PURPOSE: To evaluate the outcome of ductal carcinoma in situ (DCIS) patients who underwent surgery followed by radiation therapy (RT). MATERIALS AND METHODS: We retrospectively reviewed 106 DCIS patients who underwent surgery followed by postoperative RT between 1994 and 2006. Ninety-four patients underwent breast-conserving surgery, and mastectomy was performed in 12 patients due to extensive DCIS. Postoperative RT was delivered to whole breast with 50.4 Gy/28 fx. Tumor bed boost was offered to 7 patients (6.6%). Patients with hormonal receptor-positive tumors were treated with hormonal therapy. RESULTS: The median follow-up duration was 83.4 months (range, 33.4 to 191.5 months) and the median age was 47.8 years. Ten patients (9.4%) had resection margin <1 mm and high-grade and estrogen receptor-negative tumors were observed in 39 (36.8%) and 20 (18.9%) patients, respectively. The 7-year ipsilateral breast tumor recurrence (IBTR)-free survival rate was 95.3%. Resection margin (<1 or > or =1 mm) was the significant prognostic factor for IBTR in univariate and multivariate analyses (p < 0.001 and p = 0.016, respectively). CONCLUSION: Postoperative RT for DCIS can achieve favorable treatment outcome. Resection margin was the important prognostic factor for IBTR in the DCIS patients who underwent postoperative RT.
Breast ; Breast Neoplasms ; Carcinoma, Ductal* ; Carcinoma, Intraductal, Noninfiltrating* ; Estrogens ; Follow-Up Studies ; Humans ; Mastectomy ; Mastectomy, Segmental ; Multivariate Analysis ; Recurrence ; Retrospective Studies ; Survival Rate ; Treatment Outcome*

Substernal extension of a goiter into the thoracic inlet endows a generally benign neck mass with morbid potential. The reported incidence varies between 1% and 15% of all thyroidectomies performed. Whether all patients with a substernal goiter should undergo an operation or whether the operation should be performed selectively remains controversial. From May 1989 to March 1996, 10 patients underwent thyroidectomies for substernal goiters, and those cases of resected substernal goiters have been reviewed to access the symptoms and signs that brought patients to surgery: the size and the position of goiter, the preoperative work-up, the risk associated with the operation, and the histopathologic state of the goiter. There were 3 male and 7 female patients, and their ages ranged from 40 to 68 years. The chief complaints were cervical mass (4), dyspnea (2), facial edema (1) and chest pain (1). No symtomatic cases (2) were also found. The average mass size was 8.4 cm (5-14 cm) and the average weight was 109 gm (41-350 gm). Although chest film was the most used, computed tomography was by far the most useful study. Thyroid scans often failed to show the substernal goiter. Fine-needle aspiration was not helpful because of inaccessibility. In the majority of the patients (7 cases), the substernal goiters were removed by a cervical incision. Three cases of goiters located deep to the carina level required a combined cervical and sternotomy approach or thoracotomy. In the cervical incision group, the complications were transient hypocalcemia (1) and unilateral recurrent laryngeal nerve injury (1). In the combined cervical and sternotomy approach or thoracotomy, unilateral recurrent laryngeal nerve injury (1) and bilateral recurrent laryngeal nerve injury (1) and mediastinitis (1) were the complications. An occult papillary carcinoma, which was not identified preoperatively, was found in one case. Removal was almost always accomplished via cervical incision and with low morbidity and no deaths. Also, the substernal goiters revealed unusual symptoms and signs, such as dyspnea, facial edema and chest pain, compared to usual thyoid goiters and were relatively bigger in size. In conclusion, most substernal goiter above the carinal level could be removed by cervical incision with a low rate of complication. The threat of compression, the substantial chance of malignancy, and the safety of resection mean that the presence of a substernal goiter is an indication for surgery.
Bays ; Biopsy, Fine-Needle ; Carcinoma, Papillary ; Chest Pain ; Dyspnea ; Edema ; Female ; Goiter ; Goiter, Substernal* ; Humans ; Hypocalcemia ; Incidence ; Male ; Mediastinitis ; Neck ; Recurrent Laryngeal Nerve Injuries ; Sternotomy ; Thoracotomy ; Thorax ; Thyroid Gland ; Thyroidectomy

A C6 beta-chemokine, CKbeta8-1, suppressed the colony formation of CD34 + cells of human cord blood (CB). Molecular mechanisms involved in CKbeta8-1-medicated suppression of colony formation of CD34 + cells are not known. To address this issue, the level of various G1/S cell cycle regulating proteins in CKbeta8-1-treated CD34 + cells were compared with those in untreated CD34 + cells. CKbeta8-1 did not significantly alter the expression of the G1/S cycle regulation proteins (cyclin D1, D3, and E), CDK inhibitor (p27and Rb), and other cell proliferation regulation protein (p53) in CB CD34 + cells. Here we describe an in vitro system in which CB CD34 + cells were committed to a multipotent progenitor lineage of colony forming units-granulocyte/macrophage (CFU-GM) by a simple combination of recombinant human (rh) GM-CSF and rhIL-3. In this culture system, we found that cyclin E protein appeared later and disappeared faster in the CKbeta8-1-treated cells than in the control cells during CFU-GM lineage development. These findings suggested that cyclin E may play a role in suppressing the colony formation of CFU-GM by CKbeta8-1.
Antigens, CD34/metabolism ; Cell Cycle Proteins/metabolism ; Cell Lineage ; Cells, Cultured ; Chemokines, CC/*pharmacology ; Cyclin E/*metabolism ; Fetal Blood/*cytology ; G1 Phase/drug effects ; Gene Expression Regulation/*drug effects ; Granulocytes/cytology/*drug effects/metabolism ; Growth Substances/pharmacology ; Humans ; Macrophages/cytology/*drug effects/metabolism ; Research Support, Non-U.S. Gov't ; Stem Cells/cytology/*drug effects/metabolism

No abstract available.
Carcinoma, Transitional Cell* ; Tuberculosis, Renal* ; Ureter*

BACKGROUND: Liver failure due to ischemia-reperfusion injury is a serious problem in liver transplantation and radical wide resection of the liver. This injury is believed to be closely related to the generation of oxygen free radicals. Gabexate mesilate, a synthetic protease inhibitor, has an effect on the suppression of extracellular release of oxygen free radicals in the microvascular endothelium, as well as on protease inhibition. In order to understand the effects of gabexate mesilate on ischemia-reperfusion injury to the liver, we performed animal experiment with rats. METHODS: We divided the rats into two ischemia-reperfusion groups:the experimental group which received a 30 minutes ischemic injury along with the infusion of gabexate mesilate and a control group which received only the injury. Each group was subdivided into 4 sub-groups:ischemic injury only and ischemic injury plus 60, 120 or 180 minutes reperfusion injury. The test parameters were TNF-a and IL-6 in the serum, and superoxide dismutase(SOD), catalase, and malondialdehyde(MDA) in liver and lung tissues. RESULTS: The group receiving gabexate mesilate had a significantly higher level of liver SOD and liver catalase and a significantly lower level of liver MDA and lung MDA than the control groups. The TNF-a levels in the gabexate mesilate groups were significantly lower in the early phase, and a comparison of the IL-6 levels between two main groups yielded no significant results. The levels of lung catalase and SOD showed no significant difference between the two main groups. CONCLUSIONS: Protease inhibitor has the beneficial effect of liver ischemia-reperfusion injury suppression due to an increase in antioxidants or oxygen-free-radical suppression. The roles of TNF-a and IL-6 in liver reperfusion injury was not clear in our investigation. However, TNF-a might have an effect in the early phase. The mechanism of reperfusion injury to the lung in liver ischemia-reperfusion injury might be different from that to the liver.
Animal Experimentation ; Animals ; Antioxidants ; Catalase ; Endothelium ; Free Radicals ; Gabexate ; Interleukin-6 ; Liver Failure ; Liver Transplantation ; Liver* ; Lung ; Oxygen ; Protease Inhibitors* ; Rats* ; Reperfusion Injury* ; Superoxide Dismutase ; Superoxides

Prognostic value of p53 and bcl-2 expression on treatment outcome in breast cancer patients has been extensively evaluated, but the results were inconclusive. We evaluated the prognostic significance of these molecular markers in patients treated with breast conserving surgery and radiotherapy. One hundred patients whose immunostaining of p53 and bcl-2 expression was available among 125 patients who underwent radiotherapy after breast conserving surgery and axillary lymph node dissection were enrolled into this study. Eighty-seven patients also received adjuvant chemotherapy and/or hormonal therapy. Conventional clinicopathologic variables and treatment-related factors were also considered. The 5-yr loco-regional relapse-free and distant metastasis-free survival rates were 91.7% and 90.9%, respectively. On univariate analysis, age, T stage and the absence of bcl-2 & estrogen receptor (ER) expression were associated with loco-regional relapse-free survival. When incorporating these variables into Cox proportional hazard model, only bcl-2(-)/ER(-) phenotype was an adverse prognostic factor (P=0.018). As for the distant metastasis-free survival, age, T stage, and p53 expression were significant on univariate analysis. However, p53 expression was the only prognosticator on multivariate analysis (P=0.009). A bcl-2(-)/ER(-) phenotype and p53 expression are useful molecular markers predicting loco-regional relapse-free and distant metastasis-free survival, respectively, in patients treated with breast conserving surgery and radiotherapy.
Adult ; Aged ; Breast Neoplasms/metabolism/radiotherapy/*surgery ; Combined Modality Therapy ; Disease-Free Survival ; Female ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Multivariate Analysis ; Phenotype ; Prognosis ; Proto-Oncogene Proteins c-bcl-2/genetics/*metabolism ; Receptors, Estrogen/metabolism ; Tumor Suppressor Protein p53/genetics/*metabolism

Regulation of matrix metalloproteinases (MMPs) is important for many physiological processes involving cancers, inflammation, tissue remodeling and skin aging. Here, we report the novel finding that the expression of MMP1 mRNA is downregulated by the overexpression of miR-526b which is a member of chromosome 19 microRNA cluster (C19MC). Our analysis using reporter constructs containing the 3' untranslated region (3' UTR) of MMP1 and its mutant form showed that the region from 377-383 in the 3' UTR of MMP1 is critical for targeting by miR-526b. In addition, the expression pattern of miR-526b and MMP1 mRNA showed reverse relation between adult dermal and neonatal fibroblasts. We show for the first time that miR-526b, an miRNA belonging to C19MC, can target the 377-383 region of the MMP1 3' UTR.
3' Untranslated Regions ; Adult ; Base Sequence ; Cell Line ; Down-Regulation ; Fibroblasts/metabolism ; *Gene Expression Regulation ; HeLa Cells ; Humans ; Matrix Metalloproteinase 1/*genetics ; MicroRNAs/*genetics ; RNA, Messenger/*genetics

BACKGROUND: To evaluate the influence of bone marrow aspirate concentrate (BMAC) on tendon-to-bone healing in a rabbit rotator cuff model and to characterize the composition of growth factors in BMAC. METHODS: In this in vivo study, 40 rabbits were allocated into five groups: control (C), repair + saline (RS), repair + platelet-rich plasma (PRP; RP), repair + BMAC (RB) and repair + PRP + BMAC (RPB). A tear model was created by supraspinatus tendon transection at the footprint. Six weeks after transection, the torn tendon was repaired along with BMAC or PRP administration. Six weeks after repair, shoulder samples were harvested for biomechanical and histological testing. Ten rabbits were used for processing PRP and BMAC, followed by analysis of blood cell composition and the levels of growth factors in vitro. RESULTS: The ultimate load-to-failure was significantly higher in RPB group compared to RS group (p = 0.025). BMAC-treated groups showed higher values of biomechanical properties than RS group. The histology of BMAC-treated samples showed better collagen fiber continuity and orientation than RS group. BMAC contained significantly higher levels of the several growth factors than PRP. CONCLUSIONS: Locally administered BMAC enhanced tendon-to-bone healing and has potential for clinical applications.
Blood Cells ; Bone Marrow* ; Collagen ; In Vitro Techniques ; Intercellular Signaling Peptides and Proteins ; Platelet-Rich Plasma ; Rabbits ; Rotator Cuff* ; Shoulder ; Tears* ; Tendons

BACKGROUND: Arsenic trioxide (As2O3) is a well-known and effective treatment that can result in clinical remission for patients diagnosed with acute promyelocytic leukemia (APL). The biologic efficacy of As2O3 in APL and solid tumor cells has been explained through its actions on anti-proliferation, anti-angiogenesis, and apoptotic signaling pathways. We theorize that As2O3 activates a pathway that disrupts microtubule dynamics forming abnormal, nonfunctioning mitotic spindles, thus preventing cellular division. In this study, we investigated how As2O3 induces apoptosis by causing microtubule dysfunction. METHODS: Cultured NB4 cells were treated with As2O3, paclitaxel, and vincristine. Flow cytometric analysis was then performed. An MTT assay was used to determine drug-mediated cytotoxicity. For tubulin polymerization assay, each polymerized or soluble tubulin was measured. Microtubule assembly-disassembly was measured using a tubulin polymerization kit. Cellular microtubules were also observed with fluorescence microscopy. RESULTS: As2O3 treatment disrupted tubulin assembly resulting in dysfunctional microtubules that cause death in APL cells. As2O3 markedly enhanced the amount of depolymerized microtubules. The number of microtubule posttranslational modifications on an individual tubulin decreased with As2O3 concentration. Immunocytochemistry revealed changes in the cellular microtubule network and formation of polymerized microtubules in As2O3-treated cells. CONCLUSION: The microtubules alterations found with As2O3 treatment suggest that As2O3 increases the depolymerized forms of tubulin in cells and that this is potentially due to arsenite's negative effects on spindle dynamics.
Antimitotic Agents ; Apoptosis ; Arsenic ; Arsenicals ; Cell Line ; Fluorescence ; Humans ; Immunohistochemistry ; Leukemia, Promyelocytic, Acute ; Microtubules ; Oxides ; Paclitaxel ; Polymerization ; Polymers ; Protein Processing, Post-Translational ; Tubulin ; Vincristine

PURPOSE: Nearly half of all breast cancers are treated with breast conserving therapy (BCT). The purpose of this study was to identify the risk factors for ipsilateral breast tumor recurrence (IBTR) after BCT in T1 and T2 breast cancer patients. METHODS: The medical records of 294 T1 or T2 breast cancer patients who underwent BCT at Seoul National University Hospital between January 1998 and December 2002 were retrospectively reviewed. Kaplan-Meier curves and Cox proportional regression analysis were used to identify the significant clinicopathologic factors that influence IBTR. RESULTS: Among the 294 patients, 12 patients (4.8%) developed IBTR after a median follow-up of 82 months. Univariate analysis demonstrated that younger age (< or =35 year) had significant associations with IBTR (p=0.006). Tumor size, lymph node status, histologic grade, extensive intraductal component, lymphovascular invasion, and close resection margins were not significant factor associated with IBTR. The triple negative breast cancer subtype also did not have significant association with IBTR. Multivariate analysis showed that the younger age at diagnosis was a significant predictor of IBTR with a HR of 3.86 (p=0.036; 95% CI, 1.09-13.60). CONCLUSION: Younger age at diagnosis (< or =35) may be associated with an increased risk of IBTR in patients who underwent BCT.
Age Factors ; Breast ; Breast Neoplasms ; Follow-Up Studies ; Humans ; Lymph Nodes ; Medical Records ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Recurrence ; Retrospective Studies ; Risk Factors