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The purpose of this study is to establish the minimal injection doses of magnetic resonance imaging (MRI) contrast agents that can achieve optimized images while improving the safety of injectable MRI drugs. Gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) and ferucarbotran, commonly used in clinical practice, were selected and evaluated with in vitro and in vivo experiments. MRI was acquired using T1-weighted (T1W) and T2-weighted (T2W) sequences, and the results were quantitatively analyzed. For in vitro experiments, results showed that T1W and T2W images were optimal when Gd-DTPA-bisamide (2-oxoethyl) (Gd-DTPA-BMEA) and ferucarbotran were diluted to a volume percentage of 0.6% and 0.05%, all comparisons were significant differences in grayscale statistics using one-way analysis of variance (ANOVA). For in vivo experiments, the contrast agent with optimal concentration percentages determined from in vitro experiments were injected into mice with an injection volume of 100 &mu, L, and the images of brain, heart, liver, and mesentery before and after injection were compared. The statistical results showed that the p values of both T1W and T2W were less than 0.001, which were statistically significant. Under safety considerations for MRI contrast agent injection, optimized MRI images could still be obtained after reducing the injection concentration, which can provide a reference for the safety concentrations of MRI contrast agent injection in the future.

Aim of Study: Proanthocyanidin-rich longan flower extract (LFP) has been previously shown to inhibit the proliferation and anchorage-independent growth in soft agar of two colorectal carcinoma (CRC) cells in vitro. In this report, we further examined the effects of LFP in a CRC spheroid model. Materials and Methods: A liquid-overlay assay employing HT-29 spheroids was used to evaluate the effects of LFP on cancer cell tumorigenesis, viability, and apoptosis. Associated effects on signaling path ways (epidermal growth factor receptor [EGFR], Akt) and apoptotic regulators were measured using Western blot. Results: Treatment with LFP up to 200 μg/ml inhibited tumor growth in a dose-dependent manner and induced prominent apoptosis as measured by annexin V staining. Cells treated with LFP showed decreased EGFR and Akt phosphorylation with decreased expression of B-cell lymphoma 2. Conclusion: The ability of LFP to induce apoptosis in CRC spheroids warrants further investigation of its composition and identification of tumor-active components.

Citrus sulcata was subjected to ultrasound, high-pressure, and Soxhlet extractions. The antioxidant and anti-inflammatory activities of the extracts were evaluated qualitatively and quantitatively. The antioxidant content of the peel extract was twice that of the fruit extract. The quantitative analysis showed that the narirutin and hesperidin contents in the peel extracts were 8.8 and 7.5 mg/100 g, respectively. These extracts had a total phenolic content of 112.22 ± 2.89 gallic acid equivalent (GAE) mg/100 g, a total flavonoid content of 54.09 ± 1.01 rutin equivalent (RE) mg/100 g, DPPH radical scavenging activity of 46%, and antioxidant activity of 213.25 ± 2.82 μM of Trolox equivalents (TEAC). C. sulcata extracts could prevent hydrogen peroxide (H2O2)-induced oxidative stress, reduce expression of the inflammatory markers nuclear Factor kappa B (NFκB) and phosphorylated IκBα (p-IκBα) in A549 human lung carcinoma cells, and inhibit Lipopolysaccharide (LPS)-induced THP-1 monocyte differentiation to an extent of 85%.

This study examined the applications of novel non-polymer magnetic ferrite nanoparticles (Fe3O4 NPs) labeled with 99mTc-pertechnetate (99mTcO4 −). The radiochemistry, chemistry, and biodistribution of Fe3O4 NPs labeled with 9mTcO4 − were analyzed. This paper employed instant thin layer chromatography and magnetic adsorption to evaluate the labeling efficiency and stability of 99mTc-Fe3O4 at various reaction conditions. A scanning electron microscope, X-ray diffractometer, Fourier transform infrared spectrometer, laser particle size analyzer, and superconducting quantum interference device magnetometer were used to analyze the physical and chemical properties of the Fe3O4 and 99Tc-Fe3O4 nanoparticles. The biodistribution and excretion of 99mTc-Fe3O4 were also investigated. Radiochemical analyses showed that the labeling efficiency was over 92% after 1 min in the presence of a reducing agent. Hydroxyl and amine groups covered the surface of the Fe3O4 particles. Therefore, 99Tc (VII) reduced to lower oxidation states and might bind to Fe3O4 NPs. The sizes of the 99Tc-Fe3O4 NPs were about 600 nm without ultrasound vibrations, and the particle sizes were reduced to 250 nm under ultrasound vibration conditions. Nonetheless, Fe3O4 NPs and 99Tc-Fe3O4 NPs exhibited superparamagnetic properties, and the saturation magnetization values were about 55 and 47 emu/g, respectively. The biodistribution showed that a portion of the 99mTc-Fe3O4 nanoparticles might embolize in a pulmonary capillary initially; the embolism radioactivity was cleared from the lungs and was then taken up by the liver. 99mTc-Fe3O4 metabolized very slowly only 1–2% of the injected dose (ID) was excreted in urine and about 2.37% ID/g was retained in the liver 4 h after injection. Radiopharmaceutically, 99mTc-Fe3O4 NPs displayed long-term retention, and only 99mTc-Fe3O4 NPs that dissociated to free pertechnetate could be excreted in urine. This research evaluated the feasibility of non-polymer magnetic ferrite NPs labeled with technetium as potential radiopharmaceuticals in nuclear medicine.

The aim of this research is to use acetylacetonate as a 99mTc chelating agent label with porphyrin and evaluate its radiochemical and biological characteristics. Stannous chloride was used as a reductant to determine the chemical and biological characterization of 99mTc-complexes from labeling porphine{4′,4′′,4′′′-(2lH,23H-Porphine-5,10,15,20-terayl)tetrakis-(benzoic acid), TPPB} with 99mTc–pertechnetate. Instant thin layer chromatography (ITLC), size exclusion chromatography (SEC), paper electrophoresis, and UV/Vis spectrophotometry were used to evaluate chemical characterization. Finally, biodistribution and liver function tests were applied to evaluate biological characteristics. The results of this study show that the labeling efficiency of 99mTc(acac)–TPPB was nearly 100% when using acetylacetone (acac) as a conjugator. Three major 99mTc(acac)–TPPB complexes were separated by SEC, and all of them were hydrophilic. The UV-Vis spectra of 99mTc(acac)–TPPB complexes closely resembled those of the TPPB, but the wave lengths of their peaks changed 430, 521, 556, 591 and 647 nm after complexation. The biodistribution study selected the liver as the target organ. The 99mTc(acac)–TPPB complex may cause short-term liver injury. However, this injury can be repaired, and the reagent is quickly metabolized. Hence, the toxicity of the 99mTc(acac)–TPPB complex is within an acceptable range, and making it a promising liver imaging agent.

The use of pressurized liquid carbon dioxide to extract cantharidin from Mylabris was investigated. The study resulted in green extraction of bioactive ingredients from the insect, with extraction efficiency of 95% (three repetitions) obtained at a pressure of 1 MPa, temperature of 60°C, static extraction time of 30 minutes, and with 4 ml of acetonitrile as modifier. In addition to the identification of the extract, i.e., cantharidin, by chromatography, an in vitro assay for the effect of the extract on a cell was performed. The result reveals that cantharidin-extract is effective for primary medicinal use.

The suitability of pressurized water extraction (PWE) of crude polysaccharides as secondary metabolites from Lentinula edodes was investigated. A series of experiments were carried out to examine the effects of extraction times and pressures. The results indicated that the maximum recovery of polysaccharides was about 90% of the crude polysaccharides from mycelia pellets when the pressure was at 10.1 MPa for 70 min (28 degrees C). This was a drastic improvement over that of boiling water extraction (BWE) at 0.1 MPa for 40 min, which gave only 27.9% recovery. A nitroblue tetrazolium (NBT) reduction assay was used to examine the macrophage stimulating activities (MSA), and it was found that the PWE polysaccharides retained the MSA. The morphology of the macrophage cells treated by PWE polysaccharides was also examined and found to be similar to that of the positive control lipopolysaccharides treated. Finally, gel chromatographic and NMR experiments revealed that both PWE and BWE polysaccharides showed the presence of four similar molecular mass components and the alpha-(1--4)-D-Glcp and beta-(1--6)-D-Glcp linkage residues. The improved PWE efficiency is probably due to the possibility that under high pressure, the solid polysaccharide's hydrogen bonding is partially destroyed to increase structure elasticity and water solubility.

BACKGROUND : Primary breast lymphoma is a rare disease. The small number of patients and the paucity of data make large-series studies difficult. We conducted a pooled analysis to evaluate the treatment outcome and prognostic factors in patients with primary breast lymphoma. METHODS : In a search of PUBMED and MEDLINE we found 7 observational studies with 93 patients that were eligible for inclusion. Treatments included single therapy or combined surgery, chemotherapy and radiotherapy. We analyzed the correlation between treatment protocols, tumor relapse and survival. Histopathology and cancer stage were analyzed to evaluate their significance in treatment outcome. RESULTS : All 93 patients were female, with a mean age of 57 years. The histopathology of 63 patients (68%) was diffuse large cell lymphoma. According to Ann Arbor classification, 57% were stage I, 23% were stage II, 4% were stage III, and 16% were stage IV. Thirteen percent received surgery alone, 27% received chemotherapy alone, 7% received radiotherapy alone, 10% received surgery and chemotherapy, 10% received surgery and radiotherapy, 22% received chemotherapy and radiotherapy, and 11% received surgery combined with chemotherapy and radiotherapy. With a median follow-up duration of 34 months (mean, 53 months), 48% had relapse of disease, 50% had no relapse, while 2% had disease progression. The mean time to first tumor relapse after treatment was 20 months. The 3-year and 5-year overall survival rates were 70% and 56%, respectively. Radiotherapy was a significant prognostic factor predicting tumor relapse (P=0.044). Tumor stage was a significant prognostic factor affecting overall survival, disease-free survival and disease-specific survival (P=0.0231, 0.0015, 0.0124, respectively). CONCLUSION : With a 3-year overall survival rate of 70%, the high relapse rate of 48% is a cause for concern. Patients who received chemotherapy and radiotherapy had better survival outcome and a lower relapse rate. We suggest that chemotherapy and radiotherapy be the initial treatment for patients with primary breast lymphoma.

Cysteine was chelated with 99m/99Tc in a freeze-dried kit containing tin(II) ions, and the green 99m/99Tc-cysteine complex (complex III) was separated to study the biodistribution. The biodistribution of 99m/99Tc-cysteine complexes was performed in mice. The renal excretion patterns of rats were studied with and without the renal tubular transport inhibitor 2,4-dinitrophenol. The carrier of Tc-cysteine complex in the blood and also the radioactive compounds in the urine were studied by HPGFC and SDS-PAGE electrophoresis. The kidney was confirmed as the target organ; serum albumin functions as a carrier to transport Tc-cysteine complex to the kidney. The protein-bound Tc-cysteine complex was the primary form in excreta, and renal tubular secretion was the foremost excretory pathway.

This study compares the biological behavior of the99mTc-cysteine complex with131I-hippuran (131I-OIH). The potential role of the99mTc-cysteine complex as a renal imaging agent has also been evaluated. In addition the biological characteristics, i.e., biodistribution, blood clearance, excretory mechanism and the renal excretion pattern in the presence and absence of the tubular transport inhibitor (2,4-dinitrophenol, probenecid) has been examined. The experimental results reveal that kidneys are the target organ. The blood clearance of these radiopharmaceuticals is rapid, approximately 84% of the injected activity is excreted from the kidneys at 1 hour postinjection. Moreover, the renal inhibitor obviously depresses the excretory rate of the99mTc-cysteine and131I-OIH, suggesting that such agents are excreted by renal tubular secretion. Results presented demonstrate that the99mTc-cysteine is a remarkable renal dynamic imaging agent which is highly promising as a new renal imaging radiopharmacentical.

Cysteine was chelated with 99mTc and/or 99Tc in a freeze-dried kit containing Tin(II) ions, and the yellow 99m/99Tc-cysteine complex (complex I) was separated to study the biodistribution. Comparison of the distribution of 99m/99Tc-cysteine and 99mTc-cysteine complexes was made in rats and mice. The renal excretion patterns were studied in rats in the presence and absence of the renal tubular transport inhibitor 2,4-dinitrophenol. The carrier of Tc-cysteine complex in the blood and also the radioactive compounds in the urine were studied by HPGFC and SDS-electrophoresis. The kidney was confirmed as the target organ; serum albumin serves as a carrier for transport of Tc-cysteine complex to the kidney. The Tc-cysteine complex was the primary form in excreta, and glomerular filtration was the dominant excretory pathway.

The pertechnetate ion to forms a yellow complex with cysteine (λmax=420 nm) under anaerobic conditions. The kinetic order with respect to pertechnetate and cysteine has been determined by HPSEC and titration method. The oxidation state of the yellow Tc-cysteine complex was determined by potentiometric titration.

Chrysophanol has high pharmaceutical values. However, it was difficult to use the traditional extraction method to extract high-concentration chrysophanol. Therefore, the purpose of this study is to purify and separate chrysophanol in traditional herb, Rheum Palmatum LINN, by using supercritical fluid extraction (SFE) and preparative high-performance liquid chromatography (P-HPLC) for rapid and large-scale isolation. The method is efficient for selective extraction of chrysophanol from the herbs, which have complex compositions. The extraction efficiency of chrysophanol with SFE is 25 × higher than that of boiled water extraction under the same extraction time. The optimal conditions for SFE were 210 atm and 85 °C for 30 min; for P-HPLC, a C18 column was used with a gradient elution of methanol and 1% acetic acid at a flow rate of 10 mL/min. According to (1)H NMR and LC-MS analyses, the purity of the isolated chrysophanol was as high as 99%. The recovery for chrysophanol in Rheum after SPE/PHPLC processing was in the range of 88-91.5%. Compared with other extraction and purification methods, the sequential system (SFE/P-HPLC) achieved the highest amount of extracted chrysophanol from Rheum Palmatum LINN (0.38 mg/g) and the shortest run time (3h). Hence, this rapid and environmentally friendly method can separate compounds based on polarity with high efficiencies and, coupled with P-HPLC, it may be applicable in the large-scale production of foods and medicines in the future.

An isotopic exchange method was used to label lipiodol with 131 I. The labelling efficiency was > 92.5%, and the radiochemical purity of [ 131 I]lipiodol was above 98% as determined by ITLC. The influencing factors e.g. the heating temperature, reaction time, pH and storage conditions were studied and the optimum conditions were determined. In a pilot study injecting [ 131 I]lipiodol for the treatment of hepatoma, about 70% of hepatoma patients had a response to the treatment with a reduction of α-fetoprotein and decrease of hepatoma sizes. The overall median survival was 9 months (range 2–17 months).

Reaction of recoild38Cl atoms with o-dichlorobenzene in the presence of carbon tetrachloride or iodine has been studied by using radio-high performance liquid chromatography. The major products were detected by a 4-channel-wavelengths spectrophotometric detector. The radioactivity of38Cl compounds including minor products was measured with a NaI(T1) scintillation detector. The main products found were38Cl labeled HCl/Cl2, CHCl3, CCl4, o-, p-, m-C6H6Cl2 and polymer, whereas only minor products such as HCl/Cl2, CHCl3, C2Cl6, C6H3Cl3, and polymer were found in the radio-chromatogram. The reaction mechanisms of recoil38Cl atom are briefly described.

The labeling behavior of cysteine with99TcO4− ion and/or99mTcO4− ion at different cysteine concentrations reductant and pH values has been studied by chromatography, and the labeling yield was calculated. Three major Tc-complexes, yellow, reddish brown and green can be separated by gel filtration chromatography (GFC). Thin layer chromatography (TLC), high performance liquid chromatography (HPLC) and ion-exchange chromatography (IC) were used to separate the complexes collected from GFC. The TLC, HPLC data show the pertechnetate accompanied with a yellow complex; the green and purple complex contain more than two complexes. Electrophoresis and IC data show that the complexes carry a negative charge. The conductivity, UV-VIS, flow beta-detector with HPLC and autoradiography are also applied to analyze complex formation.

The purpose of this study is to analyze the survival rate of patients with metastatic breast cancer and to evaluate the outcome of these patients using prognostic factors and Nottingham prognostic index. From February 1992 to August 2008, 135 patients with metastatic breast cancer were treated at the Changhua Christian Hospital. In these patients, we evaluated the significance of the following factors in predicting the survival rate after the occurrence of metastasis: age, initial stage at primary diagnosis, histological grade, Karnofsky performance status (KPS), estrogen receptor (ER), progesterone receptor status, human epidermoid growth factor receptor 2 overexpression status, number of axillary lymph node metastasis, history of adjuvant radiotherapy and/or chemotherapy, disease-free interval, status of local recurrence, status of various sites of distant metastases, number of distant metastases, and Nottingham prognostic index. The 1-, 2-, and 5-year survival rates were 53.3%, 25.2%, and 1.5%, respectively. In the univariate analysis, KPS, histological grade, ER status, initial stage at primary diagnosis, number of axillary lymph node metastasis, liver metastasis, disease-free interval, first-/second-/third-line chemotherapy for recurrence or metastasis, number of metastases, and Nottingham prognostic index had significant impact on survival. The median survival of patients determined as corresponding to Nottingham low-risk group, intermediate-risk group, and high-risk group was 29.3, 17.9, and 4.6 months, respectively. In our multivariate analysis, Karnofsky performance status (p = 0.030) and Nottingham prognostic index (p ≤ 0.0001) were significant prognostic factors for survival, while first-/second-/third-line chemotherapy for recurrence or metastasis (p = 0.002) was a significant predictor for the outcome of the treatment. The prognosis of patients with metastatic breast cancer is poor. In spite of the fact that many advances in treatment have been made, numerous additional questions have arisen; new drugs and therapeutic regimens are needed to improve the outcomes of patients, and further well-designed randomized trials are warranted.

The purpose of this study is to investigate the clinical and histological features that may affect the survival of the patients and to evaluate the impact of post-operative adjuvant therapy on the outcomes of patients with stage IB and IIA carcinoma of the cervix. From August 1998 to January 2005, 140 patients with International Federation of Gynecology and Obstetrics stage IB and IIA cervical cancer were treated with radical hysterectomy and post-operative pelvic radiation therapy with or without chemotherapy. The median age was 55 years (range, 29-86 years). Seventy-six patients had stage IB and 64 patients had stage IIA disease. Tumour size was4 cm in 96 patients andor = 4 cm in 44 patients. One hundred and eleven patients had histology of squamous cell carcinoma, 12 patients has adenocarcinoma and 17 patients had other histologic types. Depth of stromal invasion was2/3 in 20 patients andor = 2/3 in 120 patients. Twenty-three patients had parametrial invasion and 117 patients had no parametrial invasion. Thirteen patients had lymphovascular space invasion and 127 had no lymphovascular space invasion. Nine patients had positive surgical margin and 131 patients had negative margin. Twenty-seven patients had pelvic lymph node metastasis and 113 patients had no pelvic lymph node metastasis. Seventy-five patients received concurrent chemoradiotherapy and 65 patients received radiotherapy alone. The 5-year overall survival (OAS) and disease-free survival were 83% and 72% respectively. In the log rank test, tumour size (P = 0.0235), pararmetrial invasion (P = 0.0121), pelvic lymph node metastasis (P0.0001) and adjuvant chemotherapy + radiotherapy (P = 0.0119) were significant prognostic factors for OAS, favouring tumour size4 cm, absence of parametrial invasion and pelvic lymph node metastasis, and those who received adjuvant chemoradiotherapy. The patients who received radiation with concomitant chemotherapy had a 5-year OAS rate of 90% versus those who received radiotherapy alone, with a rate of 76%. For patients with high-risk early stage cervical cancer who underwent a radical hysterectomy and pelvic lymphadenectomy, adjuvant chemoradiotherapy resulted in better survival than radiotherapy alone. The addition of weekly cisplatin to radiotherapy is recommended. The treatment-related morbidity is tolerable.

The purpose of this study is to analyze the overall survival rate of patients with brain metastases from breast cancer and to determine prognostic factors affecting outcomes of these patients.From July 1988 to December 2004, 48 female patients with brain metastases from breast cancer underwent full-dose whole-brain radiotherapy (WBRT). In these patients we evaluated the significance of the following factors in predicting the survival rate after WBRT: age, extracranial metastases, number of brain metastases, total dose of WBRT, Karnofsky performance status (KPS), and Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class.The median overall survival rate was 7.3 months. The 1- and 2-year overall survival rates were 37 and 20%, respectively. In univariate analysis, KPS (p0.0001), number of lesions of brain metastases (p=0.0149), age (p=0.0452), and RPA class (p0.0001) were statistically significant prognostic factors for overall survival. In multivariate analysis, KPS (p0.001) and number of brain metastases (p=0.039) were significant prognostic factors for overall survival.Survival of breast cancer patients with brain metastases treated with WBRT is poor. To improve survival, enrollment of more patients with brain metastases from breast cancer for prospective trials involving a multimodality approach that combines radiation and systemic therapies based on appropriate patient triage is warranted.

Lipiodol has excellent retainable ability in hepatoma cells. This agent can be labeled with radioisotope (131I) and mixed with tissue adhesive (Histoacryl), and then alttached on the lesion of liver by intrahepatic arterial administration. In this study, we attempt to obtain the optimal ratio of Lipiodol to Histoacryl and evaluate the consolidation of blood in vitro and toxicity and biodistribution in vivo. The ratio of131I Lipiodol/Histoacryl mixture (L/H), concentration of heparin and flow rate of blood are varied by simulating the installation of bloodstream to test the time of consolidation. In addition, the optimal ratios of the L/H mixtures are assessed in vitro in heparinized human blood. According to those results, Lipiodol and Histoacryl mixed with 1∶1 or 2∶1 ratio have an ideal time of 13 to 15 seconds in vitro; in addition, 1.2∶1 ratio is an optimal ratio in the biodistribution study. Interestingly, heparin and acetic acid does not alter the consolidation time, in addition, no variation occurs when varying the flow rate of blood. The consolidation of L/H mixture with blood is incubated in the 37°C, normal saline bath for 24 hours. No dissociation of free131I is found. The optimal mixture is also injected into the hepatic artery of the Sprague-Dawley rats carrying for 24 hours. No dissociation of free131I is found. The optimal mixture is also injected into the hepatic artery of the Sprague-Dawley rats carrying hepatocellular carcinoma (NIS1 cell line). Radioactive consolidate is well confined in the tumor without evidence of leakage of the mixture to the lung or distribution of free131I in the thyroid. In conclusion, this mixture has the merits of both irradiation and embolization of the tumor. The131I Lipiodol/Histoacryl mixture (1.2∶1) is a promising alternative for intrahepatic arterial administration to treat hepatic tumors. Histoacryl can confine the131I and, also, embolize the tumor vessels.