• Bulletin of the Korean Chemical Society
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• v.35 no.12
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• pp.3571-3575
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• 2014

Proteasome, a multicatalytic protease complex, has been validated as a promising therapeutic target in oncology. Carfilzomib (Kyprolis$^{(R)}$), a tetrapeptide epoxyketone, irreversibly inhibits the chymotrypsin-like (CT-L) activity of the proteasome and has been recently approved for multiple myeloma treatment by FDA. A chemistry effort was initiated to discover the compounds that are reversibly inhibit the proteasome by replacing the epoxyketone moiety of carfilzomib with a variety of ketones as reversible and covalent warheads at the C-terminus. The newly synthesized compounds exhibited significant inhibitory activity against CT-L activity of the human 20S proteasome. When the compounds were tested for cancer cell viability, 14-8 was found to be most potent in inhibiting Molt-4 acute lymphoblastic leukemia cell line with a $GI_{50}$ of $4.4{\mu}M$. Cytotoxic effects of 14-8 were further evaluated by cell cycle analysis and Western blotting, demonstrating activation of apoptotic pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6099-6101
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• 2014

Purpose: To retrospectively analyze variability and clinical significance of serum ferritin levels in Chinese patients with hematologic malignancies. Materials and Methods: Serum ferritin were measured by radioimmunoassay, using a kit produced by the Beijing Institute of Atomic Energy. Patients with hematologic malignancies, and treated in the Department of Hematology in Nanjing First Hospital and fulfilled study criteria were recruited. Results: Of 473 patients with hematologic malignancies, 262 patients were diagnosed with acute leukemia, 131 with lymphoma and 80 with multiple myeloma. Serum ferritin levels of newly diagnosed and recurrent patients were significantly higher than those entering complete remission stage or in the control group (p<0.001). Conclusions: Serum ferritin lever in patients with hematologic malignancies at early stage and recurrent stage are significantly increased, so that detection and surveillance of changes of serum ferritin could be helpful in assessing conditions and prognosis of this patient cohort.

• BMB Reports
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• v.46 no.2
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• pp.86-91
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• 2013

Glucose effects on the vegetative growth of Dictyostelium discoideum Ax2 were studied by examining oxidative stress and tetrahydropteridine synthesis in cells cultured with different concentrations (0.5X, 7.7 g $L^{-1}$; 1X, 15.4 g $L^{-1}$; 2X, 30.8 g $L^{-1}$) of glucose. The growth rate was optimal in 1X cells (cells grown in 1X glucose) but was impaired drastically in 2X cells, below the level of 0.5X cells. There were glucose-dependent increases in reactive oxygen species (ROS) levels and mitochondrial dysfunction in parallel with the mRNA copy numbers of the enzymes catalyzing tetrahydropteridine synthesis and regeneration. On the other hand, both the specific activities of the enzymes and tetrahydropteridine levels in 2X cells were lower than those in 1X cells, but were higher than those in 0.5X cells. Given the antioxidant function of tetrahydropteridines and both the beneficial and harmful effects of ROS, the results suggest glucose-induced oxidative stress in Dictyostelium, a process that might originate from aerobic glycolysis, as well as a protective role of tetrahydropteridines against this stress.

• Journal of Chest Surgery
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• v.12 no.3
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• pp.151-158
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• 1979

This is a report of 3 cases of tumors, which primarily originated from ribs and the sternum. In the first case of multiple myeloma, the patient was 67 year old male with a tumor located on the middle sternum invading the manubrium and the body of the sternum manifesting symptoms after a contusion of the anterior sternum. The sternum was entirely resected and was replaced by tantalum plate to reconstruct the defective chest wall in order to prevent the paradoxical movement during respiration. In the second case of osteogenic sarcoma, the patient was 43 year old male with a tumor located on the costochondral junction of the left 5th rib for 6 months. The left 5th rib was resected between the middle part and sternochondral junction of it including tumor and adjacent soft tissues. In the third case of chondrosarcoma, the patient was 36 year old male with a tumor located near the posterior angles of the right 7th and 8th ribs manifesting back pain on the area where the tumor was located. Resection of right lower lobe was performed since direct invasion of tumor was seen in the superior segment of right lower lobe. This was followed by the resection of both 7th and 8th ribs at the area between the costovertebral junction and the portion 10 em apart from the tumor including the tumor and intercostal soft tissues. Diagnoses of 3 cases of tumors described above were confirmed by histopathologic examination postoperatively. The postoperative courses were uneventful.

• Journal of Chest Surgery
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• v.26 no.6
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• pp.483-487
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• 1993

From July 1990 to August 1992,78 Hickman catheters and 22 chemoports were inserted in 98 patients for chemotherapy.We analyzed the clinical data of these patients. The results were as follows: 1]Mean age of patients was 42.8$\pm$1.6[SE] years 2]Male to female ratio was 1.09:1 3]The diseases of the cases were leukemia[66] ,lymphoma[8], stomach cancer[8],uterine cervix cancer[5],ovarian cancer[4],lung cancer[3],aplastic anemia[2],maxillary gland cancer[1],pancreas cancer[1],malignant mesothelioma[1] and multiple myeloma[1] 4]Mean values of preoperative WBC counts,platelet counts,PT and APTT were 31,500$\pm$ 8,132[SE]/mm,104,000$\pm$ 12,200 [SE]/mm,82$\pm$ 1.9[SE]% and 32$\pm$ 0.8[SE] sec,respectively. 5]The average duration of catheter uses was 121.7$\pm$ 17.3[SE]days. 6]The complications were subcutaneous tunnel bleeding or hematoma[2],exit site or subcutaneous tunnel infection[2] and catheter related septicemia[1]. 7]The causes of catheter removal were patient`s death or hopeless discharge[22],completion of treatment[6],subcutaneus hematoma or bleeding[2],exit site or subcutaneous tunnel infection[2] and catheter related septicemia[1].So,we concluded that Hickman catheter and chemoport were useful vascular access for chemotherapy in patients with malignant diseases, with low rate of complication and longterm duration.

• Korean Journal of Head & Neck Oncology
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• v.19 no.2
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• pp.179-183
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• 2003

Osteosarcoma is one of the most frequently occurring malignant bone tumor except for multiple myeloma. However, osteosarcoma of the mandible is rare and aggressive malignancy constituting about 5% to 13% of all cases of skeletal osteosarcoma. The authors experienced a case of osteosarcoma of the mandible in a 31-years old male patient. He visited our outpatient clinic with painless mass of the cheek. On the basis of the clinical and imaging findings, the differential diagnosis included giant cell tumor, histiocytosis and malignant bone tumor. In the first operation, the mass of the mandible was excised. Intraoperative microscopic examination of a frozen section did not yield a diagnosis: however, the final definitive histologic examination revealed osteoblastic osteosarcoma. After 15days, wide excision with hemimandibulectomy was completed followed by postoperative radiotherapy and chemotherapy. With our experience, we report the progression of diagnosis and management for mandibular osteosrcoma.

• YAKHAK HOEJI
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• v.55 no.6
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• pp.466-472
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• 2011

NF-E2-related factor 2 (Nrf2), a master regulator of antioxidant genes in animals, has been associated with the resistance of cancer cells to several cytotoxic chemotherapeutics. Bortezomib, a reversible inhibitor of the 26S proteasome, is a novel class anti-cancer therapeutics approved for the treatment of refractory multiple myeloma. However, the molecular mechanism of drug-resistance remains elusive. In the present study, bortezomib sensitivity has been investigated in Nrf2 knockdown ovarian cancer cells. When Nrf2 expression is stably repressed using interfering RNA expression, bortezomib-induced apoptosis and cell death were significantly enhanced compared to nonspecific RNA control cells. Knockdown cells showed elevated expression in the catalytic subunit PSMB5, PSMB6, and PSMB7 compared to the control, and failed to induce heme oxygenase-1 expression following bortezomib treatment. These indicate that differential proteasome levels and altered expression of stress-response genes could be underlying mechanisms of bortezomib sensitization in Nrf2-inhibited ovarian cancer cells.

• Bulletin of the Korean Chemical Society
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• v.34 no.5
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• pp.1425-1428
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• 2013

The proteasome, which is highly evolutionarily conserved, is responsible for the degradation of most short-lived proteins in cells. Small-molecule inhibitors targeting the proteasome's degradative activity have been extensively developed as lead compounds for various human diseases. An exemplified molecule is bortezomib, which was approved by FDA in 2003 for the treatment of multiple myeloma. Here, using transiently and stably expressed N-end rule model substrates in mammalian cells, we evaluated and identified that salinosporamide A and salinosporamide B effectively inhibited the proteasomal degradation. Considering that a variety of proteasome substrates are implicated in the pathogenesis of many diseases, they have the potential to be clinically applicable as therapeutic agents.

• The Journal of the Korean dental association
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• v.52 no.4
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• pp.203-217
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• 2014

Bisphosphonates are widely used in the treatment of many medical conditions, such as osteoporosis, multiple myeloma, Paget's disease, etc. However, side effect has been documented in the published data during the past years, osteonecrosis of the jaw in patients receiving long-term bisphosphonate therapy. Although pathogenesis of BRONJ(bisphophonate-related osteonecrosis of the jaw) is not yet fully understood, it is currently known to be a disease associated with suppressed bone turnover by bisphopbonate. Recent literature has indicated a similar association with nonbisphosphonate drugs used in cancer therapy including monoclonal antibodies denosumab and bevacizumab and multikinase inhibitor sunitinib. Accordingly, many studies have been carried out on the biochemical markers examination to assess the risk for BRONJ. The treatment of BRONI is reported with a review of the relevant literature. However, there is still a controversial discussion about the adequate treatment. It is necessary to accumulate further studies in order to establish more useful biochemical markers and effective treatment for BRONJ.

• Molecules and Cells
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• v.26 no.4
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• pp.323-328
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• 2008

Eukaryotic cells continuously integrate intrinsic and extrinsic signals to adapt to the environment. When exposed to stressful conditions, cells activate compartment-specific adaptive responses. If these are insufficient, apoptosis ensues as an organismal defense line. The mechanisms that sense stress and set the transition from adaptive to maladaptive responses, activating apoptotic programs, are the subject of intense studies, also for their potential impact in cancer and degenerative disorders. In the former case, one would aim at lowering the threshold, in the latter instead to increase it. Protein synthesis, consuming energy for anabolic processes as well as for byproducts disposal, can be a significant source of stress, particularly when difficult-to-fold proteins are produced. Recent work from our and other laboratories on the differentiation of antibody secreting cells, revealed a regulatory circuit that integrates protein synthesis, secretion and degradation (proteostasis), into cell lifespan determination. The apoptotic elimination - after an industrious, yet short lifetime - of terminal immune effectors is crucial to maintain immune homeostasis. Linking proteostasis to cell death, this paradigm might prove useful for biotechnological purposes, and the design of novel anti-cancer therapies.