• Molecules and Cells
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• 제46권8호
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• pp.496-512
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• 2023

A fructose-enriched diet is thought to contribute to hepatic injury in developing non-alcoholic steatohepatitis (NASH). However, the cellular mechanism of fructose-induced hepatic damage remains poorly understood. This study aimed to determine whether fructose induces cell death in primary hepatocytes, and if so, to establish the underlying cellular mechanisms. Our results revealed that treatment with high fructose concentrations for 48 h induced mitochondria-mediated apoptotic death in mouse primary hepatocytes (MPHs). Endoplasmic reticulum stress responses were involved in fructose-induced death as the levels of phosho-eIF2α, phospho-C-Jun-N-terminal kinase (JNK), and C/EBP homologous protein (CHOP) increased, and a chemical chaperone tauroursodeoxycholic acid (TUDCA) prevented cell death. The impaired oxidation metabolism of fatty acids was also possibly involved in the fructose-induced toxicity as treatment with an AMP-activated kinase (AMPK) activator and a PPAR-α agonist significantly protected against fructose-induced death, while carnitine palmitoyl transferase I inhibitor exacerbated the toxicity. However, uric acid-mediated toxicity was not involved in fructose-induced death as uric acid was not toxic to MPHs, and the inhibition of xanthine oxidase (a key enzyme in uric acid synthesis) did not affect cell death. On the other hand, treatment with inhibitors of the nicotinamide adenine dinucleotide (NAD)⁺-consuming enzyme CD38 or CD38 gene knockdown significantly protected against fructose-induced toxicity in MPHs, and fructose treatment increased CD38 levels. These data suggest that CD38 upregulation plays a role in hepatic injury in the fructose-enriched diet-mediated NASH. Thus, CD38 inhibition may be a promising therapeutic strategy to prevent fructose-enriched diet-mediated NASH.

• 운동영양학회지
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• 제17권2호
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• pp.35-42
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• 2013

The purpose of this study was to identify the effects of gene expression of endoplasmic reticulum (ER) stress in skeletal muscle and adipose tissue on acute exhaustive exercise. Thirty-five Sparague Dawley male rats were divided into a control group (CON, n = 7) and a exhaustive exercise group (n = 28), immediately after exhaustive exercise group (n = 7), after 30 minutes exhaustive exercise group (n = 7), after 60 minutes exhaustive exercise group (n = 7), after 180 minutes exhaustive exercise group (n = 7). As a result, changes in the composition of the blood serum triglyceride concentration increased significantly in immediately after exhaustive exercise group, On the contrary, blood glucose showed a significantly decreased (p < .05). Homeostasis of energy metabolism due to exhaustive exercise as a result of the mechanism of action of skeletal muscle in the glycogenolysis and absorption, which indicates that the process of means. On the other hand, a result of examining changes in endoplasmic reticulum stress-related proteins in skeletal muscle and adipose tissue, JNK1 except in skeletal muscle BiP, ATF4, CHOP, GRP78 mRNA increased significantly immediately after exercise, and after 30 minutes returned to normal levels that could be confirmed (p < .05). BiP mRNA in adipose tissue show a similar pattern and skeletal muscle increased significantly immediately after exercise, but other changes in the specificity of the endoplasmic reticulum stress-related proteins also did not appear. In conclusion, Exercise applies and exercise training duration and exercise intensity as well as research on the interaction of the endoplasmic reticulum stress-related genes should be study continuously, to be more clear.

• 생명과학회지
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• 제19권11호
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• pp.1637-1643
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• 2009

천연생약 자초의 한 성분인 shikonin은 항염증, 항암 및 항비만 등 다양한 분야에 효과를 보여왔다. 이번 연구에서는 shikonin이유도하는 adipogenesis억제 과정에 어떤 인자들이 작용하는지 살펴보았다. Shikonin의 효과에 대한 분자적 메커니즘을 규명하기 위해, real-time PCR을 이용하여 C/EBPs, $PPAR{\gamma}$를 포함한 다양한 adipogenesis 인자들의 mRNA 발현량을 분석하였다. 그 결과, 초기 분화의 주요 조절자인 C/$EBP{\beta}$와 C/$EPB{\delta}$는 shikonin에 의해 거의 변화가 없었으나, 후기 분화의 주요 조절자인 $PPAR{\gamma}$와 C/$EPB{\alpha}$의 mRNA 발현은 유의하게 감소하였다. Shikonin에 의한 adipogenesis억제의 메커니즘을 좀 더 자세히 밝히기 위해 adipogenesis과정의 상위 단계에 위치한 조절자들의 mRNA 발현을 분석하였다. C/$EBP{\beta}$의 상위 조절자인 C/$EBP{\gamma}$, CHOP은 shikonin에 의해 영향을 받지 않았으나, KROX20의 경우 유의하게 감소하였다. 이러한 결과는 Pro-adipogenic 인자인 KROX20의 감소가 C/$EBP{\beta}$에 영향을 주기 보다는 C/$EBP{\beta}$와 독립적으로 그 하위의 인자들에게 영향을 줄 수 있음을 제시한다. $PPAR{\gamma}$의 상위 조절자로 알려져 있는 KLF 들 중에서 pro-adipogenic 인자인 KLF15의 mRNA 발현은 shikonin에 의해 급격히 감소하였으나 anti-adipogenic 인자인 KLF2는 shikonin에 의한 변화가 거의 없었다. 또 다른 pro-adipogenic 인자인 KLF5의 경우, 주로 작용하는 초기 분화에서는 shikonin에 의해 거의 변화가 없었지만, 후기 분화에서는 조금 증가하였다. 이러한 후기 분화에서의 KLF5의 변화는 KLF15에 비해 전체 분화에 크게 영향을 주지 못하는 것 같다. 결론적으로, shikonin은 pro-adipogenic 인자인, KROX20과 KLF15의 조절을 통해 $PPAR{\gamma}$ 및 C/$EPB{\alpha}$의 mRNA 발현을 억제함으로써 지방 세포의 분화를 저해한다고 사료된다.

• 대한두경부종양학회지
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• 제16권1호
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• pp.33-36
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• 2000

Objectives: Angiocentric T-cell lymphoma of the head and neck is an angiocentric and angiodestructive lymphoreticular proliferative disorder. It has been treated with various treatment modalities, but its prognosis is poor and the treatment modality is controversial. We performed this study to suggest a treatment modality with improved results. Materials and Methods: We studied 40 cases of pathologically confirmed angiocentric T-cell lymphoma from July 1984 to December 1996, 35 cases of which showed complete response after initial treatment. All the patients were divided into two groups according to treatment modality. 15 cases received radiotherapy alone (Group I) and 20 cases received radiotherapy after five cycles of CHOP-Bleo chemotherapy(Group II). We analyzed the subsites of tumor, stage, treatment modality and treatment outcome and causes of failure for each group, and compared the three-year no evidence of disease(NED) between the two groups. Results: The three-year NED of a combined chemoradiotherapy was higher than that of a radiotherapy alone (p=0.0478). The three-year NED according to groups and stage were as follows: Group I=6/15(40.0%), stage IE=5/10(50.0%), stage IIE=1/5(20%), Group II=13/20(65.0%), stage IE=9/13(69.2%), stage IIE=4/7(57.1%). Radiotherapy alone is not well effective for the nasal cavity lymphoma extended to paranasal sinus and the palate. Conclusion: We are unable to provide clear guidelines for treatment, but recommend the initial treatment with oral alkylating agents and steroids followed by radiotherapy for Ann Arbor stage II tumors and stage I of the palate lymphoma and the nasal cavity lymphoma extended to paranasal sinus.

• 한국근적외분광분석학회:학술대회논문집
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• 한국근적외분광분석학회 2001년도 NIR-2001
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• pp.1256-1256
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• 2001

The physico-chemical and texture characteristics of meat determine the nutritional, technological and sensory quality. However, the analysis of meat quality requires expensive, laborious and time consuming analytical methods. The objective of this study was to evaluate NIR spectroscopy using transmittance for determining the moisture, fat, protein and total pigment content, the water holding capacity (WHC) and the toughness of beef meat. A total of 318 spectra were recorded from ground beef samples by a Feed Analyzer 1265 of Infratec. The samples were obtained from the Longissimus muscle of the 10$^{th}$ rib of yearling bulls, ground with an electrical chopper, vacuum packaged, aged during 7 days and frozen at -24$^{\circ}C$ until the analyses were done. Moisture content was measured by oven drying at 10$0^{\circ}C$, fat content was determined by Soxhlet extraction and protein content was estimated from nitrogen content using the Kjeldahl analysis. The total pigment content was determined by the method of Hornsey and the WHC using the method of filter paper press. The instrumental evaluation of texture (maximum load WB, maximum stress MS and toughness) was conducted in an Instron equipment with a Warner-Bratzler shearing device. This analysis was performed on a chop of 3.5 cm obtained from the longissimus of the 8$^{th}$ rib, aged during 7 days, kept frozen at -24$^{\circ}C$ and cooked before the analysis. Near infrared spectra were recorded as log 1/T (T=transmittance) at 2 nm intervals from 850 to 1050 nm using a Feed Analyzer 1265 of Infratec. Calibrations were performed with the WinISI software (vs. 1.02) using the MPLS method. To examine the effect of scatter correction o. derivation of spectra on the calibration performance, calibrations were calculated with the crude spectra or pretreated with different mathematical treatments (inverse MSC, SNVD) and/or second derivative operation. For chemical composition, the use of the scatter corrections improved the calibration statistics, in terms of lower SECV and higher $r^2$. In most of the variables, the use of the 2$^{nd}$ derivative improved the predictions, mainly when combined with the SNVD treatment. However, for predicting the texture traits, the best estimation was obtained from the crude spectrum. These results showed that the equations obtained for predicting moisture, fat and total pigments were very accurate, with $r^2$ being higher that 0.9. However, the prediction of the texture traits (WB, MS, toughness) from ground meat was poor.

• 대한두경부종양학회지
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• 제12권1호
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• pp.16-21
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• 1996

Lymphomatoid granulomatosis, polymorphic reticulosis, midline malignant reticulosis, or lethal midline granuloma have similar histologic features of an angiocentric and angiodestructive lymphoreticular proliferation representing the same nosologic entity. The term 'angiocentric immunoproliferative lesion' (AIL) was proposed by Jaffe, Costa, and Martin. The malignant potential of AILs is originally uncertain, but the facts that AILs have a relatively short survival, and most of them usually progress to an overt malignant lymphoma and survival is inversely proportional to the large, atypical lymphoreticular cells suggest that AILs are malignane. We experienced 17 AILs in nose during 16-year period and retrogradely analized them to recognize the problems in the diagnosis and to establish the further therapeutic strategies. The results were as follows; Twelve of total 17 patients who had diagnosed as histologic grade 1 and 2 had received radiation therapy as an initial treatment and the complete response rate was 91.7%(11/12), but 6 out of 11 had local recurrence and 5 had progress to overt maligant lymphoma within 2years. Three patients with the histologic grade 3 and 2 with unclear histologic grade had received CHOP chemotherapy and there was 1 case with complete response. Two patients with unclear histologic grade had been proved to be malignant histiocytosis by bone marrow biopsy during the clinical course. The overall duration of survival was 2 - 119 months and the 5-year survival rate was 71.9%. And the achievement of initial complete response was the most important prognostic factor of overall survival(P=0.006). Our results suggest that the treatment strategy according to the histologic grading scheme is efficient and more aggressive combination chemotherapy may be necessary to achieve complete response in patients with histologic grade III and II, because most of them progress to overt malignant lymphoma during its process.

• Radiation Oncology Journal
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• 제13권2호
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• pp.129-142
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• 1995

Purpose: Traditionally the patients with early stage non-Hodgkin's lymphoma of the head and neck was treated with radiotherapy. But the results were not satisfactory due to distant relapse. Although combined treatment with radiotherapy and chemotherapy was tried with some improved results and chemotherapy alone was also tried in recent years, the choice of treatment for the patients with early stage non-Hodgkin's lymphoma of the head and neck has not been defined Therefore, in order to determine the optimum treatment method, we analysed retrospectively the outcomes of the patients with Ann Arbor stage I and II non-Hodgkin's lymphoma localized to the head and neck who were treated at Severance Hospital. Materials and Methods: 159 patients with stage I and II non-Hodgkin's lymphoma localized to the head and neck were treated at our hospital from January, 1979 to December, 1992. Of these patients, 114 patients whose primary sites were Waldeyer's ring or nodal region, and received prescribed radiation dose and/or more than 2 cycles of chemotherapy. were selected to analyze the outcomes according to the treatment methods ( radiotherapy alone, chemotherapy alone. and combined treatment with radiotherapy and chemotherapy ). Results: Five year overall actuarial survival of the patients whose Primary site was Waldeyer's ring was $62.5\%.$ and that of the Patients whose primary site was nodal region was $53.8\%$ There was no statistically significant difference between survivals of both groups. Initial response rate to radiotherapy. chemotherapy, and combined treatment was $92\%,\;83\%,\;94\%$ respectively, and 5 year relapse free survival was $49.9\%,\;52.4\%,\;58.5\%$ respectively ( statistically not significant ). In the patients with stage I. 3 year relapse free survival of chemotherapy alone group was $75\%$ and superior to other treatment groups. In the Patients with stage II, combined treatment group revealed the best result with $60.1\%$ of 3 year relapse free survival. The effect of sequential schedule of each treatment method in the Patients who were treated by combined modality was analyzed and the sequence of primary chemotherapy + radiotherapy + maintenance chemotherapy showed the best result ( 3 year relapse free survival was $79.1\%).$ There was no significant survival difference between BACOP regimen and CHOP regimen. Response to treatment was only one significant (p(0.005) prognostic factor on univariate analysis and age and mass size was marginally significant ( p(0.1). On multivariate analysis, age (p=0.026) and mass size (p=0.013) were significant prognostic factor for the relapse free survival. Conclusion: In summary, the patients who have non-Hodgkin's lymphoma of the head and neck with stage I and mass size smaller than 10 cm, can be treated by chemotherapy alone, but remainder should be treated by combined treatment method and the best combination schedule was the sequence of initial chemotherapy followed by radiotherapy and maintenance chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6267-6272
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• 2015

Background: Extra nodal lymphoma (ENL) constitutes about 33 % of all non-Hodgkin's lymphoma. 18-28% develops in the head and neck region. A multimodality treatment with multi-agent chemotherapy (CT) and radiotherapy (RT) is considered optimum. Materials and Methods: We retrieved the treatment charts of patients of HNENL treated in our institute from 2001-2012. The charts were reviewed and the demographic, treatment details and outcome of HNENL patients were retrieved using predesigned pro-forma. Results: We retrieved data of 75consecutive patients HNENL. Median age was 47years (Range: 8-76 years). Of the 75 patients 51 were male and 24 were female. 55patients were evaluable. The patient and tumor characteristics are summarized in Table 1. All patients were staged comprehensively with contrast enhanced computed tomography of head, neck, thorax, abdomen, pelvis and bone marrow aspiration and biopsy 66 patients received a combination multi-agent CT with CHOP being the commonest regimen. 42 patients received 4 or lesser number of cycles of chemotherapy whereas 24received more than 4 cycles chemotherapy. Post radiotherapy, 41 out of 42 patients had a complete response at 3 months. Only 21patients had a complete response after chemotherapy. All patients received radiation (mostly involved field radiation) as a part of the treatment. The median radiation dose was 45 Gray (Range: 36 Gray-50 Gray). The radiation was planned by 2D fluoro simulation based technique in 37cases and by 3 Dimensional conformal radiation therapy (3DCRT) in 36 cases. Two patients were planned by the intensity modulated radiation therapy (IMRT) technique. IMRT was planned for one thyroid and one nasal cavity primary. 5 patients experienced relapse after a median follow up of 19 months. The median survival was not reached. The estimated two and three year survival were 92.9% (95%CI- 68.6- 95.35) and 88% (95%CI- 60.82 - 92.66) respectively. Univariate analysis revealed higher stage and poorer baseline performance status to be significantly associated with worse progression free survival. 5 patients progressed (relapse or primary disease progression) after treatment. Of the 5 patients, two patients were primary orbital NHL, two patients had NHL nasal cavity and one was NHL thyroid. Conclusions: Combined modality treatment in HNENL confers excellent disease control with acceptable side effects.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7207-7211
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• 2014

Background: The aim of this study was to assess the epidemiological and clinicopathological characteristics of primary extranodal non-Hodgkin's lymphoma (pENL) patients, focusing on treatment and survival outcome. Materials and Methods: Between October 2003 and March 2012, 802 patients with non-Hodgkin's lymphoma (NHL) were diagnosed and treated in two different cancer centers of Southern Turkey. Results: pENL, constituted 12.4% (100/802) of all NHL studied during this period. Median age of the patients was 56 years (range 17-87 years) and the male: female distribution was 3:2. Eighty-five of 100 patients (85%) were in stage I/II, 9/100 (9%) in stage III, whereas 6/100 (6%) were in stage IV. Head and neck constituted the most common site (51/100, 51%), followed by gastrointestinal tract (GIL) (37/100, 37%), and cerebrum (CL) (5/100, 5%). Diffuse large B cell lymphoma (DLBCL) was the most common histological type, observed in 53% of patients, followed by marginal zone extranodal lymphoma (13%). Most of patients (76%) received a CHOP containing regimen. Complete remission (CR) were achieved in 71% of patients. The median follow-up duration of all patients was reported as 37.6 months (range, 0.8-165 months). This period was reported as 137.5 months (range, 117.5-1578.6 months) in gastrointestinal lymphoma (GIL) patients, 119.0 months (range, 91.8-146.1 months) in head and neck lymphoma (HNL) patients, and 18.4 months (range, 12.6-24.1 months) in cerebral lymphoma (CL) patients. Conclusions: Head and neck, and the gastrointestinal tract were the two most common extranodal sites observed. Histologically DLBC accounted for the majority of cases. Most patients were on earlier stages, had low-low intermediate IPI scores and had a favorable prognosis.

• 대한두경부종양학회지
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• 제15권1호
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• pp.22-28
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• 1999

Purpose: We performed this study retrospectively to evaluate local control, survival, prognostic factors, and failure patterns in patients with non-Hodgkin's lymphoma of Waldeyer's ring. Materials and Methods: From April 1984 to November 1996,41 patients with non-Hodgkin's lymphoma of Waldeyer's ring were treated with combined chemotherapy and radiation therapy. Age was ranged from 19 to 73 years old with a median age of 55 years, and there were 26 male and 15 female patients. Primary site was tonsil in 26 and base of the tongue in 7 and nasopharynx in 8, and stage distribution showed stage I in 12 and stage II in 29 patients. Pathologic classification was done according to Working Formulation. There were 1 with follicular mixed small cleaved and large cell, 8 with diffuse small cleaved cell, 7 with diffuse mixed small and large cell, and 25 cases with diffuse large cell. All patients were treated with combination of chemotherapy and radiation therapy. Chemotherapy regimen consisted of either CHOP-Bleo(cyclophosphamide, adriamycin, vincristine, prednisolone, bleomycin) or COP-BLAM III(cyclophosphamide, vincristine, prednisolone, bleomycin, adriamycin, procarbazine). Radiation dose ranged from 3600cGy to 6620cGy with a median dose of 5040cGy. Follow-up time was ranged from 15 months to 159 months(median 55 months). Results: The complete response was achieved in 98%(40/41) and partial response in 2%(1/41). The complete response rate were the followings: 66.7% for stage I and 51.7% for stage II after chemotherapy, 100% for stage I and 96.6% for stage II after overall treatment respectively. The overall survival rate and disease-tree survival rates at 5 years were 82.6% and 79.5%, respectively. Prognostic factors for overall survival were age(p=0.007), stage(p=0.03), nodal status(p=0.006) and radiation dose(p=0.003). The factors associated with disease-tree survival were stage(p=0.04), nodal status(p=0.004) and radiation dose(p=0.009). The failure patterns were analized in evaluable 35 patients with complete response. Locoregional failure was noted in 2 patients and distant metastasis in 5 patients. Conclusion: Our results suggest that combined modality therapy is the appropriate treatment for stage I-II intermediate grade non-hodgkin's lymphoma of the Waldeyer's ring. However, our material is small and the analysis is retrospective. Randomized prospective studies for combined therapy, radiation therapy alone and chemotherapy alone are needed.