• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.267-280
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• 2024

Apoptosis, programmed cell death pathway, is a vital physiological mechanism that ensures cellular homeostasis and overall cellular well-being. In the context of cancer, where evasion of apoptosis is a hallmark, the overexpression of anti-apoptotic proteins like Bcl2, Bcl-xL and Mcl-1 has been documented. Consequently, these proteins have emerged as promising targets for therapeutic interventions. The BCL-2 protein family is central to apoptosis and plays a significant importance in determining cellular fate serving as a critical determinant in this biological process. This review offers a comprehensive exploration of the BCL-2 protein family, emphasizing its dual nature. Specifically, certain members of this family promote cell survival (known as anti-apoptotic proteins), while others are involved in facilitating cell death (referred to as pro-apoptotic and BH3-only proteins). The potential of directly targeting these proteins is examined, particularly due to their involvement in conferring resistance to traditional cancer therapies. The effectiveness of such targeting strategies is also discussed, considering the tumor's propensity for anti-apoptotic pathways. Furthermore, the review highlights emerging research on combination therapies, where BCL-2 inhibitors are used synergistically with other treatments to enhance therapeutic outcomes. By understanding and manipulating the BCL-2 family and its associated pathways, we open doors to innovative and more effective cancer treatments, offering hope for resistant and aggressive cases.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.28 no.1
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• pp.34-41
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• 2024

Backgrounds/Aims: Liver transplantation (LT) provides a favorable outcome for patients with hepatocellular carcinoma (HCC) and was launched in Vietnam in 2004. In this study, we evaluated the short-term and long-term outcomes of LT and its risk factors. Methods: This retrospective study analyzed HCC patients who underwent LT at Viet Duc University hospital, Vietnam, from 01/2012-03/2022. The following data were gathered: demographics, virus infection, tumor characteristics, alpha-fetoprotein (AFP) level, Child-Pugh and MELD scores, selection criteria, type of LT, complications, 30-day mortality, and disease-free and overall survival (DFS and OS). Results: Fifty four patients were included, the mean age was 55.39 ± 8.46 years. Nearly 90% had hepatitis B virus-related HCC. The median (interquartile range) AFP level was 16.2 (88.7) ng/mL. The average MELD score was 10.57 ± 5.95; the rate of Child-Pugh A and B were 70.4% and 18.5%, respectively. Nearly 40% of the patients were within Milan criteria, brain-dead donor was 83.3%. Hepatic and portal vein thrombosis occurred in 0% and 1.9%, respectively; hepatic artery thrombosis 1.9%, biliary leakage 5.6%, and postoperative hemorrhage 3.7%. Ninety-day mortality was 5.6%. Five-year DFS and OS were 79.3% and 81.4%, respectively. MELD score and ChildPugh score were predictive factors for DFS and OS (p < 0.05). In multivariate analysis, Child-Pugh score was the only significant factor (p < 0.05). Conclusions: In Vietnam, LT is an effective therapy for HCC with an acceptable complication rate, mortality rate, and good survival outcomes, and should be further encouraged.

• International Journal of Oncology
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• v.56 no.2
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• pp.618-629
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• 2020

Bcl2l10, also known as Diva, Bcl-b and Boo, is a member of the Bcl2 family of proteins, which are involved in signaling pathways that regulate cell apoptosis and autophagy. Previously, it was demonstrated that Bcl2l10 plays a crucial role in the completion of oocyte meiosis and is a key regulator of Aurora kinase A (Aurka) expression and activity in oocytes. Aurka is overexpressed in several types of solid tumors and has been considered a target of cancer therapy. Based on these previous results, in the present study, the authors aimed to investigate the regulatory role of Bcl2l10 in A2780 and SKOV3 human ovarian cancer cells. The protein expression of Bcl2l10 was examined in human cancer tissues and cell lines, including the ovaries, using a tissue microarray and various human ovarian cancer cell lines. It was found that Bcl2l10 regulated the protein stability and activities of Aurka in ovarian cancer cells. Although apoptosis was not affected, the cell cycle was arrested at the G0/G1 phase by Bcl2l10 knockdown. Of note, cell viability and motility were markedly increased by Bcl2l10 knockdown. On the whole, the findings of this study suggest that Bcl2l10 functions as tumor suppressor gene in ovarian cancer.

• Journal of Yeungnam Medical Science
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• v.41 no.4
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• pp.306-311
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• 2024

We report a case of a ruptured triple hormone-secreting adrenal mass with hyperaldosteronism, hypercortisolism, and elevated normetanephrine levels, diagnosed as adrenal cortical carcinoma (ACC) by histology. A 53-year-old male patient who initially presented with abdominal pain was referred to our hospital for angiocoagulation of an adrenal mass rupture. Abdominal computed tomography revealed a heterogeneous 19×11×15 cm right adrenal mass with invasion into the right lobe of the liver, inferior vena cava, retrocaval lymph nodes, and aortocaval lymph nodes. Angiocoagulation was performed. Laboratory evaluation revealed excess cortisol via a positive 1-mg overnight dexamethasone suppression test, primary hyperaldosteronism via a positive saline infusion test, and plasma normetanephrine levels three times higher than normal. An adrenal mass biopsy was performed for pathological confirmation to commence palliative chemotherapy because surgical management was not deemed appropriate considering the extent of the tumor. Pathological examination revealed stage T4N1M1 ACC. The patient started the first cycle of adjuvant mitotane therapy along with adjuvant treatment with doxorubicin, cisplatin, and etoposide, and was discharged. Clinical cases of dual cortisol- and aldosterone-secreting ACCs or ACCs presenting as pheochromocytomas have occasionally been reported; however, both are rare. Moreover, to the best of our knowledge, a triple hormone-secreting ACC has not yet been reported. Here, we report a rare case and its management. This case report underscores the necessity of performing comprehensive clinical and biochemical hormone evaluations in patients with adrenal masses because ACC can present with multiple hormone elevations.

• Yonsei Medical Journal
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• v.63 no.5
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• pp.405-412
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• 2022

Purpose We evaluated the safety, feasibility, and early treatment outcomes of intraoperative radiotherapy (IORT) using a low-energy X-ray source. Materials and Methods Patients with resectable pancreatic cancer were enrolled in this single-institution, prospective, single-arm, phase II trial. Patients underwent surgery and IORT with 10 Gy prescribed at a 5-mm depth from the tumor bed using a 50 kV X-ray source (Intrabeam, Carl Zeiss). Six cycles of adjuvant gemcitabine-based chemotherapy were administered 8-12 weeks after surgery. Results A total of 41 patients were included. Thirty-one patients (75.6%) underwent wide R0 resection, while 5 (12.2%) underwent R1 resection and 5 (12.2%) underwent narrow R0 resection (retroperitoneal margin <1 mm). Grade 3 postoperative complications were reported in only one patient (4.9%) who needed additional surgery due to ulcer perforation. At a median follow-up of 9 months, four patients showed local-only recurrence, nine had distant metastases, and two showed both local and distant recurrence. The 1-year local control rate was 76.4%. Conclusion Our preliminary report suggests that IORT is well-tolerated and feasible in patients with resectable pancreatic cancer. Further follow-up is needed to confirm the clinical benefits of IORT in terms of local control and overall survival. Trial Registration: Clinical trial registration No. (NCT03273374).

• Clinical and Experimental Vaccine Research
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• v.11 no.2
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• pp.163-172
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• 2022

Purpose: Epithelial ovarian carcinoma (EOC) is the most lethal of all human gynecologic malignancies. We previously reported that vaccination of female mice with the extracellular domain of anti-Müllerian hormone receptor II (AMHR2-ED) in complete Freund's adjuvant (CFA) generates AMHR2-ED specific immunoglobulin G (IgG) that provides prevention and therapy against murine EOCs. Although CFA is the "gold standard" adjuvant in animal studies, it is not approved for human use because it often induces painful granulomas and abscesses. Thus, the objective of this study is to identify an alternative adjuvant to CFA for use in our ovarian cancer vaccine clinical trials. Materials and Methods: Because it has been used successfully without serious adverse effects in numerous human clinical trials, we selected the IgG-inducing squalene-based adjuvant, AddaVax^TM, for evaluation of its ability to facilitate vaccine-induced prevention and treatment of EOC in mice. To this end, we immunized female C57BL/6 mice with recombinant mouse AMHR2-ED emulsified with either AddaVax or CFA as adjuvant and compared the results. Results: We found that formulation of the AMHR2-ED vaccine with AddaVax adjuvant induced high serum titers of IgG and significant inhibition of EOC growth with significantly enhanced overall survival of mice using both prevention and therapeutic protocols. These results were compared favorably with results obtained using CFA as an adjuvant in the AMHR2-ED vaccine. Conclusion: Our data indicate that the AMHR2-ED vaccine formulated with AddaVax may be used in human clinical trials and thereby serve as a novel and effective way to control human EOC.

• Radiation Oncology Journal
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• v.9 no.1
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• pp.123-130
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• 1991

A docking intraoperative electron beam applicator system, which is easily docking in the collimator for a linear accelerator after setting a sterilized transparent cone on the tumor bearing area in the operation room, has been designed to optimize dose distribution and to improve the efficiency of radiation treatment method with linear accelerator. This applicator system consisted of collimator holder with shielded metals and docking cone with transparent acrylic cylinder, A number of technical innovations have been used in the design of this system, this dooking cone gives a improving latral dose coverage at therapeutic volume. The position of $90\%$ isodose curve under suface of 8 cm diameter cone was extended $4\sim7$ mm at 12 MeV electron and the isodose measurements beneath the cone wall showed hot spots as great as $106\%$ for acrylic cone. The leakage radiation dose to tissues outside the cone wall was reduced as $3\sim5\%$ of output dose. A comprehensive set of dosimetric characteristics of the intraoperative radiation therapy applicator system is presented.

• Progress in Medical Physics
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• v.22 no.2
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• pp.72-78
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• 2011

The aim of this study is to evaluate the patient's setup errors in TomoTherapy (Hi-Art II, TomoTherapy, USA) Bodyfix system (Medical Intelligence, Ele-kta, Schwabmuchen, Germany) pressure in the vacuum compression, depending on and were evaluated. Bodyfix immobilization system and vacuum pressure was compression applied to the patients who received Tomotherapy thoracic and abdominal area, 21 patients were selected and TomoTehpay treatment total 477 of MVCT images were obtained. The translational (medial-lateral: ML, anterior-posterior: AP, superior-inferior: SI directions) and rolling were recorded and analyzed statistically. Using Pearson's product-moment coefficient and One-way ANOVA, the degree of correlation depending on the different vacuum pressure levels were statistically analyzed for setup errors from five groups (p<0.05). The largest average and standard deviation of systematic errors were 6.00, 5.95 mm in the AP and SI directions, respectively. The largest average of random errors were 4.72 mm in the SI directions. The correlation coefficients were 0.485, 0.244, and 0.637 for the ML-Roll, AP-Vector, and SI-Vector, respectively. SI-Vector direction showed the best relationship. In the results of the different degree of vacuum pressure in five groups (Pressure range: 30~70 mbar), the setup errors between the ML, SI in both directions and Roll p=0.00 (p<0.05) were shown significant differences. The average errors of SI direction in the vacuum pressure of 40 mbar and 70 mbar group were 4.78 mm and -0.74 mm, respectively. In this study, the correlation between the vacuum pressure and the setup-errors were statistically analyzed. The fact that setup-errors in SI direction is dependent in vacuum pressure considerly setup-errors and movement of interal organs was identified. Finally, setup-errors, and it, based on the movement of internal organs in Bodyfix system we should apply more than 50 mbar vacuum pressure. Based on the results of this study, it is suggested that accuracy of the vacuum pressure and the quantitative analysis of movement of internal organs and the tumor should be studied.

• Radiation Oncology Journal
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• v.11 no.1
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• pp.69-77
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• 1993

Treatment of cerebellar medulloblastoma has been much improved with modern surgical technique for gross total tumor removal and adequate radiation therapy for the whole craniospinal axis. Questions have been arosen about the optimal radiation dose for the preventive treatment of whole cranium and whole spinal axis. Recently, many authors have reported their treatment results as comparable to older data, using lower than conventional dose of 3,600 cGy-4,000 cGy. For 50 patients treated between 1981 and 1990 at the Department of Radiation Therapy of SNUH, retrospective analysis was done for the treatment result, especially the neuraxis control, by radiation dose for the presymptomatic area of the disease. Analysis only by total spinal dose did not give any significant difference. But further analysis by following patient group; 3,600 cGy/150 cGy (n=6), 3,000 cGy/150 cGy (n=10), 2,400 cGy/150 cGy (n=17) and 2,400 cGy/100-120 cGy (n=11) showed significant improvement of neuraxis control by decreasing order (p =0.003). There was no significant difference in overall survival between the groups. For the 19 patients who had been confirmed initially as having no neuraxis disease, TDF 30 was the cur-off value that could prevent neuraxis failure (p =0.004). We couldn't define any TDF value that give reasonable control for the patient group with positive CSF study at initial diagnosis.

• Radiation Oncology Journal
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• v.12 no.1
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• pp.81-90
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• 1994

Purpose : The aim of this study is to analyze the clinical results of thermo-irradiation treatment for surgically unresectable advanced hepatoma with or without hepatic arterial chemo-embolization (HACE), chemotherapy (CT) and interferon (IFN) therapy. Materials and Methods : Between February 1990 and December 1992, 45 Patients with surgically unresectable advanced hepatomas were treated by thermo-irradiation with or without hepatic arterial chemo-embolization and other treatment modalities. Among them, We analyzed retrospectively 25 patients who received more than three times of hyperthermias. Mean age was 50 years (range : 18-71 years) and male to female ratio was 20 : 5. In the study, treatment was administered as follows : 3 patients received radiation therapy(RT) and hyperthermia (HT). 3 received RT+HT+CT. 3 received RT+HT+HACE. 1 received RT+HT+CT+HACE. 2 received RT+HT+CT+IFN. 10 received RT+HT+HACE+IFN. 3 received RT+HT+CT+HACE+IFN. Radiation therapy was done by a 6 MV linear accelerator Patients were treated with daily fractions of 180 cGy to doses of 11Gy-50Gy (median 30Gy). Local hyperthermia was done by HEH-500C(Omron Co. Japan), 30-45 min/session, 2 sessions/wk and the number of HT sessions ranged from 3 to 17 (median 7 times). 15 patients of 25 were followed by abdominal CT scan or abdominal ultra-sonogram. The following factors were analyzed :Age, histologic grade, sex. number of hyperthermia, total RT dose, hepatic arterial chemo-embolization. Results : Of 25 patients. there were observed tumor regression (partial response and minimal response) in 6 (24$ \% $), no response in 8 (32$ \% $), progression in 1 (4$ \% $) and not evaluable ones in 10 (40$ \% $) radiographically. The over all 1-year survival was 25$ \% $, with a mean survival of 33 weeks. The treatment modes of partial and minimal responsive patients (PR+MR)were as follows : Two were treated with RT+HT+HACE, 2 were done with RT+HT+HACE+IFN Remaining 2 were treated with RT+HT+CT+HACE+IFN. The significant factor affecting the survival rate were RT dose (more than 25 Gy), HACE, number of HT (above 6 times), responsiveness after treatment (PR + MR). Age, sex, histologic differentiation, chemotherapy, interferon therapy were not statistically significant factors affecting the survival rate. Conclusion : Although follow-up duration was short, the thermo-irr3diBtion with/without hepatic arterial chemo-embolization was well tolerated and there were no serious complicatons. In future, it is considered the longer follow up and prospective, well controlled trials should be followed to evaluate the efficacies of survival advantage.