Biomedical subjects

Gwi Eon Kim

Publications and source records attributed to Gwi Eon Kim.

At least 19 recordsLinked to original sources

PubMed2006

Clinical significance of cyclooxygenase-2 expression in extranodal natural killer (NK)/T-cell lymphoma, nasal type.

PURPOSE: To determine whether there are any differences in therapeutic response, patterns of systemic recurrence, and prognosis of patients with extranodal natural killer (NK)/T-cell lymphoma, nasal type, by the cyclooxygenase-2 (COX-2) expression. PATIENTS AND METHODS: Thirty-four patients with Ann Arbor Stage I and II extranodal NK/T-cell lymphoma who underwent chemotherapy or radiotherapy, or both, were retrospectively reviewed. These patients were divided into two groups according to their immunohistochemical staining for COX-2 expressions: a COX-2-negative group (n = 10 patients) and a COX-2-positive group (n = 24 patients). The treatment response, patterns of treatment failure, and survival data for the patients were compared between the COX-2-positive and negative groups. RESULTS: There was no significant difference in the clinical profiles between the COX-2-negative and COX-2-positive groups. All patients (100%) in the COX-2-negative group achieved complete response after initial treatment, whereas only 14 patients (58%) in the COX-2-positive group achieved complete response (p = 0.03). Compared with the patients in the COX-2-negative group, those in the COX-2-positive group had a significantly lower 2-year systemic recurrence-free survival rate (100% for the COX-2-negative group vs. 54% for the COX-2-positive group) (p = 0.02) and a decreased 5-year overall survival rate (70% for the COX-2-negative group vs. 32% for the COX-2-positive group) (p = 0.06). CONCLUSION: Cyclooxygenase-2 expression can serve as a predictive factor for poor treatment response, higher systemic recurrence, and unfavorable prognosis in patients with extranodal NK/T-cell lymphoma, nasal type.

Adolescent↗

PubMed2006

Concurrent chemoradiotherapy followed by adjuvant chemotherapy in uterine cervical cancer patients with high-risk factors.

OBJECTIVES: To determine whether concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy is better than CCRT alone in the management of FIGO stage bulky IB and IIB uterine cervical cancer. METHODS: Two hundred and five FIGO stage bulky IB and IIB patients with squamous cell carcinoma of the uterine cervix treated with CCRT were divided into 2 groups: (1) CCRT alone (n=103, Group A) and (2) CCRT plus adjuvant chemotherapy (n=102, Group B), and treatment outcomes were retrospectively compared between the two patient groups. RESULTS: Only 63% of patients received all three planned cycles of adjuvant chemotherapy, while 16% received only one cycle because of increased treatment-related morbidity or other causes. There were no treatment-related deaths. Although 37 patients experienced failures after completion of treatment, no significant differences were found in patterns of local and regional failures between the two groups. The incidence of distant metastasis, including para-aortic or supraclavicular lymph node metastases, was not reduced in patients of Group B (8% in Group A vs. 7% in Group B). Overall five-year actuarial survival rates for Group A and Group B patients were 85% vs. 80%, and five-year disease-free survival rates were 83% vs. 78%, respectively. CONCLUSIONS: Our data failed to show discernable therapeutic advantage of adjuvant chemotherapy with given after CCRT for the management of FIGO stage bulky IB and IIB uterine cervical cancer patients. A future clinical trial will be necessary to test the clinical efficacy of the adjuvant treatment using newly developed agents in uterine cervical cancer patients.

Adult↗

PubMed2006

The changes of estrogen receptor-beta variants expression in breast carcinogenesis: Decrease of estrogen receptor-beta2 expression is the key event in breast cancer development.

BACKGROUND AND OBJECTIVES: Although more than five variant forms of estrogen receptor-beta (ERbeta) have been identified, their role has not been identified. This study was carried out to investigate the changes of ERbeta variants in breast cancer development. METHODS: Using reverse transcription polymerase chain reaction (RT-PCR) and triple primer PCR (TP-PCR), the expression levels of ERbeta variants mRNA were measured in 66 paired normal and cancer tissues. The relative expression level of ERbeta variants were compared between normal and cancer tissues, and also compared according to various clinicopathological parameters. RESULTS: Among ERbeta variants, ERbeta2 and ERbeta5 consist of the major proportion of ERbeta expression both in normal and cancer tissues. The ERbeta and ERbeta2 expression levels decreased significantly in the cancers compared with corresponding normal tissues, particularly in ERalpha-expressing cancers. However, ERbeta5 expression level increased significantly in the cancers, especially in those of postmenopausal patients. The relative increase of ERbeta5 expression in cancer tissues was associated with favorable differentiation. CONCLUSIONS: Decrease of ERbeta2 is thought to be the key reason for the decrease in ERbeta expression in cancer tissues, and it is particularly associated with the development of ERalpha-expressing breast cancer.

Breast↗

PubMed2006

The role of postoperative external-beam radiotherapy in the management of patients with papillary thyroid cancer invading the trachea.

PURPOSE: To determine the role of adjuvant external-beam radiotherapy (EBRT) in the management of patients with well-differentiated thyroid cancer invading the trachea. METHODS AND MATERIALS: Of 1,098 thyroid cancer patients, 68 (6%) were found to have tracheal invasion, and they all received "shave" excision of the tracheal cartilage. Among them, 12 patients had no postoperative residuum, 43 patients had microscopic residuum, and 13 patients had macroscopic residuum. All patients were divided into two groups according to treatment modality with or without EBRT; (1) the control group (n = 43) and (2) the EBRT group (n = 25). RESULTS: The locoregional recurrence rate for EBRT patients was much lower than that of control patients (51% for the control group vs. 8% for the EBRT group) (p < 0.01). The 10-year local progression-free survival rate for the EBRT group was significantly better than that of the control group (89% in the EBRT group vs. 38% in the control group) (log-rank, p < 0.01). The use of adjuvant EBRT after conservative surgery was an independent prognostic factor in univariate and multivariate analyses. CONCLUSIONS: External-beam radiotherapy was found to be effective, particularly in patients with thyroid cancer invading the trachea with microscopic or gross residuum after conservative surgery.

Adult↗

PubMed2006

Predictive value of p53 and PCNA expression for occult neck metastases in patients with clinically node-negative oral tongue cancer.

OBJECTIVE: In an attempt to identify molecular markers predictive of occult neck metastases, we investigated whether positive p53 or proliferating cell nuclear antigen (PCNA) immunoreactivities on deparaffinized sections of the primary tumor are correlated to the presence of occult neck node metastases in oral tongue cancer patients with clinically negative cervical nodes (N0). STUDY DESIGN AND SETTING: Between 1986 and 1997, 37 clinically N0 patients who underwent neck dissection (25 male, 12 female; mean age 54 years) were selected for p53 and PCNA staining. RESULTS: p53 and PCNA immunoreactivities were detected in 68% and 32%, respectively. There was no correlation between p53 or PCNA and other clinicopathological factors, such as tumor differentiation, tumor type, tumor size, and T-stage. Although tumor differentiation (P=0.03) and tumor size (P=0.03) were significantly correlated with occult neck metastases of oral tongue cancer by univariate analysis, no correlation was found between p53 or PCNA and the presence of occult neck metastasis. CONCLUSION: p53 and/or PCNA expression are unsuitable as biological markers predictive of lymph node metastases of oral tongue cancer. SIGNIFICANCE: p53- or PCNA-positive status are not a reliable parameter for selection of elective neck dissection in the management of N0 oral tongue cancer patients.

Female↗

PubMed2005

Three cases of diffuse large B-cell lymphoma presenting as primary splenic lymphoma.

Primary splenic lymphoma (PSL) is often defined as generalized lymphoma with splenic involvement as the dominant feature. It is a rare disease that comprises approximately 1% of all malignant lymphomas. We investigated three cases of non-Hodgkin's splenic lymphoma that had different clinical features on presentation. The patients' survival times from diagnosis ranged from 59 to 143 months, without evidence of relapse after splenectomy and chemotherapy, with or without radiotherapy. This data suggest that PSL is potentially curable. Further studies are needed to evaluate the impact that different treatment modalities without splenectomy have on patient survival.

Female↗

PubMed2005

Radiosensitivity enhancement by celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, via COX-2-dependent cell cycle regulation on human cancer cells expressing differential COX-2 levels.

To characterize the radiation-enhancing effects on human cancer cells and underlying mechanisms of celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, and to ascertain whether its effects are COX-2 dependent. Clonogenic cytotoxicity assays and radiation survival assays after treatment with celecoxib +/- radiation were done on four human cancer cell lines that expressed differential COX-2 levels. Stably COX-2 knocked down or overexpressed cell lines were developed, and clonogenic assays, apoptosis assays, or cell cycle change measurements were conducted after treatment with celecoxib +/- radiation. Prostaglandin E(2) (PGE2) was applied to medium after treatment with celecoxib +/- radiation to determine whether the radiation-enhancing effect associated with celecoxib results from reduced generation of prostaglandin. Celecoxib's radiation-enhancing effect was observed in COX-2-expressing A549 and NCI-H460 cells but was not observed in the COX-2 nonexpressing MCF-7 and HCT-116 cells. Celecoxib's radiation-enhancing effects in A549 cells were shown to disappear after the administration of COX-2 knocked down. In contrast, the HCT-116 cells were radiosensitized by celecoxib after being transfected with COX-2 expression vector. The addition of PGE2 after treatment with celecoxib +/- radiation had no significant effects on celecoxib's radiation-enhancing effects in A549 and COX-2 transfected HCT-116 cells. Radiation-induced G2-M arrest was enhanced and sustained in the COX-2-overexpressing cells compared with that seen in COX-2 low-expressing cells. Celecoxib or NS-398 effected no changes or attenuated radiation-induced G(2)-M arrest in the COX-2-overexpressing cells but further enhanced the radiation-induced G(2)-M arrest in the COX-2 low-expressing cells. Celecoxib's radiation-enhancing effects seem to occur in a COX-2 expression-dependent manner in the cancer cells. This effect does not seem to be the result of reduced PGE2 generation. Celecoxib may exert an inhibitory effect on enhanced radiation-induced G2-M arrest in the COX-2-overexpressing cells, which may allow the arrested cells to enter mitosis and die after radiation, but may also further enhance radiation-induced G2-M arrest in the COX-2 low-expressing cells, by virtue of another mechanism.

Apoptosis↗

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.

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