Purpose: Decisions as to whether to provide adjuvant treatment in older breast cancer patients remains challenging. Side effects of chemotherapy have to be weighed against life expectancy, comorbidities, functional status, and frailty. To aid decision-making, we retrospectively analyzed 110 women with breast cancer treated with a curative intention from 2006 to 2012. Survival data with clinical and pathological parameters were evaluated to address the role of adjuvant chemotherapy in this study population. Method: A total of 110 elderly (>70 years) patients that received mastectomy at two hospitals in Taiwan were observed retrospectively for a medium of 51 months. After mastectomy, patients received conservative treatment or adjuvant chemotherapy, or hormone therapy following clinical guidelines or physician's preference. Data were collected from the cancer registry system. Results: Median age at diagnosis was 75.7 years. Thirty-five percent of patients received adjuvant chemotherapy, these having a significantly younger age ($mean=74.0{\pm}5.3$ vs $77.5{\pm}5.3$, p<0.001) and higher tumor staging (p=0.003) compared with their non-chemotherapy counterparts.Five-year overall survival was non-significantly higher in patients who received adjuvant chemotherapy (with chemotherapy 64.2% vs without chemotherapy 62.6%, p=0.635), while five-year recurrence free survival was non-significantly lower (with chemotherapy 64.1% vs without chemotherapy 90.5%, p=0.80). Conclusions: In this analysis, adjuvant chemotherapy tended to be given to patients with a younger age and higher tumor staging at our institute. It was not associated with any statistically significant improvement in survival and recurrence rate. Until age specific recommendations are available, physicians must use their clinical judgment and assess the tumor biology with the patient's comorbidities to make the best choice. Clinical trials focusing on this critical issue are warranted.
BACKGROUND: Polychlorinated biphenyls (PCBs) are one of the most common environmental contaminants. Because of their recalcitrant properties and long-term toxicity, numerous studies have been performed. The toxicological concerns are focused on endocrinological effects of animal. Several different metabolites have been reported, including hydroxy PCBs, PCB quinones, and methylsulfonyl PCBs from animal tissues. However, details in plants have never been studied. It is well-known that plants can produce phytoalexin in response to chemical, physical, or pathological stress.METHODS AND RESULTS: In this study, the several PCBs and hydroxy derivatives were prepared by chemical syntheses. Their effects on secondary metabolite biosynthesis were determined in carrot roots. The levels of 6-methoxymellein were determined in several different treatments, using gas chromatography-mass spectrometry. In general, the concentration of 6-methoxymellein reached a maximum at 2 days and gradually decreased to trace level at 5 days in control experiments. However, the effects of PCBs or hydroxy derivatives were highly dependent on compounds. For example, the maximum concentrations of 6-methoxymellein were observed at 3 days for 2-hydroxy/4-hydroxybiphenyl, while 3,3',4,4',5-pentachlorobiphenyl and 3,5-dichloro-2-hydroxybiphenyl showed a rapid accumulation within 1 day, followed by rapid dissipation to undetectable levels.CONCLUSION: Biphenyl derivatives were effective elicitor of 6-methoxymellein accumulation. In general, hydroxybiphenyls (phenols) more efficiently induced phytoalexin biosynthesis than those without hydroxy groups. It can be concluded that PCBs or their possible metabolites could change the plant secondary metabolism.
The subcronic toxicity of WK-38, a herbal preparation for the atherosclerosis, was examined in male and female Sprague-Dawley rats. WK-38 is composed of Rhei Rhizoma, Magonoliae Cortx, Moutan Cortex Radicis. Rats were treated with the test substance at a dose of 5 mg/kg, 50 mg/kg and 500 mg/kg intragastrically for 13 weeks. Control rats were treated with vehicle only. No death and abnormal clinical signs were observed throughout the administration period. Also there was no difference in net body weight gain, food and water consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of the WK-38. Hematological findings and biochemical examination revealed no evidence of specific toxicity related to WK-38. The results suggested that under the condition employed in this study no observation effect level (NOEL) of WK-38 would be 500 mg/kg/day.
Jung, Ji-Yeon;Jeong, Yeon-Jin;Han, Chang-Ryoung;Kim, Sun Hun;Kim, Hyun-Jin;Lee, Ki-Heon;Park, Ha-Ok;Kim, Won-Jae
The Korean Journal of Physiology and Pharmacology
/
v.9
no.4
/
pp.239-246
/
2005
In the central nervous system, nitric oxide (NO) is associated with many pathological diseases such as brain ischemia, neurodegeneration and inflammation. The epigallocatechin gallate (EGCG), a major compound of green tea, is recognized as protective substance against neuronal diseases. This study is aimed to investigate the effect of EGCG on NO-induced cell death in PC12 cells. Administration of sodium nitroprusside (SNP), a NO donor, decreased cell viability in a dose- and time-dependent manner and induced genomic DNA fragmentation with cell shrinkage and chromatin condensation. EGCG diminished the decrement of cell viability and the formation of apoptotic morphologenic changes as well as DNA fragmentation by SNP. EGCG played as an antioxidant that attenuated the production of reactive oxygen species (ROS) by SNP. The cells treated with SNP showed downregulation of Bcl-2, but upregulation of Bax. EGCG ameliorated the altered expression of Bcl-2 and Bax by SNP. The release of cytochrome c from mitochondria into cytosol and expression of voltage -dependent anion channel (VDAC)1, a cytochrome c releasing channel in mitochondria, were increased in SNP-treated cells, whereas were attenuated by EGCG. The enhancement of caspase-9, preceding mitochondria-dependent pathway, caspase-8 and death receptor-dependent pathway, as well as caspase-3 activities were suppressed by EGCG. SNP upragulated Fas and Fas-L, which are death receptor assembly, whereas EGCG ameliorated the expression of Fas enhanced by SNP. These results demonstrated that EGCG has a protective effect against SNP-induced apoptosis in PC12 cells, through scavenging ROS and regulating the mitocondria- and death receptor-mediated signal pathway. The present study suggest that EGCG might be a natural neuroprotective substance.
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) a prototype of the highly toxid halogenated arylhydrocarbons, bioaccumulates in the food chain and induces a complex spectrum of pathological responses. However, its effect on the nerve system is relatively not well studied. In this study we evaluated TCDDs cytotoxicity on the cortical cell and investigated its effect on the expression 2,3-cyclic nucleotide 3-phosphodiesterase(CNPase), a marker for oilgodendrocytes, The survival rates of 4 DIV cortical cells, that are dissociated from E18 rat cortex and maintained in the presence of TCDD, were 88.8, 83.6, 78.5, and 78.6%(5,10, 20 and 50 nM, respectively) where the reduction in 20 and 50mM TCDD were statistically very significant(p<0.01). Imunocytochemistry of cultured cells revealed that the intensities of immunostaining with an anti-CNP1&2 antibody depended on the concentrations of the toxin. Immunoblot analysis also showed differential expression of CNP1 and CNP2 in the presence of TCDD; the CNP1 expression was dose-dependently decreased. Interestingly, the expression of CNP2 in the presence if TDCC; the CNP1 expression was dose-dependently decreased. Interestingly, the expression of CNP2 fluctuated with the TCDD concentration. These results indicated that CNP1 and 2 are differentially regulated by TCDD, implying the functions of oligodendrocytes are modulated by the toxin.
Jo, Jeong-Sig;Lee, Jun-Beom;Hwang, Min-Seob;Yoon, Jong-Hwa
Journal of Acupuncture Research
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v.24
no.3
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pp.119-126
/
2007
Objectives: The following study was undertaken in order to seek the acupuncture operation method of ${\ll}$Sang Han Lun(傷寒論)${\gg}$ Liu-Jing-Bian-Zheng(六經辯證). Methods: Based on the documents quoted in ${\ll}$Sang Han Za Bing Lun ${\cdot}$ Xu Wen(傷寒雜病論 ${\cdot}$ 序文)${\gg}$ of "Zhang, Zhong-Jing(張仲景)", the relativity of the theory of Jing-Mai(經脈) and Liu-Jing-Bian-Zheng of convalescence, and from the Liu-Jing-Bing(六經病), the origin and implication that caused So-Yang-Bing(少陽病) to form was studied on the basis of acupuncture medicine publications and the commentary writing of ${\ll}$Sang Han Lun${\gg}$. Results: 1. ${\ll}$Sang Han Lun${\gg}$ Liu-Jing-Bian-Zheng has succeeded and was developed based on Liu-Jing-Fen-Zheng(六經分證) of ${\ll}$ Su Wen ${\cdot}$ Re Lun(素問 ${\cdot}$ 熱論)${\gg}$. In addition, the summary of Liu-Jing-Bing became the general principle of Fen-Jing(分經) and Ding-Zheng(定證) that may be applicable to Fenghan(風寒), Wenre(溫熱), Lili and Zabing(雜病). 2. Most commentators of $\ll$Sang Han Lun$\gg$ in the Song, Ming and Ching Dynasties of ${\ll}$Sang Han Lun${\gg}$interpreted the So-Yang-Bing in physiological and pathological aspects of Rong-Wei(榮衛) as the disease of the bladder meridian that oversees the skin of the human body. 3. From the Liu-Jing-Bing of ${\ll}$Sang Han Lun${\gg}$, the region of acupuncture treatment of So-Yang-Bing is treated with the needle from the point of view of bing-Zheng-Lun-Zhi(辯證論治) with the basis of the important region of acupuncture of the Triple Energizer meridian and Gallbladder of meridian.
Kim, Young-Chool;Lim, Sung-Bin;Chung, Chin-Hyung;Lee, Chong-Heon
Journal of Periodontal and Implant Science
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v.33
no.4
/
pp.693-703
/
2003
The present study evaluated the effects of guided tissue regeneration using xenograft material(deproteinated bovine bone powder), with and without Calcium sulfate membrane in beagle dogs. Contralateral fenestration defects (6 ${\times}$ 4 mm) were created 4 mm apical to the buccal alveolar crest of maxillary premolar teeth in 5 beagle dogs. Deproteinated bovine bone powders were implanted into fenestration defect and one randomly covered Calcium sulfate membrane (experimental group). Calcium sulfate membrane was used to provide GTR. Tissue blocks including defects with soft tissues which were harvested following four & eight weeks healing interval, prepared for histo-phathologic analysis. The results of this study were as follows, 1. In control group, at 4 weeks after surgery, new bony trabecular contacted with interstitial tissue and osteocytes lie cell were arranged in new bony trabecule. Bony lamellation was not observed. 2. In control group , at 8 weeks after surgery, scar-like interstitial tissue was filled defect and bony trabecule form lamellation. New bony trabecular was contacted with interstitial tissue but defect was not filled yet. 3. In experimental group, at 4 weeks after surgery, new bony trabecular partially recovered around damaged bone. But new bony trabecule was observed as irregularity and lower density. 4. In experimental group, at 8 weeks after surgery, lamella bone trabecular developed around bone cavity and damaged tissue was replaced with dense interstitial tissue. In conclusion, new bone formation regenerated more in experimental than control groups and there was seen observe more regular bony trabecular in experimental than control groups at 4 weeks after surgery. In control group, at 8 weeks after surgery, the defects was filled with scar-like interstitial tissue but, in experimental group, the defects was connected with new bone. Therefore xenograft material had osteoconduction but could not fill the defects. We thought that the effective regeneration of periodontal tissue, could be achieved using GTR with Calcium sulfate membrane.
Kim, Dong-Heui;Teng, Yung-Chien;Yoon, Yang-Sook;Qi, Xu-Feng;Jeong, Hyun-Seok;Chang, Byung-Soo;Lee, Kyu-Jae
Applied Microscopy
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v.39
no.2
/
pp.125-132
/
2009
Extracts and fractions of Inonotus obliquus (Chaga in Russia) have been known to have various biological activities, including antimutagenic, anticancer, antioxidative, and immunostimulating effects. This study was performed to confirm anticancer effect of 10% superfine Chaga mushroom processed by nano-mill technology on C57BL/6 mice. Chaga particles belonged in the size of 1 ${\mu}m$ was about 40% after nanomill processing according to the volume distribution. As the result of subcutaneous injection of B16BL6 melanoma cells to the mice, the tumor volume (p<0.001) and tumor weight (p<0.01) was significantly decreased in the experimental (NCh) group as compared with control (C) group and the tumor growth inhibitory rate was 29.2%. On examination of survival rate after intraperitoneal injection of B16BL6 melanoma cells, the mean survival time per a mouse was 17.7 and 26.0 days in C and NCh group respectively. The survival rate of NCh group was 40% when that of C group was 0% at the 35th day. On the result of examination to confirm histological toxicity by Chaga superfine particles, both groups did not show any morphological and pathological changes in the small and large intestine under the light microscope. These results suggest that feeding of superfine Chaga produced by nanomill technique has a tumor growth inhibitory effect in vivo.
Kim, Kyun-Ha;Roh, Sang-Geun;Park, Hae-Ryun;Choi, Won-Chul
Journal of Life Science
/
v.19
no.2
/
pp.157-162
/
2009
Nitric oxide (NO) is a diffusible, multifunctional and transcellular messenger that has been implicated in numerous physiological and pathological conditions. It has been reported that NO induced apoptosis in tumor cells, macrophage cells and inhibited apoptosis in normal cells, endothelial cells. To examine whether NO could induce apoptosis in MCF-7 cells, cells were treated with SIN-1 (3-morpholinosydnonimine), NO donor. Cell viability did not change in SIN-1 treated cells for 48 h and there was no significantly changes in cell cycle progression or growth pattern by FACS analysis. But p53 protein, an apoptosis-related factor, increased SIN-1 treatment time dependently. Bcl-2, MDM2 and p21 were also accumulated. Bax level did not change. A major role of inhibiting apoptosis by NO in MCF-7 cells, cobalt chloride ($CoCl_2$) was added to cells preincubated with SIN-1. Whereas $CoCl_2$ treated cells underwent apoptosis, for 24 h SIN-1 preincubated cells were not induced apoptosis. Inactivated proteins, MDM2 and bcl-2, by $CoCl_2$ levels also increased in SIN-1 pre-treated cells. These results suggested that SIN-1 blocked p53 by MDM2 activation and inhibited apoptosis by inducing p21 and bcl-2 expression.
A yellow-colored pigment is found in turmeric, or Curcuma longa L. (Zingiberaceae), a perennial herb distributed mainly throughout tropical and subtropical regions. C. longa has potent antiviral, antimutagenic, anti-inflammatory, anticancer, and antioxidant properties. However, pharmacological mechanisms of ethanol extract derived from C. longa remain poorly understood. The aim of this study was to investigate the potential acute toxicity of C. longa (Curcuma longa L.) extract in BALB/c mice administered a single oral dose of 0, 20, 200, and 2,000 mg/kg by gavage. After the administration of the agent, signs of toxicity were observed every hour for the first 6 hr and every day for 14 days. No mortality, abnormal clinical signs, or pathological changes were observed compared to a control group, and there were no differences in the body weights of the control and treatment groups. Biological serum activities were not significantly changed in the treatment group compared to the control group. These results indicate that a single oral administration of C. longa extract does not exert any toxic effects at a dose of 2,000 mg/kg body weight and that the $LD_{50}$ of C. longa extract is greater than 2,000 mg/kg body weight. Accordingly, C. longa appears to have potential in various functional agents or foods, without toxicity.
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