Jin Hwa Lee

Prediction of enophthalmos by computer-based volume measurement of orbital fractures in a Korean population.

Purpose: To estimate posttraumatic enophthalmos using computer-based volume measurement of the orbital fracture to provide information on surgical guidelines. Methods: The fracture volume of orbital wall fractures in 35 patients who did not undergo surgery was measured using a Rapidia work station system. Hertel ophthalmometry, diplopia, and ocular motility were investigated. The fracture volume measurements relative to the intact contralateral orbit were correlated with enophthalmos, diplopia, and ocular motility. Patients were examined at the initial visit, then at 1 week, 1 month, and 3 months. Results: There was a correlation between the fracture volume and enophthalmos. Late enophthalmos increased in size in proportion to the volume of the fractured site. The predicted orbital fracture volume with an enophthalmos measurement of 2 mm or more was 2.30 ml. Conclusions: Computer-based measurements of orbital fracture volume can be used to predict overall enophthalmos and provide useful information to surgeons.

Oncolytic and immunostimulatory efficacy of a targeted oncolytic poxvirus expressing human GM-CSF following intravenous administration in a rabbit tumor model

Targeted oncolytic poxviruses hold promise for the treatment of cancer. Arming these agents with immunostimulatory cytokines (for example, granulocyte-monocyte colony-stimulating factor; GM-CSF) can potentially increase their efficacy and/or alter their safety. However, due to species-specific differences in both human GM-CSF (hGM-CSF) activity and poxviruses immune avoidance proteins, the impact of hGM-CSF expression from an oncolytic poxvirus cannot be adequately assessed in murine or rat tumor models. We developed a rabbit tumor model to assess toxicology, pharmacodynamics, oncolytic efficacy and tumor-specific immunity of hGM-CSF expressed from a targeted oncolytic poxvirus JX-963. Recombinant purified hGM-CSF protein stimulated a leukocyte response in this model that paralleled effects of the protein in humans. JX-963 replication and targeting was highly tumor-selective after i.v. administration, and intratumoral replication led to recurrent, delayed systemic viremia. Likewise, hGM-CSF was expressed and released into the blood during JX-963 replication in tumors, but not in tumor-free animals. hGM-CSF expression from JX-963 was associated with significant increases in neutrophil, monocyte and basophil concentrations in the peripheral blood. Finally, tumor-specific cytotoxic T lymphocytes (CTL) were induced by the oncolytic poxvirus, and expression of hGM-CSF from the virus enhanced both tumor-specific CTL and antitumoral efficacy. JX-963 had significant efficacy against both the primary liver tumor as well as metastases; no significant organ toxicity was noted. This model holds promise for the evaluation of immunostimulatory transgene-armed oncolytic poxviruses, and potentially other viral species.

A Case of Benign Metastasizing Leiomyoma with Multiple Metastasis to the Soft Tissue, Skeletal Muscle, Lung and Breast

Benign metastasizing leiomyoma (BML) is composed of well-differentiated smooth muscle cells and dense connective tissue. BML affects middle-aged women who have had previous hysterectomies due to a histologically benign-appearing uterine leiomyoma. We report here on a case of BML from the uterine leiomyoma in a 39-year-old woman that involved the soft tissues, skeletal muscles, lungs and breasts. She underwent a hysterectomy for the uterine leiomyoma, double oophorectomy for hormonal ablation and lung wedge resection to confirm the diagnosis. The microscopic findings of the breast and lung tumor were similar to those of the benign uterine leiomyoma. Therefore, we consider that these lesions were breast and pulmonary metastases of the uterine leiomyoma. We report here on a rare case of benign metastasizing uterine leiomyoma that involved the soft tissue, skeletal muscles, lungs and breasts, and we include a review of the relevant literature.

The Clinical Characteristics and Treatment Results of Ocular Adnexal Lymphoma

Purpose To assess the clinical pattern, the histopathological findings, the response to treatments, the recurrence pattern and the prognosis of malignant lymphoma in the ocular adnexa. Methods This study was performed on 22 total eyes from 17 patients who were diagnosed with ocular adnexal malignant lymphoma. We retrospectively analyzed the medical records for patient information including the histological classification based on age, the gender of each patient, the symptoms and signs at the initial diagnosis, the presence of binocular invasion, the findings of the surgical biopsy, the clinical stage of each patients tumor, and the treatment methods used and their effectiveness. The mean follow-up period was 24.8 months. Results The mean age of patients studied was 46.8 years old. Six females and 11 males were included in the study. Fifteen cases consisting of 20 total eyes represented extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT). Five of seven patients (71.4%) whose lymphoma occurred within the conjunctiva relapsed after irradiation or chemotherapy, and four of the relapsed patients were salvaged with further therapy. Conclusions Extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT) constituted 88.2% of all lymphomas involving the ocular adnexa. Lymphoma in the ocular adnexa responded well to conventional treatment, but the recurrence rate of lymphoma in the conjunctiva was significantly high.

Clinical Outcomes and Breast Cancer Subtypes in Patients with Brain Metastases

Background: The principal objective of this study was to assess clinical outcomes by breast cancer subtype in patients with brain metastases. Methods: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status was evaluated via immunohistochemical staining. Four survival time intervals were compared according to the subtype (ER+/HER2–, HER2+, triple negative (TN)). Results: 20 (30.3%) of the 66 patients in this study were ER+/HER2–, 20 (30.3%) were HER2+, and 26 (39.4%) were TN. The disease-free survival rates of ER+/HER2–, HER2+, and TN patients were 30.0, 17.0, and 17.9 months, respectively (p = 0.040). The median time intervals from distant metastasis to brain metastasis were 20.6, 19.5, and 9.0 months, respectively (p = 0.012). The times from initial diagnosis to brain metastasis were 52.9, 33.6, and 25.5 months, respectively (p = 0.026). However, the overall survival rates did not differ significantly (p = 0.276). Conclusions: Patients with TN breast cancer were more likely to develop distant metastasis earlier, and also evidenced poor overall survival. Triple receptor status may be employed as a prognostic marker for breast cancer patients with brain metastases.

Combination of vorinostat and adenovirus-TRAIL exhibits a synergistic antitumor effect by increasing transduction and transcription of TRAIL in lung cancer cells

Soluble TRAIL and adenovirus (ad)-TRAIL exhibit a strong antitumor effect by inducing apoptosis. Vorinostat is the histone deacetylase (HDAC) inhibitor that induces cell death in cancer cell lines and regulates the expression of epigenetically silenced genes, such as Coxackie adenoviral receptor (CAR), the receptor for adenoviral entry. We propose a new strategy in which vorinostat will induce high expression of ad-TRAIL and a strong antitumor response, and investigated the mechanism involved. The effect of vorinostat on transcription and expression of TRAIL from ad-TRAIL-transduced lung cancer cells were confirmed by reverse transciption-PCR (RT-PCR), quantitative real time-PCR and western blot assay. Anti-tumor effects were measured after cotreatment of vorinostat and ad-TRAIL, and the drug interactions were analyzed. After combined treatment of vorinostat and ad-TRAIL, apoptosis and western blot assays for Akt, Bcl-2 and caspase were performed. Vorinostat increased the expression of CAR in lung cancer cell lines and increased the expression of luciferase (luc) from ad-luc-transduced cells and TRAIL from ad-TRAIL-transduced cells. RT-PCR and quantitative real time-PCR, after sequential vorinostat treatment, revealed that vorinostat may enhance TRAIL expression from ad-TRAIL by increasing transduction through enhanced CAR expression and increasing adenoviral transgene transcription. Combined vorinostat and ad-TRAIL treatment showed the synergistic anti-tumor effect in lung cancer cell lines. Combined vorinostat and ad-TRAIL induced stronger apoptosis induction, suppression of NF-κB activation and breakdown of the anti-apoptotic molecule Bcl-2. In conclusion, the vorinostat synergistically enhanced the anti-tumor effect of ad-TRAIL by (1) increasing adenoviral transduction through the increased expression of CAR and (2) increasing adenoviral transgene (TRAIL) transcription in lung cancer cell lines.

Genetic immunotherapy of lung cancer using conditionally replicating adenovirus and adenovirus-interferon-beta.

Genetic immunotherapy is considered an ideal treatment modality for cancer because of its systemic nature. This study was designed to develop a potent novel genetic immunotherapy by combining conditionally replicating adenovirus (CRAd) and replication-defective adenovirus expressing interferon-β (ad-IFN-β). We investigated the efficacy of this therapy in an immunocompetent mouse tumor model. Transduction with CRAd (Δ24RGD) induced cytolysis in a mouse lung cancer cell line (Lewis lung carcinoma (LLC)). Combined transduction of ad-IFN-β and Δ24RGD in the LLC cells induced a greater and more prolonged production of IFN-β. Media transfer from the LLC-Δ24RGD-ad-IFN-β to untransduced LLC cells induced the production of IFN-β; these results confirmed the replication and release of ad-IFN-β. LLC cells transduced with ad-IFN-β and Δ24RGD had decreased tumorigenicity in syngeneic mice. Tumor vaccination with irradiated LLC-ad-IFN-β-Δ24RGD showed a significant increase in the survival of tumor-bearing syngeneic mice compared with mice with a single transduced LLC vaccination; this was mediated by an enhanced cytotoxic T-lymphocyte response against the LLC cells. The results of this study showed that cotransduced Δ24RGD to ad-IFN-β aided the replication of ad-IFN-β in the LLC cells. A high local concentration of IFN-β and local release of tumor antigen by CRAd induced strong antitumor immunity. This combination strategy might provide a powerful means by which ad-cytokines and CRAd can be combined and other adenoviruses expressing different cytokines might also be used.

Vascular administration of adenoviral vector soaked in absorbable gelatin sponge particles (GSP) prolongs the transgene expression in hepatocytes

Transcatheter hepatic arterial chemoembolization using emulsions composed of anticancer agents and gelatin sponges (GS) has been an efficient and safe palliative treatment for inoperable hepatocellular carcinoma (HCC). We employed catheter-mediated left hepatic arterial embolization (CHAE) to increase transduction efficiency of adenoviral vector in canine hepatocytes. The emulsion was prepared by mixing pieces of GSP and adenoviral vectors expressing recombinant β-galactosidase (Ad.LacZ) or human hepatocyte growth factor (Ad.hHGF). After the left hepatic artery was catheterized under angiography, CHAE with Ad.LacZ or Ad.hHGF was performed. Livers were removed and stained for LacZ activity on day 7. The expression pattern of LacZ staining was either scarce or patchy around the central hilum of the hepatic artery, or was homogeneously distributed in whole lobes, depending on whether large or small pieces of GSP were used. Hematological and serum biochemical changes during CHAE exhibited only a few effects. The chronological measurement of serum HGF concentration showed that the duration of transgene expression was greater after CHAE with Ad.hHGF. A similar pattern of transgene expression was observed in a rat model after hepatic arterial embolization with differential doses of Ad.hHGF soaked in GSP. These results suggest that hepatic arterial embolization by transcatheter mediated infusion with a mixture of adenovirus-GSP could be used for human HCC.

Clinical Image Evaluation of Film Mammograms in Korea: Comparison with the ACR Standard

Objective The goal of this study is to compare the overall quality of film mammograms taken according to the Korean standards with the American College of Radiology (ACR) standard for clinical image evaluation and to identify means of improving mammography quality in Korea. Materials and Methods Four hundred and sixty eight sets of film mammograms were evaluated with respect to the Korean and ACR standards for clinical image evaluation. The pass and failure rates of mammograms were compared by medical facility types. Average scores in each category of the two standards were evaluated. Receiver operating characteristic curve analysis was used to identify an optimal Korean standard pass mark by taking the ACR standard as the reference standard. Results 93.6% (438/468) of mammograms passed the Korean standard, whereas only 80.1% (375/468) passed the ACR standard (p < 0.001). Non-radiologic private clinics had the lowest pass rate (88.1%: Korean standard, 71.8%: ACR standard) and the lowest total score (76.0) by the Korean standard. Average scores of positioning were lowest (19.3/29 by the Korean standard and 3.7/5 by the ACR standard). A cutoff score of 77.0 for the Korean standard was found to correspond to a pass level when the ACR standard was applied. Conclusion We suggest that tighter regulations, such as, raising the Korean pass mark, subtracting more for severe deficiencies, or considering a very low scores in even a single category as failure, are needed to improve the quality of mammography in Korea.

Phase II Study of Gemcitabine plus Cisplatin in Patients with Anthracycline- and Taxane- Pretreated Metastatic Breast Cancer

PURPOSE Metastatic breast cancer patients are usually exposed to taxane and anthracycline as neoadjuvant, adjuvant and palliative chemotherapeutic agents. This study was designed to determine the efficacy and safety of the use of a gemcitabine and cisplatin (GP) combination treatment in patients with metastatic breast cancer that were pretreated with anthracycline and taxane. MATERIALS AND METHODS We evaluated the use of a GP regimen (1,000 mg/m(2) gemcitabine administered on days 1 and 8 plus 60 mg/m(2) cisplatin administered on day 1 every 3 weeks) in 38 breast cancer patients who had received prior chemotherapy with anthracycline and taxane as an adjuvant or neoadjuvant therapy, or as a palliative therapy. RESULTS The median patient age was 49 years (age range, 35 approximately 69 years). The overall response rate was 28.9% in 11 patients (95% confidence interval [CI], 14 approximately 44%). The median time to progression was 5.2 months (95% CI, 3.6 approximately 6.8 months). Median survival was 19.5 months (95% CI, 11.2 approximately 27.8 months). Major grade 3/4 hematological toxicity was due to leukopenia (36 of 157 cycles, 23.1%). Non-hematological toxicity was rarely severe; grade 1/2 nausea and vomiting were observed in 37.8% of the patients. There were no treatment related deaths. CONCLUSIONS Our results suggest that the use of gemcitabine plus cisplatin appears to be effective and has an acceptable toxicity profile in patients with advanced breast cancer that have been pretreated with anthracycline and taxane.