Thyroid cancer is one of the most common malignancies of endocrine organs, and its incidence rate has increased steadily over the past several decades. Most differentiated thyroid tumors derived from thyroid epithelial cells exhibit slow-growing cancers, and patients with these tumors can achieve a good prognosis with surgical removal and radioiodine treatment. However, a small proportion of patients present with advanced thyroid cancer and are unusually resistant to current drug treatment modalities. Thyroid tumorigenesis is a complex process that is regulated by the activation of oncogenes, inactivation of tumor suppressors, and alterations in programmed cell death. Mitochondria play an essential role during tumor formation, progression, and metastasis of thyroid cancer. Recent studies have successfully observed the mitochondrial etiology of thyroid carcinogenesis. This review focuses on the recent progress in understanding the molecular mechanisms of thyroid cancer relating to altered mitochondrial metabolism.
Carcinogenesis ; Cell Death ; Epithelial Cells ; Humans ; Incidence ; Metabolism* ; Mitochondria ; Neoplasm Metastasis ; Oncogenes* ; Prognosis ; Quality Control* ; Thyroid Gland* ; Thyroid Neoplasms*

More effective production of human insulin is important, because insulin is the main medication that is used to treat multiple types of diabetes and because many people are suffering from diabetes. The current system of insulin production is based on recombinant DNA technology, and the expression vector is composed of a preproinsulin sequence that is a fused form of an artificial leader peptide and the native proinsulin. It has been reported that the sequence of the leader peptide affects the production of insulin. To analyze how the leader peptide affects the maturation of insulin structurally, we adapted several in silico simulations using 13 artificial proinsulin sequences. Three-dimensional structures of models were predicted and compared. Although their sequences had few differences, the predicted structures were somewhat different. The structures were refined by molecular dynamics simulation, and the energy of each model was estimated. Then, protein-protein docking between the models and trypsin was carried out to compare how efficiently the protease could access the cleavage sites of the proinsulin models. The results showed some concordance with experimental results that have been reported; so, we expect our analysis will be used to predict the optimized sequence of artificial proinsulin for more effective production.
Computer Simulation ; DNA, Recombinant ; Humans* ; Insulin ; Molecular Dynamics Simulation* ; Proinsulin ; Protein Sorting Signals ; Trypsin

PURPOSE: The purpose of this study was to evaluate the anatomical similarity of three-dimensional (3D) morphometric parameters between right and left knees. MATERIALS AND METHODS: Ten fresh-frozen paired cadaveric knees were tested. Following dissection, footprint areas of the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) were measured. Surface scanning was performed using a 3D scanner. Scanned data were reproduced and morphometric parameters were measured on specialized software. After making mirror models, we compared footprint center positions of the ACL and PCL of both sides and calculated the average deviation of 3D alignment between the right- and left-side models. RESULTS: No significant side-to-side differences were found in any morphometric parameters. Bony shapes displayed a side-to-side difference of < 1 mm. Distal femoral and proximal tibial volumes did not present side-to-side differences, either; the average 3D deviations of alignment between the right and left sides were 0.8±0.4/1.1±0.6 mm (distal femur/proximal tibia). Center-to-center distances between the right and left ACL footprints were 2.6/2.7 mm (femur/tibia) for the anteromedial bundle and 2.4/2.8 mm for the posterolateral bundle. They were 1.9/1.5 mm for the anterolateral bundle and 2.2/1.8 mm for the posteromedial bundle of the PCL. CONCLUSIONS: There was a remarkable 3D morphometric similarity between right and left knees. Our results might support the concept of obtaining morphologic reference data from the uninvolved contralateral knee.
Anatomy, Comparative ; Anterior Cruciate Ligament ; Cadaver ; Imaging, Three-Dimensional ; Knee Joint ; Knee ; Posterior Cruciate Ligament

Primary thyroid cancers including papillary, follicular, poorly differentiated, and anaplastic carcinomas show substantial differences in biological and clinical behaviors. Even in the same pathological type, there is wide variability in the clinical course of disease progression. The molecular carcinogenesis of thyroid cancer has advanced tremendously in the last decade. However, specific inhibition of oncogenic pathways did not provide a significant survival benefit in advanced progressive thyroid cancer that is resistant to radioactive iodine therapy. Accumulating evidence clearly shows that cellular energy metabolism, which is controlled by oncogenes and other tumor-related factors, is a critical factor determining the clinical phenotypes of cancer. However, the role and nature of energy metabolism in thyroid cancer remain unclear. In this article, we discuss the role of cellular energy metabolism, particularly mitochondrial energy metabolism, in thyroid cancer. Determining the molecular nature of metabolic remodeling in thyroid cancer may provide new biomarkers and therapeutic targets that may be useful in the management of refractory thyroid cancers.
Carcinogenesis ; Carcinoma ; Disease Progression ; Energy Metabolism* ; Iodine ; Mitochondria ; Oncogenes ; Phenotype ; Thyroid Gland* ; Thyroid Neoplasms ; Biomarkers

BACKGROUND: The present study evaluated the efficacy of a combination of ibandronate and cholecalciferol on the restoration of the levels of 25-hydroxyvitamin D (25[OH]D) and various bone markers in postmenopausal women with osteoporosis. METHODS: This was a randomized, double-blind, active-controlled, prospective 16-week clinical trial conducted in 20 different hospitals. A total of 201 postmenopausal women with osteoporosis were assigned randomly to one of two groups: the IBN group, which received a once-monthly pill containing 150 mg ibandronate (n=99), or the IBN+ group, which received a once-monthly pill containing 150 mg ibandronate and 24,000 IU cholecalciferol (n=102). Serum levels of 25(OH)D, parathyroid hormone (PTH), and various bone markers were assessed at baseline and at the end of a 16-week treatment period. RESULTS: After 16 weeks of treatment, the mean serum levels of 25(OH)D significantly increased from 21.0 to 25.3 ng/mL in the IBN+ group but significantly decreased from 20.6 to 17.4 ng/mL in the IBN group. Additionally, both groups exhibited significant increases in mean serum levels of PTH but significant decreases in serum levels of bone-specific alkaline phosphatase and C-telopeptide of type 1 collagen (CTX) at 16 weeks; no significant differences were observed between the groups. However, in subjects with a vitamin D deficiency, IBN+ treatment resulted in a significant decrease in serum CTX levels compared with IBN treatment. CONCLUSION: The present findings demonstrate that a once-monthly pill containing ibandronate and cholecalciferol may be useful for the amelioration of vitamin D deficiency in patients with postmenopausal osteoporosis. Moreover, this treatment combination effectively decreased serum levels of resorption markers, especially in subjects with a vitamin D deficiency, over the 16-week treatment period.
Alkaline Phosphatase ; Cholecalciferol* ; Collagen Type I ; Female ; Humans ; Osteoporosis* ; Osteoporosis, Postmenopausal ; Parathyroid Hormone ; Prospective Studies ; Vitamin D Deficiency

BACKGROUND: Regarding reconstruction surgery of the anterior cruciate ligament (ACL), there is still a debate whether to perform a single bundle (SB) or double bundle (DB) reconstruction. The purpose of this study was to analyze and compare the volume and surface area of femoral and tibial tunnels during transtibial SB versus transportal DB ACL reconstruction. METHODS: A consecutive series of 26 patients who underwent trantibial SB ACL reconstruction and 27 patients with transportal DB ACL reconstruction using hamstring autograft from January 2010 to October 2010 were included in this study. Three-dimensional computed tomography (3D-CT) was taken within one week after operation. The CT bone images were segmented with use of Mimics software v14.0. The obtained digital images were then imported in the commercial package Geomagic Studio v10.0 and SketchUp Pro v8.0 for processing. The femoral and tibial tunnel lengths, diameters, volumes and surface areas were evaluated. A comparison between the two groups was performed using the independent-samples t-test. A p-value less than the significance value of 5% (p < 0.05) was considered statistically significant. RESULTS: Regarding femur tunnels, a significant difference was not found between the tunnel volume for SB technique (1,496.51 +/- 396.72 mm3) and the total tunnel volume for DB technique (1,593.81 +/- 469.42 mm3; p = 0.366). However, the total surface area for femoral tunnels was larger in DB technique (919.65 +/- 201.79 mm2) compared to SB technique (810.02 +/- 117.98 mm2; p = 0.004). For tibia tunnels, there was a significant difference between tunnel volume for the SB technique (2,070.43 +/- 565.07 mm3) and the total tunnel volume for the DB technique (2,681.93 +/- 668.09 mm3; p < or = 0.001). The tibial tunnel surface area for the SB technique (958.84 +/- 147.50 mm2) was smaller than the total tunnel surface area for the DB technique (1,493.31 +/- 220.79 mm2; p < or = 0.001). CONCLUSIONS: Although the total femoral tunnel volume was similar between two techniques, the total surface area was larger in the DB technique. For the tibia, both total tunnel volume and the surface area were larger in DB technique.
Adult ; Anterior Cruciate Ligament/injuries/surgery ; Anterior Cruciate Ligament Reconstruction/*methods ; Autografts ; Femur/*radiography/surgery ; Humans ; Imaging, Three-Dimensional ; Male ; Tendon Injuries/*radiography/rehabilitation/surgery ; Tendons/transplantation ; Tibia/*radiography/surgery

BACKGROUND: Anatomic footprint restoration of anterior cruciate ligament (ACL) is recommended during reconstruction surgery. The purpose of this study was to compare and analyze the femoral and tibial tunnel positions of transtibial single bundle (SB) and transportal double bundle (DB) ACL reconstruction using three-dimensional computed tomography (3D-CT). METHODS: In this study, 26 patients who underwent transtibial SB ACL reconstruction and 27 patients with transportal DB ACL reconstruction using hamstring autograft. 3D-CTs were taken within 1 week after the operation. The obtained digital images were then imported into the commercial package Geomagic Studio v10.0. The femoral tunnel positions were evaluated using the quadrant method. The mean, standard deviation, standard error, minimum, maximum, and 95% confidence interval values were determined for each measurement. RESULTS: The femoral tunnel for the SB technique was located 35.07% +/- 5.33% in depth and 16.62% +/- 4.99% in height. The anteromedial (AM) and posterolateral (PL) tunnel of DB technique was located 30.48% +/- 5.02% in depth, 17.12% +/- 5.84% in height and 34.76% +/- 5.87% in depth, 45.55% +/- 6.88% in height, respectively. The tibial tunnel with the SB technique was located 45.43% +/- 4.81% from the anterior margin and 47.62% +/- 2.51% from the medial tibial articular margin. The AM and PL tunnel of the DB technique was located 33.76% +/- 7.83% from the anterior margin, 45.56% +/- 2.71% from the medial tibial articular margin and 53.19% +/- 3.74% from the anterior margin, 46.00% +/- 2.48% from the medial tibial articular margin, respectively. The tibial tunnel position with the transtibial SB technique was located between the AM and PL tunnel positions formed with the transportal DB technique. CONCLUSIONS: Using the 3D-CT measuring method, the location of the tibia tunnel was between the AM and PL footprints, but the center of the femoral tunnel was at more shallow position from the AM bundle footprint when ACL reconstruction was performed by the transtibial SB technique.
Adult ; Anterior Cruciate Ligament Reconstruction/*methods ; *Femur/radiography/surgery ; Humans ; Imaging, Three-Dimensional/*methods ; Knee Joint/physiology ; Male ; Prospective Studies ; Surgery, Computer-Assisted/*methods ; *Tibia/radiography/surgery ; Tomography, X-Ray Computed

PURPOSE: Neoadjuvant chemotherapy (NC) is yet to be established as the definitive treatment regimen for locally advanced breast cancer (LABC). The aim of this study was to determine the efficacy and toxicity of NC with epirubicin and paclitaxel. METHODS: Between March 2007 and January 2009, 50 patients with LABC were enrolled in an open-label, phase II, multicenter study carried out at five distinct institutions. All patients were scheduled to receive four cycles of 60 mg/m2 epirubicin and 175 mg/m2 paclitaxel every 3 weeks, preoperatively, unless they developed profound side effects or disease progression. After curative surgery, two additional cycles of chemotherapy were administered to patients who had shown a positive response to NC. RESULTS: In all, 196 cycles of chemotherapy were administered preoperatively; 47 of the 50 patients (94%) underwent all four cycles of designated treatment. Complete disappearance of invasive foci of the primary tumor, and negative axillary lymph nodes were confirmed in eight patients (16.0%), post operation. The cumulative 5-year disease-free survival rate was 70.0% for patients with complete remission (CR) and partial remission (PR), and 33.3% for patients with stable disease (SD) and progressive disease (PD) (p=0.018). The cumulative 5-year overall survival was 90.0% for patients who achieved CR and PR and 55.6% for patients who had SD and PD (p=0.001). Neutropenia (42.0%) was the most common grade 3/4 toxicity. However, none of the toxicities resulted in cessation of the treatment. CONCLUSION: The encouraging pathologic response observed in the patients treated with epirubicin plus paclitaxel NC in this study suggests that epirubicin could be a substitute for doxorubicin, which is the most cardiotoxic agent.
Breast Neoplasms* ; Disease Progression ; Disease-Free Survival ; Doxorubicin ; Drug Therapy* ; Epirubicin* ; Humans ; Lymph Nodes ; Neoadjuvant Therapy ; Neutropenia ; Paclitaxel