Seok-Jin Nam

Interleukin 12 Gene Therapy of Cancer by Peritumoral Injection of Transduced Autologous Fibroblasts: Outcome of a Phase I Study

A phase I dose-escalation clinical trial of peritumoral injections of interleukin 12 (IL-12)-transduced autologous fibroblasts was performed in patients with disseminated cancer for whom effective treatment does not exist. The goals of this study were to assess the safety and toxicities as well as the efficacy, and ancillarily the immunomodulatory effects, of peritumoral IL-12 gene transfer. Primary dermal fibroblasts cultured from the patients were transduced with retroviral vector carrying human IL-12 genes (p35 and p40) as well as the neomycin phosphotransferase gene (TFG-hIL-12-Neo). Patients received four injections at intervals of 7 days. Nine patients were enrolled in this dose-escalation study, with secreted IL-12 doses ranging from 300 ng/24 hr for the first three patients to 1000, 3000, and 5000 ng/24 hr for two patients in each subsequent dosage level. Although a definite statement cannot be made, there appears to be perturbation of systemic immunity. Also, the locoregional effects mediated by tumor necrosis factor alpha (TNF-alpha) and CD8+ T cells were observed with tumor regression. Treatment-related adverse events were limited to mild to moderate pain at the injection site; clinically significant toxicities were not encountered. Transient but clear reductions of tumor sizes were observed at the injected sites in four of nine cases, and at noninjected distant sites in one melanoma patient. Hemorrhagic necrosis of tumors was observed in two melanoma patients. These data indicate that gene therapy by peritumoral injection of IL-12-producing autologous fibroblasts is feasible, and promising in patients with advanced cancer.

Accuracy of MRI for estimating residual tumor size after neoadjuvant chemotherapy in locally advanced breast cancer: Relation to response patterns on MRI

Background. This study evaluated the accuracy of magnetic resonance imaging (MRI) for estimating residual tumor size after neoadjuvant chemotherapy in patients with locally advanced breast cancer and assessed whether the tumor pattern on MRI after chemotherapy influenced the accuracy of the MRI measurement of the residual tumor size. Patients and methods. Fifty patients who received neoadjuvant chemotherapy with doxorubicin and docetaxel for locally advanced breast cancer were evaluated with MRI before and after chemotherapy. We compared the residual tumor size measured by MRI with the pathologically determined size and investigated the influence of the residual tumor pattern on MRI (shrinkage, nest or rim, and mixed) and pathologic characteristics on the accuracy of the MRI measurement. Results. The correlation coefficient between the residual tumor sizes determined by MRI and by pathology was 0.645. The MRI measurement agreed with the pathologically determined size in 36 patients (72%) and disagreed in 14 patients (28%), overestimating the size in 13 (26%) and underestimating the size in one (2%). Disagreement appeared to be more frequent in the cases showing a nest or rim pattern than in those exhibiting a shrinkage pattern, although this was not statistically significant (p=0.119). Conclusions. MRI is an accurate method for predicting the extent of residual tumor after neoadjuvant chemotherapy; however, it may overestimate the residual disease, especially in cases showing a nest or rim tumor pattern and in those having combined lesions with ductal carcinoma in situ or multiple scattered nodules after neoadjuvant chemotherapy.

Expression of p21Waf1, p27Kip1 and cyclin D1 proteins in breast ductal carcinoma in situ: Relation with clinicopathologic characteristics and with p53 expression and estrogen receptor status

p21Waf1 (p21), p27Kip1 (p27) and cyclin D1 have recently been reported as useful prognostic markers for patients with breast carcinoma. However, studies on these cell cycle regulators in ductal carcinoma in situ (DCIS) have been extremely limited. Therefore, we studied the immunohistochemical expression of p21, p27 and cyclin D1 proteins in 49 DCIS cases and compared the findings with the clinicopathologic parameters (age, tumor size, gross type, histologic type, histologic grade, necrosis and mitotic index), p53 and estrogen receptor (ER) status. A significant correlation was found between positive p21 immunoreactivity (67.3% of the cases) and well‐differentiated histologic grade, non‐comedo type, ER‐positive and p53‐negative (p53–) status. DCIS with p21+/p53– is likely to be the non‐comedo type. The overexpression of cyclin D1 (59.2% of the cases) correlated positively with the ER expression (P = 0.001). The p27 protein expression (46.9% of the cases) correlated with the cyclin D1 immunopositivity (P = 0.0003) and ER expression (P = 0.005). No significant associations were seen in the p27 or cyclin D1 expression and other clinicopathologic parameters. Our results suggest that p21 might be more related to the useful biologic markers in DCIS than p27 or cyclin D1. The significant positive association between p21, p27 or cyclin D1 and ER status, and close association of p27 and cyclin D1 expression might be implicated in the tumor biology of DCIS.

A case–control study on seaweed consumption and the risk of breast cancer

Gim (Porphyra sp.) and miyeok (Undaria pinnatifida) are the seaweeds most consumed by Koreans. We investigated the association between the intake of gim and miyeok and the risk of breast cancer in a case-control study. Cases were 362 women aged 30-65 years old, who were histologically confirmed to have breast cancer. Controls visiting the same hospital were matched to cases according to their age (sd 2 years) and menopausal status. Food intake was estimated by the quantitative FFQ with 121 items, including gim and miyeok. Conditional logistic regression analysis was used to obtain the OR and corresponding 95 % CI. The average intake and consumption frequency of gim in cases were lower than in controls. The daily intake of gim was inversely associated with the risk of breast cancer (5th v. 1st quintile, OR, 0.48; 95 % CI, 0.27, 0.86; P for trend, 0.026) after adjustment for potential confounders. After stratification analysis was performed according to menopausal status, premenopausal women (5th v. 1st quintile, OR, 0.44; 95 % CI, 0.24, 0.80; P for trend, 0.007) and postmenopausal women (5th v. 1st quintile, OR, 0.32; 95 % CI, 0.13, 0.80; P for trend, 0.06) showed similar inverse associations between gim intake and the risk of breast cancer after an adjustment for potential confounders except dietary factors. Miyeok consumption did not have any significant associations with breast cancer. These results suggest that high intake of gim may decrease the risk of breast cancer.

Benign papillary lesions of the breast: sonographic-pathologic correlation.

We reviewed the sonographic findings of 42 benign papillary lesions of the breast and correlated them with pathologic findings. Sonography detected 95% of papillomas (22 intraluminal masses, four extraductal masses, nine purely solid masses, and five mixed type masses). The sonographic margins of the mass were well defined in 20 lesions and poorly defined in 14 lesions. Poorly defined margins on sonography were frequent in papillomas with pathologic pseudoinvasion and in juvenile papillomatosis. Most benign papillary lesions of the breast have the sonographic findings suggestive of intraductal origin. The sonographic findings of papillary lesions correlated well with pathologic findings.

Impact of chemotherapy-induced alopecia distress on body image, psychosocial well-being, and depression in breast cancer patients.

This study aims to evaluate the impact of chemotherapy‐induced alopecia (CIA) distress on body image, psychosocial well‐being, and depression among breast cancer patients.

Sentinel lymph node biopsy in papillary thyroid cancer: Comparison study of blue dye method and combined radioisotope and blue dye method in papillary thyroid cancer

AIM Occult lymph node metastasis is common in differentiated thyroid cancer (DTC). However, the role of lymph node dissection in the treatment of DTC remains controversial. The authors investigated the usefulness of methylene blue dye only method and combined radioisotope and methylene blue dye method for detecting SLN and compared the values of these two methods in patients with DTC. METHODS From February to May 2008, 97 patients with DTC underwent sentinel lymph node biopsy (SLNB). The methylene blue dye method (dye only method) was used in 54 of the 97 patients, and radioisotope and methylene blue dye method (combined method) in 43 patients. RESULTS The SLNs were identified in 89 patients, and the sensitivity and specificity of SLNB in the 97 patients were 85% and 100% respectively. For the dye only method, sensitivity, specificity, and the false negative rate (FNR) were 79%, 100%, and 21%; and for the combined method (43 patients) the corresponding figures were, 91%, 100%, and 9%, respectively. Six patients with SLN metastasis in the lateral neck underwent additional modified radical neck dissection (MRND). CONCLUSIONS SLNB was found to be feasible, repeatable, and accurate in evaluating the lymph node status in patient with DTC. The present study indicates that the combined method could reduce false negative rate and increase detection rates of sentinel lymph node metastases, especially in lateral neck, compared to the dye only method.

A case-control study on the dietary intake of mushrooms and breast cancer risk among Korean women

To evaluate the association between dietary mushroom intake and breast cancer risk, a total of 362 women between the ages of 30 and 65 years who were histologically confirmed to have breast cancer were matched to controls by age (±2 years) and menopausal status. Mushroom intake was measured via a food frequency questionnaire that was administered by well‐trained interviewers. The associations between the daily intake and the average consumption frequency of mushrooms with breast cancer risk were evaluated using matched data analysis. Both the daily intake (5th vs. 1st quintile, OR = 0.48, 95% CI = 0.30–0.78, p for trend 0.030) and the average consumption frequency of mushrooms (4th vs. 1st quartile, OR = 0.54, 95% CI = 0.35–0.82, p for trend 0.008) were inversely associated with breast cancer risk after adjustment for education, family history of breast cancer, regular exercise [≥22.5 MET (metabolic equivalent)‐hr/week], BMI (body mass index, Kg/m2), number of children and whether they are currently smoking, drinking or using multivitamin supplements. Further adjustments were made for energy‐adjusted carbohydrate, soy protein, folate and vitamin E levels, which tended to attenuate these results. After a stratification was performed according to menopausal status, a strong inverse association was found in postmenopausal women (OR = 0.16, 95% CI = 0.04–0.54, p for trend = 0.0058 for daily intake; OR = 0.17, 95% CI = 0.05–0.54, p for trend = 0.0037 for average frequency), but not in premenopausal women. In conclusion, the consumption of dietary mushrooms may decrease breast cancer risk in postmenopausal women.

Probably Benign Breast Masses Diagnosed by Sonography: Is There a Difference in the Cancer Rate According to Palpability?

OBJECTIVE The study was designed to assess retrospectively whether there is a difference in the cancer rates between palpable and nonpalpable probably benign breast nodules detected by sonography. We further investigated the clinicopathologic results of sonographically false-negative cases. MATERIALS AND METHODS This study included 352 women who had undergone sonographically guided core biopsies for 374 BI-RADS category 3 masses between March 2004 and February 2005. No masses were diagnosed with definite malignant findings on mammography. The cancer rates of nonpalpable and palpable masses were compared using Fishers exact test. The clinicopathologic results of sonographically false-negative cases were investigated. RESULTS Among the 374 masses, 86 masses (23%) that were lost to follow-up were excluded. Of the 288 masses with follow-up or excision, the cancer rate was 2.4% (7/288). The cancer rate of the nonpalpable masses was 2.1% (4/194) (95% CI, 0.6-5.2%), and the cancer rate of the palpable masses was 3.2% (3/94) (95% CI, 0.6-9.0%), with no statistically significant difference (p = 0.6864). Of the seven cancers, five were diagnosed by a sonographically guided core biopsy and two were diagnosed by surgical excision after a benign biopsy. The seven sonographically false-negative masses in seven patients were identified as three invasive ductal carcinomas, two ductal carcinomas in situ, one mucinous carcinoma, and one papillary carcinoma on the basis of pathology results. CONCLUSION There is no statistically significant difference between the cancer rates of palpable and nonpalpable BI-RADS category 3 masses seen on sonography.

Ultrasonographic detection of occult cancer in patients after surgical therapy for breast cancer.

The purpose of this study was to investigate the efficacy of ultrasonography in detecting an occult malignancy after surgery for breast cancer and to assess the imaging and clinical findings associated with a recurrence.