• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.3
• /
• pp.1019-1024
• /
• 2015

Background: Survival of breast cancer patients depends on a number of factors which are not only prognostic but are also predictive. A number of studies have been carried out worldwide to find out prognostic and predictive significance of different clinicopathological and molecular variables in breast cancer. This study was carried out at Nuclear Medicine, Oncology and Radiotherapy Institute (NORI), Islamabad, to find out the impact of different factors on overall survival of breast cancer patients coming from Northern Pakistan. Materials and Methods: This observational retrospective study was carried out in the Oncology Department of NORI Hospital. A total of 2,666 patients were included. Data were entered into SPSS 20. Multinomial logistic regression analysis was performed to determine associations of different variables with overall survival. P values <0.05 were considered significant. Results: The mean age of the patients was 47.6 years, 49.5% being postmenopausal. Some 1,708 were ER positive and 1,615 were PR positive, while Her 2 neu oncogene positivity was found in 683. A total of 1,237 presented with skin involvement and 426 had chest wall involvement. Some 1,663 had > 5cm tumors. Lymph node involvement was detected in 2,131. Overall survival was less than 5 years in 669 patients, only 324 surviving for more than 10 years, and in the remainder overall survival was in the range of 5-10 years. Conclusions: Tumor size, lymph node metastases, receptor status, her 2 neu positivity, skin involvement, and chest wall involvement have significant effects whereas age and menopausal status have no significant effect on overall survival of breast cancer patients in Pakistan.

• The Korean Journal of Nuclear Medicine
• /
• v.24 no.1
• /
• pp.93-100
• /
• 1990

To evaluate the utility of autoradiographic technique in the detection of TRH receptor changes in brain after the various kinds of stimulation or drug administration, we tried the characterization of TRH receptor in mouse brain and autoradiography in rat brain as a preliminary study. The Kd value of [3-H] MeTRH to TRH receptors of adult male ICR mouse brain (cebellum and spinal cord were excluded) was 3.55+0.6 nM and Bmax was 3.44+0.52 fmol/mg wet tissue by saturation analysis. The Kd value of TRH to TRH receptors was 133.8+28.2 nM by competition analysis. And we could visualize the distribution of TRH receptors in rat brain by autoradiographic technique.

• BMB Reports
• /
• v.32 no.1
• /
• pp.28-32
• /
• 1999

Annexin I (also called lipocortin 1), a 37-kDa member of the annexin family of proteins, has been implicated in the mitogenic signal transduction by epidermal growth factor (EGF). Annexin I is phosphorylated by the EGF signal, however, the role of annexin I in the EGF signal transduction is still unknown. To transduce extracellular signals into the intracellular targets, selective translocation of the signaling molecules to their targets would be necessary. In this study, we examined the subcellular locations of annexin I during EGF signal transduction. Treatment of A549 cells with EGF resulted in the translocation of cytoplasmic annexin I to the nucleus and perinuclear region as determined by Western blot and immunofluorescent staining. The nuclear translocation of annexin I was inhibited by tyrphostin AG 1478 and genistein, the inhibitors of EGF receptor kinase and downstream tyrosine kineses, respectively. Pretreatment of cells with cyclohexamide did not inhibit the nuclear translocation. The results suggest that nuclear translocation of annexin I is controlled by a series of kinase dependent events in the EGF receptor signaling pathway and may be important in tranducing the signals by EGF.

• BMB Reports
• /
• v.51 no.5
• /
• pp.225-229
• /
• 2018

In humans, hormonal regulation is crucial for the preparation of uterine environment leading to either successful implantation or menstrual cycle. Estrogen is a pivotal female steroid hormone that regulates the uterine dynamics along with progesterone in the estrous and menstrual cycles in humans. Estrogen signals act via nuclear estrogen receptor or membrane-bound receptor. The membrane-bound estrogen receptor plays a crucial role in the rapid response of estrogen in the uterine epithelium. Recently, RASD1 has received attention as a novel signal transducer of estrogen in various systems including female reproductive organs. In this review, we discuss the regulation of estrogen and RASD1 signaling in the uterus and also provide insights into RAS as a novel signaling molecule in repeated implantation failure.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2003.10b
• /
• pp.136-136
• /
• 2003

Exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a variety of biological and toxicology effects, most of which are mediated by aryl hydrocarbon receptor (AhR). The ligand-bound AhR as a heterodimer with AhR nuclear translocator (ARNT) binds to its specific DNA recognition site, the dioxin-responsive element (DRE), and it results in increased transcription of CVP1A1 gene.(omitted)

• Toxicological Research
• /
• v.29 no.1
• /
• pp.21-25
• /
• 2013

The selective targeting of an integrin ${\alpha}_v{\beta}_3$ receptor using radioligands may enable the assessment of angiogenesis and integrin ${\alpha}_v{\beta}_3$ receptor status in tumors. The aim of this research was to label a peptidomimetic integrin ${\alpha}_v{\beta}_3$ antagonist (PIA) with $^{99m}Tc(CO)_3$ and to test its receptor targeting properties in nude mice bearing receptor-positive tumors. PIA was reacted with tris-succinimidyl aminotriacetate (TSAT) (20 mM) as a PIA per TSAT. The product, PIA-aminodiacetic acid (ADA), was radiolabeled with $[^{99m}Tc(CO)_3(H_2O)_3]^{+1}$, and purified sequentially on a Sep-Pak C-18 cartridge followed by a Sep-Pak QMA anion exchange cartridge. Using gradient C-18 reverse-phase HPLC, the radiochemical purity of $^{99m}Tc(CO)_3$-ADA-PIA (retention time, 10.5 min) was confirmed to be > 95%. Biodistribution analysis was performed in nude mice (n = 5 per time point) bearing receptor-positive M21 human melanoma xenografts. The mice were administered $^{99m}Tc(CO)_3$-ADA-PIA intravenously. The animals were euthanized at 0.33, 1, and 2 hr after injection for the biodistribution study. A separate group of mice were also co-injected with 200 ${\mu}g$ of PIA and euthanized at 1 hr to quantify tumor uptake. $^{99m}Tc(CO)_3$-ADA-PIA was stable in phosphate buffer for 21 hr, but at 3 and 6 hr, 7.9 and 11.5% of the radioactivity was lost as histidine, respectively. In tumor bearing mice, $^{99m}Tc(CO)_3$-ADA-PIA accumulated rapidly in a receptor-positive tumor with a peak uptake at 20 min, and rapid clearance from blood occurring primarily through the hepatobiliary system. At 20 min, the tumor-to-blood ratio was 1.8. At 1 hr, the tumor uptake was 0.47% injected dose (ID)/g, but decreased to 0.12% ID/g when co-injected with an excess amount of PIA, indicating that accumulation was receptor mediated. These results demonstrate successful $^{99m}TC$ labeling of a peptidomimetic integrin antagonist that accumulated in a tumor via receptor-specific binding. However, tumor uptake was very low because of low blood concentrations that likely resulted from rapid uptake of the agent into the hepatobiliary system. This study suggests that for $^{99m}Tc(CO)_3$-ADA-PIA to be useful as a tumor detection agent, it will be necessary to improve receptor binding affinity and increase the hydrophilicity of the product to minimize rapid hepatobiliary uptake.

• Journal of Nutrition and Health
• /
• v.24 no.4
• /
• pp.356-365
• /
• 1991

$L-Triiodothyronine(T_3)$ binding to purified plasma membrane and to isolated nuclei from the same liver in obese(ob/ob) mice and their lean littermates was examined. The maximal binding capacity(Bmax) for $T_3$ receptor of liver nuclei, as compared to lean control, was significantly lower in the obese mouse$(obese 527{\pm}80fmol/mg\;DNA ; lean 883{\pm}62fmol/mg\;DNA)$, without an apparent difference in dissociation constant(Kd). The finding that obese mice have fewer liver nuclear $T_3$ receptors confirms previous reports. The Bmax and Kd of liver plasma membrane $T_3$ receptor were not significantly different between obese and lean mouse, which suggests no defect to be occurring in the function of the plasma membrane $T_3$ receptor and reinforces the view that the peripherally impaired thyroid hormone action in obese mice is a post plasma membrane receptor event. These results further support the hypothesis that the major defect of the thyroid hormone metabolism in genetic obesity occurs at the level of the nuclear receptor.

• Journal of Radiation Protection and Research
• /
• v.35 no.1
• /
• pp.6-11
• /
• 2010

Embodying the safety of radioactive waste disposal requires the relevant safety criteria and the corresponding stylized methods to demonstrate its compliance with the criteria. This paper proposes a conceptual model of risk-based safety evaluation for integrating complex potential radiation exposure situations in radioactive waste disposal. For demonstrating compliance with a risk constraint, the approach deals with important exposure scenarios from the viewpoint of the receptor to estimate the resulting risk. For respective exposure situations, it considers the occurrence probabilities of the relevant exposure scenarios as their probability of giving rise to doses to estimate the total risk to a representative person by aggregating the respective risks. In this model, an exposure scenario is simply constructed with three components:radionuclide release, radionuclide migration and environment contamination, and interaction between the contaminated media and the receptor. A set of exposure scenarios and the representative person are established from reasonable combinations of the components, based on a balance of their occurrence probabilities and the consequences. In addition, the probability of an exposure scenario is estimated on the assumption that the initiating external factors influence release mechanisms and transport pathways, and its effect on the interaction between the environment and the receptor may be covered in terms of the representative person. This integrated approach enables a systematic risk assessment for complex exposure situations of radioactive waste disposal and facilitates the evaluation of compliance with risk constraints.

• Journal of Society of Preventive Korean Medicine
• /
• v.14 no.2
• /
• pp.77-89
• /
• 2010

Objectives : This study was performed to evaluate the effect of CJ(Cuscuta japonica Chois) on osteoclast differentiation and gene expression. Methods : The osteoclastogenesis and gene expression were determined in RANKL(receptor activator of nuclear factor kappa B ligand)－stimulated RAW 264.7. The results were summarized as followes. Results : CJ decreased the number of TRAP positive cell in RANKL-stimulated RAW264.7 cell. CJ decreased the expression of RANK(receptor activator of nuclear factor kappa B), $TNF{\alpha}$, and IL-6 in RANKL-stimulated RAW264.7 cell. CJ decreased the expression of iNOS and COX-2 in RANKL-stimulated RAW264.7 cell. CJ decreased the expression of Cathepsin K in RANKL-stimulated RAW264.7 cell. Conclusions : It is concluded that CJ might decrease the bone resorption resulted from decrease of osteoclast differentiation and it's related gene expression.

• Biomedical Science Letters
• /
• v.23 no.4
• /
• pp.295-302
• /
• 2017

Mononuclear osteoclast precursors derived from hematopoietic progenitors fuse together and then become multinucleated mature osteoclasts by macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL). Especially, the binding of RANKL to its receptor RANK provides key signals for osteoclast differentiation and bone-resorbing function. RANK transduces intracellular signals by recruiting adaptor molecules such as TNFR-associated factors (TRAFs), which then activate mitogen activated protein kinases (MAPKs), Src/PI3K/Akt pathway, nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and finally amplify NFATc1 activation for the transcription and activation of osteoclast marker genes. This review will briefly describe RANKL-RANK signaling pathways and key molecules critical for osteoclast differentiation.