• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.457-468
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• 2022

It has been demonstrated that APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) is involved in the regulation of several growth-related signaling pathways and thus closely associated with the development and progression of some cancers. Diallyl trisulfide (DAT), a garlic-derived bioactive compound, exerts selective cytotoxicity to various human cancer cells through interfering with pro-survival signaling pathways. However, whether and how DAT affects survival of human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we tested the hypothesis of the involvement of APPL1 in DAT-induced cytotoxicity in HCC HepG2 cells. We found that Lys 63 (K63)-linked polyubiquitination of APPL1 was significantly decreased whereas phosphorylation of APPL1 at serine residues remained unchanged in DAT-treated HepG2 cells. Compared with wild-type APPL1, overexpression of APPL1 K63R mutant dramatically increased cell apoptosis and mitigated cell survival, along with a reduction of phosphorylation of STAT3, Akt, and Erk1/2. In addition, DAT administration markedly reduced protein levels of intracellular TNF receptor-associated factor 6 (TRAF6). Genetic inhibition of TRAF6 decreased K63-linked polyubiquitination of APPL1. Moreover, the cytotoxicity impacts of DAT on HepG2 cells were greatly attenuated by overexpression of wild-type APPL1. Taken together, these results suggest that APPL1 polyubiquitination probably mediates the inhibitory effects of DAT on survival of HepG2 cells by modulating STAT3, Akt, and Erk1/2 pathways.

• The Korean Journal of Nuclear Medicine
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• v.22 no.1
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• pp.59-64
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• 1988

Because carcinoma of breast is known to readily metastasize to the bone, early detection of metastasis spread is very important. Two hundred thirty four consecutive patients who had $^{99m}Tc-MDP$ bone scans prior to treatment and during the follow up period were studied retrospectively to determine the contribution of the scans to staging, treatment and follow up examination between Jan. 1980 and Apr. 1987 in Seoul National University Hospital. 1) Positive bone scan rates in initial clinical stage I, II, III and IV were 0%, 4%, 14% and 53%, respectively. 2) The higher clinical stage is, the more cumulative risk of conversion to positive bone scan is during the same follow up period. 3) Conversion rate to positive bone scan in patients with lymph node metastasis is higher (50%) than those without metastasis (18%) (P < 0.001). We concluded that the bone scan in primary breast cancer was very useful to evaluate initial clinical stage and to perform the follow up examination.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8525-8531
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• 2016

Background: Cancer has become a major health problem associated with high mortality worldwide, especially in developing countries. The aim of our study was to evaluate the incidence rates of different types of cancer in Sulaymaniyah from January-2006 to January-2014. The data were compared with those reported for other middle east countries. Materials and Methods: This retrospective study depended on data collected from Hiwa hospital cancer registry unit, death records and histopathology reports in all Sulaymaniyah teaching hospitals, using international classification of diseases. Results: A total of 8,031 cases were registered during the eight year period, the annual incidence rate in all age groups rose from 38 to 61.7 cases/100,000 population/year, with averages over 50 in males and 50.7 in females. The male to female ratio in all age groups were 0.98, while in the pediatric age group it was 1.33. The hematological malignancies in all age groups accounted for 20% but in the pediatric group around half of all cancer cases. Pediatric cancers were occluding 7% of total cancers with rates of 10.3 in boys and 8.7 in girls. The commonest malignancies by primary site were leukemia, lymphoma, brain, kidney and bone. In males in all age groups they were lung, leukaemia, lymphoma, colorectal, prostate, bladder, brain, stomach, carcinoma of unknown primary (CUP) and skin, while in females they were breast, leukaemia, lymphoma, colorectal, ovary, lung, brain, CUP, and stomach. Most cancers were increased with increasing age except breast cancer where decrease was noted in older ages. High mortality rates were found with leukemia, lung, lymphoma, colorectal, breast and stomach cancers. Conclusions: We here found an increase in annual cancer incidence rates across the period of study, because of increase of cancer with age and higher rates of hematological malignancies. Our study is valuable for Kurdistan and Iraq because it provides more accurate data about the exact patterns of cancer and mortality in our region.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7819-7824
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• 2015

Purpose: To subtype breast cancer (BC) in Saudi women according to the recent molecular classification and to correlate these subtypes with available clinicopathological parameters. Materials and Methods: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (Her2/neu) immunostaining was semi-quantitatively assessed to define molecular subtypes of luminal A and B, HER-2 and triple negative (basal-like) in BC paraffin embedded sections from 115 Saudi female patients diagnosed between 2005 to 2015 at the Department of Pathology, King Fahd Hospital, Almadinah, Saudi Arabia. Results: The most common subtypes were luminal A (47%), followed by luminal B (27.8%) and basal like subtypes (18.3%), whereas HER-2 was the least common subtype (6.9%). Luminal A was predominantly found in the old age group, with low tumor grade (p<0.001) and small tumor size, whereas HER-2 and basal-like subtypes were significantly associated with young age, high tumor grade, lymph node metastasis and lymphovascular invasion (p<0.03, 0.004, 0.05 and 0.04 respectively). All subtypes showed advanced clinical stage at the time of presentation. Conclusions: Molecular subtypes of Saudi BC patients in Almadinah region are consistent with most of the worldwide subtyping. The biological behaviour of each molecular subtype could be expected based on its characteristic clinicopathological features. Along with other prognostic indicators, molecular subtyping would be helpful in predicting prognosis and management of our BC patients. We recommend screening and early diagnosis of BC in our population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3857-3862
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• 2012

A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7737-7740
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• 2014

Background: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with pancreatic, colorectal, lung, gastric cancer and renal cell carcinoma. The aim of this study was to determine the relationship between pathological complete response (pCR) and pretreatment NLR values in locally advanced breast cancer (BC) patients receiving neoadjuvant chemotherapy (NACT). Materials and Methods: Datawere collected retrospectively from the Akdeniz University School of Medicine Database for locally advanced BC patients treated with NACT between January 2000-December 2013. Results: A total of 78 patients were analyzed. Sixteen (20%) patients achieved pCR. Estrogen receptor (ER) positivity was lower in pCR+ than pCR-cases (p=0.011). The median NLR values were similar in both arms. The optimum NLR cut-off point for BC patients with PCR+ was 2.33 (AUC:0.544, 95%CI [0.401-0.688], p=0.586) with sensitivity, specificity, positive predictive value and negative predictive value (NPV) of 50%, 51,6%, 21,1%, and 80%, respectively. Conclusions: This study showed no relationship between the pCR and pretreatment NLR values. Because of a considerable high NPV, in the patients with higher NLR who had luminal type BC in which pCR is lower after NACT, such treatment may not be recommended.

• Journal of Haehwa Medicine
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• v.13 no.1
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• pp.129-146
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• 2004

From the study of Prescription on mammary diseases, the following conclusions are obtained. 1. The Lurosan (漏蘆散), Jechetang (猪蹄湯), Tongyutang (湧泉散) are often used for galactostasis in Prescription. The classification of prescription by efficacy is Chungyelyak(淸熱解毒藥), Lisuyak (利尿通淋藥), Hwalyelyak(活血祛瘀藥), etc. and the frequency of used medicines is Luro(漏蘆),Tongcho(通草),Jejo(제조), Chensangab(穿山甲),etc.. 2. The Makyajeon(麥芽煎), Sipjeondaebotang(十全大補湯) are often used for galactorrhea in Prescription. The classification of prescription by efficacy is Bogiyak(補氣藥), Bohelyak(補血藥), Sosikyak (消食藥), etc., and the frequency of used medicines is Insam (人蔘), Dangggwi(當歸), Makya(麥芽),etc.. 3. The Jogaksan(조角散), Gwarusan(瓜蔞散) are often used for mammary abscess in Prescription. The classification of prescription by efficacy is Hwalyelyak(活血祛瘀藥), Chunghwaye1damyak(淸化熱痰藥), Ligiyak(理氣藥), etc., and the frequency of used medicines is Jogakja(조角刺), Sahyang(麝香), Chongpee(靑皮),etc.. 4. The Yengyotang(連翹湯), Makyatang(麥芽湯), Lyengpayujagenbang(令敗乳自退方)are often used for distending pain of the breast due to galactostasis in Prescription. The classification of prescription by efficacy is Chungyelhaedokyak(淸熱解毒藥), Chunghwayeldamyak(淸化熱痰藥)etc., and the frequency of used medicines is Yengyo(連翹), Gwaru (瓜樓),etc.. 5. The Gwarusan (瓜蔞散), Danchungpitang(單靑皮湯), Yengyotang(連翹湯), Gamisoyosan(加味逍 遙散)are often used for mammay abscess in Prescription. The classification of prescription by efficacy is Chunghwayeldamyak(淸化熱痰藥), Hwalyelgeoyak(活血祛瘀藥), Chungyelyak(淸熱解毒藥),etc., and the frequency of used medicines is Jogakja(조角刺), Yengyo(連翹), Chongpee(靑皮),etc.. 6. The Sipyukmi1yugium(十六味流氣飮), Chungpitang(靑皮湯)are often used for breast carcinoma in Prescription. The classification of prescription by efficacy is Hwalyelyak(活血祛瘀藥), Ligiyak(理氣藥)etc., and the frequency of used medicines is Doyin(桃仁), Jogakja, Chongpee(靑皮), Jagak(枳殼),etc.

• The Korean Journal of Cytopathology
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• v.5 no.1
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• pp.10-14
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• 1994

The expression of sex steroid hormone receptors by neoplastic cells is an important predictor of response to hormone therapy. Thus, the selection of treatment modality is often based on the identification of receptors in tumor tissue. Various monoclonal antibodies of high specificity are now available for analyzing the estrogen receptor (ER). With these antibodies, biochemical enzyme immunoassay and immunohistochemistry using histologic sections have been used for ER analysis. We used fine needle aspirates from 15 human primary breast carinomas for the analysis of ERs. The semiquantitative receptor values obtained in cytologic specimens were correlated well with those from histologic specimens. The results of ER in fine needle aspirates were concordant with ER in histologic specimens(r=0.94). Only three cases showed a little difference in staining intensity and proportion of positive cells. Our results showed a good correlation between the receptor values determined in cytologic smears and those determined in tissue sections. It is suggested that measurement of the ER in cytologic smears may be a reliable technique which can be performed on aspiration cytologic samples.

• JSTS:Journal of Semiconductor Technology and Science
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• v.7 no.3
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• pp.140-150
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• 2007

A simple, label-free microfluidic cell purification method is presented for separation of cancer cells by exploiting difference in cell adhesion. To maximize the adhesion difference, three types of polymeric nanostructures (50nm pillars, 50nm perpendicular and 50nm parallel lines with respect to the direction of flow) were fabricated using UV-assisted capillary moulding and included inside a polydimethylsiloxane (PDMS) microfluidic channel bonded onto glass substrate. The adhesion force of human breast epithelial cells (MCF10A) and human breast carcinoma (MCF7) was measured independently by injecting each cell line into the microfluidic device followed by culture for a period of time (e.g., one, two, and three hours). Then, the cells bound to the floor of a microfluidic channel were detached by increasing the flow rate of medium in a stepwise fashion. It was found that the adhesion force of MCF10A was always higher than that of MCF cells regardless of culture time and surface nanotopography at all flow rates, resulting in a label-free detection and separation of cancer cells. For the cell types used in our study, the optimum separation was found for 2 hours culture on 50nm parallel line pattern followed by flow-induced detachment at a flow rate of $300{\mu}l/min$.

• Analytical Science and Technology
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• v.35 no.4
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• pp.161-168
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• 2022

Wheat is rich in sources of fiber, oligosaccharides, and resistant starch, simple carbohydrates which may have a protective role against carcinoma. Additionally, Whole wheat/bran as well includes contains phytochemicals such as flavonoids, lignans, folate, phytosterols, phenolic acids, and tocols. The above phytochemicals suitable forms antioxidant and cholesterol-reducing activities. Phytoestrogens are regarded as especially essential in the preventative measures of hormonally dependent malignancies such as breast cancer (BC). In this study lowered BC risk has been associated with whole grain/bran consumption with an odds ratio (OR=0.24 and 95 %CI=0.10-0.56). Wheat/bran appears to have a reliable protective impact against BC. While intake of white bread has been associated with a high risk of BC (OR=2.63 and CI 95 %=1.07-6.48). Also, the E-Selectin (SELE) Single nucleotide polymorphisms (SNPs) rs5353 A/G and rs932307 C/T were investigated using the sanger sequences approach. There was a positive association between genotypes (rs5353 GG+AG) and (rs932307 TT+CT) with rate consumption of wheat-white/bread and these genotypes were more frequent in patients had BC in comparison with a significant difference (P=0.03) (P=0.01), respectively. The genotypes (GG+AG) frequency of the rs5353 polymorphism and (TT+CT) genotypes of the rs932307 polymorphism in the present study had a high risk of cancer with (OR=3.05), (OR=4.17) respectively. While these genotypes showed no significant association with the rate of whole grain consumption in patients and control. Therefore, the type of wheat may associate with increased incidence of disease-related with type of Polymorphism because some present genotypes of SNPs showed high (OR) which may refer to their positive associated with disease, the white wheat consumption may active the risky association between SNPs and BC.