Mison Chun

Synchronous Coexpression of Epidermal Growth Factor Receptor and Cyclooxygenase-2 in Carcinomas of the Uterine Cervix A Potential Predictor of Poor Survival

Purpose: To evaluate the potential of the new prognostic information gained by analyzing the coexpression of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in cervical cancer patients. Experimental Design: Sixty-eight patients with International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix, who underwent concurrent chemoradiotherapy between 1993 and 1996, were divided into the following four groups according to their immunoreactivities for EGFR and COX-2 in paraffin-embedded sections: (a) the EGFR-negative/COX-2-negative group (n = 11); (b) the EGFR-negative/COX-2-positive group (n = 8); (c) the EGFR-positive/COX-2-negative group (n = 27); and (d) the EGFR-positive/COX-2-positive group (n = 22). The clinical features, patterns of treatment failure, and survival data in the four groups were compared. Results: Positive immunoreactivity for EGFR and COX-2 was observed in 49 of 68 (72%) and 19 of 68 (28%), respectively. However, no strong correlation was found between the levels of EGFR and COX-2 immunopositivity (R2 = 0.05, P = 0.07). Patients in the EGFR-positive/COX-2-positive group had a higher likelihood of locoregional recurrence than those in the other three groups (P = 0.02). Of the patients in the four groups, patients positive for both oncoproteins were found to have the worst prognosis with an overall 5-year disease-free survival rate of 55% compared with 91% for the EGFR-negative/COX-2-negative patients, 88% for the EGFR-negative/COX-2-positive patients, and 69% for the EGFR-positive/COX-2-negative patients (P = 0.05, log-rank test). In addition, the synchronous coexpression of the EGFR and COX-2 oncoproteins was found to be an independent prognostic factor by univariate and multivariate analyses (relative risk = 4.0, P = 0.03). Conclusions: Given these observations, we conclude that the coexpression of EGFR and COX-2 immunoreactivity may be used as a potent molecular risk factor for predicting the poor survival of patients with the International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix.

Anti-inflammatory effects of Scutellaria baicalensis extract via suppression of immune modulators and MAP kinase signaling molecules

AIM OF THE STUDY A herbal preparation using Scutellaria baicalensis (S. baicalensis) Georgi (Huang Qin, SB) was formulated to effectively protect cancer patients from inflammatory reactions. Although SB, is one of the most widely used herbs in oriental medicine for anti-inflammation, anti-cancer, anti-viral, anti-bacterial and tonifying the immune response, the underlying mechanism(s) by which these effects are induced remains unclear. RESULTS Here, we report that SB displays anti-inflammatory effects in a zymosan-induced mouse air-pouch model by reducing the expression of nitric oxide (NO), inducible NOS (iNOS), Cyclooxygenase2 (COX-2), Prostaglandin E2 (PGE2), Nuclear Factor-kappaB (NF-kappaB) and IkappaBalpha as well as inflammatory cytokines, such as IL-1beta, IL-2, IL-6, IL-12 and TNF-alpha. In a similar manner, SB also reduced the production of nitric oxide, PGE2, IL-1beta, IL-2, IL-6, IL-12 and TNF-alpha, by decreasing the expression of iNOS, COX-2, IkappaB kinase alphabeta (IKKalphabeta) phosphorylation, IkappaBalpha and IkappaBalpha phosphorylation in LPS-treated Raw 264.7 cells. Additionally, SB interfered with the nuclear translocation of NF-kappaB p65 and p50, resulting in NF-kappaB-dependent transcriptional repression. We further demonstrate that SB attenuated the activity of c-Raf-1/MEK1/2, Erk1/2, p38 and JNK phosphorylation in LPS-treated Raw 264.7 cells. CONCLUSIONS Taken together, these results confirm the strong anti-inflammatory properties of SB by inhibition of iNOS, COX-2, PGE2, IL-1beta, IL-2, IL-6, IL-12 and TNF-alpha expression. This was achieved through the down-regulation of IKKalphabeta, IkappaBalpha, NF-kappaB activation via suppression of c-Raf-1/MEK1/2 (Mitogen-activated protein kinase/ERK kinase) and MAP kinase phosphorylation in the zymosan-induced mice air-pouch and Raw 264.7 cells. These results support the use of SB herbs for its potent anti-inflammatory activity.

Attitudes of cancer patients, family caregivers, oncologists and members of the general public toward critical interventions at the end of life of terminally ill patients

Background: Whereas most studies have focused on euthanasia and physician-assisted suicide, few have dealt comprehensively with other critical interventions administered at the end of life. We surveyed cancer patients, family caregivers, oncologists and members of the general public to determine their attitudes toward such interventions. Methods: We administered a questionnaire to four groups about their attitudes toward five end-of-life interventions — withdrawal of futile life-sustaining treatment, active pain control, withholding of life-sustaining measures, active euthanasia and physician-assisted suicide. We performed multivariable analyses to compare attitudes and to identify sociodemographic characteristics associated with the attitudes. Results: A total of 3840 individuals — 1242 cancer patients, 1289 family caregivers and 303 oncologists from 17 hospitals, as well as 1006 members of the general Korean population — participated in the survey. A large majority in each of the groups supported withdrawal of futile life-sustaining treatment (87.1%–94.0%) and use of active pain control (89.0%–98.4%). A smaller majority (60.8%–76.0%) supported withholding of life-sustaining treatment. About 50% of those in the patient and general population groups supported active euthanasia or physician-assisted suicide, as compared with less than 40% of the family caregivers and less than 10% of the oncologists. Higher income was significantly associated with approval of the withdrawal of futile life-sustaining treatment and the practice of active pain control. Older age, male sex and having no religion were significantly associated with approval of withholding of life-sustaining measures. Older age, male sex, having no religion and lower education level were significantly associated with approval of active euthanasia and physician-assisted suicide. Interpretation: Although the various participant groups shared the same attitude toward futile and ameliorative end-of-life care (the withdrawal of futile life-sustaining treatment and the use of active pain control), oncologists had a more negative attitude than those in the other groups toward the active ending of life (euthanasia and physician-assisted suicide).

Rectal bleeding and its management after irradiation for uterine cervical cancer

PURPOSE To present an evaluation of the risk factors of radiation-induced rectal bleeding and discuss its optimal management in patients with cancer of the cervix. METHODS AND MATERIALS A total of 213 patients treated with radiotherapy (RT) alone were included. All patients underwent external beam radiotherapy with high-dose-rate brachytherapy. The rectal dose was calculated by both the International Commission on Radiation Units and Measurements (ICRU) Report 38 guidelines and the anterior rectal wall point on radiographs. Rectal bleeding was scored using the late effects normal tissue-subjective, objective, management, and analytic criteria. RESULTS The incidence was 12.7% (27 of 213; Grade 1 in 9, Grade 2 in 16, and Grade 3 in 2). Most (92.6%) developed rectal bleeding within 2 years after RT completion (median 16 months). In univariate analysis, three significant factors were found: ICRU cumulative rectal biologically equivalent dose (CRBED) >100 Gy (19.7% vs. 4.2%), external beam RT dose to the parametrium >55 Gy (22.1% vs. 5.1%), and advanced stage (III-IV; 31.8% vs. 10.5%). In multivariate analysis, the ICRU-CRBED was the only significant factor. Six patients with Grade 1 bleeding experienced immediate relief with sucralfate enema for 1 month. For Grade 2 bleeding, sucralfate enema and/or coagulation were effective. Grade 3 bleeding lasted for 1 year despite frequent transfusions and coagulation. CONCLUSION Grade 2 and 3 rectal bleeding occurred in 8.5% of patients. The most significant risk factor was the ICRU-CRBED. Prompt treatment with a combination of sucralfate enema and coagulation was effective in controlling Grade 1 and 2 rectal bleeding without the development of fistula or stricture.

Differential diagnosis in idiopathic granulomatous mastitis and tuberculous mastitis.

Purpose Idiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory disease of unknown etiology. The diagnosis of IGM requires that other granulomatous lesions in the breast be excluded. Tuberculous mastitis (TM) is also an uncommon disease that is often difficult to differentiate from IGM. The purpose of this study is to develop a new algorithm for the differential diagnosis and treatment of IGM and TM. Methods Medical records of 68 patients (58 with IGM and 10 with TM) between July 1999 and February 2009 were retrospectively reviewed. Results The mean age of the patients was 33.5 (IGM) and 40 (TM) years (p=0.018). The median follow-up was 84 months. Of the total 10 patients with TM, 5 patients had a history of pulmonary tuberculosis. The most common symptoms of the diseases were breast lump and pain. However, axillary lymphadenopathy was more seen in TM (50%) compared to IGM (20.6%) (p=0.048). TM showed more cancer-mimicking findings on radiologic study (p=0.028). In IGM, 48 patients (82.7%) underwent surgical wide excision and 21 patients (36.2%) were managed with corticosteroid therapy and antibiotics. All of the TM patients received anti-tuberculosis medications and 9 patients (90%) underwent wide excision. The mean treatment duration was 2.8 months in IGM and 8.4 months in TM. Recurrence developed in 5 patients (8.6%) in IGM and 1 patient (10%) in TM. Conclusion This study shows different characteristics between IGM and TM. The IGM patients were younger and had more mastalgia symptoms than the TM patients. Axillary lymphadenopathy was seen more often in TM patients. Half of the TM patients had pulmonary tuberculosis or tuberculosis lymphadenitis. Surgical wide excision might be both therapeutic and useful for providing an exact diagnosis.

Vascular endothelial growth factor in the serum of patients with non-small cell lung cancer: correlation with platelet and leukocyte counts.

BACKGROUND Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide expressed in a wide variety of tumors, and it stimulates angiogenesis and increases vascular permeability. Increased expression of VEGF may be associated with advanced stage and poor prognosis in patients with non-small cell lung cancer (NSCLC). METHODS Using enzyme-linked immunosorbent assay, the levels of VEGF were determined in serum from 41 patients with untreated NSCLC (Stage: IIB, 3; IIIA, 6; IIIB, 17; IV, 15; HISTOLOGY squamous cell carcinoma, 18; adenocarcinoma. 14; undetermined, 9). RESULTS The median VEGF level was 312 pg/ml, ranging from 70 to 1440 pg/ml. Patients were divided into high VEGF (>312 pg/ml) and low VEGF (< or =312 pg/ml) groups using the median value as a cut-off. There were no significant associations between the serum VEGF levels and various clinicopathologic characteristics including age, gender, histologic type, stage and treatment. A significant positive correlation was found between serum VEGF levels and platelet counts (r=0.495; P=0.001). In addition, serum VEGF levels also correlated with leukocyte counts (r=0.478; P=0.002). In seven patients with measurement of follow-up serum VEGF levels at the end of treatment (chemotherapy and/or radiotherapy), the median serum VEGF level significantly decreased after the treatment (416 pg/ml; range, 96-812 pg/ml vs. 185 pg/ml; range, 49-487 pg/ml; P=0.028). However, the median platelet count (317,000/microl; range, 190,000-395,000/microl vs. 246,000/microl; range, 72,000-271,000/microl; P=0.028) and leukocyte count (10,000/microl; range, 8700-17,200/microl vs. 5100/microl; range, 3900-9500/microl; P=0.018) also decreased after the treatment. There was no statistically significant difference in the median survival of the patients between high VEGF group and low VEGF group (8 months vs. 9 months, P=0.647). CONCLUSIONS Although serum VEGF level was significantly associated with platelet and leukocyte counts in NSCLC patients, it did not correlate with tumor burden and prognosis of the patients.

Low expression of Bax predicts poor prognosis in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy.

Purpose: The present study evaluated the prognostic significance of apoptosis-related proteins, p53, Bcl-2, Bax, and galectin-3 in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy. Experimental Design: A total of 63 patients with locally advanced esophageal cancer (squamous cell carcinoma: 62; adenocarcinoma: 1; stages II-IV) were treated with definitive chemoradiotherapy using 5-fluorouracil and cisplatin combined with radiotherapy. Pretreatment tumor biopsy specimens were analyzed for p53, Bcl-2, Bax, and galectin-3 expression by immunohistochemistry. Results: High expression of Bax, p53, Bcl-2, and galectin-3 was observed in 67%, 47%, 24%, and 29% of patients, respectively. The median overall survival (OS) of total patients was 14 months with 16% of 3-year OS. High expression of p53, Bcl-2, and galectin-3 did not show correlation with clinicopathologic characteristics, including patient outcome. Low expression of Bax was significantly correlated with lack of clinical complete response (P = 0.023). Low expression of Bax was also associated with poor OS (median, 8 months versus 16 months; P = 0.0008) in univariate analysis. In multivariate analysis, low expression of Bax was the most significant independent predictor of poor OS (P = 0.009), followed by low dose intensity of cisplatin and lack of clinical complete response. Conclusions: Low expression of Bax was significantly associated with the poor survival of patients with locally advanced esophageal cancer treated with chemoradiotherapy using 5-fluorouracil and cisplatin. Immunohistochemical staining for Bax with a pretreatment biopsy specimen might be useful to select the optimal treatment options for these patients.

Expression of Bcl-2 predicts outcome in locally advanced non-small cell lung cancer patients treated with cisplatin-based concurrent chemoradiotherapy

BACKGROUND Platinum-based concurrent chemoradiotherapy (CCRT) is a standard treatment for locally advanced unresectable non-small cell lung cancer (NSCLC). The determination of parameters that may predict the result of the treatment has strong clinical implications. PATIENTS AND METHODS Pretreatment tumor biopsy specimens from 39 patients with locally advanced NSCLC (stage IIIA: 5, stage IIIB: 34) were analyzed for p53, Bcl-2, Bax and ERCC1 expression by immunohistochemistry. All patients were treated with cisplatin-based CCRT. Twenty-four patients received induction chemotherapy followed by CCRT (60Gy/30 fractions, 6mg/m(2) of cisplatin daily). The most commonly administered induction chemotherapy regimen was VIP (etoposide, ifosfamide, cisplatin; 20 patients). Fifteen patients received the same CCRT without induction chemotherapy. RESULTS High expression of p53, Bcl-2, Bax and ERCC1 was observed in 15 (38%), 19 (49%), 17 (44%) and 12 (31%) patients, respectively. High expression of Bcl-2 was significantly associated with longer survival duration (20 months vs. 9 months, P=0.008) and better response to the treatment (74% vs. 30%, P=0.01). In multivariate analysis, Bcl-2 expression was the only significant independent prognostic factor of overall survival (P=0.007) among the pretreatment patients characteristics. CONCLUSIONS High expression of Bcl-2 may be a useful prognostic factor in locally advanced NSCLC patients treated with cisplatin-based CCRT.

Chemotherapy-related amenorrhea in premenopausal women with breast cancer.

Objective: To report the incidence of chemotherapy-related amenorrhea (CRA) from chemotherapy with/without adjuvant endocrine therapy in premenopausal women with breast cancer and to analyze the related factors. Design: From January 2000 to August 2006, 326 premenopausal women (≤50 y old) who completed chemotherapy were available for analysis. The CRA definitional criterion in this study was no menstruation for 6 months in a woman who was premenopausal at diagnosis. As risk factors for CRA, womans age, the type of chemotherapy regimen, adjuvant endocrine therapy use, and body mass index were evaluated. Results: The median age was 42 years (range, 22-50 y). The median follow-up period was 37 months (range, 12-80 mo). Women were divided into two groups by age at diagnosis: 128 women in group 1 (less than 40 years old) and 198 women in group 2 (age ≥40 y). CRA occurred in a total of 223 (68%) women: 43% in group 1 and 85% in group 2 (P < 0.001). Despite CRA, 14% resumed menstruation: 24% in group 1 and 11% in group 2. Another 40 (12%) women had less than 6 months of menstruation interruption. Permanent CRA was related with age at diagnosis and use of adjuvant endocrine therapy (P < 0.05). In this study, there were four pregnancies, two of which resulted in therapeutic abortion due to ongoing chemotherapy. Conclusions: This study confirmed that the rate of CRA depends on age at diagnosis and the use of adjuvant endocrine therapy. It is essential to inform young women of reproductive age of the possibility of amenorrhea or resumption of menstruation and contraceptive options.

Complementary and alternative medicine in the undergraduate medical curriculum: A survey of Korean medical schools

BACKGROUND The current status of complementary and alternative medicine (CAM) education in Korean medical schools is still largely unknown, despite a growing need for a CAM component in medical education. The prevalence, scope, and diversity of CAM courses in Korean medical school education were evaluated. DESIGN Participants included academic or curriculum deans and faculty at each of the 41 Korean medical schools. A mail survey was conducted from 2007 to 2010. Replies were received from all 41 schools. RESULTS CAM was officially taught at 35 schools (85.4%), and 32 schools (91.4%) provided academic credit for CAM courses. The most common courses were introduction to CAM or integrative medicine (88.6%), traditional Korean medicine (57.1%), homeopathy and naturopathy (31.4%), and acupuncture (28.6%). Educational formats included lectures by professors and lectures and/or demonstrations by practitioners. The value order of core competencies was attitude (40/41), knowledge (32/41), and skill (6/41). Reasons for not initiating a CAM curriculum were a non-evidence-based approach in assessing the efficacy of CAM, insufficiently reliable reference resources, and insufficient time to educate students in CAM. CONCLUSIONS This survey reveals heterogeneity in the content, format, and requirements among CAM courses at Korean medical schools. Korean medical school students should be instructed in CAM with a more consistent educational approach to help patients who participate in or demand CAM.