Biomedical subjects

Gwi Eon Kim

Publications and source records attributed to Gwi Eon Kim.

At least 19 recordsLinked to original sources

PubMed2005

Coexpression of cyclooxygenase-2 and thymidine phosphorylase as a prognostic indicator in patients with FIGO stage IIB squamous cell carcinoma of uterine cervix treated with radiotherapy and concurrent chemotherapy.

PURPOSE: To evaluate the prognostic significance of thymidine phosphorylase (TP) and coexpression of cyclooxygenase-2 (COX-2)/TP, and to investigate the relationship between COX-2 and TP expression in squamous cell carcinoma of the uterine cervix. METHODS AND MATERIALS: Cancer specimens from 75 patients with International Federation of Gynecology and Obstetrics Stage IIB squamous cell carcinoma of the uterine cervix who had undergone radiotherapy and concurrent chemotherapy were immunohistochemically stained with COX-2 and TP antibodies and scored. The prognostic significance of their expression status, and the relationship between COX-2 and TP was investigated. RESULTS: TP predominantly stained cytoplasm and the cell membrane of the tumor cells mainly in a diffuse and intense manner. TP was negative (<10% distribution) in 17%, 1+ (10-50%) in 25%, and 2+ (>50%) in 57% of patients. TP overexpression was related to a marginal prognostic significance of a poor 5-year overall survival (p = 0.082, log-rank test) and a high locoregional recurrence rate (p < 0.1, chi-square test). COX-2 and TP coexpression was observed in 24% of patients and was significantly related to poor 5-year disease-free and overall survival rates (p = 0.0083 and p = 0.025, respectively), a high pelvic lymph node involvement rate, a poor response to treatment, and a greater incidence of locoregional recurrence (p < 0.05). By multivariate analyses, only COX-2, TP, and coexpression of COX-2/TP were significant independent prognostic indicators of patient survival. All tumors showed 1+ or 2+ TP expression when COX-2 was positive, and no tumor expressed COX-2 when TP was negative (p = 0.03). In contrast, 77% of tumors expressed 1+ or 2+ TP without the synchronous expression of COX-2. CONCLUSIONS: Thymidine phosphorylase expression or COX-2/TP coexpression may be used as a molecular prognostic marker for squamous cell carcinoma of the uterine cervix. TP appears to be an important downstream molecule of COX-2 during angiogenesis and may be a new target for the treatment of uterine cervical cancer.

Carcinoma, Squamous Cell↗

PubMed2005

Gemcitabine monotherapy as salvage chemotherapy in heavily pretreated metastatic breast cancer.

PURPOSES: We evaluated the efficacy and tolerability of gemcitabine monotherapy in heavily pretreated, breast cancer patients as salvage chemotherapy. METHODS: A weekly infusion of gemcitabine at 850 mg/m2 for 30 min, for 3 of every 4 weeks, was introduced in advanced breast cancer patients who had failed previous doxorubicin and taxane based chemotherapy. There was no dose modification, and the treatment was delayed until the leukopenia was recovered with G-CSF support. The efficacy was evaluated every three cycles and the treatment was continued until either disease progression or 12 cycles. RESULTS: Of 41 enrolled patients, 38 were evaluable with a median age of 47. Total 178 cycles of gemcitabine was administered and the relative dose intensity was 89. The toxicity was mild with 12 of grade III neutropenia and 14 of grade III/IV thrombocytopenia without clinical symptoms. The response rate was 20 (8/38), comprising two complete and six partial responses. The median response duration and overall survival were 9 (2-25) and 11 months, respectively. The overall survival of 12 months was better in the third line patients than the 7 months in the fourth line treatment group. CONCLUSION: Gemcitabine monotherapy is effective and safe as salvage treatment in heavily pretreated, breast cancer patients.

Adult↗

PubMed2005

Coxsackie and adenovirus receptor binding ablation reduces adenovirus liver tropism and toxicity.

Human adenovirus-based vectors have emerged as a new promising vehicle for in vivo gene transfer-mediated therapy. However, the full potential of this methodology has not been fully realized because of the nonspecific tissue distribution of adenoviral vectors. Adenovirus infection is initiated by forming a complex between the fiber protein and a ubiquitously expressed host cell membrane protein, coxsackie B virus and adenovirus receptor (CAR). Therefore, ablating the adenovirus vector's ability to bind to the CAR is the first step in redirecting adenoviral tropism. To ablate CAR binding, we mutated the Bbeta sheet of the fiber knob, generating CAR-binding ablated replication-incompetent (dl-K420A-Z) and replication-competent (YKLK420A) adenoviral vectors. The in vitro transduction efficiency of dl-K420A-Z was significantly reduced in comparison to dl-LacZ carrying the wild-type fiber in CAR-positive cells but not in CAR-negative cells, suggesting that the mutation introduced in the Bbeta sheet of the fiber knob could disable the CAR-dependent transduction pathway. The in vivo transduction was also dramatically reduced in the liver and other organs for mice treated with dl-K420A-Z, compared with a cognate control vector, dl-LacZ. Concomitant with this attenuated gene transfer efficiency in vivo was a substantial reduction in the amount of general toxicity observed in the YKL-K420A-treated mice. Diminished toxicity was surmised from quantitative measurement of serum level of enzymes for liver and kidney function, hematologic chemistries, histopathology, and differences in lethality. Significant decrease in serum transaminases (alanine transferase [ALT] and aspartate transferase [AST]) was observed in mice treated with YKL-K420A. In addition, the lethality was lower in the YKLK420A- treated groups compared to the YKL-1-treated groups at all doses examined. Furthermore, the hepatopathologic analysis revealed that YKL-1 induced focal zonal necrosis and hepatocyte degeneration, while YKL-K420A induced mild spotty necrosis. In summary, this decreased vector tropism of CAR-binding ablated adenoviruses in normal tissues may increase the amount of virus available for infecting tumor cells and thus increase the antitumor efficacy with fewer unwanted side effects.

Adenoviridae↗

PubMed2004

Differential cyclooxygenase-2 expression in squamous cell carcinoma and adenocarcinoma of the uterine cervix.

PURPOSE: To determine the differential expression of cyclooxygenase-2 (COX-2) in patients with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the uterine cervix and the prognostic significance of COX-2 expression in these histologic types. METHODS AND MATERIALS: A total of 105 International Federation of Gynecology and Obstetrics Stage IIB uterine cervical cancer patients were screened for COX-2 expression immunohistochemically. COX-2 expression was determined in invasive cervical SCC (n = 84) and invasive cervical ADC (n = 21). To determine the clinical significance of COX-2 expression by histologic type, the patients were arbitrarily divided into four groups: SCC/COX-2 negative (n = 64); SCC/COX-2 positive (n = 20); ADC/COX-2 negative (n = 9); and ADC/COX-2 positive (n = 12). The clinical response to treatment, patterns of treatment failure, and survival data by COX-2 expression were compared for these two major histologic types. Univariate and multivariate analyses were performed to identify the prognostic factors influencing survival. RESULTS: Immunohistochemical examination showed that COX-2 expression was more frequently observed in ADC than in SCC (57% vs. 24%, p = 0.007). Moreover, COX-2 expression was an important predictor of treatment response, irrespective of the histologic type. All COX-2-negative patients achieved complete remission after initial treatment; 17% of SCC patients and 33% of ADC patients with COX-2 expression did not have complete remission after the initial treatment. The incidence of local failure for those with COX-2 expression was significantly greater than for COX-2-negative patients, regardless of histologic type. With a minimal follow-up of 60 months, the overall 5-year actuarial survival rate for SCC and ADC patients was 79% and 62%, respectively (p = 0.05). The 5-year disease-free survival rate for SCC and ADC patients was 73% and 56%, respectively (p = 0.13). Irrespective of the pathologic type, COX-2-positive patients had an unfavorable prognosis. The overall 5-year actuarial survival rate was 57% for COX-2-positive patients and 83% for COX-2-negative patients (p = 0.001). When patients were stratified into the four groups according to histologic type and COX-2 expression status, ADC/COX-2-positive patients had the worst prognosis, with an overall 5-year actuarial survival rate of 49% compared with 78% for ADC/COX-2-negative patients, 62% for SCC/COX-2-positive, and 84% for SCC/COX-2-negative patients (p = 0.007, log-rank test). Irrespective of histologic type, COX-2 expression was an independent prognostic factor by univariate and multivariate analyses. CONCLUSION: In uterine cervical cancer, COX-2 was expressed in a greater proportion of ADC patients than SCC patients. COX-2 expression was also identified as a major determiner of a poor response to treatment and of an unfavorable prognosis, irrespective of the histologic type, reflecting the importance of the COX-2 protein in the acquisition of biologic aggressiveness and more malignant phenotype or increased resistance to the standard chemotherapy and radiotherapy in both histologic types. Given these observations, we believe that that ADC/COX-2-positive patients might be appropriate candidates for future trials of selective COX-2 inhibitor adjunctive therapy.

Adenocarcinoma↗

PubMed2004

Surgical outcome of radical maxillectomy in advanced maxillary sinus cancers.

We investigated the surgical outcome of radical maxillectomy in advanced maxillary sinus cancers invading through the posterior wall and into the infratemporal fossa. Twenty-eight patients with maxillary sinus squamous cell carcinoma, who visited the Otorhinolaryngology Department at Severance Hospital from March, 1993 to February, 2001 and underwent the surgery, were analyzed retrospectively by reviewing clinical medical records and radiologic test results. The mean follow- up period was 78.8 months.(26-162 months) Local recurrence, sites of local recurrence, and the 2-year disease-free survival rate were analyzed. Of the total 28 cases, 9 cases were T3, and 19 cases were T4. Total maxillectomy was performed in 12 cases (42.9%) and radical maxillectomy in 16 cases (57.1%). Regardless of staging, radical maxillectomy was performed only when cancers invaded through the posterior wall and into the infratemporal fossa. When cancers only maginally or did not invade the posterior wall, total maxillectomy was performed. The 2-year disease-free survival rate was 75% for both total and radical maxillectomy, and the local recurrence rates were 8.3% and 18.7% respectively. All recurrence occurred at the posterior resection margin of the maxillectomy. We strongly recommend the use of radical maxillectomy in the cases of advanced maxillary sinus cancers invading the infratemporal fossa. Radical maxillectomy can provide sufficient safety margins and lower the local recurrence rate.

Adult↗

PubMed2004

Angiocentric T-cell and NK/T-cell lymphomas: radiotherapeutic viewpoints.

PURPOSE: To investigate the patterns of local failure and the risk factors predictive of local failure and to establish the dose-response relationships influencing the probability of local control in patients with Stage I and II angiocentric T-cell or natural killer (NK)/T-cell lymphoma who were treated with radiotherapy (RT) alone. METHODS AND MATERIALS: We retrospectively reviewed the data from 102 patients with Ann Arbor Stage I and II angiocentric T-cell or NK/T-cell lymphoma who underwent RT alone to a median dose of 45 Gy (range, 20-70 Gy) between 1976 and 1998. The patterns of local failure, risk factors predictive of local failure, dose-response relationships, and survival data were analyzed. Because of the protean feature of local recurrences, the sites of local failure were allocated to one of three categories: true recurrence (TR), marginal recurrence (MR), and elsewhere recurrence (ER). RESULTS: Despite a higher complete remission rate (72%) after RT, 60 patients experienced treatment failure, including local failure in 48 (47%), regional failure in 3 (3%), and systemic failure in 28 (27%). The patterns of local failure were TR in 42, MR in 3, and ER in 5 patients. The median time to recurrence for TR/MR was shorter than that for ER (1 month for TR/MR vs. 12 months for ER). Patients with TR/MR had a more unfavorable prognosis than those experiencing ER (2-year survival rate after salvage treatment: 6% for TR/MR vs. 80% for ER; p <0.01). The dose-response curve was sigmoid in shape within the range of 20-54 Gy, which followed the plateau at doses in excess of about 54 Gy. A positive correlation was observed in the dose-response curve for the probability of local control (p = 0.017, logistic regression analysis). The overall 5-year actuarial survival and local recurrence-free survival rate for all patients was 42% and 53%, respectively. Achievement of complete remission was the most statistically significant risk factor predictive of TR/MR and the most important prognostic factor. CONCLUSION: Our data confirm that local failure remains the major obstacle for patients who receive RT alone and that achievement of complete remission is a particularly important determinant of treatment success. Although dose escalation up to >54 Gy cannot entirely reduce the incidence of TR/MR, we believe it is important to identify an appropriate subset of patients for whom an additional boost dose may be beneficial. Given the high rate of local failure, an investigational approach should be conducted to supplement RT using radiosensitizers or more effective chemotherapeutic agents in future trials.

Adolescent↗

PubMed2004

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 (R(2) = 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.

Adult↗

PubMed2004

Clinical relevance of three subtypes of primary sinonasal lymphoma characterized by immunophenotypic analysis.

BACKGROUND: The purpose of this study was to investigate the clinical relevance of subtypes categorized by immunophenotypic analysis in primary sinonasal lymphomas. METHODS: Eighty patients with localized non-Hodgkin's lymphoma involving the nasal cavity and/or paranasal sinuses were divided into three subtypes on the basis of their immunohistochemical findings: (A) B-cell lymphoma (n = 19), (B) T-cell lymphoma (n = 27), and (C) natural killer (NK)/T-cell lymphoma (n = 34). The clinicopathologic profiles, immunophenotypic data, patterns of treatment failure, and survival data among the three patient groups were retrospectively compared. RESULTS: The nasal cavity was the predominant site of involvement in T-cell and NK/T-cell lymphoma, whereas sinus involvement without nasal disease was common in B-cell lymphoma. Systemic B symptoms were frequently observed in NK/T-cell lymphoma. Almost all patients with NK/T-cell lymphoma showed a strong association with the Epstein-Barr virus by in situ hybridization studies. Sixty-five patients (81%) patients achieved complete remission after initial treatment, but 36 (55%) of these subsequently experienced treatment failure. Although there were no significant differences in locoregional failure rates among the patients of the three groups, distant failure was far more common in B-cell or NK/T-cell lymphoma than in T-cell lymphoma (p =.005). Most B-cell lymphoma cases showed a predilection for sites of systemic failure in the nodal and extranodal sites below the diaphragm, such as the paraaortic lymph nodes or the gastrointestinal (GI) tract, whereas patients with NK/T-cell lymphoma showed an increased risk of systemic dissemination to the skin, testes, or GI tract, including the development of hemophagocytic syndrome. The 5-year actuarial and disease-free survival rates for all patients were 57% and 51%, respectively. Of the three subtypes of primary sinonasal lymphomas, T-cell lymphoma seemed to carry the most favorable prognosis and NK/T-cell lymphoma the worst. (The 5-year actuarial survival rate was 57% for B-cell lymphoma, 80% for T-cell lymphoma, 37% for NK/T-cell lymphoma; p =.02, log-rank.) By univariate and multivariate analyses, immunophenotype was identified as the most important prognostic factor. CONCLUSIONS: Our data indicate that the three subtypes of primary sinonasal lymphomas classified by immunohistochemical studies exhibit different clinical profiles, different patterns of failure, and different treatment outcomes. Given these observations, it is concluded that the recognition of these distinct subsets, diagnosed on the basis of immunophenotypic study, is very important and clinically relevant in predicting their potential behavior and prognosis.

Adolescent↗

PubMed2004

Patterns of treatment failure following radiotherapy with combination chemotherapy for patients with high-risk stage IIB cervical carcinoma.

BACKGROUND: To evaluate the patterns of treatment failure in patients with stage IIB cervical carcinoma with high-risk factors following radiotherapy given concurrently with combination chemotherapy. METHODS: A retrospective analysis of 349 patients with stage IIB cervical carcinoma with high-risk factors (lesion size >/= 4 cm, lymph node metastasis, high-risk cell type) treated by radiotherapy and cisplatin-based chemotherapy was performed. Sites of treatment failure were categorized as pelvic, pelvic plus distant metastases, and distant metastases alone. Pelvic failure included local and pelvic nodal failures. RESULTS: Of the 349 patients, treatment failure occurred in 79 patients (22.6%). Forty-six (13.2%) had persistent disease and 33 (9.5%) had recurrent disease. Among these 79 patients, overall pelvic failure was observed in 67%, of whom 72% had local failure; 19%, pelvic nodal failure; and 9%, local with pelvic nodal failure. Incidences of distant metastases alone and pelvic with distant metastases were 24% and 9%. In the 26 patients with distant metastases either alone or combined with pelvic failure, the most frequent metastatic region was the paraaortic lymph node (50%). The distant metastasis rate was 6.5% (19/289) in the pelvic tumor control group and 11.6% (7/60) in the pelvic failure group. Pelvic failure was the most frequent failure in the group with tumor size of 4 cm or more, whereas, for the positive-lymph-node group, distant metastasis was most frequent and metastases to paraaortic lymph nodes were common. The incidences of pelvic failure alone and distant metastases were similar in the high-risk cell-type group, and the distant metastasis regions were mostly paraaortic lymph nodes. CONCLUSION: Although systemic chemotherapy was administered concurrently with radiotherapy, the incidence of pelvic failure was highest, followed by paraaortic lymph node metastases, in patients with stage IIB cervical carcinoma with high-risk factors, following radiotherapy with combination chemotherapy. To evaluate the patterns of treatment failure in patients with stage IIB cervical carcinoma with high-risk factors following radiotherapy given concurrently with combination chemotherapy.

Adult↗

PubMed2004

Lack of correlation between P-glycoprotein and chemotherapy resistance in nasal NK/T-cell lymphomas.

Thirty patients with nasal natural killer (NK)/T-cell lymphoma, who underwent systemic chemotherapy with or without involved-field radiotherapy between 1993 and 1998, were retrospectively reviewed to determine the clinical significance of P-glycoprotein immunohistochemically identified in tumor specimens. Eighty percent of previously untreated patients expressed P-glycoprotein. According to P-glycoprotein immunoreactivity, all patients with nasal NK/T-cell lymphoma were divided into 2 groups; (a) P-glycoprotein-negative group (N = 6) and (b) P-glycoprotein-positive group (N = 24). There was no significant difference in clinical profiles between both groups. Regardless of the P-glycoprotein expressions, Epstein-Barr virus genomes were almost identically detected in patients of the 2 groups. Contrary to our expectations, however, P-glycoprotein expressions were not found to be a strong predictor of chemotherapy resistance. Although 2 (33%) of 6 P-glycoprotein-negative patients and 10 (42%) of the 24 P-glycoprotein-positive patients showed a favorable response to systemic chemotherapy, 4 (67%) of 6 P-glycoprotein-negative patients did not achieve complete response (CR) to chemotherapy, which led to an early death, whereas 4 (17%) of the 24 P-glycoprotein-positive patients achieved CR to chemotherapy despite positive P-glycoprotein immunoreactivity. Overall, there were no significant differences in either CR rate or the response rate of patients in the two groups. Overall 5-year actuarial survival and disease-free survival for all patients were 44% and 47%, respectively, but no differences in survival rates were observed between 2 groups. (5-year actuarial survival rate: 33% for the P-glycoprotein-negative, 50% for the P-glycoprotein-positive) (P = 0.7093, log-rank). On univariate and multivariate analyses, P-glycoprotein expressions by immunohistochemical study were not found to be an important prognostic factor. Given these observations, we conclude that the molecular mechanisms of resistance to chemotherapy in nasal NK/T-cell lymphoma patients are not entirely dependent on P-glycoprotein, and that other complex mechanisms of drug action and resistance may be likely to be involved.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Combination of external beam irradiation and high-dose-rate intraluminal brachytherapy for inoperable carcinoma of the extrahepatic bile ducts.

PURPOSE: To assess the feasibility and therapeutic benefits of a combination of external beam radiotherapy (EBRT) and high-dose-rate intraluminal brachytherapy (ILBT) for treating patients with inoperable carcinoma of the extrahepatic bile ducts. METHODS AND MATERIALS: Of 31 patients who received RT at the Yonsei Cancer Center, Yonsei University College of Medicine in Seoul, Korea between 1986 and 1995, 17 patients underwent EBRT alone (Group 1) and 14 patients were treated with EBRT in combination with high-dose-rate ILBT (Group 2). After external drainage, EBRT was delivered with a total dose ranging from 36 to 55 Gy (median 50.4) in both groups. High-dose-rate ILBT for the patients in Group 2 was performed using a high-intensity (192)Ir source (Gamma-med remote afterloading system) within the expandable intrabiliary prosthesis (Gianturco stent), inserted transhepatically at the site of the obstruction. The radiation dose of the high-dose-rate ILBT was prescribed at 1.5 cm from the center of the source with a single daily dose of 5 Gy to a total of 15 Gy given in three fractions. The response rate, patterns of treatment failure, treatment morbidity, and survival data in the two groups were compared. RESULTS: Although locoregional recurrence was the most common pattern of failure in both groups, no statistically significant difference was found in the recurrence rates between those who did and did not receive ILBT (53% for Group 1 vs. 36% for Group 2; p > 0.05). However, a prolongation of the median time to tumor recurrence was observed in the Group 2 patients (5 months for Group 1 vs. 9 months for Group 2; p = 0.06). When the EBRT dose delivered was >50 Gy, most patients experienced various degrees of GI symptoms, but the frequency of radiation-induced complications in the two groups was similar. No enhancement in treatment morbidity was attributed to the addition of high-dose-rate ILBT to EBRT. With a median follow-up of 12 months, the overall actuarial 2-year survival rate for Group 2 patients was significantly better than that for Group 1 patients (0% for Group 1 vs. 21% for Group 2; p = 0.015). CONCLUSION: Given these observations, we believe that the combined use of EBRT and high-dose-rate ILBT is a beneficial, relatively safe, and effective method of improving the treatment outcome in selected patients with inoperable carcinoma of the extrahepatic bile ducts.

Adult↗

PubMed2003

P63 and EGFR as prognostic predictors in stage IIB radiation-treated cervical squamous cell carcinoma.

OBJECTIVES: The purpose of this study was to determine the relation between p63, p53-related gene, epidermal growth factor receptor (EGFR), and spontaneous apoptosis in relation to radiotherapy in patients with FIGO stage IIB cervical carcinoma, who had undergone radiation and concurrent chemotherapy, retrospectively. METHODS: Eighty-four patients with FIGO stage IIB squamous cell carcinoma (SCC) of the uterine cervix, who were treated with radiotherapy and concurrent chemotherapy between 1991 and 1996, were included in the present study. The clinicopathologic features, patterns of treatment failure, and survival data were compared with the expressions of p63 and EGFR, which were determined by immunohistochemistry and with apoptosis by TUNEL on tissue-arrayed slides. Univariate and multivariate analyses were performed to determine the prognostic factors that influence patient survival. RESULTS: Overall the indices of the expressions of p63 and EGFR in stage IIB cervical carcinoma were 18.7 and 26.6%, respectively, and these were found to be correlated. EGFR expression was significantly associated with extrapelvic failure (P = 0.03), whereas p63 was associated with locoregional failure (P = 0.03). The spontaneous apoptotic index showed no prognostic value, but the immunoreactivities of p63 and EGFR were associated with a worse prognosis by both univariate (P = 0.01 and 0.04, respectively) and multivariate analysis (95% CI:2.0-4.4, RR:3.2 and 95% CI:4.9-8.7, RR:6.7, respectively). CONCLUSIONS: The expression of p63 gene is associated with poor survival and locoregional failure, whereas EGFR expression was found to be a prognostic predictor of extrapelvic failure. Both molecules were found to be potent molecular risk factors in patients with FIGO stage IIB SCC of the uterine cervix, who had received radiotherapy and concurrent chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Clinical results of 3-dimensional conformal radiotherapy combined with transarterial chemoembolization for hepatocellular carcinoma in the cirrhotic patients.

PURPOSE: Recent reports have shown that a portion of the liver can tolerate higher radiation doses, which can be further accomplished by the application of 3-dimensional conformal radiotherapy (3-DCRT). The purpose of this study was to investigate the efficacy and toxicity of 3-DCRT combined with transcatheter arterial chemoembolization (TACE) for HCC in the cirrhotic patients. METHODS AND MATERIALS: From 1994 to 2000, 50 HCC patients with liver cirrhosis (LC) were included in this study. The degree of LC was Child A in 38 and Child B in 12. The UICC stages were II in 12, III in 16, and IVa in 22. The mean tumor size was 8.3+/-3.5 cm. Patients were treated with TACE and then followed by 3-DCRT within 7-14 days. 3-DCRT planning was used to define both the target and normal liver volumes. The total dose of radiation (mean 50.1+/-8.3 Gy) was determined by the fractional volume of normal liver receiving 50% of the isocenter dose. RESULTS: A partial response (PR) was observed in 33 patients (66%). A subsequent surgical resection was successful in three patients, showing complete necrosis in one and near total necrosis in two. Most common acute toxicity was alteration in liver function test (13 patients) and none of the patients showed an acute toxicity more than grade 3. Subacute and chronic toxicity involved radiation induced liver disease (RILD) (six patients) and gastrointestinal toxicity (seven patients; ulcer in five and hemorrhagic mucositis in two). The actuarial survival rate at 3 years was 43% from the commencement of radiotherapy. CONCLUSIONS: Radiotherapy using 3-DCRT combined with TACE can achieve a substantial tumor response and survival rate for HCC in the cirrhotic patients.

Journal Article↗

PubMed2003

Expression of estrogen receptor-beta in normal mammary and tumor tissues: is it protective in breast carcinogenesis?

Using messenger RNA (mRNA) in situ hybridization, we investigated estrogen receptor-beta (ERbeta) mRNA levels in normal mammary, benign breast tumor (BBT), breast cancer (BC), and metastatic lymph node tissues to verify the role of ERbeta in BC development and progression. ERbeta expression was significantly decreased in BC and metastatic lymph node tissues compared with normal mammary and BBT tissues (p < 0.01). The intensity and extent of ERbeta mRNA signals were also significantly lower in BC and metastatic lymph node tissues than in the normal mammary and BBT tissues (p < 0.01). An inverse relationship was found between ERbeta mRNA level and both histologic grade (p = 0.091) and progesterone receptor expression (p = 0.052) with marginal significance, but no significant association was noted between ERbeta expression in cancer tissues and the other clinico-pathologic data. The 3-year distant relapse-free survival probability was found to be independent of ERbeta expression. Collectively, ERbeta mRNA decreases in the process of BC development, but seems to be associated with poor differentiation.

Biomarkers, Tumor↗

PubMed2003

Primary NK/T cell lymphoma of the testis. A case report and review of the literature.

We report a case of aggressive 'nasal type' natural killer (NK)/T cell lymphoma initially presenting as a testicular tumor in a Korean man, which quickly took a fatal course by widespread dissemination. Histologically, the testicular mass showed a diffuse dense infiltrate of medium-sized and atypical large lymphoid cells with angiocentric and angiodestructive infiltration and areas of coagulative necrosis on hematoxylin-eosin stained sections. Immunophenotyping by immunohistochemistry yielded surface markers consistent with NK/T cell lymphoma. The Epstein-Barr virus genome was detected by in situ hybridization. During involved-field irradiation and chemotherapy following radical orchiectomy, the tumor disseminated shortly to the skin and soft tissue of his anterior chest wall and central nervous system (CNS). Identical lymphoid infiltrates were present in the patient's skin. CNS involvement was interpreted as having a leptomeningeal seeding. To the best of our knowledge, this is the 9th reported case of confirmed NK/T cell lymphoma arising from the testis. Relevant literature is reviewed, and the clinicopathologic features, natural history, and treatment options for primary testicular NK/T cell lymphoma are discussed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Overexpression of cyclooxygenase-2 is associated with a poor prognosis in patients with squamous cell carcinoma of the uterine cervix treated with radiation and concurrent chemotherapy.

BACKGROUND: The objective of this study was to determine whether cyclooxygenase-2 (COX-2) overexpression was an indicator of prognosis in patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IIB uterine cervical carcinoma who underwent radiation and concurrent chemotherapy. METHODS: Seventy-five patients with FIGO Stage IIB squamous cell carcinoma (SCC) of the uterine cervix who were treated with radiotherapy and concurrent chemotherapy between 1991 and 1996 were divided into two groups according to their COX-2 level in an immunohistochemical study: the COX-2 negative group (n = 54 patients) and the COX-2 positive group (n = 21 patients). The clinicopathologic features, patterns of treatment failure, and survival data for patients in the COX-2 positive group were compared with data from the patients in the COX-2 negative group. Univariate and multivariate analyses were performed to determine the prognostic factors that influenced patient survival. RESULTS: In the immunohistochemical study, COX-2 overexpression was observed in approximately 30% of patients with FIGO Stage IIB SCC of the uterine cervix. With delayed regression to the initial treatment, the treatment failure rate of patients in the COX-2 positive group was much higher compared with the treatment failure rate of patients in the COX-2 negative group. The higher incidence of central failure and lymph node failure for patients in the COX-2 positive group was statistically significant (48% for the COX-2 positive group vs. 13% for the COX-2 negative group). However, there was no difference in the incidence of hematogenous metastases between the two groups (5% for the COX-2 positive group vs. 7% for the COX-2 negative group). In addition, increased COX-2 expression in tumor cells also was correlated with a shorter interval to tumor recurrence (median interval to recurrence, 9 months in the COX-2 positive group vs. 26 months in the COX-2 negative group). Compared with patients in the COX-2 negative group, patients in the COX-2 positive group had lower overall actuarial and disease free survival rates (overall 5-year actuarial survival rates: 56% for the COX-2 positive group vs. 94% for the COX-2 negative group; P = 0.003). Univariate and multivariate analyses showed that COX-2 overexpression was an independent prognostic factor that surpassed other well-known clinicopathologic parameters. CONCLUSIONS: COX-2 overexpression can be used as a potent molecular risk factor in patients with FIGO Stage IIB SCC of the uterine cervix who are treated with radiotherapy and concurrent chemotherapy.

Adult↗

PubMed2002

Dose optimization of fractionated external radiation and high-dose-rate intracavitary brachytherapy for FIGO stage IB uterine cervical carcinoma.

PURPOSE: To determine the optimal dose combination scheme of external beam radiotherapy (EBRT) and high-dose-rate (HDR) intracavitary radiation (ICR) for maximizing tumor control while conferring an acceptable late complication rate in the treatment of Stage IB uterine cervical cancer. METHODS AND MATERIALS: We retrospectively analyzed 162 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IB squamous cell carcinoma of the uterine cervix who received definitive RT between May 1979 and December 1990. Before HDR-ICR, all patients received EBRT to a total dose of 40-46 Gy (median 45), administered during 4-5 weeks to the whole pelvis. HDR-ICR was given 3 times weeks to a total dose of 24-51 Gy (median 39) at point A, using a dose of 3 Gy/fraction. Central shielding from EBRT was begun after the delivery using 20-45 Gy (median 40) of the external dose. The total dose to point A, calculated by adding the EBRT biologically effective dose (BED) and the ICR BED to point A, was 74.1-118.1 Gy (mean 95.2). The rectal point dose was calculated at the anterior rectal wall at the level of the cervical os. The local control rate, survival rate, and late complication rate were analyzed according to the irradiation dose and BED. RESULTS: The initial complete response rate was 99.4%. The overall 5-year survival rate and 5-year disease-free survival rate was 91.1% and 90.9%, respectively. The local failure rate was 4.9%, and the distant failure rate was 4.3%. Late complications were mild and occurred in 23.5% of patients, with 18.5% presenting with rectal complications and 4.9% with bladder complications. The mean rectal BED (the sum of the external midline BED and the ICR rectal point BED) was lower in the patients without rectal complications than in those with rectal complications (125.6 Gy vs. 142.7 Gy, p = 0.3210). The late rectal complication rate increased when the sum of the external midline BED and the rectal BED by ICR was >or=131 Gy (p = 0.1962). However, 5-year survival rates did not increase with the external midline BED (p = 0.4093). The late rectal complication rate also increased, without a change in the survival rate, when the sum of the external midline BED and the ICR point A BED was >90 Gy. CONCLUSION: In treating Stage IB carcinoma of the uterine cervix with HDR-ICR, using fractions of 3 Gy, it is crucial to keep the point A BED at <or=90 Gy to minimize late rectal complications without compromising the survival rate. To achieve this goal, appropriate central shielding from EBRT is needed.

Adult↗

PubMed2002

Effective local control of malignant melanoma by intratumoural injection of a beta-emitting radionuclide.

Intratumoural injection of an unsealed beta-emitting radionuclide is a new technique for the local control of tumours that has the advantage of delivering a higher radiation dose to tumour while minimising radiation hazard to the surrounding normal tissues. In this study, therapeutic effect, morphological alterations and biological responses to the high-dose continuous irradiation delivered using this new technique were evaluated in an animal model with B16 melanoma. For evaluation of the therapeutic effect, 92 C57BL/6 mice with B16 melanoma were divided into four groups. In each group, intratumoural injections were performed when the tumour measured approximately 1 cm along its long axis. Group 1 (n=25) received 0.3 ml of normal saline, group 2 (n=15) 37 MBq of carrier-free holmium-166 in 0.3 ml saline, group 3 (n=27) 185 MBq of 166Ho in 0.3 ml saline and group 4 (n=25) 185 MBq of 166Ho in 0.5 ml saline. In addition, another 30 mice were used for morphological and biological analysis of the radiation effect. These 30 mice were injected with 185 MBq of 166Ho in 0.3 ml saline, and five were sacrificed at each of the following six time points: before injection and 1, 2, 3, 6 and 14 days post injection. Haematoxylin-eosin (H&E) staining, immunohistochemical analysis for p53, p21, PCNA and cyclin D1, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) staining, reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry were performed. For visual side-by-side comparison, melanoma cells were inoculated bilaterally into the back of ten additional mice, and 185 MBq of 166Ho in 0.3 ml of saline or an equal volume of normal saline was injected separately into the bilateral tumours. Nine days after inoculation of melanoma cells, mean tumour volume reached 492.5-631.9 mm3. Tumours of the control group (group 1) showed rapid growth, and the mean tumour volume reached approximately 30 times the original volume. None of the control group lived for more than 16 days following the injection of normal saline. On the other hand, mean tumour volume of the treated groups showed a gradual decrease, and 67%-74% of the treated animals were alive when all the control animals had died. The median survival of the control group was 9 days following injection, whereas it was 29 days in group 2, 33 days in group 3 and 33 days in group 4. The survival rate of group 3 was higher than that of groups 2 and 4, but statistical significance was not observed. H&E stain of the tumours demonstrated central necrosis and peripheral residual cells with progressive cytoplasmic and nuclear swelling without apoptotic features. Expression of proteins and mRNAs of p53 and bax increased until 3 days, as compared with 48 h for p21; thereafter, the expression gradually decreased. TUNEL-positive nuclei could be seen from 2 days until 2 weeks after treatment. Flow cytometry did not demonstrate an increase in apoptotic features as compared with the control animals. In conclusion, intratumoural injection of the unsealed beta-emitting radionuclide 166Ho appears to be a promising alternative radiotherapeutic modality for the local control of malignant melanoma. The main cell death mechanisms with this technique seem to be radiation-induced central necrosis and peripheral growth arrest or secondary necrosis of tumour cells, rather than apoptosis.

Animals↗