2% respectively. Through the experiment of UV fluorescence method we acquire that the relation between the concentration of SO2 and the voltage is linear, and the linearity is 99.5%. Research shows that the system is able to be applied to detect the polluted gas by absorption spectrum method and UV fluorescence method. Combing these two measurement methods decreases the costing and the volume, and this system can also be used to measure the other gases. Such system has a certain value of application.

[Determination of the Sodium Methylparaben Content Based on Spectrum Fluorescence Spectral Technology and GA-BP Neural Network].

Sodium methylparaben as one kind of preservatives is widely used in our life, but it will do harm to health if it is eaten too much. So there are strict rules on the dosage of sodium methylparaben in every country. The fluorescence spectral properties of sodium methylparaben in aqueous solution and orange juice solution are analyzed with FS920 fluorescence spectrometer. The research result shows that the fluorescence characteristic peak of sodium methylparaben solution is in λ(ex)/λ(em) = 380/5 10 nm, while sodium methylparaben orange juice solution has two fluorescence characteristic peaks which are in λ(ex)/λ(em) = 440/520 nm and 470/530 nm, and its best excitation wavelength is 440 nm. So it can be concluded from the result that there is a significant change between the characteristic peaks of sodium methylparaben in the two solution. Compared with the fluorescence characteristic peak of sodium methylparaben solution, thoses of sodium methylparaben orange juice solution are changed significantly, which are caused by the interference of orange juice fluorescence characteristics. In order to determine the content of sodium methylparaben in the fresh orange juice, a detection model of sodium methylparaben content in orange juice is built based on GA-BP neural network, according to the relationship between fluorescence intensity in λ(ex) = 440 nm and the content of sodium methylparaben orange juice solution. When the accuracy of the mean square error in the process of network training reaches 10(-3), the correlation coefficient of network output and that of the expected is 0.996. At the same time, a better prediction result can be obtained that the average recovery of the forecast samples is 98.67% and the average relative standard deviation is 0.86%. When the concentration ranges from 0.02 to 1.0 g x L(-1), the results testify that detection method based on fluorescence spectroscopy and GA-BP neural network can accurately determine the content of sodium methylparaben in orange juice. This method has the features of novelty and simplicity and it is expected to be applied to the determination of sodium methylparaben in other kinds of drink.

Application of capillary electrophoresis-frontal analysis for comparative evaluation of the binding interaction of captopril with human serum albumin in the absence and presence of hydrochlorothiazide.

The application of capillary electrophoresis-frontal analysis for comparative evaluation of the binding interaction between antihypertensive drug captopril and human serum albumin in the absence and presence of diuretic drug hydrochlorothiazide was presented in this work. At near-physiological conditions (67mM phosphate buffer, pH 7.4, I=0.17, 37°C), the individual solution of 100µM captopril and the co-binding solution with 60µM hydrochlorothiazide added were pre-equilibrated with series concentrations of HSA (10-475µM) respectively, introducing hydrodynamically into an uncoated fused silica capillary (35cm×50µm I.D. with 26.5cm effective length). The values of number of binding sites, the binding constant for captopril and hydrochlorothiazide binding to HSA were obtained, respectively. It can be found that both drugs exhibit moderate binding properties towards HSA and there does not exist significant competitive binding effects between them.

A New Method for the Determination of Potassium Sorbate Combining Fluorescence Spectra Method with PSO-BP Neural Network.

In this paper, fluorescence spectra properties of potassium sorbate in aqueous solution and orange juice are studied, and the result.shows that in two solution there are many difference in fluorescence spectra of potassium sorbate, but the fluorescence characteristic peak exists in λ(ex)/λ(em) = 375/490 nm. It can be seen from the two dimensional fluorescence spectra that the relationship between the fluorescence intensity and the concentration of potassium sorbate is very complex, so there is no linear relationship between them. To determine the concentration of potassium sorbate in orange juice, a new method combining Particle Swarm Optimization (PSO) algorithm with Back Propagation (BP) neural network is proposed. The relative error of two predicted concentrations is 1.83% and 1.53% respectively, which indicate that the method is feasible. The PSO-BP neural network can accurately measure the concentration of potassium sorbate in orange juice in the range of 0.1-2.0 g · L⁻¹.

Determination of pK(a) values of a triptolide derivative and its impurities by pressure-assisted capillary electrophoresis.

A pressure-assisted capillary zone electrophoresis method was developed to determine the pKa values of a triptolide derivative (LLDT-246) and its impurities. The method was performed in an uncoated fused-silica capillary under the electric voltage of 18kV and 50mbar of external pressure applied simultaneously. A series of running electrolyte buffers were used with pH ranging between 2.2 and 10.0 with the constant ionic strength of 0.05M. The values of pKa of LLDT-246 and two impurities were calculated based on the pH dependence of effective mobilities (µeff). The pKa value of LLDT-246 was in good agreement with that of determined by potentiometric titration method.

[Associated factors for the occurrence of lupus enteritis].

OBJECTIVE: To explore the clinical and laboratory characteristics of patients with lupus enteritis to provide rationales for clinical diagnosis and treatment. METHODS: A retrospective group control study was conducted for systemic lupus erythematosus (SLE) patients with complaints of acute abdominal pain from 2004 to 2011. They were divided into 2 groups: lupus enteritis (n = 66) and non-lupus related abdominal pain (n = 73). The associated factors included demographic, laboratory, clinical and radiographic data. RESULTS: Lupus enteritis (39.3%) was the most common cause of lupus patients with acute abdominal pain. There were no differences in autoantibody profiles, complement, erythrocyte sedimentation rate, C reactive protein and SLE disease activity index (SLEDAI) score between two groups. The level of D-dimer and European consensus lupus activity measurement (ECLAM) score were significantly higher in the group of lupus enteritis than those in non-lupus related gastrointestinal injury. Lupus enteritis had significantly higher percentage of complications with multiple serous cavity effusions and ascites. But after adjusting with logistic regression multivariate analysis, only the level of D-dimer, ECLAM and volume of ascites were associated with occurrence of lupus enteritis. CONCLUSION: Lupus enteritis is the most common cause of acute abdominal pain. D-dimer is an excellent predictor for lupus abdominal pain. As compared with SLEDAI, ECLAM may be more suitable for assessment in SLE patients with alimentary tract injury.

[Polymorphism of the 5R-5-hydroxytriptolide].

5R-5-hydroxytriptolide (LLDT-8) is a new drug candidate which is in clinical trial treating rheumatoid arthritis. Polymorph screening of the compound was carried out in this study. Polymorph of LLDT-8 was prepared by evaporative crystallization and antisolvent crystallization methods and was characterized by powder X-ray diffraction (p-XRD), infrared spectrometry (IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TG). It was found that p-XRD patterns, DSC curves, TG curves and IR spectra of the LLDT-8 samples prepared by the above recrystallization methods were all consistent. The 20 of main peaks in the p-XRD patterns appeared at 7.58 degrees, 8.14 degrees, 8.66 degrees, 15.46 degrees, 16.46 degrees, 29.54 degrees, 31.16 degrees and 38.26 degrees, while the infrared absorption peaks appeared at 3 471.3, 2 962.2, 2 887.0, 1 762.6, 1 677.8, 1 432.9, 1 365.4, 1 247.7, 1 080.0, 1 031.7 and 877.5 cm(-1). LLDT-8 was decomposed at 271.2 degrees C based on the determination from DSC and TG. It was showed in single crystal X-ray diffraction study that LLDT-8 crystal was monoclinic with the space group being P2 (1). The cell parameters were found to be: a = 11.460 1 (11), b = 6.320 5 (6), c = 13.028 1 (12), alpha = 90.00, beta = 115.557 (2) and gamma = 90.00. The crystal was a hydrogen-bonded dimmer. The slurry experiments, which were further conducted in solvents with different polarities, confirmed the stability of solid state of LLDT-8 based on the p-XRD determination. The polymorph of LLDT-8 made assurance of its efficacy consistence during its clinical trials.

Application of phase optimized liquid chromatography to oligopeptide separations.

Stationary phase optimized liquid chromatography (POPLC) has been applied to the separation of oligopeptides. The retention factors and theoretical plate numbers of 13 peptides were determined on five different stationary phases. Based on these values, an optimal stationary phase composition of 250mm total length consisting of 3 segments of 20mm octadecyl silica, 10mm phenyl silica and 220mm embedded polar octadecyl silica was calculated by the optimizer software. Good agreement between the calculated and experimental chromatograms was observed. In order to achieve short analysis time and baseline separation of all peptides gradient elution and optimization of the column temperature were performed. The optimized mobile phase conditions consisted of (A) acetonitrile and (B) 0.025M aqueous sodium phosphate buffer, pH 3.0, operated at 10% A (0-12min) followed by 10-50% A (12-32min) at a flow rate of 0.5mLmin(-1) and column temperature of 35 degrees C. Using these conditions all peptides could be separated in less than 30min with good resolution and peak symmetry.

[Cytokine in synovial monocytic cells from rheumatoid arthritis patients].

OBJECTIVE: To evaluate the inhibitory effect of blockade of Rho kinase upon mediating the secretion of proinflammatory cytokine in monocytic cells from rheumatoid arthritis (RA) patients. METHODS: Synovial fluid (SF) monocytic cells and peripheral blood monocytes (PB) from active RA patients were treated with TNFalpha or LPS respectively in the presence or absence of a specific ROK inhibitor, Y27632. ROK activity was assessed by Western blot and cytokine secretion measured by ELISA. RESULTS: Elevated ROK activity was found in synovial fluid monocytic cells from active RA patients. ROK activity was correlated with DAS, an index of disease activity of RA patients. ROK inhibitor Y27632 reduced the secretion of TNFalpha, IL-1beta and IL-6 in RA SF monocytic cells, but had no effect upon the secretion of IL-10, an anti-inflammatory cytokine. CONCLUSION: The present study provides novel evidence that ROK mediates the secretion of proinflammatory cytokines in monocytic cells from RA synovial fluids, suggesting a critical role of ROK in macrophage-mediated synovial inflammation of RA. Thus inhibition of ROK may be a new therapeutic target for RA.

Application of headspace solid phase microextraction for study of noncovalent interaction of borneol with human serum albumin.

AIM: To investigate noncovalent interactions between borneol and human serum albumin (HSA) under near-physiological conditions. METHODS: A 65-microm polydimethylsiloxane (PDMS) fiber was selected for sampling. The extraction temperature was kept at 37 degrees C, and the extraction time was optimized at 10 min. Borneol solutions of different concentrations were equilibrated in 600 micromol/L HSA and 67 mmol/L phosphate buffer solution (pH 7.4, 37 degrees C) for 24 h prior to solid phase microextraction (SPME) using headspace mode. The binding properties were obtained based on the calculation of extracted borneol amount using gas chromatography (GC) determination. RESULTS: The headspace SPME extraction method avoided disturbance from the HSA binding matrix. The recovery showed good linearity for the borneol concentrations over the range of 0.4-16.3 mumol/L with a regression coefficient (R(2)) of 0.9998. The limit of detection and lower limit of quantitation were determined to be 0.01 micromol/L and 0.4 micromol/L, respectively. The binding constant and the percentage binding rate were estimated to be 2.4 x 10(3)(mol/L)(-1) and 59.5%, respectively. CONCLUSION: Headspace SPME coupled to GC is a simple, sensitive and rapid method for the study of borneol binding to HSA. The method may be applied in the determination of other protein binding properties in human plasma.

[Comparative study of systemic lupus erythematosus in children and adults].

OBJECTIVE: To discuss the differences in the clinical features, laboratory tests and renal pathology between children and adults with systemic lupus erythematosus (SLE). METHODS: A retrospective study was performed in 198 children and 200 adults with SLE. RESULTS: Fever, rash, arthritis, anemia and renal involvement were the most common symptoms in both groups. The incidence of hepatomegaly, splenomegaly, lymphadenectasis, anemia, renal involvement, nervous system involvement and digestive apparatus involvement were higher in children with SLE. The mean SLE Disease Activity Index score was also higher in the children. Immunological findings showed that a greater proportion of children with SLE were positive for anti-double stranded DNA antibody, anticardiolipin antibody and perinuclear antineutrophil cytoplasmic antibody. Renal pathological examinations showed that children with SLE patients were more likely to have serious renal involvement. The misdiagnosis rate was higher in children with SLE patients. During the hospital stay, 12 (6.1%) children with SLE died, with an average disease course of 6.8 months; 9 (4.5%) adults with SLE died with an average disease course of 4.2 years. CONCLUSION: Children with SLE patients are liable to have systemic involvement and higher misdiagnosis rate, often with poorer prognosis than the adult patients.

[Role of gonadotropin releasing hormone analogues for ovarian protection in systemic lupus erythematosus patients treated with cyclophosphamide].

OBJECTIVE: To evaluate the effectiveness of gonadotropin releasing hormone analogues (GnRH-a) in protection against premature ovarian failure during cyclophosphamide (CTX) therapy for systemic lupus erythematosus (SLE). METHODS: 28 female patients with SLE, aged 35.3 +/- 2.4 (30-39) were treated with prednisone orally 1 mg/kg daily for 8 weeks, and then the dose was decreased by 10% every 10 days. CTX 200 mg with normal saline 200 ml was intravenously injection every other day for 4 months. Peripheral white blood cell (WBC) count was made every week. If the WBC count was less than 3.5 x 10(9)/L, the use of CTX should be stopped temporarily until the WBC count became normal. And then, the CTX administration should be adjusted to 400 mg intravenously every week. All patients were offered treatment with Hypodermic injection of GnRH-a 3.75 mg was given monthly just at the beginning of the standard CTX regimen for 3 months. Follow-up was conducted for 6 months after the last prescription of GnRH-a. RESULTS: All patients developed amenorrhea after treated by GnRH-a. Menstruation recovered 73 days (69-82 days) after the last subcutaneous injection in 25 patients. Among these 25 patients, one developed amenorrhea again after two normal menses periods. The other 3 patients were in persistent amenorrhea during the following 6 months after the GnRH-a treatment. The levels of plasma estradiol (E2) was 998 +/- 308 pmol/L before GnRH-a treatment, and decreased significantly 1, 2, and 3 months after the last injection of GnRH-a (132 +/- 44 pmol/L, 88 +/- 37 pmol/L and 81 +/- 29 pmol/L respectively, all P < 0.05). The level of plasma E2 increased 2 months after the last injection of GnRH-a in the 25 patients with return of menses, and the level of plasma E2 returned to the normal baseline level after 6 months in 24 patients. CONCLUSION: Treatment with GnRH-a during CTX therapy is associated with a significant reduction of premature ovarian failure in most women with SLE.

Investigating noncovalent interactions of rutin-serum albumin by capillary electrophoresis-frontal analysis.

The application of capillary electrophoresis-frontal analysis (CE-FA) to study noncovalent interaction between rutin and serum albumin (bovine serum albumin, BSA and human serum albumin, HSA) in phosphate buffer solution (67 mM, pH 7.4) at 37 degrees C is presented. Using fixed HSA or BSA concentration and increasing rutin concentration, the number of primary binding sites per HSA or BSA molecules, and the affinity constants were obtained. Both affinity constants are in a comparable range suggesting the similarity of affinity properties of HSA and BSA towards rutin. The proposed CE-FA method is simple, rapid and cost-effective which may be useful in further high-throughput protein binding studies of multi-components in traditional herbal medicines for pharmacological effect evaluations.

Development and validation of a sensitive liquid chromatography-tandem mass spectrometry method for the determination of paeoniflorin in rat brain and its application to pharmacokinetic study.

A sensitive and specific method was developed and validated for the determination of paeoniflorin in rat brain with liquid chromatography-tandem mass spectrometry. Sample pretreatment involved protein precipitation following solid-phase extraction. Paeoniflorin and geniposide (internal standard) were separated isocratically on a Waters Symmetry C18 column (150 mm x 2.1 mm i.d., 5 microm), using a mobile phase of methanol/water with 0.1% formic acid (50:50, v/v) at a flow-rate of 200-300 microL/min in 4min. A Finngan LTQ tandem mass spectrometer equipped with electrospray ionization source was operated in the positive ion mode. Selective reaction monitoring was performed to quantify paeoniflorin and the internal standard at m/z transitions of 503-->381 and 411-->231, respectively. A good linearity was found in the range of 2-500 ng/mL (R(2)=0.9939). The intra- and inter-batch assay precisions (coefficient of variation, CV) at 5, 50 and 400 ng/mL (n=5) ranged from 6.3% to 9.7% and 1.2% to 7.2%, respectively, and the accuracies were from 95.9% to 101.6% and 99.4% to 102.9%, respectively. The mean recoveries of paeoniflorin were 81.2%, 80.9% and 82.3% at 5, 50 and 400 ng/mL (n=5), respectively, and the mean recovery of the internal standard was 76.7% with a concentration of 50 ng/mL (n=5). Stability studies showed that paeoniflorin was stable in different conditions. Finally, the method was successfully applied to the pharmacokinetic study of paeoniflorin in rat brain following a single subcutaneous administration (10 mg/kg) to rats.

Primary carcinosarcoma of the liver: clinicopathologic features of 5 cases and a review of the literature.

Carcinosarcoma of the liver is very rare worldwide. The terminology and pathogenesis of hepatic carcinosarcoma remain controversial issues. In this article, we studied the clinicopathologic features of 5 cases of hepatic carcinosarcomas (matching the World Health Organization definition), analyzed the clinical data, histologic and immunohistochemical (IHC) results, and discussed the terminology, pathologic differential diagnoses, pathogenesis, and prognosis. The patients were 40 to 68 years old, and included 4 males and 1 female. All patients were Hepatitis B surface antigen positive with para-tumorous cirrhosis. The largest dimensions of the neoplasms ranged from 6.0 to 14.0 cm. Satellite nodules, portal vein tumor thrombi, direct invasion into local tissues (right diaphragm, right adrenal gland, and gastric wall) as well as metastatic foci in lungs and abdominal lymph nodes were identified. Pathologically, the neoplasms consisted of carcinomatous and sarcomatous components. The carcinomatous components were exclusively conventional hepatocellular carcinomas in all 5 cases, whereas the sarcomatous components exhibited complex features. Confirmed by IHC studies, the sarcomatous elements in different cases included rhabdomyosarcomas, malignant fibrous histiocytomas, fibrosarcoma, and poorly differentiated spindle cells without distinctive differentiation. Furthermore, the sarcomatous elements in these 5 neoplasms stained negative for all the epithelial markers we applied for IHC staining, which support the pathologic diagnosis of carcinosarcoma rather than sarcomatoid carcinoma. The presence of transitional zones between carcinomatous and sarcomatous components may support the transformation theory. Four patients with palliative hepatectomy died within 6 months, whereas 1 patient is still alive 21 months after radical resection. The poor prognosis of hepatic carcinosarcoma may be due to their highly invasive and metastatic features. Radical resection of early stage hepatic carcinosarcoma may contribute to a relatively optimistic prognosis.

[The relationship between expression of interleukin-8 and prognosis of breast cancer].

OBJECTIVE: To investigate the expression of interleukin-8 (IL-8) and its prognostic significance in breast cancer. METHODS: Expression of IL-8 in 113 breast cancers, 19 breast benign tumors and 20 breast normal tissues was examined by tissue microarray using immunohistochemistry, and the association of IL-8 expression with patient's clinico-pathological characteristics and prognosis was further analyzed. RESULTS: The positive rate of IL-8 expression in breast cancer was 27.4%, which was significantly higher than that in benign tumor and normal tissue of breast (P = 0.002). IL-8 expression related to histological type (P = 0.040) and lymph node status (P = 0.021). The expression of IL-8 was observed to correlate negatively with ER and PR status (P = 0.015 and P = 0.034), and correlate positively with C-erbB-2 status (P = 0.002). In addition, Kaplan-Meier curves of disease-free survival analysis showed a significant difference between IL-8 positive groups and negative group (P = 0.031). CONCLUSIONS: IL-8 might be a poor prognostic factor for human breast cancer, and also might be a novel molecular marker to predicate the occurrence and progression of breast cancer.

Tumor angiogenesis and dynamic CT in colorectal carcinoma: radiologic-pathologic correlation.

AIM: To investigate the correlation between microvessel density and spiral CT perfusion imaging in colorectal carcinoma. METHODS: Thirty-seven patients, with histologically proven colorectal carcinoma, underwent water enema spiral CT scan. The largest axial surface of the primary tumor was searched on unenhanced spiral CT images. At this level, the enhanced dynamic scan series was acquired. Time-density curves (TDC) were created from the region of interest drawn over the tumor, target artery by Toshiba Xpress/SX spiral CT with perfusion functional software. Then the perfusion was calculated. Microvessel density (MVD) was evaluated using immunohistochemical staining of surgical specimens with anti-CD34, and then MVD was correlated with perfusion. RESULTS: MVD of colorectal carcinomas was 33.11-173.44, mean 87.28, and perfusion was 15.60-64.80 mL/min/100 g, mean 39.74 mL/min/100 g. MVD and perfusion were not associated with invasive depth, metastasis and disease stage, and they all decreased with increasing Dukes' stage, but no significant correlation was found between them (r = 0.18, P = 0.29). CONCLUSION: There is no significant correlation between MVD and perfusion. Neovascularizaton and perfusion are highly presented in early colorectal carcinoma. CT perfusion imaging may be more suited for assessing tumorigenesis in colorectal carcinoma than histological MVD technique.