Objective: Regional control is occasionally unsatisfactory in cervical cancer, with the optimal radiation dose for nodal metastases in definitive radiotherapy (RT) with concurrent chemotherapy (CRT) remaining controversial. We investigated dose-response relationship for nodal local control in cervical cancer. Methods: We identified 115 patients with 417 metastatic nodes who received definitive CRT for cervical cancer with nodal metastases. External beam radiation therapy and brachytherapy plans were summated to determine total dose received by each node. Prognostic factors of nodal control and dose-response relationship were investigated using Cox-regression and restricted cubic spline function. Results: The 2-year progression-free survival rate was 69.4%. Among 43 patients with failures, 17 patients (37.5%) had regional failure included in first failure sites of which all except one were in-field only regional failures. Total 30 nodes showed recurrence at initial metastatic site after treatment. Neutrophil-to-lymphocyte ratio (NLR) ≥3.1, total radiation dose (minimum dose received by 98% of the target volume in equivalent dose in 2 Gy per fractions), and initial nodal volume ≥5.29 mL were poor prognostic factors (all p<0.050) of nodal local control. Restricted cubic spline functions revealed strongest dose-response relationship in high NLR (NLR ≥3.1) and initial nodal volume ≥5.29 mL subgroup. Conclusion Initial nodal volume, radiation dose, and NLR were significant factors of nodal local control in cervical cancer; a stronger dose-response relationship was seen in bulky nodes with high NLR. Clinicians may consider these factors when determining the RT dose and the need for boost to nodal metastases in cervical cancer.

Background: Increased sebum secretion is considered the main causative factor in the pathogenesis of acne. There is an unmet pharmacological need for a novel drug that can control sebum production with a favorable adverse effect profile. Objective: To investigate the effect of azidothymidine on lipid synthesis in sebocytes and to identify the underlying mechanism of the inhibitory effect of azidothymidine on insulin-like growth factor (IGF)-1-induced lipid synthesis in sebocytes. Methods: Immortalized human sebocytes were used for the analysis. Thin-layer chromatography (TLC) and Oil Red O staining were performed to evaluate lipid synthesis in the sebocytes. The differentiation, lipid synthesis, mitochondrial biogenesis, and mitophagy in sebocytes were investigated. Results: TLC and Oil Red O staining revealed that azidothymidine reduced IGF-1 induced lipid synthesis in the immortalized human sebocytes. Azidothymidine also reduced IGF-1-induced expression of transcriptional factors and enzymes involved in sebocyte differentiation and lipid synthesis, respectively. Moreover, we found that IGF-1 upregulated the levels of peroxisome proliferator-activated receptor-gamma coactivator-1α, LC-3B, p62, and Parkin, major regulators of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. In contrast, azidothymidine inhibited IGF-1 induced mitochondrial biogenesis and mitophagy in the sebocytes. Conclusion These results suggest that azidothymidine downregulates IGF-1-induced lipogenesis by dysregulating the quality of mitochondria through suppression of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. Our study provides early evidence that azidothymidine may be an effective candidate for a new pharmacological agent for controlling lipogenesis in sebocytes.

Background: Increased sebum secretion is considered the main causative factor in the pathogenesis of acne. There is an unmet pharmacological need for a novel drug that can control sebum production with a favorable adverse effect profile. Objective: To investigate the effect of azidothymidine on lipid synthesis in sebocytes and to identify the underlying mechanism of the inhibitory effect of azidothymidine on insulin-like growth factor (IGF)-1-induced lipid synthesis in sebocytes. Methods: Immortalized human sebocytes were used for the analysis. Thin-layer chromatography (TLC) and Oil Red O staining were performed to evaluate lipid synthesis in the sebocytes. The differentiation, lipid synthesis, mitochondrial biogenesis, and mitophagy in sebocytes were investigated. Results: TLC and Oil Red O staining revealed that azidothymidine reduced IGF-1 induced lipid synthesis in the immortalized human sebocytes. Azidothymidine also reduced IGF-1-induced expression of transcriptional factors and enzymes involved in sebocyte differentiation and lipid synthesis, respectively. Moreover, we found that IGF-1 upregulated the levels of peroxisome proliferator-activated receptor-gamma coactivator-1α, LC-3B, p62, and Parkin, major regulators of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. In contrast, azidothymidine inhibited IGF-1 induced mitochondrial biogenesis and mitophagy in the sebocytes. Conclusion These results suggest that azidothymidine downregulates IGF-1-induced lipogenesis by dysregulating the quality of mitochondria through suppression of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. Our study provides early evidence that azidothymidine may be an effective candidate for a new pharmacological agent for controlling lipogenesis in sebocytes.

BACKGROUND: Isoflurane, a common anesthetic for cardiac surgery, reduced myocardial contractility in many experimental studies, few studies have determined isoflurane's direct impact on the left ventricular (LV) contractile function during cardiac surgery. We determined whether isoflurane dose-dependently reduces the peak systolic velocity of the lateral mitral annulus in tissue Doppler imaging (S′) in patients undergoing cardiac surgery. METHODS: During isoflurane-supplemented remifentanil-based anesthesia for patients undergoing cardiac surgery with preoperative LV ejection fraction greater than 50% (n = 20), we analyzed the changes of S′ at each isoflurane dose increment (1.0, 1.5, and 2.0 minimum alveolar concentration [MAC]: T1, T2, and T3, respectively) with a fixed remifentanil dosage (1.0 μg/min/kg) by using transesophageal echocardiography. RESULTS: Mean S′ values (95% confidence interval [CI]) at T1, T2, and T3 were 10.5 (8.8–12.2), 9.5 (8.3–10.8), and 8.4 (7.3–9.5) cm/s, respectively (P < 0.001 in multivariate analysis of variance test). Their mean differences at T1 vs. T2, T2 vs. T3, and T1 vs. T3 were −1.0 (−1.6, −0.3), −1.1 (−1.7, −0.6), and −2.1 (−3.1, −1.1) cm/s, respectively. Phenylephrine infusion rates were significantly increased (0.26, 0.22, and 0.47 μg/kg/min at T1, T2, and T3, respectively, P < 0.001). CONCLUSION: Isoflurane increments (1.0–2.0 MAC) dose-dependently reduced LV systolic long-axis performance during cardiac surgeries with a preserved preoperative systolic function.
Anesthesia ; Echocardiography ; Echocardiography, Transesophageal ; Heart Function Tests ; Heart Valves ; Humans ; Isoflurane ; Multivariate Analysis ; Phenylephrine ; Thoracic Surgery

PURPOSE: The purpose of this study is to compare the treatment outcomes for locally advanced resectable hypopharyngeal cancer between organ-preserving chemoradiotherapy (CRT) and surgery followed by radiotherapy (SRT). MATERIALS AND METHODS: We reviewed 91 patients with stage III/IV hypopharyngeal squamous cell carcinoma treated with radiotherapy (RT). In the CRT group (n=34), 18 patients were treated with concurrent CRT and 16 patients with induction chemotherapy plus concurrent CRT. In the SRT group (n=57), six patients were treated with total laryngopharyngectomy, 34 patients with total laryngectomy (TL) and partial pharyngectomy (PP), and 17 patients with PP, which were followed by adjuvant radiotherapy (n=41) or CRT (n=16). The median RT dose was 70 Gy for CRT and 59.4 Gy for SRT. RESULTS: Five-year local control (84.1% vs. 90.9%), and disease-free survival (DFS, 51.0% vs. 52.7%) and overall survival (OS, 58.6% vs. 56.6%) showed no significant difference between the CRT and SRT groups. The functional larynx-preservation rate was higher in the CRT group (88.2% vs. 29.8%). Treatment-related toxicity, requiring surgical intervention, occurred more frequently in the SRT group (37% vs. 12%). In the SRT group, TL resulted in a significantly higher DFS than larynx-sparing surgery (63.9% vs. 26.5%, p=0.027). Treatment outcome of the SRT group improved when only patients with TL were considered (n=40); however, 5-year OS (67.1% vs. 58.6%, p=0.830) and DFS (63.9% vs. 51.0%, p=0.490) did not improve significantly when compared to the CRT group. CONCLUSION: Organ preserving CRT provided a treatment outcome that is comparable to SRT for locally advanced hypopharyngeal cancer, while offering an opportunity for functional larynx-preservation and reduced treatment-related toxicity.
Carcinoma, Squamous Cell ; Chemoradiotherapy* ; Disease-Free Survival ; Humans ; Hypopharyngeal Neoplasms* ; Induction Chemotherapy ; Laryngectomy ; Organ Preservation ; Pharyngectomy ; Radiotherapy ; Radiotherapy, Adjuvant* ; Treatment Outcome

PURPOSE: To evaluate the efficacy and safety of gemcitabine and carboplatin (GC) in the treatment of advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Between November 1999 and April 2001, 34 patients were enrolled in this study. The median age was 66 (range: 52-74) years old and all were male. Sixteen patients demonstrated stage IIIB, 15 stage IV, and 3 recurrence of disease after surgery. Twenty-two patients showed a ECOG performance status of 0 or 1 and 12 had 2. Twenty patients presented with squamous cell carcinoma, 11 adenocarcinoma and 3 unclassified NSCLC. The treatment regimen consisted of intravenous carboplatin AUC of 6 on day 1 and gemcitabine 1,250 mg/m2 on day 1 and 8. The treatment was repeated every 28 days. Toxicities were evaluated according to WHO toxicity criteria. RESULTS: All thirty-four patients were evaluable. Partia responses were observed in 15 patients. The overall response rate was 44% (95% confidence interval: 27-61%) and the median response duration was 26 (range 8-60 ) weeks. The median survival of all patients was 50 (range 8-70 ) weeks. During a total of 144 cycles, granulocytopenia greater than WHO grade 2 occurred in 2%, thrombocytopenia in 2%, and anemia in 3%, respectively. Non- hematologic toxicities were minor and easily controlled. CONCLUSION: A combination chemotherapy of intravenous gemcitabine and carboplatin has a relatively high activity with acceptable toxicities in patients with advanced NSCLC.
Adenocarcinoma ; Agranulocytosis ; Anemia ; Area Under Curve ; Carboplatin* ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Drug Therapy, Combination ; Humans ; Lung Neoplasms ; Male ; Recurrence ; Thrombocytopenia

PURPOSE: This study is a prospective randomized clinical trial comparing the efficacy and complication of anti-emetic drugs for prevention of nausea and vomiting after radiotherapy which has moderate emetogenic potential. The aim of this study was to investigate whether the anti-emetic efficacy of ondansetron (Zofran(R)) 8 mg bid dose (Group O) is better than the efficacy of metoclopramide 5 mg tid dose (Group M) in patients undergoing fractionated radiotherapy to the abdominal region. MATERIALS AND METHODS: Study entry was restricted to those patients who met the following eligibility criteria: histologically confirmed malignant disease; no distant metastasis; performance status of not more than ECOG grade 2; no previous chemotherapy and radiotherapy. Between March 1997 and February 1998, 60 patients enrolled in this study. All patients signed a written statement of informed consent prior to enrollment. Blinding was maintained by dosing identical number of tablets including one dose of matching placebo for Group O. The extent of nausea, appetite loss, and the number of emetic episodes were recorded everyday using diary card. The mean score of nausea, appetite loss and the mean number of emetic episodes were obtained in a weekly interval. RESULTS: Prescription error occurred in one patient. And diary cards have not returned in 3 patients due to premature refusal of treatment. Card from one patient was excluded from the analysis because she had a history of treatment for neurosis. As a result, the analysis consisted of 55 patients. Patient characteristics and radiotherapy charcteristics were similar except mean age was 52.9+/-11.2 in group M, 46.5+/-9.6 in group O. The difference of age was statistically significant. The mean score of nausea, appetite loss and emetic episodes in a weekly interval was higher in group M than O. In group M, the symptoms were most significant at 5th week. In a panel data analysis using mixed procedure, treatment group was only significant factor detecting the difference of weekly score for all three symptoms. Ondansetron (Zofran ) 8 mg bid dose and metoclopramide 5 mg tid dose were well tolerated without significant side effects. There were no clinically important changes in vital signs or clinical laboratory parameters with either drug. CONCLUSION: Concerning the fact that patients with younger age have higher emetogenic potential, there are possibilities that age difference between two treatment groups lowered the statistical power of analysis. There were significant difference favoring ondansetron group with respect to the severity of nausea, vomiting and loss of appetite. We concluded that ondansetron is more effective anti-emetic agents in the control of radiotherapy-induced nausea, vomiting, loss of appetite without significant toxicity, compared with commonly used drug, i.e., metoclopramide. However, there were patients suffering emesis despite the administration of ondansetron. The possible strategies to improve the prevention and the treatment of radiotherapy-induced emesis must be further studied.
Appetite ; Drug Therapy ; Humans ; Informed Consent ; Metoclopramide* ; Nausea* ; Neoplasm Metastasis ; Ondansetron* ; Prescriptions ; Prospective Studies* ; Radiotherapy* ; Statistics as Topic ; Tablets ; Treatment Refusal ; Vital Signs ; Vomiting*

PURPOSE: The incidence of adenocarcinoma of the uterine cervix is low. Traditionally, Low Dose R ate (LDR) brachytherapy has been used as a standard modality in the treatment for patients with carcinoma of the uterine cervix. The PURPOSE of this report is to evaluate the effects of the High dose rate (HL)R) brachytherapy in the patients with adenocarcinoma of the uterine cervix compared with the LDR. MATERIALS AND METHODS: From January 1971 to December 1992, 106 patients of adenocarcinoma of uterine cervix were treated with radiation therapy in the Department of Radiation Oncology, Yonsei University with curative intent. LDR brachytherapy was carried out on 35 patients and 7 1 patients w -re treated with HDR brachytherapy. In LDR Group, 8 patients were in stage I, 18 in stage II and 9 in st;ge III. External radiation therapy was delivered with 10 MV X-ray, daily 2 Gy fractionation, total dose 40-46 Gy (median 43 Gy), And LDR Radium intracavitary irradiation was performed with Henschke applicator, 22-59 Gy to point A (median 43 Gy). In HDR Group, there were 16 patients in stage I, 38 in stag <, II and 17 in stage III. The total dose of external radiation was 40-61 Gy(median 45 Gy), daily 1.8-2.0 3y. HDR Co-60 intracavitary irradiation was performed with RALS (Remote Afterloading System), 30-57 Gy (median 39 Gy) to point A, 3 times a week, 3 Gy per fraction. RESULTS: The 5-year overall survival rate in LDR Group was 72.9%, 6 1.9%, 45.0% in stage I, II, III, respectively and corresponding figures for HDR were 87.1%, 58.3%, 41.2%, respectively (p>0.05). There was no statistical difference in terms of the 5-year overall survival rate between HDR Group and LDR Group in a denocarcinoma of the uterine cervix. There was 1 1% of late complication rates in LDR Group and 27% in HDR Group. There were no prognostic factors compared HDR with LDR group. The incidence of the late complication rate in HDR Group stage II, III was higher than that in LDR Group ( 16.7% vs. 31.6% in stage II, 11. 1% vs. 35.3% in stage III, p>0.05). Although the incidence of radiation induced late complication rate was higher in HDR Group stage II and III patients than that in the LDR Group, statistical significance was not detected and within acceptable level. CONCLUSION: There was no difference in terms of 5-year survival rate and failure pattern in the patients with adenocarcinoma of the uterine cervix treated with HDR and LDR brachytherapy. Even late complication rates were higher in the HDR group it was an acceptable range. This retrospective study suggests that HDR brachytherapy seems to replace the LDR brachytherapy in the adenocarcinoma of the uterine cervix. However, further studies will be required to refine the dose rate effects.
Adenocarcinoma* ; Brachytherapy ; Cervix Uteri* ; Female ; Humans ; Incidence ; Radiation Oncology ; Radium ; Retrospective Studies ; Survival Rate

PURPOSE: To investigate the role of adjuvant chemoradiotherapy in adenocarcinoma of the rectum, we retrospectively compared the treatment results between postoperative adjuvant radiotherapy alone and combined chemoradiotherapy. MATERIAL AND METHODS: From October 1989 to May 1994, 141 patients with rectal carcinoma were treated by postoperative adjuvant therapy in Yonsei Cancer Center. Sixty eight patients were treated by radiation therapy alone. Seventy three patients were treated by combined chemoradiotherapy. Radiation therapy was delivered with 10 MV linear accelerator, 180cGy fraction/5 days per week. Total radiation doses were 5400cGy in the postoperative radiotherapy alone group. Three to twelve cycles of Fluorouracil (mean dose 393.9mg/m2) with Leucovorin (20mg/m2) and 5040cGy of radiation were delivered in the combined chemoradiotherapy group. Third and 4th cycle of chemotherapy were administrated during the radiation treatment in the combined group. The median follow up was 38 months with a range of 3 to 81 months. RESULTS: The 5 year overall survival rate of radiation alone group and combined group were 60.1% and 66.3%, respectively. The 5 year disease free survival rate of radiation alone group and combined group were 54.2% and 65.5%, respectively. There was no significant difference of overall survival and disease free survival between RT alone group and combined group (P<0.05). But the 5 year Local failure free survival rate of combined group was significantly better than radiotherapy alone group (65.8% vs. 50.3%, P=0.04). CONCLUSION: There was no significant difference in overall survival, disease free survival, and distant metastasis free survival between postoperative adjuvant radiotheray alone group and combinded chemoradiotherapy group. Only the Local failure free survival rate was superior in the combined treatment group. These results confirm the radiosensitizing effect of the chemotherapeutic agent in the combined chemoradiotherapy treatment.
Adenocarcinoma* ; Chemoradiotherapy* ; Chemoradiotherapy, Adjuvant ; Disease-Free Survival ; Drug Therapy ; Fluorouracil ; Follow-Up Studies ; Humans ; Leucovorin ; Neoplasm Metastasis ; Particle Accelerators ; Radiation-Sensitizing Agents ; Radiotherapy ; Radiotherapy, Adjuvant ; Rectal Neoplasms ; Rectum* ; Retrospective Studies ; Survival Rate