• Environmental Mutagens and Carcinogens
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• v.22 no.2
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• pp.112-124
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• 2002

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to exert detrimental toxicities on various organ systems including reproductive, cardiovascular, nervous, or dermal system. Immunomodulatory effects of TCDD is thymic atrophy, downregulation of cytotoxic T or B lymphocyte differentiation and activation, which were demonstrated using experimental animals, whereas immunotoxicity in human has not been investigated well. This study was proceeded to evaluate general immunologic spectrum of the Korean Vietnam War veterans exposed to TCDD during their operation, and compare with that of the non-exposed control subjects with similar age. Regarding composition and quantity, immune cells in peripheral blood collected from the TCDD-exposed was not much different from those of the control except decreased red blood cell, hemoglobin and hematocrit level. Furthermore, plasma IgG2, G3, and G4 isotype distribution was similar between two groups, but IgG1 level was significantly lowered in the TCDD-exposed, indicating a TCDD-mediated functional alteration of B cells. Significantly enhanced level of IgE in plasma, a hallmark of dermal or respiratory allergic response, was also observed in the TCDD-exposed compared with that of the control. Elevated generation of IL-4 and IL-10 was resulted from in vitro stimulation of T cells with PMA plus ionomycin or PHA, respectively, from the TCDD-exposed in comparison to those of the control, suggesting a skewed type-2 response. In addition, the level of IFN${\gamma}$, a multifunctional cytokine for T cell-mediated immunity, was lowered in the TCDD-exposed with upregulation of tumor necrosis factor $\alpha$. The present study suggests that TCDD exposure disturbs immunohomeostasis in humans observed as an aberrant plasma IgE and IgG1 levels and dysregulation of T cell activities.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.12
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• pp.1724-1731
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• 2009

This study was aimed to investigate the effect of phyto-extract fermented mixture (MP119) on the male sexual functions. The MP119 was evaluated for anti-impotency and anti-hypertensive effects via ACE (angiotensin converting enzyme) or PDE (phosphodiesterase) inhibition assay. $IC_{50}$ values of MP119 against ACE and PDE were 241.3${\pm}$35.5 ppm and 372.2${\pm}$33.8 ppm, respectively. To investigate the effect of testosterone expression by MP119, we performed cell media test using mouse Leydig-derived TM3 cells. Production of testosterone in TM3 cell was increased by MP119. Also, NO (nitric oxide) production of HUVEC (human umbilical vein endothelial cell) was increased when MP119 was added to the cultures. Forty male ICR mice were divided into 4 groups. MP119 was orally intubated for 7 days to group 1 and 3, and same volume of vehicle to group 2 and 4 as controls. After that, group 3 and 4 were intraperitoneally injected cadmium chloride at a single dose of 2 mg/kg. On the 8th experimental day, weights of testis, epididymis and seminal vesicle, number of sperm, concentrations of serum testosterone and cGMP were determined. The number of sperm, the concentrations of testosterone and cGMP were significantly increased in two experimental groups (group 1, 3). These results suggest that MP119 enhanced the sexual function of male mice, and could protect the sexual organs from the cadmium chloride as one of the endocrine disrupters.

• The Journal of Pediatrics of Korean Medicine
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• v.27 no.1
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• pp.69-81
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• 2013

Objectives In this study, effects of Macmundongtang (MMT) on ATP or TNF-${\alpha}$ or PMA or EGF induced MUC5AC mucin production and gene expression from human airway epithelial cells and the increase in airway epithelial mucosubstances of rats were investigated. Materials and Methods Confluent NCI-H292 cells were pretreated for 30min in the presence of MMT and treated with ATP ($200{\mu}M$) or PMA (10 ng/ml) or EGF (25 ng/ml) or TNF-${\alpha}$ (0.2 nM) for 24hrs, to assess the effect of MMT both on ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production using enzyme-linked immunosorbent assay (ELISA) and on gene expression by the same inducers using reverse transcription-polymerase chain reaction (RT-PCR). At the same time, hypersecretion of airway mucus was induced by exposure of rats to SO2 during 3 weeks. Effect of orally-administered MMT during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats was assesed using histopathological analysis after staining the epithelial tissue with PAS-alcian blue. Possible cytotoxicity of MMT was assessed by investigating the potential damage of kidney and liver functions by measuring serum GOT/GPT activities and serum BUN concentration of rats and the body weight gain during experiment, after administering MMT orally. Results (1) MMT did not only inhibit but also increased MUC5AC mucin productions and expression levels of MUC5AC gene from NCI-H292 cells. (2) MMT did not decrease the amount of intraepithelial mucosubstances of trachea of rats. (3) MMT did not show renal and hepatic toxicities and did not affect body weight gain of rats during experiment. Conclusions The result from the present study suggests that MMT might normalize the production and gene expression of airway mucin observed in various respiratory diseases accompanied by yin-deficiency, without in vivo toxicity to liver and kidney functions after oral administration.

• Clinical and Experimental Pediatrics
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• v.52 no.1
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• pp.119-123
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• 2009

Renal cell carcinoma (RCC) arising from epithelial cells of the renal tubules is a highly aggressive and malignant tumor in all ages; however, it rarely occurs in children. the standard treatment for RCC is radical nephrectomy with lymph node dissection when the tumor is localized and can be completely resected. Adjuvant chemotherapy, radiotherapy, and immunotherapy are used for pediatric patients with advanced RCC involving lymph nodes or metastatic lesions. Sorafenib is an oral, multikinase inhibitor that has recently been approved for use in metastatic RCC. Common toxicities that have been reported include dermatologic changes such as rash or desquamation and hand-foot skin reaction, diarrhea, fatigue, alopecia, and hypertension. In particular, hand-foot syndrome (HFS) an erythematous skin lesion of the palms and solesis most often caused by cytostatic chemotherapeutic agents. In this report, we have studied a 14-year-old female patient with hand-foot syndrome that occurred in association with sorafenib for the treatment of metastatic RCC. Furthermore, this case demonstrates that reversal of complications can be achieved by discontinuing the drug and intervention with topical steroids, vitamin E, and high-dose pyridoxine.

• Toxicological Research
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• v.21 no.4
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• pp.325-332
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• 2005

The developmental toxicity of water extract of licorice (Glycyrrhiza glabra) was evaluated in rats. Licorice extract (500, 1,000 or 2,000 mg/kg) was dissolved in drinking water and orally administered to male rats from 9 weeks before mating to the day of copulation, and to females from 2 weeks before mating to gestational day 19. On gestational day 20, the animals were sacrificed for Cesarian section, and maternal and fetal abnormalities were examined. Licorice extract neither induce clinical signs, nor affect the body weight gain, feed and water intake, estrous cycle, copulation and fertility rates, blood $17\beta-estradiol$ level and organ weights of dams. Also, the implantation and development including body weights, absorption and death of embryos and fetuses were not influenced by in utero exposure to licorice. In addition, there were no increases in external, visceral and skeletal abnormalities of fetuses. Taken together, it is suggested that no observed adverse effect level of licorice extract is higher than 2,000 mg/kg, and that long-term in utero exposure to licorice might not cause developmental toxicities of embryos and fetuses.

• Journal of Yeungnam Medical Science
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• v.21 no.2
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• pp.198-206
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• 2004

Background: To evaluate the efficacy and safety of paclitaxel and cisplatin against advanced non-small cell lung cancer (NSCLC) as a second-line chemotherapy. Subjects and Methods: Twenty-five patients were enrolled. The patients received 200 $mg/m^2$ paclitaxel as a 3-hour intravenous infusion and 60 $mg/m^2$ cisplatin as 2D-minute intravenous infusion with vigorous hydration on day 1 every 28 days. The response was assessed every 2 cycles. Results: All 25 patients were assessed for their response and toxicity. Partial responses were observed in 5 patients. The overall response rate was 20%(95% confidence interval, 4%-36%) and the median response duration was 4.5(range, 2-11) months. The median time to progression was 3.3(range, 0-14) months. The median overall survival of all patients was 7.4(range, 1.3-39) months. The hematologic toxicities were minor and easily controlled. Conclusion: The combination chemotherapy of paclitaxel and cisplatin as a second-line treatment has a moderate efficacy with an acceptable toxicity in patients with advanced NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7867-7869
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• 2015

Objective: To assess the safety and effectiveness of thalidomide (produced by CHANGZHOU PHARMACEUTICAL FACTORY CO.LTD) combined with chemotherapy in treating patients with advanced colorectal cancer. Method: A consecutive cohort of pretreated patients with advanced colorectal cancer were treated with thalidomide combined with chemotherapy. And chemotherapy for patients with advanced colorectal cancer were administered according to the condition of patients. Thalidomide was orally administered at a dosage of 50mg/day to 150mg/day before sleeping for at least 14 days. After at least 14 days of treatment, safety and side effects were evaluated. Results: There were 12 female and 3 male patients with advanced cancer recruited into this study, including 9 patients with colon, 6 patients with rectal cancer. The median age of patients was 57(41-82) years. Partial response was observed in 2 patients (2/15), and stable disease in 3 patients(3/15). Incidences of Grade 1 to 2 myelosuppression was observed in 1/15 patients, and Grade 1 to 2 elevation of hepatic enzyme was recorded in 1/15 patients. Adverse effects on the gastrointestinal tract were documented in 1/15 patients, and were Grade 1. No Grade 3-4 toxicities were diagnosed. No treatment related death was found. Conclusions: Thalidomide combined with chemotherapy was safe and mildly effective in treating patients with advanced colorectal cancer. However, further study should be conducted to clarify the effectiveness of this combination.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7119-7123
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• 2014

Background: The role of second-line therapy in metastatic pancreatic cancer is not clear. In this study, we aimed to explore the second-line efficiency of capecitabine and oxaliplatin (XELOX) in patients with advanced pancreatic cancer who have received gemcitabine-based first-line therapy. Materials and Methods: We retrospectively evaluated 47 patients with locally advanced or metastatic pancreatic cancer previously treated with gemcitabine-based first-line regimens. Treatment consisted of oxaliplatin $130mg/m^2$ and capecitabine $1000mg/m^2$ twice daily with a 3 week interval, until unacceptable toxicity or disease progression. Results: Median number of cycles was 4 (range, 2-10). The overall disease control rate was 38.3%. The median overall survival and progression-free survival from the start of second-line therapy were 23 weeks (95%CI: 16.6-29.5 weeks) and 12 weeks (95%CI: 9.8-14.4 weeks), respectively. The most common grade 3-4 toxicities were nausea, vomiting and hematologic side effects. Conclusions: Our result suggests that the combination of capecitabine and oxaliplatin was tolerated with manageable toxicity and showed encouraging activity as second-line treatment of advanced or metastatic pancreatic cancer patients with ECOG performance status 0-2.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6663-6667
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• 2013

Purpose: The current research was conducted to investigate the efficacy and safety of pemetrexed given continuously as a basement agent for first-, second- to third line chemotherapy of patients with metastatic lung adenocarcinoma. Patients and Methods: Patients with metastatic lung adenocarcinoma who were diagnosed in Jiangsu Cancer Hospital and Research Insitute, were enrolled. All received pemetrexed 500 $mg/m^2$ (intravenous; on day 1), and another chemotherapieutic agent every 3 weeks until disease progression, or intolerable toxicity. Then the patients were changed to a second line chemotherapy that was still based on pemetrexed 500 $mg/m^2$ and another chemotherapeutic agent differing from the first line example, until disease progression, or intolerable toxicity. When third line chemotherapy was needed, pemetrexed 500 $mg/m^2$ and another new chemotherapeutic agent were combined until disease progression. Evaluation of efficacy was conducted after two cycles of chemotherapy using the Response Evaluation Criteria for Solid Tumors. Toxicity was recorded according to NCI Criteria for Adverse Events version 3.0. Results: From January 2010 to September 2013, 15 patients were enrolled. Their median age was 56 years (range 43 to 77 years). Eight patients were male and 7 female. Five patients (33.3%) achieved PR, while 6 patients (40.0%) remained stable, no CR on first line; and 1 PR (7.7%), 5 stable (38.5%) were recorded when pemetrexed was ordered in second line; 5 patients (41.7%) were stable after pemetrexed was combined in third line; no complete response was observed. Main side effects were grade 1 to 2 neutrophil suppression and thrombocytopenia. Other toxicities included elevated transaminase and oral mucositis, but no treatment related death occurred. Conclusions: Pemetrexed continuously as a basement agent from first-, second- to third line chemotherapy is mildly effective in treating patients with metastatic lung adenocarcinoma with tolerable toxicity.

• Toxicological Research
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• v.23 no.4
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• pp.405-413
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• 2007

This study was to investigate single and repeated-dose toxicities of Tensolin-$F^{(R)}$, an anti-wrinkle agent, in Sprague-Dawley (SD) rats or ICR mice. In single-dose oral toxicity study, the test materials were administered once by gavage to male and female SD rats at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and Tensolin-$F^{(R)}$ treated group. Therefore, the approximate lethal dose of Tensolin-$F^{(R)}$ was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test material was administered once daily by gavage to male and female ICR mice at dose levels of 0, 25, 50 and 100 mg/kg/day for 4-weeks. In the results, no abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, necropsy findings, histopathological findings. In hematological analysis, there was a trend of increase in reticulocyte at male 25 mg/kg, although such changes were in normal ranges. On the other hand, there was a trend of decrease in hemoglobin at female 50, 100 mg/kg, such changes were in normal ranges. In addition, serum biochemical parameters including sodium, BUN and chloride increased at 25, 50 and 100 mg/kg. Relative organ weights of right testis, brain, lung and left epididymis were increased in 100 mg/kg groups of male rats in contrast to not change in female groups. However, these changes of relative organ weights, hematological and serum biochemical parameters were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, 4-week repeated oral dose of Tensolin-$F^{(R)}$ to ICR mice did not cause apparent toxicological change at the dose of 25, 50, 100 mg/kg body weight. Consequently the no-observed-adverse-effect level (NOAEL) for Tensolin-$F^{(R)}$ in ICR mice following gavage for at least 4-week is higher than 100 mg/kg/day.