• Title/Summary/Keyword: Dose-response

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Retrospective Analysis of Neoadjuvant Chemotherapy for Breast Cancer in Turkish Patients

  • Duman, Berna Bozkurt;Afsar, Cigdem Usul;Gunaldi, Meral;Sahin, Berksoy;Kara, I. Oguz;Erkisi, Melek;Ercolak, Vehbi
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.4119-4123
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    • 2012
  • Background: Neoadjuvant systemic chemotherapy is the accepted approach for women with locally advanced breast cancer. Anthracycline- and taxane-based regimens have been extensively studied in clinical trials and consequently are widely used. In this study aimed to research the complete response (pCR) rates in different regimens for neoadjuvant setting and determine associated clinical and biological factors. Methods: This study included 63 patients diagnosed with breast carcinoma among 95 patients that had been treated with neoadjuvant chemotherapy between 2007 and 2010. TNM staging system was used for staging. The histologic response to neoadjuvant chemotherapy was characterized as a pCR when there was no evidence of residual invasive tumor in the breast or axillary lymph nodes. Biologic subclassification using estrogen receptor (ER), progesterone receptor (PR), HER2 were performed. Luminal A was defined as ER+, PR+, HER2-; Luminal B tumor was defined as ER+, PR-, HER2-; ER+, PR-, HER2+; ER-, PR+, HER2-; ER+, PR+, HER2+; HER2 like tumor ER-, PR+, HER2+; and triple negative tumor ER, PR, HER2 negative. Results: Patients median age was 54.14 (min-max: 30-75). Thirty-two patients (50.8%) were premenapousal and 31 (49.2%) were postmenapousal. Staging was performed postoperatively based on the pathology report and appropriated imaging modalities The TNM (tumor, lymph node, metastasis) system was used for clinical and pathological staging. Fifty-seven (90.5%) were invasive ductal carcinomas, 6 (9.5%) were other subtypes. Thirty nine (61.9%) were grade II and 24 (38.1%) were grade III. Seven (11.1%) patients were stage II and 56 (88.9) patients were stage III. The patients were classified for ER, PR receptor and HER2 positivity. Seventeen patients had complete response to chemotherapy. Forty patients (63.5%) were treated with dose dense regimen (cyclophosphamide 600 mg/m2 and doxorubicine 60 mg/m every two weeks than paclitaxel 175 mg/m2 every two weeks with filgrastim support) 40 patients (48%) were treated anthracycline and taxane containing regimens. Thirteen patients (76%) from 17 patients with pCR were treated with the dose dense regimen but without statistical significance (p=0.06). pCR was higher in HER2(-), ER(-), grade III, premenopausal patients. Conclusion: pCR rate was higher in the group that treated with dose dense regimen, which should thus be the selected regimen in neoadjuvant setting. Some other factors can predict pCR in Turkish patients, like grade, menopausal status, triple negativity, percentage of ER positivity, and HER2 expression.

Vegetable Oil Intake and Breast Cancer Risk: a Meta-analysis

  • Xin, Yue;Li, Xiao-Yu;Sun, Shi-Ran;Wang, Li-Xia;Huang, Tao
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.5125-5135
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    • 2015
  • Background: Total fat intake may be associated with increased risk of breast cancer, and fish oil has been suggested as a protection factor to breast cancer. But the effect of vegetable oils is inconclusive. We aimed to investigate the association with high vegetable oils consumption and breast cancer risk, and evaluated their dose-response relationship. Design: We systematically searched the MEDLINE, EMBASE, Cochrane databases, and CNKI updated to December 2014, and identified all observational studies providing quantitative estimates between breast cancer risk and different vegetable oils consumption. Fixed or random effect models were used to estimate summary odds ratios for the highest vs. lowest intake, and dose-response relationship was assessed by restricted cubic spline model and generalized least-squares trend (GLST) model. Results: Five prospective cohort studies and 11 retrospective case-control studies, involving 11,161 breast cancer events from more than 150,000 females, met the inclusion criteria. Compared with the lowest vegetable oils consumption, higher intake didn't increased the risk of breast cancer with pooled OR of 0.88 (95% CIs:0.77-1.01), and the result from dose-response analyses didn't show a significant positive or negative trend on the breast cancer risk for each 10g vegetable oil/day increment (OR=0.98, 95% CIs: 0.95-1.01). In the subgroup analyses, the oils might impact on females with different strata of BMI. Higher olive oil intake showed a protective effect against breast cancer with OR of 0.74 (95% CIs: 0.60-0.92), which was not significant among the three cohort studies. Conclusions: This meta-analyses suggested that higher intake of vegetable oils is not associated with the higher risk of breast cancer. Olive oil might be a protective factor for the cancer occurrence among case-control studies and from the whole. Recall bias and imbalance in study location and vegetable oils subtypes shouldn't be ignored. More prospective cohort studies are required to confirm the interaction of the impact of vegetable oils on different population and various cancer characteristic, and further investigate the relationship between different subtype oils and breast cancer.

Effect of Mercury Chloride on Humoral and Cell-mediated Immune Responses in Mice (수은이 마우스의 체액성 및 세포성 면역반응에 미치는 영향)

  • Youm, Jung-Ho
    • Journal of Preventive Medicine and Public Health
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    • v.28 no.1 s.49
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    • pp.27-42
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    • 1995
  • The in vivo and in vitro humoral and cell-mediated immune responses of lymphocytes of BALB/c mouse exposed to mercury chloride$(HgCl_2)$ were investigated. In vitro exposure of the splenocytes to mercury chloride produced overt cytotoxicity in 3 hours period. The $IC_{50}$(the concentration required to inhibit a splenocyte viability by 50%) for mercury chloride was >0.1mM for cytotoxicity. In vivo mercury chloride exposed mice were significantly depressed delayed type hypersensitivity(DTH) response to sheep red blood cells(SRBC) in a dose-dependent manner compared with control group. Mercury chloride inhibited the proliferative responses of splenocytes to lipopolysaccharide, pokeweed mitogen, concanavalin A and phytohemagglutinin in a dose-dependent manner. Hemagglutinin response to SRBC in mercury chloride exposed mice was significantly depressed in a dose-dependent manner compared with control group. After 7 weeks of mercury chloride exposure in vivo, mercury chloride induced an increase of nonspecific serum $IgG_1$ and IgE levels in BALB/c mice.

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Photon Energy Dependence of the Sensitivity of LiF TLDs Loaded with Thin Material (얇은 박막을 얹은 TLD 반응감도의 광자 에너지에 대한 의존성)

  • Min Byongim J;Kim Sookil;Loh John J.K;Cho Young Kap
    • Radiation Oncology Journal
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    • v.17 no.3
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    • pp.256-260
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    • 1999
  • Purpose : An investigation has been carried out on the factors which affect the response reading of thermoluminescent dosimeters (TLD-100) loaded with thin material in high energy Photon. The aim of the study was to assess the energy response of TLD-100 to the therapeutic ranges of photon beam. Materials and Methods : In this technique, TLD-100 (abbreviated as TLD) chips and three different thin material (Tin, Gold, and Tissue equivalent plastic plate) which mounted on the TLD chip were used in the clinical photon beam. The thickness of each metal plates was 0.1 mm and TE plastic plate was 1 mm thick. These compared with the photon energy dependence of the sensitivities of TLD (normal chip), TLD loaded with Tin or Gold plate, for the photon energy range 6 MV to 15 MV, which was of interest in radiotherapy. Results : The enhancement of surface dose in the TLD with metal plate was clearly detected. The TLD chips with a Gold plate was found to larger response by a factor of 1.83 in 10 MV photon beam with respect to normal chip. The sensitivity of TLD loaded with Tin was less than that for normal TLD and TLD loaded with Gold. The relative sensitivity of TLD loaded with metal has little energy dependence. Conclusion : The good stability and linearity with respect to monitor units of TLD loaded with metal were demonstrated by relative measurements in high energy Photon ($6\~15$ MV) beams. The TLD laminated with metals embedded system in solid water phantom is a suitable detector for relative dose measurements in a small beam size and surface dose.

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Bupivacaine-induced Vasodilation Is Mediated by Decreased Calcium Sensitization in Isolated Endothelium-denuded Rat Aortas Precontracted with Phenylephrine

  • Ok, Seong Ho;Bae, Sung Il;Kwon, Seong Chun;Park, Jung Chul;Kim, Woo Chan;Park, Kyeong Eon;Shin, Il Woo;Lee, Heon Keun;Chung, Young Kyun;Choi, Mun Jeoung;Sohn, Ju Tae
    • The Korean Journal of Pain
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    • v.27 no.3
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    • pp.229-238
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    • 2014
  • Background: A toxic dose of bupivacaine produces vasodilation in isolated aortas. The goal of this in vitro study was to investigate the cellular mechanism associated with bupivacaine-induced vasodilation in isolated endothelium-denuded rat aortas precontracted with phenylephrine. Methods: Isolated endothelium-denuded rat aortas were suspended for isometric tension recordings. The effects of nifedipine, verapamil, iberiotoxin, 4-aminopyridine, barium chloride, and glibenclamide on bupivacaine concentration-response curves were assessed in endothelium-denuded aortas precontracted with phenylephrine. The effect of phenylephrine and KCl used for precontraction on bupivacaine-induced concentration-response curves was assessed. The effects of verapamil on phenylephrine concentration-response curves were assessed. The effects of bupivacaine on the intracellular calcium concentration ($[Ca^{2+}]_i$) and tension in aortas precontracted with phenylephrine were measured simultaneously with the acetoxymethyl ester of a fura-2-loaded aortic strip. Results: Pretreatment with potassium channel inhibitors had no effect on bupivacaine-induced relaxation in the endothelium-denuded aortas precontracted with phenylephrine, whereas verapamil or nifedipine attenuated bupivacaine-induced relaxation. The magnitude of the bupivacaine-induced relaxation was enhanced in the 100mM KCl-induced precontracted aortas compared with the phenylephrine-induced precontracted aortas. Verapamil attenuated the phenylephrine-induced contraction. The magnitude of the bupivacaine-induced relaxation was higher than that of the bupivacaine-induced $[Ca^{2+}]_i$ decrease in the aortas precontracted with phenylephrine. Conclusions: Taken together, these results suggest that toxic-dose bupivacaine-induced vasodilation appears to be mediated by decreased calcium sensitization in endothelium-denuded aortas precontracted with phenylephrine. In addition, potassium channel inhibitors had no effect on bupivacaine-induced relaxation. Toxic-dose bupivacaine-induced vasodilation may be partially associated with the inhibitory effect of voltage-operated calcium channels.

A Comparison of Dose-Response Assessments for CMR Materials in the Workplace (작업장에서 취급하는 CMR물질의 용량반응평가 방법 비교)

  • Lee, Kyung Hwa;Choi, Han Young;Kim, Chi Nyon;Roh, Young Man;Choi, Hee Jin;Park, Chae Ri
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.28 no.1
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    • pp.51-60
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    • 2018
  • Objectives: Currently, there is only limited knowledge regarding the hazard of low-level exposure to CMR materials in workplaces. To overcome this limitation, a reference concentration for workers($RfC_w$) from among the risk assessment tools proposed by the US EPA is widely used to set a provisional workplace exposure level(PWEL) for CMR materials for which there are no established Korea Occupational Exposure Limits(KOELs) or subjective chemicals for work environment measurements as regulated by Korea Ministry of Employment and Labor(KMOEL). A simple European calculator of derived no effect level(SECO-DNEL) as proposed by REACH can also be used in place of $RfC_w$ to set the PWEL for chemicals. This study was performed to test the acceptability of using SECO-DNEL as an alternative to $RfC_w$ when setting a PWEL for low-level exposures. Methods: The $RfC_w$ and DNEL for the five CMR materials of dinitrogen oxide, catechol, 2-phenoxy ethanol, carbitol, and carbon black were calculated using the dose-response assessments of the US EPA for $RfC_w$ and REACH guidance for SECO-DNEL, respectively. They were compared using paired t-tests to determine the statistical differences between them. Results: For the five chemicals, the $RfC_w$ were 2.53 ppm, 0.10 ppm, 1.73 ppm, 1.66 ppm, and $0.05mg/m^3$, respectively, while the SECO-DNEL were 2.01 ppm, 0.11 ppm, 1.83 ppm, 1.77 ppm, $0.14mg/m^3$, respectively. There was no statistically significant difference between $RfC_w$ and SECO-DNEL. Conclusions: This study suggests that the SECO-DNEL could be applied in place of $RfC_w$ to set a PWEL for low-level exposure to chemicals, especially CMR materials. To further ensure the reliability of SECO-DNEL as an alternative tool, more chemicals should be applied for calculation and comparison with $RfC_w$.

Glucose Tolerance and Insulin Response to Intravenous Glucose Load in Sheep Fed on Germinated Sorghum Grain

  • Achmadi, Joelal;Pangestu, Eko;Wahyono, Fajar
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.10
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    • pp.1575-1579
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    • 2007
  • The glucose tolerance and pancreatic insulin secretion response to glucose in sheep fed on germinated sorghum grain were determined using an intravenous glucose load. Twelve male Thin Tail sheep (an Indonesian native sheep, 12 months old and 14.8 kg average body weight) were divided randomly into sorghum grain-based (S), germinated sorghum grain-based (G) and maize grain-based (C) diets. Sheep were maintained at the same daily intake levels of metabolizable energy and crude protein in the diets throughout the experimental period. After two months of the experimental conditions, each diet group was subjected to an intravenous glucose load experiment in which five doses of glucose (0, 10, 20, 40 and 80 mg/kg BW) were injected to estimate the rate of glucose removal from blood and the pancreatic insulin secretion response. For each sheep and each glucose load dose, the incremental blood serum glucose and insulin concentrations above pre-injection concentration were calculated as serum glucose and insulin response areas. At all glucose doses, sheep fed on S diet had a greater (p<0.05) glucose response area compared to those of sheep fed on G and C diets. Likewise at all glucose doses, the insulin response area was smaller (p<0.05) in sheep fed on S diet than in sheep fed on G and C diets. The glucose and insulin response areas in sheep fed on G and C diets differed slightly. It was concluded that the portion of maize grain in the ruminant ration could be substituted by germinated sorghum grain.

Clinical application of anti-M$\ddot{u}$llerian hormone as a predictor of controlled ovarian hyperstimulation outcome

  • Lee, Jae Eun;Lee, Jung Ryeol;Jee, Byung Chul;Suh, Chang Suk;Kim, Ki Chul;Lee, Won Don;Kim, Seok Hyun
    • Clinical and Experimental Reproductive Medicine
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    • v.39 no.4
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    • pp.176-181
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    • 2012
  • Objective: In 2009 anti-M$\ddot{u}$llerian hormone (AMH) assay was approved for clinical use in Korea. This study was performed to determine the reference values of AMH for predicting ovarian response to controlled ovarian hyperstimulation (COH) using the clinical assay data. Methods: One hundred sixty-two women who underwent COH cycles were included in this study. We collected data on age, basal AMH and FSH levels, total dose of gonadotropins, stimulation duration, and numbers of oocytes retrieved and fertilized. Blood samples were obtained on cycle day 3 before gonadotropin administration started. Serum AMH levels were measured at a centralized clinical laboratory center. The correlation between the AMH level and COH outcomes and cut-off values for poor and high response after COH was analyzed. Results: Concentration of AMH was significantly correlated with the number of oocytes retrieved (OPU; r=0.700, p<0.001). The mean${\pm}$SE serum AMH levels for poor ($OPU{\leq}3$), normal ($4{\leq}OPU{\leq}19$), and high ($OPU{\geq}20$) response were $0.94{\pm}0.15$ ng/mL, $2.79{\pm}0.21$ ng/mL, and $6.94{\pm}0.90$ ng/mL, respectively. The cut-off level, sensitivity and specificity for poor and high response were 1.08 ng/mL, 85.8%, and 78.6%; and 3.57 ng/mL, 94.4%, and 83.3%, respectively. Conclusion: Our data present clinical reference values of the serum AMH level for ovarian response in Korean women. The serum AMH level could be a clinically useful predictor of ovarian response to COH.

Radicicol Inhibits iNOS Expression in Cytokine-Stimulated Pancreatic Beta Cells

  • Youn, Cha Kyung;Park, Seon Joo;Li, Mei Hong;Lee, Min Young;Lee, Kun Yeong;Cha, Man Jin;Kim, Ok Hyeun;You, Ho Jin;Chang, In Youp;Yoon, Sang Pil;Jeon, Young Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.4
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    • pp.315-320
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    • 2013
  • Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-${\kappa}B$/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.

Immune Responses in Broiler Chicks Fed Propolis Extraction Residue-supplemented Diets

  • Eyng, C.;Murakami, A.E.;Santos, T.C.;Silveira, T.G.V.;Pedroso, R.B.;Lourenco, D.A.L.
    • Asian-Australasian Journal of Animal Sciences
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    • v.28 no.1
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    • pp.135-142
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    • 2015
  • This study was conducted to evaluate the effect of inclusion of propolis extraction residue in the feed of broilers from 1 to 21 d of age on phagocytic activity of macrophages, cutaneous basophil hypersensitivity response to phytohemagglutinin, antibody production against Newcastle disease, lymphoid organ weight and hematological profile and to determine the optimal level of inclusion. 120 chicks, reared in metabolism cages until 21 days of age, were distributed in a completely randomized design, with five treatments (0%, 1%, 2%, 3%, and 4% of propolis residue) and six replications. The relative weight of thymus and monocyte percentage were affected by propolis residue, with a quadratic response (p<0.05) and lowest values estimated at 2.38% and 2.49%, respectively. Changes in relative weight of cloacal bursa and spleen, percentage of lymphocyte, heterophil, basophil, eosinophil, and heterophil:lymphocyte ratio, antibody production against Newcastle disease, phagocytic activity of macrophages and the average number of phagocytosed erythrocytes were not observed. The nitric oxide production with regard to positive control (macrophages+erythrocytes) decreased linearly (p<0.05) with increased doses of propolis residue. The remaining variables of nitric oxide production (negative control - macrophages, and difference between the controls) were not affected by propolis residue. The cutaneous basophil hypersensitivity response to phytohemagglutinin as determined by the increase in interdigital skin thickness exhibited a quadratic response (p<0.05), which predicted a lower reaction response at a dose of 2.60% of propolis residue and highest reaction response after 43.05 hours of phytohemagglutinin injection. The inclusion of 1% to 4% of propolis extraction residue in broiler diets from 1 to 21 days of age was not able to improve the immune parameters, despite the modest changes in the relative weight in thymus, blood monocyte percentage, nitric oxide concentration, and interdigital reaction to phytohemagglutinin.