• BMB Reports
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• v.56 no.5
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• pp.265-274
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• 2023

Defects in DNA double-strand break (DSB) repair signaling permit cancer cells to accumulate genomic alterations that confer their aggressive phenotype. Nevertheless, tumors depend on residual DNA repair abilities to survive the DNA damage induced by genotoxic stress. This is why only isolated DNA repair signaling is inactivated in cancer cells. DNA DSB repair signaling contributes to general mechanism for various types of lesions in diverse cell cycle phases. DNA DSB repair genes are frequently mutated and amplified in cancer; however, limited data exist regarding the overall genomic prospect and functional result of these modifications. We list the DNA repair genes and related E3 ligases. Mutation and expression frequencies of these genes were analyzed in COSMIC and TCGA. The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. DNA damage response-related E3 ligases, such as RNF168, FBXW7, and HERC2, were generated with more than 10% mutation in several cancer cells. This study provides a broad list of candidate genes as potential biomarkers for genomic instability and novel therapeutic targets in cancer. As a DSB related proteins considerably appear the possibilities for targeting DNA repair defective tumors or hyperactive DNA repair tumors. Based on recent research, we describe the relationship between unstable DSB repairs and DSB-related E3 ligases.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.10.1-10.14
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• 2020

Immune checkpoint inhibitors (ICIs) have shown remarkable benefit in the treatment of patients with non-small-cell lung cancer (NSCLC) and have emerged as an effective treatment option even in the first-line setting. ICIs can block inhibitory pathways that restrain the immune response against cancer, restoring and sustaining antitumor immunity. Currently, there are 4 PD-1/PD-L1 blocking agents available in clinics, and immunotherapy-based regimen alone or in combination with chemotherapy is now preferred option. Combination trials assessing combination of ICIs with chemotherapy, targeted therapy and other immunotherapy are ongoing. Controversies remain regarding the use of ICIs in targetable oncogene-addicted subpopulations, but their initial treatment recommendations remained unchanged, with specific tyrosine kinase inhibitors as the choice. For the majority of patients without targetable driver oncogenes, deciding between therapeutic options can be difficult due to lack of direct cross-comparison studies. There are continuous efforts to find predictive biomarkers to find those who respond better to ICIs. PD-L1 protein expressions by immunohistochemistry and tumor mutational burden have emerged as most well-validated biomarkers in multiple clinical trials. However, there still is a need to improve patient selection, and to establish the most effective concurrent or sequential combination therapies in different NSCLC clinical settings. In this review, we will introduce currently used ICIs in NSCLC and analyze most recent trials, and finally discuss how, when and for whom ICIs can be used to provide promising avenues for lung cancer treatment.

• Journal of the Korean Society of Radiology
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• v.84 no.6
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• pp.1244-1256
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• 2023

In prostate cancer, the bone is the most common site of metastasis, and it is essential to evaluate metastatic bone lesions to assess the tumor burden and treatment response. Castration-resistant prostate cancer refers to the state wherein the cancer continues to progress despite a significant reduction of the sex hormone level and is associated with frequent distant metastasis. The Prostate Cancer Working Group 3 (PCWG3) released guidelines that aimed to standardize the assessment of treatment effects in castration-resistant prostate cancer using bone scintigraphy. However, these guidelines can be challenging to comprehend and implement in practical settings. The purpose of this review was to provide an overview of a specific image acquisition method and treatment response assessment for bone scintigraphy-based evaluation of bone lesions in metastatic castration-resistant prostate cancer, in accordance with the PCWG3 guidelines.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.1
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• pp.31-39
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• 2022

In patients with neuroendocrine tumors with liver metastases (NETLMs), complete resection of both the primary and liver metastases is a potentially curative option. When complete resection is not possible, debulking of the tumour burden has been proposed to prolong survival. The objective of this systematic review was to evaluate the effect of curative surgery (R0-R1) and debulking surgery (R2) on overall survival (OS) in NETLMs. For the subgroup of R2 resections, outcomes were compared by the degree of hepatic debulking (≥ 90% or ≥ 70%). A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines using PubMed, Medline, CINAHL, Cochrane, and Embase databases. Hazard ratios (HRs) were estimated for each study and pooled using a random-effects inverse-variance meta-analysis model. Of 538 articles retrieved, 11 studies (1,729 patients) reported comparisons between curative and debulking surgeries. After pooling these studies, OS was found to be significantly shorter in debulking resections, with an HR of 3.49 (95% confidence interval, 2.70-4.51; p < 0.001). Five studies (654 patients) compared outcomes between ≥ 90% and ≥ 70% hepatic debulking approaches. Whilst these studies reported a tendency for OS and progression-free survival to be shorter in those with a lower degree of debulking, they did not report sufficient data for this to be assessed in a formal meta-analysis. In patients with NETLM, OS following surgical resection is the best to achieve R0-R1 resection. There is also evidence for a progressive reduction in survival benefit with lesser debulking of tumour load.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.1
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• pp.39-43
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• 2008

Purpose: We evaluated whether it was necessary to perform whole body acquisition of $^{18}F$-FDG PET/CT including whole skull and lower extremity (LE) distal to mid-thigh (MT) in patients with multiple myeloma (MM). Materials and Methods: Thirty patients underwent 45 whole body $^{18}F$-FDG PET/CT scans including skull and LE distal to MT. PET scans were divided by 2 subgroups according to the presence of abnormal focal $^{18}F$-FDG uptake in skull or LE distal to MT. Clinical characteristics including age, sex, and stages were compared between the 2 subgroups. Results: Of total 45 whole body PET/CT scans, focally increased abnormal FDG uptake in the skull or LE distal to MT suggesting myeloma involvement was found in 22 scans (48.9%) of 14 patients (46.7%). Skull lesions were more frequently observed than LE lesions distal to MT on PET (86.4% vs. 40.9%, p<0.005). There were no significant differences in age, sex, initial Durie/Salmon stage, and tumor burden at the time of PET scan suggested by serum hemoglobin level, serum calcium level, serum and urine paraprotein level, and serum creatinine level between the two subgroups. The presence of the skull or LE distal MT lesions on PET did not affect on the Durie/Salmon plus stage except only 1 case (1/22, 4.5%, p>0.05). Conclusion: Abnormal lesions in the skull or LE distal to MT on $^{18}F$-FDG PET/CT did not affect significantly on the tumor burden and Durie/Salmon plus stage of MM. Therefore, torso PET acquisition including head may be sufficient for evaluating patients with MM.

• Radiation Oncology Journal
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• v.6 no.2
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• pp.183-194
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• 1988

Twenty five patients with histologically proven medulloblastoma received craniospinal radiotherapy (CSRT) at the Seoul National University Hospital from 1979 to 1984. The extent of tumor removal was biopsy only in 2 patients, partial in 18, and near total in 5. With orthogonal technique of CSRT, mainly 55Gy was delivered to the posterior fossa (PF), 40Gy to whole brain (WB), and 30Gy to whole spine (WS). And with AP; PA technique, 50Gy to PF, 45-50Gy to WB, and 36 Gy to WS. Complete remission was obtained in $84\%$ of patients. Among 21 CR's 10 failures were observed, thus total failure rate was $56\%$ (14/25). Of 14 faiure 13 had the primary failure, 11 failed in primary site alone, 1 failure was combined with ventricular seeding, and another 1 was combined with neck node metastasis. There was 1 isolated spinal failure. Actuarial overall survival rates at 3 and 5 years were $75\%$ and $54\%$, and disease-free survival rates were $58\%$ and $36\%$, respectively. Better 5 year disease-free survival was noted in patients with 55 Gy to the posterior fossa than those with 50Gy $(62\%\;vs\;17\%,\;p<0.05)$, in patients treated with orthogonal technique than those treated with AP:PA technique $(87\%\;vs\;12\%,\;p<0.05)$, and in patients with near total removal than those with partial or less removal of tumor $(56\%\;vs\;30\%,\;N.S.)$ Re-irradiation was not satisfactory No severe late sequelae was noted among the survivors. For the higher control of medulloblastoma, dose to posterior fossa should be at least 55Gy with orthogonal CSRT to small tumor burden. And dose reduction in the subarachnoidal spaces might be safe, but optimal dose to the subarchnoidal spaces should be determined by the thorough tumor staging before radiotherapy.

• Radiation Oncology Journal
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• v.20 no.3
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• pp.215-220
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• 2002

Purpose : Preoperative radiotherapy has been used to induce tumor regression and allow complete resection of rectal cancer with a sphincter preservation surgery. This study was performed to determine the effectiveness of preoperative radiotherapy for $T_2,\;T_3$ distal rectal carcinoma. Materials and Methods : From November 1995 to June 1997, fifteen patients with invasive distal rectal cancer were treated with preoperative radiotherapy followed by sphincter preservation surgery. Classification by preoperative T stage consisted of 7 $T_2$ and 8 $T_3$ tumors. Radiation therapy was delivered with 6 MV and 15 MV linear accelerator, at 1.8 Gy fractions for 5 days per week. Total radiation doses were 45 Gy to 50.4 Gy (median : 50.4 Gy). Sphincter preservation surgery was peformed $4\~6$ weeks after the completion of radiotherapy. Median follow-up was 22 months (range : $16\~37\;months$). Results : One patient $(6.7\%)$ had a complete pathologic response. Comparing the stage at the diagnostic workup with the pathologic stage, tumor downstaging of T stages occurred in 11 of 15 patients $(73.3\%)$ and $N_1$ stages occurred in 2 of 5 patients $(40\%)$. No patient developed progressive disease undergoing treatment. Two patients suffered local recurrence at 7 and 20 months, and one a distant metastasis at 30 months. No grade 3 or 4 toxicity was observed. Conclusion : Our experience suggests that preoperative radiotherapy followed by sphincter preservation surgery is well tolerated, and can significantly reduce the tumor burden for $T_2\;T_3$ distal rectal cancer.

• Korean Journal of Psychosomatic Medicine
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• v.22 no.1
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• pp.13-22
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• 2014

Objectives : Breast cancer has been the most prevalent female cancer in South Korea since 2001. Early detection of this disease is the most effective strategy for reducing mortality. The objective of this study was to identify factors which could predict advanced stage at diagnosis of breast cancer. Methods : Participants who were initially diagnosed with breast cancer and referred to the Stress Clinic of the Breast Cancer Center at Kyungpook National University Hospital were included. Through a semi-structured interview, the authors investigated psychosocial variables such as the extent of marital and family functioning and emotional-economic family burden as well as sociodemographic and health behavior-, health characteristic- and cancer-related variables. Results : Data were collected from 219 participants. One hundred and twenty(54.8%) subjects were diagnosed with advanced-stage breast cancer. Variables that were significantly different between the advanced-stage and early-stage groups included : monthly breast self examination(p<0.000), annual mammographic screening(p<0.000), mode of tumor detection(p<0.000), nature of the first symptoms(p<0.000), time to treatment after diagnosis(p<0.000), overloaded economic and family burden(p=0.018), marital functioning(p<0.000) and family functioning(p<0.00). Logistic regression analysis indicated that irregular annual mammography screening(OR=7.431 ; 95% CI 2.407-22.944) or a lack of screening(OR=25.299 ; 95% CI 7.855-81.482) and a dysfunctional marital relationship(OR=4.772 ; 95% CI 2.244-10.145) were significantly associated with advanced stage at diagnosis of breast cancer. Conclusions : We reconfirmed screening behavior to be a risk factor for delayed diagnosis of breast cancer. Our findings also emphasized the importance of psychosocial factors such as marital functioning in early detection of breast cancer. Psychiatric consultation in the area of martial functioning could be beneficial for increasing early detection in breast cancer.

• Journal of Korean Neurosurgical Society
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• v.63 no.4
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• pp.433-443
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• 2020

Objective : Osteoporosis is a disease of unbalanced bone metabolism that results in low bone mineral density with increased bone fragility and propensity for fractures. The increased rate of bone fracture due to osteoporosis places a significant burden on public health care expenditures. Therefore, numerous studies have been designed and performed to identify the drugs or health foods that can improve the bone quality or quantity. This study was designed to evaluate and analyze the therapeutic effects of rutin on histomorphometric values of the spine and femur in an osteoporotic mouse model induced by bilateral ovariectomy. Methods : Thirty female ICR mice (8 weeks old) underwent either a sham operation (only abdominal incision, sham group, n=10) or bilateral ovariectomy (n=20). The ovariectomized (OVX) animals were randomly divided into two groups : untreated OVX group (OVX-C, n=10), or rutin-administered group (OVX-R, n=10). The OVX-C group received weight-adjusted doses of saline vehicle and the OVX-R group received 50 mg/kg of rutin intraperitoneally, starting 1 day after surgery. At 4 and 8 weeks after surgery, serum estrogen, osteocalcin, alkaline phosphatase (ALP), and the telopeptide fragment of type I collagen C-terminus (CTX-1) were analyzed. Interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor (TNF)-α were also analyzed. Bone histomorphometric parameters of the 4th lumbar vertebra and femur were determined by micro-computed tomography. Results : In OVX-C group, ALP, osteocalcin, CTX-1, IL-1β, IL-6, and TNF-α levels were significantly increased at 4 and 8 weeks compared to sham operation group. Rutin administration after OVX statistically significantly reduced ALP, CTX-1, IL-1β, IL-6, and TNF-α levels at 4 and 8 weeks. Rutin administration also improves bone histomorphometric parameters including trabecular bone volume fraction, trabecular thickness, and trabecular number. Trabecular separation was also decreased in OVX-R group compared to OVX-C group. Conclusion : The present study demonstrated that rutin has therapeutic effects on improving bone histomorphometric values in an OVX mouse model. The improvement in histomorphometric values may be associated with the reduction of osteoclastic activity via inhibition of IL-1β, IL-6, and TNF-α. In future studies, the mechanism for the effect of rutin on osteoporosis should be demonstrated more clearly to use rutin in human osteoporosis.

• The Korean journal of internal medicine
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• v.33 no.6
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• pp.1224-1233
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• 2018

Background/Aims: The objective of this study was to determine the efficacy and safety of add-on therapy with certolizumab pegol (CZP) in active rheumatoid arthritis (RA) patients of a single ethnicity. Methods: In this 24-week, phase 3, randomized, double-blind, placebo-controlled trial, eligible patients (n = 127) were randomized 2:1 to subcutaneous CZP + methotrexate (MTX; 400 mg at week 0, 2, and 4 followed by 200 mg every 2 weeks) or placebo + MTX. Results: At week 24, the American College of Rheumatology criteria for 20% (ACR20) response rate was significantly greater with CZP + MTX than with placebo (66.7% vs. 27.5%, p < 0.001). Differences in ACR20 response rates for CZP vs. placebo were significant from week 1 (p < 0.05) and remained significant through week 24. The CZP group reported significant improvement in physical function and disability compared to the placebo group (p < 0.001) at week 24, as assessed by Korean Health Assessment Questionnaire-Disability Index (KHAQ-DI). Post hoc analysis indicated that the proportion of patients who had ACR70 responses, Disease Activity Score 28 (DAS28) low disease activity, and DAS28 remission at week 24 was greater in CZP + MTX-treated patients who achieved a decrease in DAS28 ${\geq}1.2$ (43.8%) at week 4 than in nonresponders. Among 18 (22.2%) and 14 patients (35.0%) in CZP and placebo groups who had latent tuberculosis (TB), none developed active TB. Most adverse events were mild or moderate. Conclusions: CZP treatment combined with MTX in active RA patients with moderate to severe disease activity and an inadequate response to MTX resulted in rapid onset of efficacy, which is associated with better clinical outcome at week 24 and has an acceptable safety profile, especially in an intermediate TB-burden population.