BACKGROUND: Despite major progress in stem cell therapy, our knowledge of the characteristics and tissue regeneration potency of long-term transported cells is insufficient. In a previous in vitro study, we established the optimal cell transport conditions for amniotic fluid stem cells (AFSCs). In the present study, the target tissue regeneration of long-term transported cells was validated in vivo. METHODS: For renal regeneration, transported AFSCs were seeded on a poly(lactide-co-glycolide) scaffold and implanted in a partially resected kidney. The target tissue regeneration of the transported cells was compared with that of freshly harvested cells in terms of morphological reconstruction, histological microstructure reformation, immune cell infiltration, presence of induced cells, migration into remote organs, expression of inflammation/fibrosis/renal differentiation-related factors, and functional recovery. RESULTS: The kidney implanted with transported cells showed recovery of total kidney volume, regeneration of glomerular/renal tubules, low CD4/CD8 infiltration, and no occurrence of cancer during 40 weeks of observation. The AFSCs gradually disappeared and did not migrate into the liver, lung, or spleen. We observed low expression levels of proinflammatory cytokines and fibrotic factors; enhanced expression of the genes Wnt4, Pax2, Wt1, and Emx2; and significantly reduced blood urea nitrogen and creatinine values. There were no statistical differences between the performance of freshly harvested cells and that of the transported cells. CONCLUSION: This study demonstrates that long-term transported cells under optimized conditions can be used for cell therapy without adverse effects on stem cell characteristics, in vivo safety, and tissue regeneration potency.
Amniotic Fluid ; Blood Urea Nitrogen ; Cell- and Tissue-Based Therapy ; Creatinine ; Cytokines ; Female ; In Vitro Techniques ; Kidney ; Liver ; Lung ; Polyglactin 910 ; Regeneration ; Spleen ; Stem Cells

BACKGROUND: The concept of the ideal morphology for the alveolar bone form is an important element to reconstruct or restore the in maximizing esthetic profile and functional alveolar bone restoration. The purpose of this preliminary study is to evaluate the normal alveolar bone structure to provide the standard reference and guide template for use in diagnosing for implant placement, determining the correct amount of bone augmentation in actual clinical practice and producing prostheses based on three-dimensional imaging assessment of alveolar bone. METHODS: This study was included 11 men and 11 women (average age, 22.6 and 24.5 years, respectively) selected from among 127 patients. The horizontal widths of alveolar bone of maxilla and mandible were measured at the crestal, mid-root, and root apex level on MDCT (multi-detector computed tomography) images reconstructed by medical imaging software. In addition, tooth dimensions of the central incisors, canines, second premolars, and first molars of maxilla and mandible, including the horizontal width of the interdental alveolar bone crest, were also measured and statistically analyzed. RESULTS: The horizontal alveolar bone width of the palatal side of maxilla showed a distinct increment from the alveolar bone crest to the apical region in both anterior and posterior areas. The average widths of the maxillary alveolar ridge were as follows: central incisor, 7.43 mm; canine, 8.91 mm; second premolar, 9.57 mm; and first molar, 12.38 mm. The average widths of the mandibular alveolar ridge were as follows: central incisor, 6.21 mm; canine, 8.55 mm; second premolar, 8.45 mm; and first molar, 10.02 mm. In the buccal side, the alveolar bone width was not increased from the crest to the apical region. The horizontal alveolar bone width of an apical and mandibular border region was thinner than at the mid-root level. CONCLUSIONS The results of the preliminary study are useful as a clinical guideline when determining dental implant diameter and position. And also, these measurements can also be useful during the production of prefabricated membranes and customized alveolar bone scaffolds.

BACKGROUND: Kidney ischemia-reperfusion (IR) via laparotomy is a conventional method for kidney surgery in a mouse model. However, IR, an invasive procedure, can cause serious acute and chronic complications through apoptotic and inflammatory pathways. To avoid these adverse responses, a Non-IR and dorsal slit approach was designed for kidney surgery. METHODS: Animals were divided into three groups, 1) sham-operated control; 2) IR, Kidney IR via laparotomy; and 3) Non-IR, Non-IR and dorsal slit. The effects of Non-IR method on renal surgery outcomes were verified with respect to animal viability, renal function, apoptosis, inflammation, fibrosis, renal regeneration, and systemic response using histology, immunohistochemistry, real-time polymerase chain reaction, serum chemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and Masson's trichrome staining. RESULTS: The Non-IR group showed 100% viability with mild elevation of serum blood urea nitrogen and creatinine values at day 1 after surgery, whereas the IR group showed 20% viability and lethal functional abnormality. Histologically, renal tubule epithelial cell injury was evident on day 1 in the IR group, and cellular apoptosis enhanced TUNEL-positive cell number and Fas/caspase-3 and KIM-1/NGAL expression. Inflammation and fibrosis were high in the IR group, with enhanced CD4/CD8-positive T cell infiltration, inflammatory cytokine secretion, and Masson's trichrome stain-positive cell numbers. The Non-IR group showed a suitable microenvironment for renal regeneration with enhanced host cell migration, reduced immune cell influx, and increased expression of renal differentiation-related genes and anti-inflammatory cytokines. The local renal IR influenced distal organ apoptosis and inflammation by releasing circulating pro-inflammatory cytokines. CONCLUSION: The Non-IR and dorsal slit method for kidney surgery in a mouse model can be an alternative surgical approach for researchers without adverse reactions such as apoptosis, inflammation, fibrosis, functional impairment, and systemic reactions.
Animals ; Apoptosis ; Blood Urea Nitrogen ; Cell Count ; Cell Movement ; Chemistry ; Creatinine ; Cytokines ; DNA Nucleotidylexotransferase ; Epithelial Cells ; Fibrosis ; Immunohistochemistry ; Inflammation ; Kidney ; Laparotomy ; Methods* ; Mice* ; Nephrectomy* ; Real-Time Polymerase Chain Reaction ; Regeneration*

Urine-derived stem cells (USCs) are considered as a promising cell source capable of neuronal differentiation. In addition, specific growth factors and extracellular matrix are essential for enhancing their neuronal differentiation efficiency. In this study, we investigated the possibility of neuronal differentiation of USCs and the role of laminin and platelet-derived growth factor BB (PDGF-BB) as promoting factors. USCs were isolated from fresh urine of healthy donors. Cultured USCs were adherent to the plate and their morphology was similar to the cobblestone. In addition, they showed chromosome stability, rapid proliferation rate, colony forming capacity, and mesenchymal stem cell characteristics. For inducing the neuronal differentiation, USCs were cultured for 14 days in neuronal differentiation media supplemented with/without laminin and/or PDGF-BB. To identify the expression of neuronal markers, RT-PCR, flow cytometry analysis and immunocytochemistry were used. After neuronal induction, the cells showed neuron-like morphological change and high expression level of neuronal markers. In addition, laminin and PDGF-BB respectively promoted the neuronal differentiation of USCs and the combination of laminin and PDGF-BB showed a synergistic effect for the neuronal differentiation of USCs. In conclusion, USCs are noteworthy cell source in the field of neuronal regeneration and laminin and PDGF-BB promote their neuronal differentiation efficiency.
Chromosomal Instability ; Extracellular Matrix ; Flow Cytometry ; Humans* ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; Laminin* ; Mesenchymal Stromal Cells ; Neurons* ; Platelet-Derived Growth Factor ; Regeneration ; Stem Cells* ; Tissue Donors

PURPOSE: This study aimed to investigate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG), which are volume-based PET parameters, using 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in patients with surgically resectable lung adenocarcinoma.METHODS: We retrospectively evaluated 149 patients with lung adenocarcinoma who underwent 18F-FDG PET/CT before surgical resection. Maximum standardized uptake value (SUVmax), MTV, and TLG of the primary tumor with threshold value of SUVmax 30, 40, and 50% were calculated, respectively. To compare the predictive performance of volume-based PET parameters, recurrence-free survival was assessed using the Kaplan-Meier method.RESULTS: The study included 70 males and 79 females with an average age of 65.8 years. The median follow-up time was 45.4 months. Recurrence was observed in 53 patients (35.6%). The mean ± SD SUVmax, MTV30%, and TLG(30%) of the entire cohort were 4.79 ± 2.94, 19.45 ± 24.85, and 56.43 ± 101.88, respectively. The cut-off values of MTV30% and TLG(30%) for recurrence were 11.07 ad 30.56, respectively. The 1-year recurrence-free survival (RFS) rate was 96.5% in low-MTV30% patients compared with 86.2% in high-MTV30% patients (p = 0.018) and 96.0% in low-TLG(30%) patients compared with 88.5% in high-TLG(30%) patients (p < 0.001). On univariate and multivariate analysis, TLG(30%) (HR, 2.828, p < 0.001; HR, 2.738, p < 0.001, respectively) was an independent prognostic factor for predicting recurrence-free survival (RFS).CONCLUSION: TLG(30%) value was observed to be a significant prognostic factor for RFS in patients with lung adenocarcinoma treated by surgical resection.
Adenocarcinoma ; Cohort Studies ; Electrons ; Female ; Fluorodeoxyglucose F18 ; Follow-Up Studies ; Glycolysis ; Humans ; Lung ; Male ; Methods ; Multivariate Analysis ; Positron-Emission Tomography and Computed Tomography ; Recurrence ; Retrospective Studies ; Tumor Burden

BACKGROUND: Anti-Mullerian hormone (AMH) in women is secreted by granulosa cells of antral follicles. AMH appears to be a very stable marker for ovarian function. It may be used to diagnosis cases of premature ovarian failure, polycystic ovary syndrome (PCOS), and ovarian tumors. It has been suggested that cadmium exposure can reduce female fecundity. The purpose of this study was to investigate whether environmental exposure to cadmium was associated with alterations in AMH with regards to age. METHODS: In a cross-sectional study, the data of premenopausal women living in Seoul, ranging from 30 to 45 of age was collected. The study included a total of 283 women who completed serum AMH and whole blood cadmium assessments. Linear regression analyses were used in order to examine the association between cadmium and AMH. Given that age was the strongest confounder in both cadmium and AMH concentrations, we stratified subjects by 5 years old and analyzed their data. RESULTS: Geometric mean concentrations of blood cadmium and AMH were 0.97 μg/L and 3.02 ng/ml, respectively. Total association between cadmium and AMH was statistically significant (adjusted coefficient = − 0.34 (0.15), p = 0.02). After stratification, the only age group with a negative association between cadmium and AMH were the women raging between 30 and 35 years (adjusted coefficient = − 0.43 (0.18), p = 0.01). CONCLUSIONS: The results of this study suggest that environmental exposure to cadmium may alter the AMH level of premenopausal women, depending on their age group.
Anti-Mullerian Hormone ; Cadmium ; Cross-Sectional Studies ; Diagnosis ; Environmental Exposure ; Female ; Fertility ; Granulosa Cells ; Humans ; Linear Models ; Polycystic Ovary Syndrome ; Primary Ovarian Insufficiency ; Rage ; Seoul

PURPOSE: This study aimed to investigate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG), which are volume-based PET parameters, using 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in patients with surgically resectable lung adenocarcinoma. METHODS: We retrospectively evaluated 149 patients with lung adenocarcinoma who underwent 18F-FDG PET/CT before surgical resection. Maximum standardized uptake value (SUVmax), MTV, and TLG of the primary tumor with threshold value of SUVmax 30, 40, and 50% were calculated, respectively. To compare the predictive performance of volume-based PET parameters, recurrence-free survival was assessed using the Kaplan-Meier method. RESULTS: The study included 70 males and 79 females with an average age of 65.8 years. The median follow-up time was 45.4 months. Recurrence was observed in 53 patients (35.6%). The mean ± SD SUVmax, MTV30%, and TLG(30%) of the entire cohort were 4.79 ± 2.94, 19.45 ± 24.85, and 56.43 ± 101.88, respectively. The cut-off values of MTV30% and TLG(30%) for recurrence were 11.07 ad 30.56, respectively. The 1-year recurrence-free survival (RFS) rate was 96.5% in low-MTV30% patients compared with 86.2% in high-MTV30% patients (p = 0.018) and 96.0% in low-TLG(30%) patients compared with 88.5% in high-TLG(30%) patients (p < 0.001). On univariate and multivariate analysis, TLG(30%) (HR, 2.828, p < 0.001; HR, 2.738, p < 0.001, respectively) was an independent prognostic factor for predicting recurrence-free survival (RFS). CONCLUSION TLG(30%) value was observed to be a significant prognostic factor for RFS in patients with lung adenocarcinoma treated by surgical resection.

PURPOSE: Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). MATERIALS AND METHODS: Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m² or Genexol 175 mg/m² intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). RESULTS: The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m² (95.0%), and that of Genexol was 168.3±10.6 mg/m² (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (p(non-inferiority)=0.021, p(superiority)=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments. CONCLUSION: Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.
Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Incidence ; Neutropenia ; Paclitaxel* ; Peripheral Nervous System Diseases ; Polymers* ; Treatment Outcome

PURPOSE: This study analyzed the role of plasma biomarkers for TSU-68 in a previous phase II trial comparing TSU-68 plus docetaxel and docetaxel alone in patients with metastatic breast cancer. MATERIALS AND METHODS: A total of 77 patients were eligible for this study (38 in the TSU-68 plus docetaxel arm and 39 in the docetaxel alone arm). Blood samples were collected prior to the start of each cycle, and vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-AA, -AB, -BB, fibroblast growth factor, M30, C-reactive protein (CRP), and interleukin 6 (IL-6) levels were measured using enzyme linked immunosorbent assay. The primary endpoint was progression-free survival (PFS). RESULTS: In patients with baseline PDGF-AA ≥ median, median PFS was significantly worse in the TSU-68 plus docetaxel group than in the docetaxel alone group (5.4 months vs. 13.7 months, p=0.049), while a trend toward a PFS benefit was observed in those with baseline PDGF-AA < median (9.7 months vs. 4.0 months, p=0.18; p for interaction=0.03). In the TSU-68 plus docetaxel group, PFS showed significant association with fold changes in CRP (p=0.001), IL-6 (p < .001), PDGF-BB (p=0.02), and VEGF (p=0.047) following the first treatment cycle. CONCLUSION: Baseline PDGF-AA levels and dynamics of VEGF, PDGF-BB, CRP, and IL-6 levels were predictive for the efficacy of TSU-68.
Arm ; Biological Markers* ; Breast Neoplasms* ; Breast* ; C-Reactive Protein ; Disease-Free Survival ; Enzyme-Linked Immunosorbent Assay ; Fibroblast Growth Factors ; Humans ; Interleukin-6 ; Pharmacology ; Plasma* ; Platelet-Derived Growth Factor ; Vascular Endothelial Growth Factor A