Biomedical subjects

D H Lee

Publications and source records attributed to D H Lee.

At least 19 recordsLinked to original sources

PubMed2006

Role of peripheral hyperpolarization-activated cyclic nucleotide-modulated channel pacemaker channels in acute and chronic pain models in the rat.

Hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels contribute to rhythmic spontaneous activity in the heart and CNS. Ectopic spontaneous neuronal activity has been implicated in the development and maintenance of acute and chronic hyperalgesia, allodynia and spontaneous pain. Previously, we documented that systemic administration of ZD7288, a specific blocker of pacemaker current (I(h)), decreased ectopic activity in dorsal root ganglion (DRG) and reversed tactile allodynia in spinal nerve ligated (SNL) rats [Chaplan SR, Guo HQ, Lee DH, Luo L, Liu C, Kuei C, Velumian AA, Butler MP, Brown SM, Dubin AE (2003) Neuronal hyperpolarization-activated pacemaker channels drive neuropathic pain. J Neurosci 23:1169-1178]. Spontaneous pain is the chief clinical manifestation of peripheral nerve injury; however, a role for I(h) in spontaneous pain has not been described. Here, in further rat studies, we report that systemic administration of ZD7288 reversed spontaneous pain induced by mild thermal injury (MTI) and tactile allodynia induced by SNL and MTI. In contrast, ZD7288 did not reduce thermal hyperalgesia. An important locus of action appears to be in the skin since intraplantar (local) administration of ZD7288 completely suppressed tactile allodynia arising from MTI and SNL and reduced spontaneous pain due to MTI. Immunohistochemical staining of plantar skin sections detected HCN1-HCN4 expression in mechanosensory structures (e.g., Meissner's corpuscles and Merkel cells). Collectively, these data suggest that expression and modulation of I(h) in the peripheral nervous system, including specialized sensory structures, may play a significant role in sensory processing and contribute to spontaneous pain and tactile allodynia.

Acute Disease↗

PubMed2006

Phase contrast radiography of Lewy bodies in Parkinson disease.

Parkinson's disease (PD), defined as a neurodegenerative disorder, is characterized by the loss of dopaminergic neurons and the presence of Lewy bodies in neurons. Morphological study of Lewy bodies is important to identify the causes and the processes of PD. Here, we investigate a possibility of phase contrast radiography using coherent synchrotron X-rays to explore the microscopic details of Lewy bodies in thick (approximately 3 mm) midbrain tissues. Autopsied midbrain tissues of a PD patient were sliced in 3 mm thickness and then examined using synchrotron X-rays from the 7B2 beamline of the Pohang Light Source. Refraction-enhanced phase contrast radiography and microtomography were adopted to identify dark core and dim edge of Lewy bodies in neurons. The morphology of Lewy bodies was clearly revealed by the phase contrast radiography in very thick (3 mm) midbrain tissues without any staining treatment. Three-dimensional volume rendered microtomography of the autopsied midbrain tissues demonstrates striking evidence that several Lewy bodies are agglomerated by dim edges in a neuron. We suggest that the phase contrast radiography could be a useful tool to morphologically investigate the causes or the processes in PD.

Dopamine↗

PubMed2006

Acquisition of MR perfusion images and contrast-enhanced MR angiography in acute ischaemic stroke patients: which procedure should be done first?

Multimodal MRI for acute ischaemic stroke usually includes perfusion imaging (PI) and contrast-enhanced neck MR angiography (CE-MRA), as well as diffusion-weighted imaging and T2* weighted imaging. Because both PI and CE-MRA require the infusion of contrast medium, the likelihood exists that one study may conflict with the other due to the accumulation of previously injected contrast medium. The purpose of this study is to determine the appropriate order of PI and CE-MRA in this multimodal MRI protocol for evaluation of acute ischaemic stroke. We studied 35 patients with acute ischaemic stroke in the unilateral middle cerebral artery territory. 17 patients underwent CE-MRA following PI (group A) and 18 patients underwent PI following CE-MRA (group B). For qualitative analysis of the CE-MRA and colour-coded maps of the PI, two independent observers graded the image quality. Interobserver agreement was assessed using kappa statistics, and we assessed the statistical differences of imaging quality between groups A and B using the Mann-Whitney U-test). For the quantitative analysis of PI, two parameters--the maximum change in the transverse relaxation rate (DeltaR2(max)) and the relative signal drop (DeltaS/S(0))--were calculated from the time-signal intensity curve of an unaffected middle cerebral artery territory, and we compared the differences in the parameters of group A and B (t-test). Interobserver agreements for CE-MRA and PI were good. In the qualitative analysis of CE-MRA and PI, no significant difference was observed between groups A and B. In the quantitative analysis of PI, there were no relevant differences in DeltaR2(max) and DeltaS/S(0) between the two groups. In simultaneous CE-MRA and PI, there was no deterioration of diagnostic imaging quality with regard to the order of the two post-contrast sequences. They can be performed according to the preference of each institution.

Acute Disease↗

PubMed2006

Identification of penumbra and infarct in acute ischemic stroke using computed tomography perfusion-derived blood flow and blood volume measurements.

BACKGROUND AND PURPOSE: We investigated whether computed tomography (CT) perfusion-derived cerebral blood flow (CBF) and cerebral blood volume (CBV) could be used to differentiate between penumbra and infarcted gray matter in a limited, exploratory sample of acute stroke patients. METHODS: Thirty patients underwent a noncontrast CT (NCCT), CT angiography (CTA), and CT perfusion (CTP) scan within 7 hours of stroke onset, NCCT and CTA at 24 hours, and NCCT at 5 to 7 days. Twenty-five patients met the criteria for inclusion and were subsequently divided into 2 groups: those with recanalization at 24 hours (n=16) and those without (n=9). Penumbra was operationally defined as tissue with an admission CBF <25 mL x 100 g(-1) x min(-1) that was not infarcted on the 5- to 7-day NCCT. Logistic regression was applied to differentiate between infarct and penumbra data points. RESULTS: For recanalized patients, CBF was significantly lower (P<0.05) for infarct (13.3+/-3.75 mL x 100 g(-1) x min(-1)) than penumbra (25.0+/-3.82 mL x 100 g(-1) x min(-1)). CBV in the penumbra (2.15+/-0.43 mL x 100 g(-1)) was significantly higher than contralateral (1.78+/-0.30 mL x 100 g(-1)) and infarcted tissue (1.12+/-0.37 mL x 100 g(-1)). Logistic regression using an interaction term (CBFxCBV) resulted in sensitivity, specificity, and accuracy of 97.0%, 97.2%, and 97.1%, respectively. The interaction term resulted in a significantly better (P<0.05) fit than CBF or CBV alone, suggesting that the CBV threshold for infarction varies with CBF. For patients without recanalization, CBF and CBV for infarcted regions were 15.1+/-5.67 mL x 100 g(-1) x min(-1) and 1.17+/-0.41 mL x 100 g(-1), respectively. CONCLUSIONS: We have shown in a limited sample of patients that CBF and CBV obtained from CTP can be sensitive and specific for infarction and should be investigated further in a prospective trial to assess their utility for differentiating between infarct and penumbra.

Acute Disease↗

PubMed2006

Staurosporin induces neurite outgrowth through ROS generation in HN33 hippocampal cell lines.

Staurosporin, a specific inhibitor of PKC, is widely used in studies of signal transduction pathways. Previous studies have shown that staurosporin induces neurite outgrowth, but the underlying mechanisms remain unclear. Here we report that staurosporin induces neurite outgrowth in HN33 hippocampal cells. Two other PKC inhibitors, Go 6976 (specific for alpha- and beta-isoforms) and rotterlin (a selective inhibitor of PKC delta), have no neuritogenic effect. In addition, staurosporin specifically increases ROS generation. NAC, which inhibits the generation of ROS, suppresses the staurosporin-induced neurite outgrowth in HN33 cells. Further, H(2)O(2) causes neurite outgrowth. Taken together, these results confirm a neuritogenic effect of staurosporin and point to ROS as the signal mediator of staurosporin-induced neurite outgrowth in HN33 hippocampal cells. Theme: Development and regeneration Topic: Neurotrophic factors: receptors and cellular mechanisms.

Animals↗

PubMed2006

Serum HER-2 concentration in patients with primary breast cancer.

OBJECTIVE: To evaluate whether serum HER-2/neu (HER-2) concentration is a valid index of HER-2 status in women with primary breast cancer, and to establish a normal reference range for serum HER-2 concentration in Korean women. METHODS: Serum HER-2 concentration was measured and immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH) carried out on tissue samples from 86 consecutive female patients. The results of the three datasets were compared. The cut off value of HER-2 concentration was determined from the mean +2SD values derived from the serum of 93 healthy volunteers. RESULTS: The IHC and FISH data were significantly correlated (p<0.01), but neither showed significant correlation with the serum HER-2 data. The cut off value of serum HER-2 was 10.2 microg/l, and the serum HER-2 concentration of patients with primary breast cancer ranged from 5.0 to 17.5 microg/l. Only five patients had a serum HER-2 value above the cut off value. CONCLUSIONS: Serum HER-2 concentration cannot be substituted for IHC or FISH to evaluate HER-2 status, nor can it be used as a diagnostic tumour marker in primary breast cancer, considering the low prevalence of serum HER-2 elevation.

Adult↗

PubMed2006

Effects of hydrogen peroxide (H2O2) on alkaline phosphatase activity and matrix mineralization of odontoblast and osteoblast cell lines.

Hydrogen peroxide (H(2)O(2)), an oxidizing agent, has been widely used as a disinfectant. Recently, because of its reactive properties, H(2)O(2) has also been used as a tooth bleaching agent in dental care. This is a cause for concern because of adverse biological effects on the soft and hard tissues of the oral environment. To investigate the influence of H(2)O(2) on odontoblasts, the cells producing dentin in the pulp, we assessed cellular viability, generation of reactive oxygen species (ROS), alkaline phosphatase (ALP) activity, and nodule formation of an odontoblastic cell line (MDPC-23) after treatment with H(2)O(2), and compared those with the effects on preosteoblastic MC3T3-E1 cells. Cytotoxic effects of H(2)O(2) began to appear at 0.3 mmol/L in both MDPC-23 and MC3T3-E1 cells. At that concentration, the accumulation of intracellular ROS was confirmed by a fluorescent probe, DCFH-DA. Although more ROS were detected in MDPC-23, the increasing pattern and rate are similar between the two cells. When the cells were treated with H(2)O(2) at concentrations below 0.3 mmol/L, MDPC-23 displayed a significant increase in ALP activity and mineralized bone matrix, while MC3T3-E1 cells showed adverse effects of H(2)O(2). It is known that ROS are generally harmful by-products of aerobic life and represent the primary cause of aging and numerous diseases. These data, however, suggest that ROS can induce in vitro cell differentiation, and that they play a more complex role in cell physiology than simply causing oxidative damage.

Alkaline Phosphatase↗

PubMed2006

Usefulness of (18)F-fluorodeoxyglucose PET for radiosurgery planning and response monitoring in patients with recurrent spinal metastasis.

INTRODUCTION: With the advancement and successful treatment of metastatic spinal cord disease, newer treatments are needed for the long-term survivors of recurrent disease. The lack of a standardized re-treatment regimen and the difficulty in delineating the tumor margins among patients who have received the treatment with metallic spinal fixation and conventional radiation are two of the challenges to be faced in recurrent metastatic spinal cord disease. In these patients, we applied hypofractionated stereotactic radiosurgery by defining the tumor margin with (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). PATIENTS AND METHODS: Three consecutive recurrent spinal metastasis patients underwent the CyberKnife treatment (Accuray, Inc., Sunnyvale, CA) from March 2004 to July 2004. A three-fraction schedule was applied at approximately 24 hour intervals. One patient had sarcoma and the other two patients had breast cancer. All patients had received previous conventional radiotherapy after operation ranging from 30 Gy to 45 Gy. CT-based planning was corrected by the FDG-PET hyperuptake area with the help of nuclear medicine. The mass responses were followed not only by MRI but also by FDG-PET, which was taken prior to treatment, and at one and six months after the treatment. The changes in standard uptake value (SUV) of serial PET were taken as a measure of response. To evaluate the relative SUV changes from different pretreatment values, we set a reduction index (RI), which represents the ratio of SUV change to pretreatment SUV. RESULTS: No significant complications were noted during treatment with a mean follow-up of 13.3 months. The tumor volume on CT-based planning was 2.2 times larger than that of the CT-PET combined planning in case 1 of paraspinal muscle invasion. But the tumor volumes showed minimal changes in the other cases, in which the metastatic tumors were confined to the vertebral bodies. The SUV one month after treatment showed variable decreases and the RI ranged from 0.07 to 0.7. However, the SUVs at 6 months were well correlated with the clinical results. One patient showed marginal failure and the other two patients showed local control of the tumor, as their RI values were 0.65 and 0.87, respectively. CONCLUSION: To our knowledge, this is the first report using FDG-PET with radiosurgery in patients with recurrent spinal metastases hidden under metallic artifacts. The mass responses measured by SUV changes in FDG-PET correlated with the clinical results.

Adult↗

PubMed2006

Hepatic intra-arterial injection of 3-bromopyruvate in rabbit VX2 tumor.

PURPOSE: To evaluate the antitumoral effects of an intra-arterial injection of 3-bromopyruvate (3-BrPA) on liver VX2 tumor in rabbits. MATERIAL AND METHODS: Twenty rabbits with surgically implanted liver VX2 tumors were used. The rabbits were divided into three groups: a control, a saline, and a 3-BrPA group. Four rabbits were not treated at all, and they served as the control group. The saline group (n = 6) received only intra-arterial saline injection. The 3-BrPA group (n = 10) received an intra-arterial injection of 3-bromopyruvate through the hepatic artery. The delivered amounts of 3-bromopyruvate were as follows: 25 ml of 0.5 mM in six rabbits, 25 ml of 1.0 mM in two rabbits, and 25 ml of 2.0 mM in two rabbits. Four days after intra-arterial injection, the rabbits were sacrificed and histopathologic analysis of the explanted livers was performed with comparison of the tumor necrosis ratio (a percentage of the necrotic area versus the entire tumorous area) in each group. RESULTS: The mean tumor necrosis ratio was 12.5+/-4.2%, 44.8+/-24.7%, and 49.4+/-14.3% in the control, saline, and 3-BrPA groups, respectively. Between the control and the saline group, and between the control and the 3-BrPA group the mean tumor necrosis ratio appeared to be significantly different (P<0.05). However, there was no statistical difference in the mean tumor necrosis ratio between the saline and the 3-BrPA group (P = 0.416). CONCLUSION: A single session of intra-arterial injection of 3-BrPA showed no better results in terms of tumor necrosis than that of saline injection in a rabbit VX2 tumor model.

Animals↗

PubMed2006

Clinical features and risk factors for striae distensae in Korean adolescents.

BACKGROUND: Despite the high prevalence of striae distensae, clinical studies are few in number, and their pathophysiology still obscure. OBJECTIVES: To determine the prevalence and clinical characteristics of striae distensae that occur in Korean adolescents, and to correlate their clinical features with family history, other dermatological conditions, and body measurements. METHODS: One hundred and fifty-seven healthy Korean students, aged 15 to 17, were studied. A questionnaire and physical examination were employed to assess the subjects' past and family history, and the distribution, clinical features and severity of striae distensae. RESULTS: Striae distensae were present in 131 subjects (83.4%). Ninety-four (88.2%) of 109 male and 37 (77.1%) of 48 female subjects were affected. The striae were white in colour in 69.5% and asymptomatic in most of the subjects. They developed at an average age of 13.8 years. Family history was present in 18 subjects (11.5%). Seborrhoea of the face was positively correlated (P < 0.035) with striae distensae, and atopic dermatitis negatively correlated (P < 0.001). In both sexes, the buttock was the most prevalent area of striae development, followed by the lower back and knee in boys and by the thigh and calf in girls. Striae were significantly more common on the thigh of girls and on the knee of boys. CONCLUSIONS: Our results indicate that striae distensae are a common skin condition that occurs early in puberty regardless of gender, and that they have a different anatomical distribution and relationship with body measurements in each gender.

Adolescent↗

PubMed2006

Life-threatening common carotid artery blowout: rescue treatment with a newly designed self-expanding covered nitinol stent.

Carotid blowout is a devastating complication in patients with head and neck malignancy. A covered stent offers an alternative to treatment of a carotid blowout patient thought to be at high risk for surgery or carotid occlusion. Stent placement in the common carotid artery or carotid bulb is a technical challenge because of large luminal diameter and luminal calibre discrepancy between internal carotid artery and common carotid artery. We present four patients with common carotid rupture and massive bleeding who were treated with self-expanding covered stents, among them, two cases were treated with newly designed self-expanding polytetrafluoroethylene (PTFE)-covered nitinol stents.

Aged↗

PubMed2006

Effect of salinity on osmoregulatory patch epithelia in gills of the blue crab Callinectes sapidus.

In euryhaline crabs, ion-transporting cells are clustered into osmoregulatory patches on the lamellae of the posterior gills. To examine changes in the branchial osmoregulatory patch in the blue crab Callinectes sapidus in response to change in salinity and to correlate these changes with other osmoregulatory responses, crabs were acclimated to a range of salinities between 10 and 35 ppt. When crabs that had been acclimated to 35 ppt were subsequently transferred to 10 ppt, both the size of the osmoregulatory patch on individual gill lamellae and the specific activity of Na+, K+-ATPase in whole-gill homogenates increased only after the first 24 h of exposure to dilute seawater. Enzyme activity and size of patch area increased gradually and reached their maxima (increasing by 200% and 60%, respectively) 6 days following transfer to 10 ppt seawater and then remained at these levels. Patch size at acclimation varied inversely with the salinity for seawater dilutions below 26 ppt (the isosmotic point of the crab), although it did not vary in salinities at or above 26 ppt. Thus, the size of the patch clearly is modulated with acclimation salinity, but it increases only in those salinities in which the crab hyperosmoregulates. An increase in the total RNA/DNA ratio in gill homogenates, the lack of mitotic figures in the lamellae, and the lack of incorporation of bromodeoxyuridine into nuclei of lamellar epithelial cells during acclimation to dilute seawater were interpreted as evidence that no cell proliferation had occurred and that increases in the size of the osmoregulatory patch occurred through differentiation of existing gas exchange cells or of undifferentiated epithelial cells into ion-transporting cells.

Adaptation, Physiological↗

PubMed2005

Cyclin G1 overcomes radiation-induced G2 arrest and increases cell death through transcriptional activation of cyclin B1.

Although cyclin G1 has been implicated in certain p53-related biological phenomena, other aspects of its function remain unclear. Here we report hitherto unknown mechanism by which cyclin G1 increases radiation sensitivity by regulating the level of cyclin B1. Overexpression of cyclin G1 was observable in lung carcinoma tissues. Irradiation of human lung cells with cyclin G1 overexpression resulted in increased cell death and gamma-H2AX foci suggesting that cyclin G1 rendered the cells more susceptible to DNA damage. Enhanced radiosensitivity by cyclin G1 was correlated with increased cyclin B1, CDC2/cyclin B1 complex, and MPM2. Cell cycle synchronization clearly showed coexpression of cyclin G1 and cyclin B1 in G2/M phase. Depletion of cyclin G1 by interference RNA revealed that cyclin G1 regulated transcription of cyclin B1 in a p53-independent manner, and confirmed that the increased mitotic cells and cell death by cyclin G1 were dependent upon cyclin B1. Therefore, our data suggest that cyclin G1 enhanced radiation sensitivity by overriding radiation-induced G2 arrest through transcriptional upregulation of cyclin B1.

Adenocarcinoma, Papillary↗

PubMed2005

Genotypic resistance of hepatitis B virus to lamivudine in renal transplant recipients.

Renal recipients with hepatitis B virus (HBV) should be treated with prolonged lamivudine. However, lamivudine resistance usually results after YMDD mutation within the HBV polymerase gene. Thereupon, the aim of this study was to investigate the genotypic resistance to lamivudine among renal transplant recipients to identify its effect on the clinical course of HBV in these patients. Between March 1997 and September 2003, eight of 17 renal transplant patients with hepatitis B virus were enrolled into this study and treated with 100 mg of lamivudine once each day. We amplified a selected region of the polymerase gene of HBV in order to confirm mutations in the YMDD motif. Mutations of YMDD region were observed in five of eight patients (62.5%). Out of five patients positive for HBV DNA, three (60%) showed genotypic resistance (YMDD mutation) with a normal ALT level. Two patients converted to HBV DNA negative. But, they were not associated with HBeAg seroconversion. Out of three patients who were pretransplant HBV DNA negative, genotypic resistance was observed in two patients (67%) revealing both positivity of HBe antibody and negativity of HBV DNA. In conclusion, although a normal ALT level and HBV DNA negative are maintained, the mutation of the YMDD locus may develop. Accordingly, we suggest that if the YMDD mutation is not involved in the progression of hepatitis B, lamivudine therapy should be continued despite genotypic resistance.

Adult↗

PubMed2005

Cerebral fat embolism: diffusion-weighted magnetic resonance imaging findings.

PURPOSE: To demonstrate the diffusion-weighted (DWI) magnetic resonance imaging (MRI) findings, and the follow-up MRI findings, of cerebral fat embolism in the acute stage. MATERIAL AND METHODS: The initial DWI and clinical findings of six patients with cerebral fat embolism were retrospectively evaluated. The finding of DWI with a b-value of 1000 s/mm2 (b=1000) was compared with that of DWI with a b-value of 0 s/mm2 (b=0). In three patients who underwent follow-up MRI, the interval change of the lesion on T2-weighted images was investigated. RESULTS: The characteristic DWI finding of cerebral fat embolism in the acute stage was multiple, hyperintense, dot-like lesions disseminated in the brain. These lesions were distributed dominantly in the bilateral border-zone areas. Some lesions had an ancillary location including the cortex, deep white matter, basal ganglia, and cerebellum. The lesions were more intense and numerous in DWI (b=1000) than in DWI (b=0). The findings on the follow-up T2-weighted images were multiple confluent hyperintense lesions in the white matter with progression since the initial MRI. CONCLUSION: DWI could be a sensitive tool for detecting cerebral fat embolism in the acute phase. It is recommended that DWI be included in the initial evaluation of cerebral fat embolism with MRI.

Adult↗

PubMed2005

Adjuvant use of abciximab for balloon angioplasty of symptomatic middle cerebral artery stenosis.

PURPOSE: To evaluate the safety of adjuvant intravenous use of abciximab in balloon angioplasty for symptomatic middle cerebral artery stenosis. MATERIAL AND METHODS: Seven patients with symptomatic stenosis at the main trunk (n=5), or proximal post-trifurcation portion (n=2) of the middle cerebral artery, were enrolled in the study. A bolus dose of abciximab (0.15 mg/kg) was given intravenously immediately before the procedure. The immediate morphologic results as well as the presence of hyperacute thrombosis or hemorrhage after angioplasty were evaluated. Clinical evaluation was performed 1 day and 1 month following angioplasty. Oral antiplatelets were administered during the follow-up period. Follow-up angiography was performed after 7 to 14 (mean 10.4) months. Stenosis of a vessel greater than 50% was considered as restenosis. RESULTS: The procedure was technically successful in all patients. Immediate residual stenosis was insignificant in 4 and mild (less than 50%) in 3 patients. There was no evidence of intimal dissection. Mild gum bleeding was noted in two patients. All study patients were clinically stable at follow-up without newly developed neurological abnormality even though there was one case of occlusion and one case of restenosis on follow-up angiography. Angiographic patency rate was 71%. CONCLUSION: In performing proximal middle cerebral artery balloon angioplasty, abciximab may be safely used to prevent acute thrombosis. The mid-term patency of the vessels was also acceptable.

Abciximab↗

PubMed2005

Doxorubicin loaded pH-sensitive micelle targeting acidic extracellular pH of human ovarian A2780 tumor in mice.

The purpose of this study was to examine the efficacy of a chemotherapeutic drug, doxorubicin (DOX), loaded in pH-sensitive micelles poly(l-histidine) (M(n):5K)-b-PEG (M(n):5K) micelles. The micelles were designed to target the acidic extracellular pH of solid tumors. Studies of pH-dependent cytotoxicity, growth rate of the tumor, pharmacokinetics and biodistribution were conducted. In vitro DOX uptake upon A2780 cells by incubating the cells in a pH 6.8 complete medium at a concentration of 20 microg DOX/ml in the micelle formulation was more than five times that of pH 7.4 condition for initial 20 min. In vivo pharmacokinetic data showed that AUC (area under concentration curve) and half life time (t(1/2)) (plasma half life) of DOX in the pH sensitive micelles increased about 5.8- and 5.2-fold of free DOX in phosphate buffered saline (PBS), respectively. It appeared that DOX in the pH-sensitive micelles preferentially accumulated in the tumor site. The distributions at 12 h post injection in other organs including liver, kidney, spleen, lung and heart were not significantly different from those of DOX in PBS at a 6 mg DOX/kg dose. The in vivo test of anti-tumor activity was performed with human ovarian carcinoma A2780 which was subcutaneously xenografted in female nu/nu athymic mice. The pH-sensitive micelle formulation significantly retarded tumor growth rate without serious body weight loss. The triggered drug release by the reduced tumor pH is believed to be a major mechanism of the observed efficacy after passive accumulation of the micelles by EPR effect. This may have resulted in a local high dose of drug in the tested solid tumor.

Animals↗

PubMed2005

Thymidine phosphorylase expression in tumour cells and tumour response to capecitabine plus docetaxel chemotherapy in non-small cell lung cancer.

BACKGROUND: Thymidine phosphorylase (TP) is the key enzyme for capecitabine activation in tumour cells. AIMS: To examine whether TP expression in tumour cells and stroma is predictive of the tumour response to capecitabine plus docetaxel chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Tumour samples were available from 30 of 39 patients enrolled in a previous phase II study of capecitabine/docetaxel chemotherapy in patients with advanced NSCLC. Stromal and tumour cell TP expression was evaluated by immunohistochemistry using monoclonal antibody PD-ECGF. RESULTS: High tumour cell TP expression was found in 13 of 30 cases and was negatively associated with stromal TP expression (p = 0.000). High stromal TP expression was found in 16 of 28 cases and was strongly associated with intense macrophage infiltration (p = 0.002), suggesting that macrophages are the major component of TP expression in the stroma. Tumour response to capecitabine/docetaxel was significantly associated with high tumour cell TP expression (p = 0.004) and low stromal TP expression (p = 0.009). Moreover, high tumour cell TP expression was significantly associated with severe hand-foot syndrome, a toxic side effect of capecitabine (p = 0.01). Improved survival was seen for high tumour cell and low stromal TP expression, although results were not significant (p = 0.6 and 0.3, respectively). CONCLUSIONS: In advanced NSCLC, TP expression in tumour cells and stroma is associated with tumour response to capecitabine/docetaxel chemotherapy, and might be a useful predictor of tumour response to capecitabine based chemotherapy. A large scale prospective study is needed to confirm the prognostic significance of TP expression in NSCLC.

Adult↗