Disruptive expression patterns of the circadian clock genes are highly associated with many human diseases, including cancer. Cell cycle and proliferation is linked to a circadian rhythm; therefore, abnormal clock gene expression could result in tumorigenesis and malignant development. The molecular network of the circadian clock is based on transcriptional and translational feedback loops orchestrated by a variety of clock activators and clock repressors. The expression of 10~15% of the genome is controlled by the overall balance of circadian oscillation. Among the many clock genes, Period 1 (Per1) and Period 2 (Per2) are clock repressor genes that play an important role in the regulation of normal physiological rhythms. It has been reported that PER1 and PER2 are involved in the expression of cell cycle regulators including cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors. In addition, correlation of the down-regulation of PER1 and PER2 with development of many cancer types has been revealed. In this review, we focused on the molecular function of PER1 and PER2 in the circadian clock network and the transcriptional and translational targets of PER1 and PER2 involved in cell cycle and tumorigenesis. Moreover, we provide information suggesting that PER1 and PER2 could be promising therapeutic targets for cancer therapies and serve as potential prognostic markers for certain types of human cancers.
Background: Acyl protein thioesterase-1 (APT1) is a cytosolic protein that may function in the depalmitoylation of numerous proteins, including the Ras family. However, the clinical role of depalmitoyl thioesterase in human cancer is not known. We evaluated the APT1 expression in lung cancer tissue and its clinicopathological findings according APT1 expression pattern. Methods: APT1 expression was examined by immunohistochemistry in the tumor tissue from 79 patients, who had undergone curative surgical removal of the primary lesion; all patients had been diagnosed with stage I non-small cell lung cancer between 1993 and 2004, at Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. Results: The APT1 expression was seen in 50 out of 79 (63.3%) cases. The positive APT1 expression was significantly related with histologic subtype and T stage, but was not influenced by differentiation. The positive APT1 expression was not significantly related to patient age, gender, or smoking history. The median follow-up duration was 10.0 years; the 5-year survival rate was 71.0%. The positive APT1 expression group showed significantly worse overall survival and worse disease-free survival without statistical significance. Conclusion: We conclude that positive APT1 expression in stage I lung cancer after surgery is closely associated with overall survival. To evaluate APT1 as a prognostic marker in lung cancer, comprehensive studies on advanced stage cases are needed.
Purpose: The aim of this study was to report the improvement of Guillain-Barre syndrome after long-term combination treatment with Korean medicine. Methods: A patient was diagnosed with Guillain-Barre syndrome and treated with herbal medicine, acupuncture, pharmacopuncture, moxibustion, and exercise, including quadruped walking after three hospital admissions. To evaluate muscle strength and weakness, we measured manual muscle function, gait pattern, and the speed of quadruped walking. Results: The patient's muscle weakness in the extremities and gait stance were improved. The speed of quadruped walking was increased. Conclusion: We consider that combined treatment with Korean medicine might be effective for the muscle weakness of Guillain-Barre syndrome with a poor prognostic factor. To verify the effectiveness of this treatment, further research is needed.
Jun, Baek Gyu;Kim, Young Don;Cheon, Gab Jin;Kim, Eun Seog;Jwa, Eunjin;Kim, Sang Gyune;Kim, Young Seok;Kim, Boo Sung;Jeong, Soung Won;Jang, Jae Young;Lee, Sae Hwan;Kim, Hong Soo
The Korean journal of internal medicine
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v.33
no.6
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pp.1093-1102
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2018
Background/Aims: The aim of this study was to investigate parameters that predict radiation-induced liver disease (RILD) following stereotactic body radiotherapy (SBRT) in patients with hepatocellular carcinoma (HCC) and to identify the clinical significance of RILD. Methods: We retrospectively reviewed the medical records of 117 HCC patients who were treated by SBRT from March 2011 to February 2015. RILD was defined as elevated liver transaminases more than five times the upper normal limit or a worsening of Child-Pugh (CP) score by 2 within 3 months after SBRT. All patients were assessed at 1 month and every 3 months after SBRT. Results: Median follow-up was 22.5 months (range, 3 to 56) after SBRT. RILD was developed in 29 of the 117 patients (24.7%). On univariate analysis, significant predictive factors of RILD were pretreatment CP score (p < 0.001) and normal liver volume (p = 0.002). Multivariate analysis showed that CP score was a significant predictor of RILD (p < 0.001). The incidence of RILD increased above a CP score of 6 remarkably. The rate of recovery from RILD decreased significantly above a CP score of 8. Survival analysis showed that CP score was an independent prognostic factor of overall survival (p = 0.001). Conclusions: CP score is a significant factor to predict RILD in patients with chronic liver disease. RILD can be tolerated by patients with a CP score ${\leq}7$. However, careful monitoring of liver function is needed for patients with a CP score 7 after SBRT.
Intestinal failure (IF) is the critical reduction of the gut mass or its function below the minimum needed to absorb nutrients and fluids required for adequate growth in children. Severe IF requires parenteral nutrition (PN). Pediatric IF is most commonly due to congenital or neonatal intestinal diseases or malformations divided into 3 groups: 1) reduced intestinal length and consequently reduced absorptive surface, such as in short bowel syndrome (SBS) or extensive aganglionosis; 2) abnormal development of the intestinal mucosa such as congenital diseases of enterocyte development; 3) extensive motility dysfunction such as chronic intestinal pseudo-obstruction syndromes. The leading cause of IF in childhood is the SBS. In clinical practice the degree of IF may be indirectly measured by the level of PN required for normal or catch up growth. Other indicators such as serum citrulline have not proven to be highly reliable prognostic factors in children. The last decades have allowed the development of highly sophisticated nutrient solutions consisting of optimal combinations of macronutrients and micronutrients as well as guidelines, promoting PN as a safe and efficient feeding technique. However, IF that requires long-term PN may be associated with various complications including infections, growth failure, metabolic disorders, and bone disease. IF Associated Liver Disease may be a limiting factor. However, changes in the global management of IF pediatric patients, especially since the setup of intestinal rehabilitation centres did change the prognosis thus limiting "nutritional failure" which is considered as a major indication for intestinal transplantation (ITx) or combined liver-ITx.
Lee, Subum;Roh, Sung Woo;Jeon, Sang Ryong;Park, Jin Hoon;Kim, Kyoung-Tae;Lee, Young-Seok;Cho, Dae-Chul
Journal of Korean Neurosurgical Society
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v.64
no.5
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pp.791-798
/
2021
Objective : The period of mechanical ventilator (MV)-dependent respiratory failure after cervical spinal cord injury (CSCI) varies from patient to patient. This study aimed to identify predictors of MV at hospital discharge (MVDC) due to prolonged respiratory failure among patients with MV after CSCI. Methods : Two hundred forty-three patients with CSCI were admitted to our institution between May 2006 and April 2018. Their medical records and radiographic data were retrospectively reviewed. Level and completeness of injury were defined according to the American Spinal Injury Association (ASIA) standards. Respiratory failure was defined as the requirement for definitive airway and assistance of MV. We also evaluated magnetic resonance imaging characteristics of the cervical spine. These characteristics included : maximum canal compromise (MCC); intramedullary hematoma or cord transection; and integrity of the disco-ligamentous complex for assessment of the Subaxial Cervical Spine Injury Classification (SLIC) scoring. The inclusion criteria were patients with CSCI who underwent decompression surgery within 48 hours after trauma with respiratory failure during hospital stay. Patients with Glasgow coma scale 12 or lower, major fatal trauma of vital organs, or stroke caused by vertebral artery injury were excluded from the study. Results : Out of 243 patients with CSCI, 30 required MV during their hospital stay, and 27 met the inclusion criteria. Among them, 48.1% (13/27) of patients had MVDC with greater than 30 days MV or death caused by aspiration pneumonia. In total, 51.9% (14/27) of patients could be weaned from MV during 30 days or less of hospital stay (MV days : MVDC 38.23±20.79 vs. MV weaning, 13.57±8.40; p<0.001). Vital signs at hospital arrival, smoking, the American Society of Anesthesiologists classification, Associated injury with Injury Severity Score, SLIC score, and length of cord edema did not differ between the MVDC and MV weaning groups. The ASIA impairment scale, level of injury within C3 to C6, and MCC significantly affected MVDC. The MCC significantly correlated with MVDC, and the optimal cutoff value was 51.40%, with 76.9% sensitivity and 78.6% specificity. In multivariate logistic regression analysis, MCC >51.4% was a significant risk factor for MVDC (odds ratio, 7.574; p=0.039). Conclusion : As a method of predicting which patients would be able to undergo weaning from MV early, the MCC is a valid factor. If the MCC exceeds 51.4%, prognosis of respiratory function becomes poor and the probability of MVDC is increased.
Background and Objectives: MYC, also known as an oncogenic reprogramming factor, is a multifunctional transcription factor that maintains induced pluripotent stem cells (iPSCs). Although MYC is frequently upregulated in various cancers and is correlated with a poor prognosis, MYC is downregulated and correlated with a good prognosis in lung adenocarcinoma. MYC and two other MYC family genes, MYCN and MYCL, have similar structures and could contribute to tumorigenic conversion both in vitro and in vivo. Methods and Results: We systematically investigated whether MYC family genes act as prognostic factors in various human cancers. We first evaluated alterations in the expression of MYC family genes in various cancers using the Oncomine and The Cancer Genome Atlas (TCGA) database and their mutation and copy number alterations using the TCGA database with cBioPortal. Then, we investigated the association between the expression of MYC family genes and the prognosis of cancer patients using various prognosis databases. Multivariate analysis also confirmed that co-expression of MYC/MYCL/MYCN was significantly associated with the prognosis of lung, gastric, liver, and breast cancers. Conclusions: Taken together, our results demonstrate that the MYC family can function not only as an oncogene but also as a tumor suppressor gene in various cancers, which could be used to develop a novel approach to cancer treatment.
Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.
Kay Chul-Seoung;Jang Hong-Suk;Kim Sung-hwan;Ryu Mi-Ryeong;Kim Yeon-Shil;Chung Su-Mi;Yoon Sei-Chul
Radiation Oncology Journal
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v.17
no.3
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pp.209-216
/
1999
Purpose : To evaluate the effectiveness of external radiation therapy and the prognostic factors, we retrospectively analyzed therapeutic results of malignant extrahepatic biliary obstruction (EHBO). Methods and Materials : We analyzed the results of the external radiation therapy in 59 patients of inoperable malignant EHBO who had been treated with more than 10 Gy of external radiation therapy from April 1984 to December 1990. There were 21 stomach cancer ($35.6\%$), 12 pancreas cancer ($20.3\%$), 15 extrahepatic biliary cancer ($18.0\%$) and 11 another cancer ($18.0\%$). Their pathologies were confirmed in 31 patients ($52.5\%$). They divided into 27 adenocarcinoma and 4 nonadenocarcinoma. Their chief complaints were jaundice in 47 patients ($79.7\%$) and abdominal pain in 15 patients ($49.2\%$). Twelve patients had slightly increased bilirubin level in liver function test without jaundice. We treated twenty four patients ($40.6\%$) with percutaneous transhepatic biliary drainage (PTBD) and 32 patients ($54\%$) with systemic chemotherapy (CT). We performed external radiation therapy (ERT) upto $10.8\~55.8$ Gy (median 37.8 Gy) with palliative aim. Results : Overall median survival duration was $7.80\pm1.15$ months. The response rates of jaundice were $81.8\%$ in PTBO group and $66.7\%$ in non-PTBD group without statistical significance. The improving rate of jaundice was not significantly different in decreased ratio of total bilirubin level. But abdominal pain was more decreased in CT group than non-CT group (p<0.05). The significant prognostic factors were high performance status (Karnofski Performance Status >70), total radiation dose more than 35 Gy and good response of pain after therapy. There were increased in bacterial cholagitis in PTBD group and gastrointestinal complications in CT group. Conclusion : External radiotheapy could improve jaundice and abdominal pain in malignant EHBO patients, Overall survival duration was prolonged in patients with higher performance status and patients who had been treated with more than 35 Gy of total radiation dose. In the future, we expect not only better palliative role but also the prolongation of survival of using the ERT combined with other treatment method. But to achieve certain conclusion, we need luther study consisted with many kinds of treatment methods including new technologies in RT.
Lee, Sang-Do;Seo, Kwang Won;Lee, Jung Yeon;Huh, Jin Won;Choi, Ik Su;Park, Jae Sun;Shim, Tae Sun;Oh, Yeon-Mok;Park, In Won;Ryu, Wang-Seong;Choi, Byoung Whui
Tuberculosis and Respiratory Diseases
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v.57
no.4
/
pp.320-328
/
2004
Background : Pulmonary vascular changes which occur early in the course of chronic obstructive pulmonary disease (COPD) are prevalent manifestation and later cause pulmonary hypertension, which is a bad prognostic factor in COPD. Beraprost sodium (BPS), an orally active prostacyclin analogue, has been shown to improve survival in patients with primary pulmonary hypertension. This study investigated the effect of BPS in the patients with COPD. Methods : This is a double-blind randomized placebo-controlled, two center clinical trial. Twenty one consecutive patients with COPD were enrolled from June 2003 to June 2004 (patients treated with BPS for 3 months, BPS group, n=11; those with placebo, placebo group, n=10). The baseline demographic, pulmonary function and hemodynamic data were not significantly different between two groups. Results : On echocardiographic examination, trans tricuspid valve pressure gradient has decreased significantly after 3 months with beraprost in the BPS group [17.7(${\pm}11.4$) to 8.2(${\pm}8.9$) mm Hg, p-value<0.05], while there was no significant change in the control group. Six-minute walking distance has decreased in the control group and increased in the BPS group, but there was no statistical significance. Conclusion : In patients with COPD oral administration of BPS reduced the pulmonary arterial pressure. The clinical significance of this finding, that is improving symptoms and natural course of the disease, needs further study.
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