Combined Treatment of an Intratumoral Injection of Dendritic Cells and Systemic Chemotherapy (Paclitaxel) for Murine Fibrosarcoma

A novel combined treatment of conventional chemotherapy with an intratumoral injection of syngeneic dendritic cells (DCs) has emerged as a potent cancer treatment strategy. In this study, we evaluated the synergistic effect of an intraperitoneal (i.p.) injection of a chemotherapeutic drug, paclitaxel, and an intratumoral (i.t.) injection of syngeneic bone marrow-derived DCs for the treatment of pre-existing fibrosarcoma. Subcutaneous tumors were established using MCA102 fibrosarcoma cells in syngeneic C57BL/6 mice. The results demonstrated that the combined treatment of paclitaxel chemotherapy and the injection of DCs led to complete tumor regression, in contrast to only partial eradication of the tumors with chemotherapy or DCs alone. Furthermore, the tumor-free mice were able to resist a repeat challenge with the same type of tumor. These findings suggest that a combination therapy of systemic chemotherapy along with the intratumoral administration of DCs is a potent treatment strategy for fibrosarcoma

Impact of Parenchymal Tuberculosis Sequelae on Mediastinal Lymph Node Staging in Patients with Lung Cancer

Because tuberculous (TB) involvement of mediastinal lymph nodes (LN) could cause false positive results in nodal staging of lung cancer, we examined the accuracy of nodal staging in lung cancer patients with radiographic sequelae of healed TB. A total of 54 lung cancer patients with radiographic TB sequelae in the lung parenchyma ipsilateral to the resected lung, who had undergone at least ipsilateral 4- and 7-lymph node dissection after both chest computed tomography (CT) and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT were included for the analysis. The median age of 54 subjects was 66 yr and 48 were males. Calcified nodules and fibrotic changes were the most common forms of healed parenchymal pulmonary TB. Enlarged mediastinal lymph nodes (short diameter > 1 cm) were identified in 21 patients and positive mediastinal lymph nodes were identified using FDG-PET/CT in 19 patients. The overall sensitivity and specificity for mediastinal node metastasis were 60.0% and 69.2% with CT and 46.7% and 69.2% with FDG-PET/CT, respectively. In conclusion, the accuracy of nodal staging using CT or FDG-PET/CT might be low in lung cancer patients with parenchymal TB sequelae, because of inactive TB lymph nodes without viable TB bacilli

Frequency and predictors of miliary tuberculosis in patients with miliary pulmonary nodules in South Korea: A retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Miliary pulmonary nodules are commonly caused by various infections and cancers. We sought to identify the relative frequencies of various aetiologies and the clinical and radiographic predictors of miliary tuberculosis (TB) in patients with miliary pulmonary nodules.</p> <p>Methods</p> <p>We performed a retrospective cohort study of patients who presented with micronodules occupying more than two-thirds of the lung volume, based on computed tomography (CT) of the chest, between November 2001 and April 2007, in a tertiary referral hospital in South Korea.</p> <p>Results</p> <p>We analyzed 76 patients with miliary pulmonary nodules. Their median age was 52 years and 38 (50%) were males; 18 patients (24%) had a previous or current malignancy and five (7%) had a history of TB. The most common diagnoses of miliary nodules were miliary TB (41 patients, 54%) and miliary metastasis of malignancies (20 patients, 26%). Multivariate analysis revealed that age ≤30 years, HIV infection, corticosteroid use, bronchogenic spread of lesions, and ground-glass opacities occupying >25% of total lung volume increased the probability of miliary TB. However, a history of malignancy decreased the probability of miliary TB.</p> <p>Conclusion</p> <p>Miliary TB accounted for approximately half of all causes of miliary pulmonary nodules. Young age, an immune-compromised state, and several clinical and radiographic characteristics increased the probability of miliary TB.</p

Prognostic impact of clinicopathologic parameters in stage II/III breast cancer treated with neoadjuvant docetaxel and doxorubicin chemotherapy: paradoxical features of the triple negative breast cancer

<p>Abstract</p> <p>Background</p> <p>Prognostic factors in locally advanced breast cancer treated with neoadjuvant chemotherapy differ from those of early breast cancer. The purpose of this study was to identify the clinical significance of potential predictive and prognostic factors in breast cancer patients treated by neoadjuvant chemotherapy.</p> <p>Methods</p> <p>A total of 145 stage II and III breast cancer patients received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. We examined the clinical and biological factors (ER, PR, p53, c-erbB2, bcl-2, and Ki-67) by immunohistochemistry. We analyzed clinical outcome and their correlation with clinicopathologic parameters.</p> <p>Results</p> <p>Among the clinicopathologic parameters investigated, none of the marker was correlated with response rate (RR) except triple negative phenotype. Patients with triple negative phenotype showed higher RR (83.0% in triple negative <it>vs</it>. 62.2% in non-triple negative, <it>p </it>= 0.012) and pathologic complete RR (17.0% in triple negative <it>vs</it>. 3.1% in non-triple negative, <it>p </it>= 0.005). However, relapse free survival (RFS) and overall survival (OS) were significantly shorter in triple negative breast cancer patients (<it>p </it>< 0.001, <it>p </it>= 0.021, respectively). Low histologic grade, positive hormone receptors, positive bcl-2 and low level of Ki-67 were associated with prolonged RFS. In addition, positive ER and positive bcl-2 were associated with prolonged OS. In our homogeneous patient population, initial clinical stage reflects RFS and OS more precisely than pathologic stage. In multivariate analysis, initial clinical stage was the only significant independent prognostic factor to impact on OS (hazard ratio 3.597, <it>p </it>= 0.044).</p> <p>Conclusion</p> <p>Several molecular markers provided useful predictive and prognostic information in stage II and III breast cancer patients treated with neoadjuvant docetaxel/doxorubicin chemotherapy. Triple negative phenotype was associated with shorter survival, even though it was associated with a higher response rate to neoadjuvant chemotherapy.</p

한국인 월경혈손실량과 철분영양상태 및 자궁내피임장치의 영향

The upper normal limit of menstrual blood loss associated with iron deficiency, and the change in MBL and length of time necessary for development of iron depletion after IUDs insertion in healthy 193 Korean women were studied. The mean of MBL was 33.4 ± 23.4(SD) ml and the variation of MBL in different marital, age, and parity groups showed no statistical significance except for the higher values in young married women. Serum ferritin concentration was markedly decreased in women showing MBL above 40 ml and the frequency of subjects with serum ferritin below anemia criteria were increased in women showing MBL above 50 ml. Other parameters for assessing the iron nutriture showed no significant difference in different range of MBL. The mean MBL in women fitted with Alza-T IPCS 52 was significantly decreased after 3 months of insertion, but the increases in hemoglobin a1d serum ferritin levels were statistically significant at 12 month after insertion. The mean MBL in other IUD groups was remarkably increased at 1 month in T-Cu 220C group and during 1 to 12 month in Lippes Loop D group. Significant decrease in serum ferritin level was observed at 6 and 12 month in both groups

Characterization of H460R, a Radioresistant Human Lung Cancer Cell Line, and Involvement of Syntrophin Beta 2 (SNTB2) in Radioresistance

A radioresistant cell line was established by fractionated ionizing radiation (IR) and assessed by a clonogenic assay, flow cytometry, and Western blot analysis, as well as zymography and a wound healing assay. Microarray was performed to profile global expression and to search for differentially expressed genes (DEGs) in response to IR. H460R cells demonstrated increased cell scattering and acidic vesicular organelles compared with parental cells. Concomitantly, H460R cells showed characteristics of increased migration and matrix metalloproteinase activity. In addition, H460R cells were resistant to IR, exhibiting reduced expression levels of ionizing responsive proteins (p-p53 and γ-H2AX); apoptosis-related molecules, such as cleaved poly(ADP ribose) polymerase; and endoplasmic reticulum stress-related molecules, such as glucose-regulated protein (GRP78) and C/EBP-homologous protein compared with parental cells, whereas the expression of anti-apoptotic X-linked inhibitor of apoptosis protein was increased. Among DEGs, syntrophin beta 2 (SNTB2) significantly increased in H460R cells in response to IR. Knockdown of SNTB2 by siRNA was more sensitive than the control after IR exposure in H460, H460R, and H1299 cells. Our study suggests that H460R cells have differential properties, including cell morphology, potential for metastasis, and resistance to IR, compared with parental cells. In addition, SNTB2 may play an important role in radioresistance. H460R cells could be helpful in in vitro systems for elucidating the molecular mechanisms of and discovering drugs to overcome radioresistance in lung cancer therapy

Maternal exposure to environmental tobacco smoke, GSTM1/T1 polymorphisms and oxidative stress

Environmental tobacco smoking (ETS) is known to be associated with adverse pregnancy outcomes. The purpose of this study was to investigate the relationship between maternal exposure to ETS and oxidative stress for neonates, as well as the effect of maternal genetic polymorphisms, glutathione-S-transferase M1 (GSTM1) and GSTT1, on this relationship. We used the radioimmunoassay to measure the urinary concentration of cotinine in 266 pregnant women who denied smoking cigarettes during pregnancy and in their singleton babies. In addition, the urinary concentration of malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OH-dG) were assessed using high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. We also extracted DNA from whole blood obtained from the mothers and then conducted polymerase chain reaction on the samples to determine the GSTM1 and GSTT1 genotypes. The maternal cotinine concentration was found to be significantly associated with the fetal cotinine concentration, particularly for mothers whose urine cotinine concentrations were above 120 microg/gcr (p<0.01). The fetal urine cotinine concentration was also found to be significantly associated with the fetal urine MDA concentration (p<0.01). When the null type maternal GSTM1 or the wild type GSTT1 was present, the maternal oxidative stress level increased significantly as the maternal continine concentration increased (MDA: p<0.01; 8-OH-dG: p<0.01). No significant relationships were found between maternal cotinine and fetal oxidative stress markers, however, the fetal MDA levels increased significantly as fetal cotinine levels increased. These results suggest that the maternal exposure to ETS affects the fetal urine cotinine concentration and induces production of maternal oxidative stress. In addition, maternal genetic polymorphisms of GSTM1 and GSTT1 may modify the oxidative stress by maternal exposure to ETS

Xenoreactivity of human clonal mesenchymal stem cells in a major histocompatibility complex-matched allogeneic graft-versus-host disease mouse model

Effects of mesenchymal stem cells (MSCs) on graft-versus-host disease (GVHD) have been actively investigated since the discovery of the immunomodulation property of MSCs about a decade ago. Human clonal MSCs (hcMSCs) were isolated from human bone marrow aspirate according to our newly established isolation protocol called suffractionation culturing method, and were evaluated for their efficacy on GVHD treatment, using a mouse MHC-matched B6 -> BALB.B GVHD model system. Although the hcMSCs can suppress the allogeneic proliferation of human peripheral blood mononuclear cells in in vitro, the administration of the hcMSCs failed to reduce the GVHD-related mortality of the murine recipients. One of the reasons might be that murine cytokines such as IFN-gamma and TNF-alpha cannot activate the hcMSCs. Based on these results, we suggest that xenogeneic MSCs may not be used for the treatment of GVHD. (C) 2009 Elsevier Inc. All rights reserved.This study was supported by a grant of the Korea Helath 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (D06- 0001-AY1316-06N1-00010A), a research grant of Korean Airline (36088-01), and from the Brain Korea 21 Project in 2009. This work was also supported by a grant (Molecular and Cellular BioDiscovery Research Program 2007-03619) from the Korea Research Foundation.Liao WB, 2009, TRANSPLANTATION, V87, P350, DOI 10.1097/TP.0b013e318195742eLi WJ, 2009, J TISSUE ENG REGEN M, V3, P1, DOI 10.1002/term.127Uccelli A, 2008, NAT REV IMMUNOL, V8, P726, DOI 10.1038/nri2395Polchert D, 2008, EUR J IMMUNOL, V38, P1745, DOI 10.1002/eji.200738129Dazzi F, 2008, EUR J IMMUNOL, V38, P1479, DOI 10.1002/eji.200838433Song SU, 2008, STEM CELLS DEV, V17, P451, DOI 10.1089/scd.2007.0167LeBlanc K, 2008, LANCET, V371, P1579, DOI 10.1016/S0140-6736(08)60690-XMorandi F, 2008, STEM CELLS, V26, P1275, DOI 10.1634/stemcells.2007-0878Katz JB, 2008, IMMUNOL REV, V222, P206, DOI 10.1111/j.1600-065X.2008.00610.xRen GW, 2008, CELL STEM CELL, V2, P141, DOI 10.1016/j.stem.2007.11.014Rasmusson I, 2007, J LEUKOCYTE BIOL, V82, P887, DOI 10.1189/jlb.0307140Min CK, 2007, BONE MARROW TRANSPL, V39, P637, DOI 10.1038/sj.bmt.1705644Augello A, 2007, ARTHRITIS RHEUM, V56, P1175, DOI 10.1002/art.22511Itakura S, 2007, AM J TRANSPLANT, V7, P336, DOI 10.1111/j.1600-6143.2006.01643.xYan H, 2007, ARTHROSCOPY, V23, P178, DOI 10.1016/j.arthro.2006.09.005Sato K, 2007, BLOOD, V109, P228, DOI 10.1182/blood-2006-02-002246Zhao CP, 2007, CYTOTHERAPY, V9, P414, DOI 10.1080/14653240701376413Ringden O, 2006, TRANSPLANTATION, V81, P1390, DOI 10.1097/01.tp.0000214462.63943.14Lazarus HM, 2005, BIOL BLOOD MARROW TR, V11, P389, DOI 10.1016/j.bbmt.2005.02.001Falkenburg JHF, 2004, BEST PRACT RES CL HA, V17, P415, DOI 10.1016/j.beha.2004.05.008Le Blanc K, 2004, LANCET, V363, P1439, DOI 10.1016/S0140-6736(04)16104-7Rasmusson I, 2003, TRANSPLANTATION, V76, P1208, DOI 10.1097/01.TP.0000082540.43730.80Spierings E, 2003, BLOOD, V102, P621, DOI 10.1182/blood-2003-01-0260Krampera M, 2003, BLOOD, V101, P3722, DOI 10.1182/blood-2002-07-2104Tse WT, 2003, TRANSPLANTATION, V75, P389, DOI 10.1097/01.TP.0000045055.63901.A9Choi EY, 2002, BLOOD, V100, P4259, DOI 10.1182/blood-2002-05-1299Saito T, 2002, ANN THORAC SURG, V74, P19, DOI 10.1016/S0003-4975(02)03591-9Di Nicola M, 2002, BLOOD, V99, P3838, DOI 10.1182/blood.V99.10.3838Schwartz RE, 2002, J CLIN INVEST, V109, P1291, DOI 10.1172/JCI200215182Toma C, 2002, CIRCULATION, V105, P93, DOI 10.1161/hc0102.101442Bartholomew A, 2002, EXP HEMATOL, V30, P42, DOI 10.1016/S0301-472X(01)00769-XChoi EY, 2001, J IMMUNOL, V166, P4370Liechty KW, 2000, NAT MED, V6, P1282Woodbury D, 2000, J NEUROSCI RES, V61, P364, DOI 10.1002/1097-4547(20000815)61:43.0.CO2-CProckop DJ, 1997, SCIENCE, V276, P71, DOI 10.1126/science.276.5309.71CAPLAN AI, 1991, J ORTHOPAED RES, V9, P641, DOI 10.1002/jor.1100090504Horowitz M M, 1990, Clin Transpl, P41OREILLY RJ, 1983, BLOOD, V62, P941GOLDMAN JM, 1982, LANCET, V2, P623FRIEDENSTEIN AJ, 1976, EXP HEMATOL, V4, P267