PURPOSE: The purpose of this study is to evaluate the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) after microfracture on the remodeling of subchondral bone and cartilage healing in a model of full-thickness articular cartilage injury in a rabbit. MATERIALS AND METHODS: A full thickness articular cartilage defect of 6x3-mm-size was created in the trochlear groove of the right femur in 24 rabbits. The defect was left empty in six rabbits, and microfracture was done in 18 rabbits. After microfracture, no treatment was done in six rabbits, defect was filled with fibrin glue in six rabbits, and with fibrin glue and rhBMP-2 in six rabbits. The effect of rhBMP-2 after microfracture was evaluated based on histological analysis and real-time polymerase chain reaction (PCR) for analysis of collagen type at 8 weeks after surgery. RESULTS: The score of histological grade scale of six rabbits in which the defect was filled with fibrin glue and rhBMP-2 was better than that of others and real-time PCR also showed a higher amount of collage type 1 and collage type 2 in these six rabbits. CONCLUSION: We consider that fibrin glue and rhBMP-2 after microfracture may accelerate cartilage healing in an articular cartilage defect and maybe helpful in healing the articular cartilage defect into more closely native hyaline cartilage.
Cartilage* ; Cartilage, Articular* ; Collagen ; Femur ; Fibrin Tissue Adhesive ; Humans ; Hyaline Cartilage ; Rabbits ; Real-Time Polymerase Chain Reaction

BACKGROUND: Abdominal pain is a common complaint seen at emergency centers. Various diseases can cause abdomin al pain making it difficult to make a correct diagnosis. In the elderly, however, the consequences of an incorrect or delayed diagnosis can be more critical. We investigated the accuracy of initial diagnoses in the emergency center and analyzed the associations among medical factors including age. METHODS: We compared the ICD 10 codes of initial diagnoses to the codes of final diagnoses, defined the 'degree of agreement' using a 5 point scale, and classified patients into 'high degree of agreement' or 'low degree of agreement' groups. According to the severity of illness, we classified patients as 'admission' or 'out patient follow up'. According to their illness, we classified them as 'surgical' or 'medical'. According to age, we classified them as 'elderly' or 'adult'. Finally, we analyzed the statistical significance of each association. RESULTS: Overall, admitted patients and surgical diagnoses had higher degrees of agreement. 'Elderly' patients had no significant difference in 'degree of agreement' from 'adult' patients. CONCLUSION: Among patients presenting with acute abdominal pain to the emergency center, the degree of agreement between initial diagnosis and final diagnosis is dependent on the diagnostic characteristics of the disease, and not on the age of the patients. Further studies on the diagnostic accuracy of individual diseases are needed. Additional diagnosis associated variables, for example comorbidity and prognosis, needs to be studied regarding relationship to diagnostic accuracy.
Abdominal Pain ; Aged ; Comorbidity ; Delayed Diagnosis ; Emergencies ; Humans ; Prognosis

PURPOSE: To overcome the limitations of cancer gene therapy using replication-incom- petent adenovirus, we generated E1B 55 kD-deleted adenovirus (YKL-1) by polymerase chain reaction (PCR) and homologous recombination. We then investigated tumor-specific virus replication and cytotoxicity of YKL-1 in vitro and in vivo. MATERIALS AND METHODS: YKL-1 was constructed by reintroducting E1A and E1B 19 kD into pTG-CMV El/E3-deficient adenoviral vector and inducing homologous recombination in E. coli. The recombinant vector pYKL-1 was transfected into 293 cells to generate YKL-1. The properties of newly constructed YKL-1 was defined by PCR and immuno- blotting analysis. Virus replication was examined by infecting human normal and cancer cells on 6-wells at multiplicity of infection (MOI) of 10 for 3 days. Virus was then recovered and titered. Cytopathic effect was analyzed by infecting human normal and cancer cells on 24-wells at MOIs of 10, 1 or 0.1 for 7 to 10 days and staining them with crystal violet solution. Inhibition of tumor growth was examined in human cancer cell xenografts in nu/nu mice by intratumoral injection of YKL-l. RESULTS: PCR and immunoblotting analysis confirmed that YKL-1 contained E1A and E1B 19 kD but not E1B 55 kD. In human normal cells, virus replication and subsequent cytopathic effect of E1B 55 kD-deleted adenovirus YKL-1 was markedly attenuated by larger than 2 to 3 log in magnitude, compared to that of wild-type ad-XJ. In contrast, YKL-1 was capable of replicating and inducing cytotoxicity i.n most human cancer cells. C33A and Hep3B containing p53 mutation were much more sensitive, whereas HeLa and H460 with wild type p53 were relatively resistant to YKL-1. Finally, the tumor growth was dramatically retarded by intratumoral injection of YKL-1 in C33A cervical cancer xenograft and the histology showed significant necrosis by intratumoral injection of YKL-1. CONCLUSION: The results here demonstrated the ability of preferential virus replication and cytotoxicity of ElB 55 kD-deleted adenovirus YKL-1 in human cancer cells. Therefore, these indicated a promising potential of YKL-1 as an antitumoral virus agent and a selective replication-competent virus vector.
Adenoviridae* ; Animals ; Genes, Neoplasm ; Genetic Therapy ; Gentian Violet ; Heterografts ; Homologous Recombination ; Humans ; Immunoblotting ; Mice ; Necrosis ; Polymerase Chain Reaction ; Uterine Cervical Neoplasms ; Virus Replication*

PURPOSE: The high mobility group box 1 (HMGB1) protein has roles in apoptosis and immune responses by acting as a ligand for receptor for advanced glycation end products (RAGE), Toll-like receptors (TLRs), and triggering receptor expressed on myeloid cells 1. In particular, HMGB1/RAGE is involved in tumor metastasis by inducing matrix metalloproteinase 2 (MMP2) and MMP9 expression. We investigated the associations between genetic variations in HMGB1-related genes and disease-free survival (DFS) and overall survival (OS) in Korean female breast cancer patients. METHODS: A total of 2,027 patients in the Seoul Breast Cancer Study were included in the analysis. One hundred sixteen single nucleotide polymorphisms (SNPs) were extracted from eight genes. A multivariate Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval (CI) of each SNP. The effects of the SNPs on breast cancer prognosis were assessed at cumulative levels with polygenic risk scores. RESULTS: The SNPs significantly associated with DFS were rs243867 (hazard ratio, 1.26; 95% CI, 1.05–1.50) and rs243842 (hazard ratio, 1.24; 95% CI, 1.03–1.50); both SNPs were in MMP2. The SNPs significantly associated with OS were rs243842 in MMP2 (hazard ratio, 1.33; 95% CI 1.03–1.71), rs4145277 in HMGB1 (hazard ratio, 1.29; 95% CI, 1.00–1.66), rs7656411 in TLR2 (hazard ratio, 0.76; 95% CI, 0.60–0.98), and rs7045953 in TLR4 (hazard ratio, 0.50; 95% CI, 0.29–0.84). The polygenic risk score results for the DFS and OS patients showed third tertile hazard ratios of 1.72 (95% CI, 1.27–2.34) and 2.75 (95% CI, 1.79–4.23), respectively, over their first tertile references. CONCLUSION: The results of the present study indicate that genetic polymorphisms in HMGB1-related genes are related to breast cancer prognosis in Korean women.
Advanced Glycosylation End Product-Specific Receptor ; Apoptosis ; Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Female ; Genetic Predisposition to Disease* ; Genetic Variation ; HMGB1 Protein ; Humans ; Matrix Metalloproteinase 2 ; Myeloid Cells ; Neoplasm Metastasis ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Prognosis* ; Proportional Hazards Models ; Seoul ; Toll-Like Receptors

Background/Aims: The study investigated the incidence of thromboembolic events (TEE) in head and neck (H&N) cancer patients who received concurrent chemoradiotherapy (CCRT) with cisplatin, and analyzed the factors affecting TEE occurrence Methods: Two hundred and fifty-seven patients who started CCRT with cisplatin for H&N cancer from January 2005 to December 2019 were analyzed. Results: TEE occurred in five patients, an incidence rate of 1.9%. The 2-, 4-, and 6-month cumulative incidences of TEE were 0.8%, 1.6%, and 1.9%, respectively. Khorana score was the only factor associated with TEE occurrence (p = 0.010). Conclusions The incidence of TEE in H&N cancer patients who underwent CCRT with cisplatin was relatively low when compared to other types of cancer. However, patients with a high Khorana score require more careful surveillance for possible TEE occurrence.

Purpose: We developed a comprehensive return to work (RTW) intervention covering physical, psycho-social and practical issues for patients newly diagnosed and evaluated its efficacy in terms of RTW. Materials and Methods: A multi-center randomized controlled trial was done to evaluate the efficacy of the intervention conducted at two university-based cancer centers in Korea. The intervention program comprised educational material at diagnosis, a face-to-face educational session at completion of active treatment, and three individualized telephone counseling sessions. The control group received other education at enrollment. Results: At 1-month post-intervention (T2), the intervention group was more likely to be working compared to the control group after controlling working status at diagnosis (65.4% vs. 55.9%, p=0.037). Among patients who did not work at baseline, the intervention group was 1.99-times more likely to be working at T2. The mean of knowledge score was higher in the intervention group compared to the control group (7.4 vs. 6.8, p=0.029). At the 1-year follow-up, the intervention group was 65% (95% confidence interval, 0.78 to 3.48) more likely to have higher odds for having work. Conclusion The intervention improved work-related knowledge and was effective in facilitating cancer patients’ RTW.