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Biomedical subjects

Kyung-Ja Cho

Publications and source records attributed to Kyung-Ja Cho.

At least 19 recordsLinked to original sources

Utility of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography and positron emission tomography/computed tomography imaging in the preoperative staging of head and neck squamous cell carcinoma.

The combination of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) has been reported to be more accurate than CT or PET alone in a preoperative setting. We compared the diagnostic utility of preoperative PET/CT, PET and CT/MRI in 167 patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), of whom 104 underwent FDG PET and 63 underwent combined PET/CT with all receiving CT/MRI. These preoperative PET, PET/CT, and CT/MRI results were reviewed and their accuracies were compared in patients in whom diagnosis was confirmed histopathologically. Age, sex, primary sites and stage, and nodal involvement were comparable between two groups. The accuracy of PET and PET/CT for detecting primary tumors and cervical metastases was comparable, but significantly higher than that of CT/MRI (98%-97% vs. 86-88% for primary; 92%-93% vs. 85%-86% for neck on a level-by-level basis; P<.05). PET and PET/CT gave false negative results: in 2 (2%) and 2 (3%) patients for primary tumors; in 6 (6%) and 3 (5%) patients for neck metastases, respectively. PET and PET/CT also gave false-positive results for cervical metastases in 5 (5%) and 4 (6%) patients, respectively. Compared with PET alone, preoperative FDG PET/CT may not yield significantly improved diagnostic accuracy in patients with HNSCC. Moreover, despite their high accuracy, PET and PET/CT may not abrogate the need for conventional imaging and pathologic staging based on primary resection and neck dissection.

Adult↗

In vivo tumor targeting and radionuclide imaging with self-assembled nanoparticles: mechanisms, key factors, and their implications.

The development of more selective delivery systems for cancer diagnosis and chemotherapy is one of the most important goals of current anticancer research. The purpose of this study is to evaluate various self-assembled nanoparticles as candidates to shuttle radionuclide and/or drugs into tumors and to investigate the mechanisms underlying the tumor targeting with self-assembled nanoparticles. By combining different hydrophobic moieties and hydrophilic polymer backbones, various self-assembled nanoparticles were prepared, and their in vivo distributions in tumor-bearing mice were studied by radionuclide imaging. One type of nanoparticles (fluorescein isothiocyanate-conjugated glycol chitosan (FGC) nanoparticles) exhibited highly selective tumoral localization. Scintigraphic images obtained 1 day after the intravenous injection of FGC nanoparticles clearly delineated the tumor against adjacent tissues. The mechanisms underlying the tumor targeting with self-assembled nanoparticles were investigated in terms of the physicochemical properties of nanoparticles and tumor microenvironments. FGC nanoparticles were preferentially localized in perivascular regions, implying their extravasation to tumors through the hyperpermeable tumor vasculature. The magnitude and pattern of tumoral distribution of self-assembled nanoparticles were influenced by several key factors--(i) in vivo colloidal stability: nanoparticles should maintain their intact nanostructures in vivo for a long period of time, (ii) particle size, (iii) intracellular uptake of nanoparticle: fast cellular uptake greatly facilitates the tumor targeting, (iv) tumor angiogenesis: pathological angiogenesis permits access of nanoparticles to tumors. We believe that this work can provide insight for the engineering of nanoparticles and be extended to cancer therapy and diagnosis, so as to deliver multiple therapeutic agents and imaging probes at high local concentrations.

Animals↗

Alpha-lipoic acid suppresses the development of collagen-induced arthritis and protects against bone destruction in mice.

OBJECTIVE: To test the ability of alpha-lipoic acid (LA) to attenuate the development of collagen-induced arthritis (CIA) in mice. METHODS: Mice were divided into three groups and treated with intraperitoneal administration of LA (10 or 100 mg/kg) or placebo. Clinical, histologic, and biochemical parameters were assessed. Human synovial fibroblasts and peripheral blood mononuclear cells were cocultured in various concentrations of LA to evaluate the effects on osteoclastogenesis. RESULTS: LA was associated with a dose-dependent reduction of CIA, as well as preventing bone erosion and destructive changes. Intracellular reactive oxygen species in lymphocytes obtained from inguinal lymph nodes, which was significantly higher in CIA than control mice, was significantly reduced in CIA by LA. The concentrations of TNF-alpha, IL-1beta, and IL-6 in the paws, and synovial NF-kappaB binding, all of which were markedly higher in CIA than control mice, were reduced by treatment with LA. In addition, LA inhibited the formation of human osteoclasts in vitro. CONCLUSION: Amelioration of joint disease by LA was associated with reduction in oxidative stress, as well as inhibition of inflammatory cytokine activation and NF-kappaB DNA binding activity. Moreover, LA inhibited bone destruction in vivo and osteoclastogenesis in vitro. Collectively, these results indicate that LA may be a new adjunctive therapy for rheumatoid arthritis.

Animals↗

Chemopreventive efficacy of all-trans-retinoic acid in biodegradable microspheres against epithelial cancers: results in a 4-nitroquinoline 1-oxide-induced oral carcinogenesis model.

Retinoids are known to suppress carcinogenesis in various epithelial tissues. Among them, all-trans-retinoic acid (atRA) is recognized as one such active retinoid. However, despite the known anticarcinogenic activity of atRA, it exhibits its short plasma half-life during repeated oral administration due to the "acute retinoid resistance" in the liver. This has been the major limitation in clinical applications of atRA. Therefore, in order to render atRA more suitable for clinical uses, sustained delivery of atRA using biodegradable microspheres is suggested in this study. When 50 mg atRA/kg of atRA-loaded microspheres were subcutaneously administered to rats once, the atRA concentration in plasma was maintained around 6.5 ng/ml for 7 weeks, with only minor signs of toxicity. When the chemopreventive efficacy of atRA-loaded microspheres was evaluated using a model of 4-nitroquinoline 1-oxide-induced oral carcinogenesis in F344 rats, a single injection of atRA-loaded microspheres significantly suppressed oral carcinogenesis. Additional injections of atRA-loaded microspheres, however, did not indicate further suppression of carcinogenesis.

4-Nitroquinoline-1-oxide↗

Clinical significance of beta1 integrin expression as a prediction marker for radiotherapy in early glottic carcinoma.

OBJECTIVE: To determine the significance of beta1 integrin expression as a prediction marker for the response to radiotherapy in patients with early glottic carcinoma. STUDY DESIGN: Retrospective study in a tertiary referral center. METHODS: Among the T1/T2 glottic carcinoma patients treated with radiotherapy from 1992 to 2002, 52 had more than 2 years of follow-up and available pretreatment biopsy specimens. The immunohistochemical staining was performed for the assay of beta1 integrin expression, and the staining pattern of each was classified as diffuse, localized, or negative. The associations between the patterns of beta1 integrin expression and clinicopathologic parameters, including response to radiotherapy, involvement of the anterior commissure, and grade of histologic differentiation, were evaluated. RESULTS: After radiotherapy, 42 patients remained tumor free, and 10 patients had recurrent or persistent disease. Six (12%) specimens were negative for beta1 integrin expression, 39 (75%) had a localized staining pattern, and 7 (13%) had a diffuse staining pattern. Recurrence rate was significantly higher in the diffuse group (53%) than in the localized (13%) or negative (17%) groups (P=.023). The pattern of beta1 integrin expression was also closely related to histologic differentiation (P=.008), although the association between response to radiotherapy and histologic differentiation was not significant CONCLUSION: The pattern of expression of beta1 integrin, which has been known as a stem cell marker of the epidermis, may be helpful in predicting the response to radiation in patients with early glottic carcinoma.

Adult↗

Primary intraosseous melanotic schwannoma of the fibula associated with the Carney complex.

Described herein is a rare case of intraosseous melanotic schwannoma (MS) occurring in a long bone of a 13-year-old girl with a loss of heterozygosity (LOH) at 17q22-24, which contains the PRKAR1A gene encoding the protein kinase A regulatory subunit 1-a. Plain radiography and magnetic resonance imaging revealed a 10 cm expansile osteolytic lesion involving the proximal fibula. An excisional biopsy revealed a cellular tumor consisting of mildly pleomorphic spindle or oval to polygonal cells with frequent intranuclear pseudoinclusions, intracytoplasmic melanin pigments, nuclear palisades, Verocay body-like structures, and psammomatous calcifications. The tumor cells showed strong immunoreactivity for S-100 protein, HMB-45, and neuron-specific enolase. Ultrastructurally, the tumor cells were invested by continuous, multiplied external lamina and conspicuous melanosomes in various stages of maturation. These observations were compatible with psammomatous melanotic schwannoma (PMS). In addition, the detection of LOH for PRKAR1A strongly suggests that PMS in the present case is a manifestation of the Carney complex (CNC).

Adolescent↗

Heterotopic intrathymic thyroid tissue.

Heterotopic intrathymic thyroid tissue is an extremely rare condition, but it is important to distinguish it from metastases of clinically undetected thyroid carcinoma because metastatic papillary thyroid carcinoma is often so well differentiated, simulating normal thyroid tissue. Described herein are histological findings of heterotopic intrathymic thyroid tissue that was incidentally identified in a woman with papillary thyroid carcinoma during histological examination of a radical neck dissection specimen. These findings emphasize that this rare incidence may occur and should be differentiated from metastatic papillary carcinoma. Histologically, the patient's intrathymic thyroid follicles were identical to the normal thyroid follicles, having flat cuboidal cells with uniformly small nuclei without nuclear grooves or inclusions. The follicular cells had a low Ki-67 labeling index close to zero, and immunonegativity for galectin-3, HBME-1, and RET oncoprotein, in contrast to the tumor cells in primary papillary thyroid carcinoma of the patient. To the authors' knowledge this is the first case report of intrathymic heterotopic thyroid tissue posing a diagnostic difficulty in a patient with papillary thyroid carcinoma.

Biomarkers, Tumor↗

Expressions of Ku70 and DNA-PKcs as prognostic indicators of local control in nasopharyngeal carcinoma.

PURPOSE: The objective of this study was to determine whether the expressions of the two components of DNA-dependent protein kinase, Ku70 and DNA-protein kinase catalytic subunit (DNA-PKcs), influence the response to radiotherapy (RT) and outcome of treatment of nondisseminated nasopharyngeal carcinoma (NPC) in patients who received definitive RT. METHODS AND MATERIALS: Sixty-six patients with NPC who were treated with radiotherapy alone or with concurrent chemotherapy between June 1995 and December 2001 were divided into groups based on the levels of immunoreactivity for Ku70 and DNA-PKcs in pretreatment biopsy specimens. The overexpression of Ku70 or DNA-PKcs groups included patients whose biopsy specimens showed at least 50% immunopositive tumor cells; patients in which less than 50% of the tumor cells in the biopsy tissues were immunopositive were placed in the low Ku70 and DNA-PKcs groups. The immunoreactivities for Ku70 and DNA-PKcs were retrospectively compared with the sensitivity of the tumor to radiation and the patterns of therapy failure. Univariate analyses were performed to determine the prognostic factors that influenced locoregional control of NPC. RESULTS: The 5-year locoregional control rate was significantly higher in the low Ku70 group (Ku-) (85%) than in the high Ku70 group (Ku+) (42%) (p = 0.0042). However, there were no differences in the metastases-free survival rates between the 2 groups (Ku70+, 82%; Ku70- 78%; p = 0.8672). Univariate analysis indicated that the overexpression of Ku70 surpassed other well-known predictive clinicopathologic parameters as an independent prognostic factor for locoregional control. Eighteen of 22 patients who had locoregional recurrences of the tumor displayed an overexpression of Ku70. No significant association was found between the level of DNA-PKcs expression and the clinical outcome. CONCLUSIONS: Our data suggest that the level of Ku70 expression can be used as a molecular marker to predict the response to RT and the locoregional control after RT and concurrent chemotherapy in patients with nondisseminated NPC.

Adult↗

FDG-PET in the prediction of pathologic response after neoadjuvant chemoradiotherapy in locally advanced, resectable esophageal cancer.

PURPOSE: To assess the efficacy of 18Fluorodeoxyglucose-positron emission tomography (FDG-PET) for predicting a pathologic response in locally advanced esophageal cancer after neoadjuvant chemoradiotherapy. METHODS AND MATERIALS: All enrolled patients were treated with neoadjuvant chemoradiotherapy followed by esophagectomy and underwent two FDG-PET scans, before and after neoadjuvant chemoradiotherapy. We compared the results of the preoperative FDG-PET scans with the pathologic results. RESULTS: From July 2001 to July 2004, 32 patients (29 men and 3 women) were enrolled in this study. Pathologic complete response (pCR) in the esophagus was achieved in 21 of 32 patients (66%). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in the primary tumors of the preoperative FDG-PET were 27%, 95%, 75%, and 71%, respectively. In regional lymph nodes, these values were 16%, 98%, 36%, and 93%, respectively. The mean standardized uptake value (SUV) of primary tumors was initially 5.6 +/- 3.6 and changed to 1.5 +/- 1.3 after neoadjuvant chemoradiotherapy (p < 0.05). If analysis of metabolic response (SUV decrease, DeltaSUV) was limited to initially highly metabolic primary tumors (SUV > or =4.0), pathologic response was correlated with metabolic response (p = 0.006). CONCLUSIONS: This study suggested that the pathologic response of an initially highly metabolic tumor after neoadjuvant chemoradiotherapy could be correlated with the metabolic response, and FDG-PET can provide additional information on tumor response to chemoradiotherapy.

Aged↗

CD34 expressing ameloblastic fibrosarcoma arising in the maxilla: a new finding.

Ameloblastic fibrosarcoma (AFS) is a rare malignant tumor of the jaw. The malignant mesenchymal component of AFS has been described as 'fibroblast-like', although little is known about the immunophenotype, except for vimentin expression. Here, we present a case of AFS in a 62-year-old woman. The mesenchymal component displayed the features of either dermatofibrosarcoma protuberans or fibrosarcoma, and was positive for CD34. This is the first reported case of CD34 expressing AFS in the maxilla.

Aged↗

Radiation therapy with UFT and low dose weekly cisplatin for nasopharyngeal carcinoma.

OBJECTIVE: We conducted this study to determine the effectiveness and toxicity of chemoradiation therapy using UFT and low-dose cisplatin in 37 patients with nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Between March 1999 and December 2001, 37 patients with newly diagnosed and histologically proven nasopharyngeal carcinoma treated in Department of Radiation Oncology, Asan Medical Center were enrolled in this protocol. Cisplatin was administered weekly, starting on day 1 of radiation therapy, as an intravenous infusion at 20 mg/m2 of body-surface area. Oral UFT was administered daily, at a dose of 300 mg in three divided doses. Radiation therapy was given in doses of 1.8-2.0 Gy, 5 days per week, with 4-15 MV photons. The dose of elective nodal area was 60 Gy, and primary tumors and enlarged lymph nodes were boosted with intracavitary brachytherapy or 3D conformal therapy. RESULTS: All patients received the planned doses of radiation. Cisplatin was administered for a median of 6 cycles, and 81% of patients received UFT for more than 5 weeks. The complete response rate was 95% for all patients, and the overall response rate was 100%. No patient experienced hematologic toxicity of grade 3 or higher. Five patients experienced grade 3 non-hematologic toxicity but recovered with conservative management. There was no treatment-related hospitalization or death. CONCLUSION: These findings suggest that UFT and low-dose cisplatin is a safe and effective regimen of concurrent chemoradiation therapy for patients with nasopharyngeal carcinoma.

Adult↗

A study of moderately differentiated neuroendocrine carcinomas of the larynx and an examination of non-neoplastic larynx tissue for neuroendocrine cells.

OBJECTIVES/HYPOTHESIS: To determine the most appropriate terminology for neuroendocrine carcinomas (NEC) of the larynx, successive clinicopathologic studies are encouraged. The typical location and immunophenotype of laryngeal NEC raise a question of whether any precursor cells exist. STUDY DESIGN: Six patients with laryngeal NEC were analyzed. Another 20 laryngectomy specimens were examined for the presence of non-neoplastic neuroendocrine cells. METHODS: Tumor morphology and patient outcome were determined, and tumor tissue underwent immunohistochemical examination to identify cytokeratin, neuroendocrine markers (chromogranin, synaptophysin, CD56, calcitonin), S-100 protein, and p53 protein. A neuroendocrine marker study was also performed on non-neoplastic regions of another 20 laryngectomy specimens to identify any neuroendocrine cells. RESULTS: Laryngeal NEC, all submucosal, exhibited various morphology with or without histologic evidences of neuroendocrine differentiation. The tumors showed frequent (67%) calcitonin expression, calcitonin secretion in one case, and common (50%) p53 over-expression. Three patients died within 3 years. In the non-neoplastic larynx specimens, Kulchitsky cell-like bipolar neuroendocrine cells were identified in the basal and middle layer of the respiratory epithelium of the ventricle and subglottis but none in the submucosal layer of the supraglottic region. The neuroendocrine cells did not express calcitonin. CONCLUSIONS: Moderately differentiated or large-cell NEC is a more favored term than atypical carcinoid until more refined classifications for upper respiratory tract NEC are agreed on. Despite the confirmed presence of neuroendocrine cells in the respiratory epithelium of the larynx, the origin of laryngeal NEC remains unknown. p53 mutation might be one of the major molecular steps in the pathogenesis of laryngeal NEC.

Aged↗

Overexpression of Glut1 in lymphoid follicles correlates with false-positive (18)F-FDG PET results in lung cancer staging.

UNLABELLED: The evaluation of mediastinal lymph node involvement in non-small cell lung carcinoma (NSCLC) is very important for the selection of surgical candidates. PET using (18)F-FDG has remarkably improved mediastinal staging in NSCLC. However, false (18)F-FDG PET results remain a problem. This study was undertaken to identify histologic and immunohistochemical differences between cases showing false and true results of mediastinal lymph node involvement assessed by (18)F-FDG PET. METHODS: Preoperative (18)F-FDG PET examinations were performed on 62 patients with NSCLC, and mediastinal lymph node sampling was done at thoracotomy or mediastinoscopy. In 111 lymph nodes, the size, glucose transporter 1 (Glut1) expression, grade of follicular hyperplasia, and involved proportion of tumor were examined and compared with the (18)F-FDG PET findings. RESULTS: Lymphoid follicular cells were strongly positive for the expression of Glut1. The grade of follicular hyperplasia in false-positive lymph nodes was higher than that in true-negative nodes (P < 0.001). The Glut1 expression of metastatic tumors was higher in true-positive nodes than that in false-negative nodes (P < 0.001). Metastatic squamous cell carcinomas showed stronger Glut1 expression than adenocarcinomas and no false-negative results on (18)F-FDG PET. On the other hand, metastatic adenocarcinomas exhibited focal and weak Glut1 expression with frequent false-negative results. CONCLUSION: The results of this study indicate that (a). lymphoid follicular hyperplasia with Glut1 overexpression may have a causal relationship with high (18)F-FDG uptake of false-positive nodes and (b). the lower expression of Glut1 in metastatic tumors, such as adenocarcinomas, might be responsible for false-negative lymph nodes.

Adult↗

Laryngotracheal involvement of relapsing polychondritis in a Korean girl.

We describe a young girl presenting with acute dyspnea because of laryngotracheal involvement of relapsing polychondritis (RP). RP, a multisystemic disorder of unknown etiology, is a very rare disease in children. It is characterized by inflammation and destruction of the cartilaginous structure of many organs, including the respiratory tract. Early respiratory tract involvement in younger patients is the greatest threat to life, and aggressive therapy, including tracheostomy and intravenous high-dose steroids, is advocated.

Adolescent↗

Triple synchronous neoplasms in one kidney: report of a case and review of the literature.

We report the case of a patient with three synchronous but histologically different primary renal tumors that were all in the same kidney. Two tumors were different subtypes of renal cell carcinoma (RCC), and the third was a variant form of angiomyolipoma. The patient was a 62-year-old man who was receiving antihypertensive drugs and came to our hospital for a regular check-up. Ultrasonography performed during the visit revealed a left renal mass, but the patient had no related symptoms. Subsequent computed tomography revealed two round, high-density masses, one in the mid-portion and the other in the lower pole of the left kidney, and multiple cysts in the right kidney and the liver. The mass in the mid-portion measured 3.3 x 3.0 x 2.8 cm, and the mass in the lower pole measured 1.7 x 1.1 x 0.9 cm. A left radical nephrectomy was performed. On gross examination, an additional ovoid nodule (0.6 cm in the greatest dimension) was found in the lower pole. Microscopically, the largest tumor consisted of a broad alveolar arrangement of large round cells with abundant eosinophilic or clear cytoplasm, distinct cell borders, and perinuclear halos, features consistent with chromophobe RCC. The smallest tumor was a conventional (clear-cell) RCC. The third tumor was composed solely of atypical epithelioid cells with prominent nucleoli and yellowish-brown to black pigments. The tumor cells were positive for melanin (Fontana-Masson stain), the melanoma marker HMB45, vimentin, smooth-muscle actin, and the macrophage marker CD68 and were negative for cytokeratin. This tumor was considered a pigmented epithelioid type of angiomyolipoma. The histologic, histochemical, and immunohistochemical features in this case confirmed the presence of three synchronous primary tumors, a chromophobe and a clear-cell type RCC and a pigmented epithelioid angiomyolipoma, all of which were in the same kidney. This case is the first of its type reported in the literature.

Angiomyolipoma↗

Chondromyxoid fibroma of the sternum.

Primary chondromyxoid fibroma (CMF) of the sternum is quite rare with only four cases documented in the literature. We present a new case of CMF arising from the sternum of a 47-year-old man and compare it with the previous cases.

Biopsy, Needle↗

Solitary fibrous tumor of the parapharyngeal space: MR imaging findings.

We report the MR imaging findings of a solitary fibrous tumor involving the parapharyngeal space. The tumor was a well-circumscribed solid mass with a lobulated contour. It had the same signal intensity as the muscle on T1-weighted MR images, heterogeneously high signal intensity on T2-weighted images, and homogeneous strong enhancement after the administration of contrast material. It mimicked a tumor originating from the deep lobe of the parotid gland.

Diagnosis, Differential↗

Intra-articular elastofibroma of the shoulder joint.

A 19-year-old man presented with an elastofibroma in his left shoulder joint. The patient had had limitation of motion in his left arm for 3 years, especially when rotating internally. Radiography of his left shoulder showed bone erosion in the neck of the humerus. On MR imaging, a soft tissue mass was noted in the shoulder joint eroding bone. The mass showed similar signal intensity to that of surrounding muscles on T1- and T2-weighted images. At surgery, a soft, encapsulated mass was found attached to the subscapularis muscle. It was pathologically confirmed as an elastofibroma. This unusual manifestation of an elastofibroma is discussed.

Adult↗