• Title/Summary/Keyword: HER2 positive

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Comparison and evaluation of 89Zr-labeled trastuzumab and Thio-trastuzumab : a potential immuno-PET probe for HER2-positive carcinomas

  • Un Chol Shin;Seoku Bae;Suk-man Kim;Min-Woo Lee;Han Sang Jin;Hyun Park;Kyo Chul Lee;Jung Young Kim;Ji Woong Lee
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.7 no.2
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    • pp.105-111
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    • 2021
  • 89Zr is a positron-emitting radioisotope, which has known as well-suited radioisotope for use in a monoclonal antibody-based imaging agent for immuno-PET. The purpose of this study was to quantitatively evaluate the diagnostic ability of general trastuzumab and thio-trastuzumab as HER2 positive receptors based on Df hexadentate iron chelator. Desferrioxamine-p-SCN (Df-Bz-NCS) and desferroixamine-maleimide (Df-Mal) were purchased from Macrocyclics (Dallas, TX, USA). The trastuzumab was purchased from Roche (Schweiz), and thio-trastuzumab was obtained from professor Hyo-Jeong Hong group (Kangwon National University). The radioisotope 89Zr was produced by domestic purification system and KIRAMS using medical cyclotron (50 MeV, Scantronix). The conjugates of Df-trastuzumab and Df-thio-trastuzumab were prepared with Df-Bz-NCS and Df-Mal under basic aqueous solution (pH 8-9) at room temperature, respectively. The conjugates purified by PD-10 column were mixed with dried 89Zr chloride. 89Zr-labeled conjugates were purified and concentrated by Amicon ultra centrifugal filter. The preparation step and time of 89Zr-labeled conjugates was shorted as 4 steps within 2 hours. 89Zr-labeled conjugates showed the highly radiochemical purity of over 98%, and were very stable until 7 days by the analysis of radio-ITLC method. Each radio-labeled conjugates were also exhibited the highly stability in both PBS buffer and mouse serum. Immuno-PET imaging of 89Zr-labeled conjugates in mice bearing gastric cancer xenograft tumors with HER2 expression showed high tumor uptake in the NCI-N87 HER2-expressing. However, 89Zr-Df-Mal-thio-trastuzumab showed a relatively lower tumor-to-background ratio than 89Zr-Df-Bz-trastuzumab, as well as whole-body distribution. In the results, 89Zr-Df-Bz-trastuzumab was evaluated to have a relatively higher HER2 diagnostic ability than 89Zr-Df-Mal-thio-trastuzumab.

Pre-treatment Elevated Platelet Count Associates with HER2 Overexpression and Prognosis in Patients with Breast Cancer

  • Gu, Mei-Ling;Yuan, Cai-Jun;Liu, Xiao-Mei;Zhou, Yi-Chao;Di, Shu-Huan;Sun, Fei-Fei;Qu, Quan-Ying
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.13
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    • pp.5537-5540
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    • 2015
  • Purpose: To research the association between pre-treatment elevated platelet count and clinicopathologic characteristics in breast cancer (BC), as well as explore the relationship between pre-treatment elevated platelet count and HER2 status and prognosis of BC patients. Materials and Methods: A retrospective cohort of BC patients who were newly diagnosed or treated by surgery only and had pathological detection results and platelet values in the Department of Oncology, the First Affiliated Hospital of Liaoning Medical College were enrolled from 1/1/2008 until 31/12/2009, and followed up until 31/12/2014. Age, thrombocyte parameters before chemotherapy and/or radiotherapy, immunohistochemical (IHM) indexes, and regional lymph node (LN) involvement and progression-free survival (PFS) were recorded. Results: A total of 447 eligible subjects were included in this research. As we analyzed, for HER2, positive and negative, the incidence rates of elevated platelet count were 25.8% and 14.7% (P<0.05). In the Cox proportional hazards model both variables were independent risk factors for BC (for HER2, OR, 0.592, 95% confidence interval, CI, 0.355 to 0.985, P=0.044;f or PLT, OR, 0.998, 95% CI, 0.996 to 1.000, P=0.042). For ER, PR, Ki67 and LN involvement, the differences were not statistically significant (P>0.05). Conclusions: In this research, pre-treatment elevated level of platelet count demostrated a significantrelationship with HER2 amplification/overexpression, and both variables significantly influenced the prognosis of BC. However, elevated platelet count did not exhibit any association with ER, PR, Ki67 and LN involvement.

Interpersonal support, Tension in life changes & Life satisfaction in Urban Housewives (도시주부의 대인적 지지, 생활긴장감 및 만족도)

  • ;吳京姬
    • Journal of Families and Better Life
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    • v.16 no.4
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    • pp.83-83
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    • 1998
  • The purpose of this study is to investigate interpersonal support, tension in lifechanges & satisfaction. The selected sample is composed of 387 housewives in ChongJoo city. SAS pc program was used for the statistical analysis of the data. Data was analyzed by frequency, F-test, percentage, mean, Duncan's Multiple Range Test, Pearson's correlation coefficient, Regression Analysis. Major findings as follows: 1)At wedding & funeral ceremony, kin networks of her parents & parents-in law side were variables to have influence on tension in life changes. And the number of social organization participated were a variable to have influence on the satisfaction. The age of couple, education of couple, duration of marriage, income, family lifecycle, the number of children, pattern of family were variables to influence tension in life changes, but were not variables to influence on the satisfaction. 2) At usual or wedding & funeral ceremony, kin networks of her parents side were variables to influence on instrumental & companionship support. And the number of friends was a variable to influence on companionship & informational support. The number of neighbors was a variable to influence on instrumental, companionship & informational support. The number of social organization participated was a variable to influence on companionship & emotional support. The age of couple, education of couple,income, duration of marriage, family life cycle, number of children, family size, family type were variables to influence on interpersonal support. 3)The relationship between tension and satisfaction in life changes was negative, and between instrumental support and satisfaction was negative also. But between companionship support and satisfaction was positive relationship and between tension of personal &social life and instrumental support was positive relationship. The relationship between tension of marriage life and companionship support was negative and between tension of family life and information support was negative relationships. The received companionship support was lower tension in life changes than not received it. But the received instrumental support was higher tension of personal & social life. The received companionship & informational support was higher satisfaction than not received them. But the received instrumental support was lower satisfaction than not received it. 4) Instrumental & companionship support, at usual kin network of her parents in taw side, at wedding & funeral ceremony kin network of her parents side,were variables to influence on tension in life changes. Instrumental, companionship& informational support, at wedding & funeral ceremony kin network of her parents side, were variables to influence on the satisfaction

Comparative Study of Cyclioxygenase-2 Expression and HER-2/neu Amplification in Korean and Caucasian Women with Early-Onset Breast Carcinoma (한국인과 백인 젊은 여성 유방암 환자에서 Cyclooxygenase-2 발현과 HER-2/neu 증폭의 비교 연구)

  • Choi, Doo-Ho;Kim, Eun-Seog;Kim, Yong-Ho;Jin, So-Young;Lee, Dong-Wha;Haffty, Bruce G.
    • Radiation Oncology Journal
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    • v.22 no.4
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    • pp.307-315
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    • 2004
  • Purpose: The purpose of this work was to study the differences of cyclooxygenase (COX-2) expression between Korean and Caucasian patients with early-onset breast carcinoma by immunohistochemistry. The test were analyzed to find a correlation between COX-2 and other biomarkers including HER-2/neu amplification, because we previously reported that a significant difference had been found in the expression of HER-2/neu between the two races. Furthermore, we investigated prognostic significance of COX-2 in korean patients. Materials and Methods: Sixty Korean women who were diagnosed breast carcinoma at 45 years old or younger and 60 Caucasian women with breast carcinoma were selected for this study. The median age of both groups was 37 years and tumor sizes were distributed evenly between the two group. Paraffin embedded blocks of primary tumor were processed for immunohistochemical staining of COX-2. The COX-2 expression was evaluated according to the percentage of positive cells and the intensity of staining. And the results were compared with the data of the previous studies to find correlation between COX-2 and other parameters and survival data. Results: Proportion of the COX-2 expression in total patients was $27.6\%$. The percentage of tumors that stained positive for COX-2 in korean and Caucasian women with early-onset breast carcinoma were $37.9\%$ and $20.8\%$, respectively. The difference was statistically not significant(p=0.090). Expression of COX-2 was not associated with several clinicopathologic parameters including HER-2/neu overexpression, but negative estrogen receptor status was correlated with significance (p=0.046). The 5 year disease free survival rate for patients with COX-2 expression was $67.9\%$, compared to $81.9\%$ of the COX-2 negative patients and the result was statistically not significant. Conclusions : A significant difference was not found in the expression of COX-2 between the two groups of patients with early-onset breast carcinoma. And correlation between COX-2 and other parameters was not observed except estrogen receptor negativity. Large scaled further research including radiotherapy factors will be needed to identify COX-2 as a prognostic role in patients with early-onset breast carcinoma.

Influences of Personality Patterns on Marital Adjustment by Interacting with Conflict Resolution Styles (다문화부부의 성격특성과 갈등대처방식의 상호작용이 부부적응에 미치는 효과)

  • Chang, Jin-Kyung;Shin, Yoo-Kyung
    • Journal of Families and Better Life
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    • v.31 no.2
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    • pp.109-126
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    • 2013
  • This study seeks to determine how personality patterns on marital adjustment are influenced by interacting with conflict resolution styles. Data for this study were collected from intermarriage couples comprising 293 pairs (586 patients) who lived in Korea for at least 5years. Snowball sampling was carried out from August to October 2011. SPSS 18.0 was used to analyze the collected data. The results of this study are as follows: (a) The conscientiousness and openness of personality patterns turned out to be common personality factors that represent a positive affect on the intermarried couples' effort to adapt. (b) The extroversions, agreeableness, and neuroticism shown significantly increase and decrease the intermarried husband's marital adjustment, but the same did not have a significant influence on the intermarried wife's marital adjustment. (c) Factors that affect marital adjustment, the conflict resolution styles of intermarriage couples showed different results depending on the gender. (d) The Intermarried wife's personality patterns represented a positive affect on her marital adjustment by interacting with her husband's conflict resolution styles, while the intermarried husband's personality patterns represented a positive affect on his marital adjustment by interacting with his wife's conflict resolution styles. The implications of this study will be discussed in the conclusion.

Transformational Experience of a Student Nurse with Diabetes: A Case Study

  • Choi, Hye-Jung;Hong, Young-Sang
    • Journal of Korean Academy of Nursing
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    • v.37 no.2
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    • pp.192-200
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    • 2007
  • Purpose. The current study was aimed to investigate the transformational experience of a female student nurse living with type 1 diabetes. Methods. A case study of a 24-year-old diabetes patient was conducted, with interviews concerning the evolving process she had lived through during the period from her later high school years to her graduation from nursing college. Results. Followings were identified as 5-transformation process: With her diabetes-related limitation, the participant experienced 'conflict involving choosing a college and major'. The participant tried to be in charge of managing her diabetes and stepped forward to 'adaptation to college life as a new environment', and she learned more about the process of 'evolving awareness of caring' and developed herself further through the process of 'integration of the nurse identity into self-identity', and finally through the process of 'progression and preparation for getting a job' she achieved her goals, being positive about the future. Conclusions. The results of the study can provide individuals with diabetes a way of self-management and help the patients and their families in diabetes education. Further research will be needed to refine the results of this study and to learn more about the experiences of patients with type I diabetes in college years.

Meta-analysis of Six Randomized Control Trials of Chemotherapy Plus Anti-HER Monoclonal Antibody for Advanced Gastric and Gastroesophageal Cancer

  • Luo, Huai-Qing;Han, Li;Jiang, Yan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5343-5348
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    • 2014
  • Background: A meta-analysis was performed to examine the benefit/risk ratio for the addition of anti- HER MoAbs to chemotherapy in patients with advanced gastric and gastroesophageal cancer from six randomized phase II/III trials. Materials and Methods: We searched relative trials from Pubmed, EMBASE, Cochrane library databases, China National Knowledge Infrastructure databases, Google Scholar and the NIH ClinicalTrials. Primary outcomes were overall response rate (ORR), progression-free survival (PFS), overall survival (OS). Secondary outcomes were toxicities. All analyses were performed using STATA 12.0. Results: This meta-analysis included six randomized controlled trials (RCTs) with 2, 297 patients and we demonstrated that the anti-HER MoAbs arm did have a positive effect on ORR in the anti-HER MoAbs arm (OR 1.28, 95% CI 1.00-1.64, p=0.01). There was an increasing benefit regarding OS (HR 0.74, 95% CI 0.60-0.88, p<0.05) and PFS (HR 0.72, 95% CI 0.60-0.84, p<0.05) in the anti-HER2 subgroup, but a reduction of OS (HR 1.11, 95% CI 0.87-1.36, p<0.05) and PFS (HR 1.13, 95% CI 0.98 -1.28, P<0.05) in anti-EGFR subgroup. Some grade 3-4 toxicity had a significantly higher incidence in the anti-HER MoAbs arm. There was no significant publication bias for all endpoints. Conclusions: The addition of trstuzumab MoAb to chemotherapy for gastric and gastroesophageal cancer significantly improved outcome of OS and PFS endpoints, while other MoAbs led to no improvement in results. Some adverse events were increased in anti-HER MoAbs arm compared with the control.

Substitution of Heavy Complementarity Determining Region 3 (CDR-H3) Residues Can Synergistically Enhance Functional Activity of Antibody and Its Binding Affinity to HER2 Antigen

  • Moon, Seung Kee;Park, So Ra;Park, Ami;Oh, Hyun Mi;Shin, Hyun Jung;Jeon, Eun Ju;Kim, Seiwhan;Park, Hyun June;Yeon, Young Joo;Yoo, Young Je
    • Molecules and Cells
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    • v.39 no.3
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    • pp.217-228
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    • 2016
  • To generate a biobetter that has improved therapeutic activity, we constructed scFv libraries via random mutagenesis of several residues of CDR-H3 and -L3 of hu4D5. The scFv clones were isolated from the phage display libraries by stringent panning, and their antiproliferative activity against HER2-positive cancer cells was evaluated as a primary selection criterion. Consequently, we selected AH06 as a biobetter antibody that had a 7.2-fold increase in anti-proliferative activity ($IC_{50}$: 0.81 nM) against the gastric cancer cell line NCI-N87 and a 7.4-fold increase in binding affinity ($K_D$: 60 pM) to HER2 compared to hu4D5. The binding energy calculation and molecular modeling suggest that the substitution of residues of CDR-H3 to W98, F100c, A101 and L102 could stabilize binding of the antibody to HER2 and there could be direct hydrophobic interactions between the aromatic ring of W98 and the aliphatic group of I613 within HER2 domain IV as well as the heavy and light chain hydrophobic interactions by residues F100c, A101 and L102 of CDR-H3. Therefore, we speculate that two such interactions were exerted by the residues W98 and F100c. A101 and L102 may have a synergistic effect on the increase in the binding affinity to HER2. AH06 specifically binds to domain IV of HER2, and it decreased the phosphorylation level of HER2 and AKT. Above all, it highly increased the overall level of p27 compared to hu4D5 in the gastric cancer cell line NCIN82, suggesting that AH06 could potentially be a more efficient therapeutic agent than hu4D5.

A Study of college Women's view on Marriage According to Self-Actualization Degree -centering around seoul city- (여대생의 自我實現性에 따른 결혼관에 관한 연구-서울시를 중심으로-)

  • 정현아;서병숙
    • Journal of Families and Better Life
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    • v.3 no.1
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    • pp.94-106
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    • 1985
  • The purpose of this study is to apprehend college women's views on marriage in order to systematize the view theoretically, and to investigate the relationship between the self-actualization and their marriage perspective. Futhermore, it is my hope to provide some basic materials for making an desirable view on marriage. The measuring tools used for preparing this study are self-actualization test, which were designed originally by Shostrom and standardized to be suitable for Korean society by Kim Jae Ean and Lee Kwang Ja and a questionnaire about one's view on marriage. Statistical methods such as frequency, percentile, arithmetic mean, analysis of variances(X2 and F values)were used for data analysis. The results of this study are as follows; 1) It is revealed that more than half(59.7%) of the college women achieve normal or above normal degree of self-actualization. 2)It is revealed that most college women's attitude toward matrimony is positive and they have a large acquaintance with the opposite sex. Especially, they are eager to became employed after entering into matrimony. 3) It is revealed that the more satisfaction a college woman's mother feels about her own matrimony, the more positive attitude her daughter has toward marriage. some college women who do not want to have a child have a positive attitude toward divorce. This means that their matrimony depends upon their view of marriage. 4) It is revealed that the more self-actualization college women feel, the more negative attitude they have toward selecting their husband. 5)It is revealed that the less self-actualization college women feel, the more negative attitude they have toward having a large acquaintance with the opposite sex and they have a dependent attitude toward living with their parents 6) It is revealed that most college women want their husband to have higher academic career than hers regardless of her own self-actualization degree and they want have a job after entering into matrimony. It seems to be dispassionate reflection of contemporary thought.

The Vision of Sustainability through the Readjustment of Environment and Consciousness: Karen Hesse's Out of the Dust (환경과 의식의 재조정을 통한 생명지속성의 비전 -카렌 헤세의 『모래폭풍을 지나며』)

  • Lee, Chung-Hee
    • Journal of English Language & Literature
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    • v.56 no.2
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    • pp.383-408
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    • 2010
  • This paper intends to suggest the positive, ecological vision of sustainability in Karen Hesse's Out of the Dust that Billie Jo Kelby recovers herself through her readjustment of interior consciousness and outer environment in her tragic situations caused by the Dust Bowl. In spite of her desires for happiness and affluence of home, she loses her mother and brother, and her musical talent as a pianist, and lies in self-abandonment. But she finally raises up herself with her courage and patience, reconciliating with the nature and ameliorating the community by taking care of the devastated landscapes. Hence it is appropriate to approach the loss-recovery process of nature and consciousness with ecological solutions, The Dust Bowl breaks down human mind and body, and eventually leads to the situations of despairs and death. Hesse proposes the primary solution that humans should reconstruct their interior consciousness and participate in recovering the nature because humans are inevitably linked with nature. In this novel, the nature takes a dynamic and active role as a catalyst, reconciling the self with other humans and settling with the conflicting situations in history and culture. This verse novel as an active, self-ordering, and corrective process gives the more intense ecological message. As Hesse defines the setting of Dirty Thirties as a channel of energy, she creates the utmost effects of ecological process that human and environment are part of a total situation, representing the transactional formulation, each conditioned by conditioning to the other. Therefore Billie Jo takes her part as an interpreter and actualizes herself, understanding the nature with metaphor and symbol. Eventually Billie Jo realizes that she should rebuild her environment not out of the dust but in the dust, accepting the reality of Dust Bowl.