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Combination Treatment with Arsenic Trioxide and Sulindac Induces Apoptosis of NCI-H157 Human Lung Carcinoma Cells via ROS Generation with Mitochondrial Dysfunction (NCI-H157 폐암 세포주에서 활성산소종의 생성과 미토콘드리아 기능변화를 한 Arsenic Trioxide와 Sulindac 병합요법의 세포고사효과)

  • Kim, Hak-Ryul;Yang, Sei-Hoon;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.1
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    • pp.30-38
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    • 2005
  • Background : Arsenic trioxide ($As_2O_3$) has been used to treat acute promyelocytic leukemia, and it induces apoptosis in a variety of solid tumor cell lines including non-small cell lung cancer cells. However, nonsteroidal antiinflammatory drugs (NSAID) can enhance tumor response to chemotherapeutic drugs or radiation. It was previously demonstrated that a combination treatment with $As_2O_3$ and sulindac induces the apoptosis of NCI-H157 human lung carcinoma cells by activating the caspase cascade. This study aimed to determine if a combination treatment augmented its apoptotic potential through other pathways except for the activation of the caspase cascade. Material and Methods : The NCI-H157 cells were treated with $As_2O_3$, sulindac and antioxidants such as glutathione (GSH) and N-acetylcysteine (NAC). The cell viability was measured by a MTT assay, and the level of intracellular hydrogen peroxide ($H_2O_2$) generation was monitored fluorimetrically using a scopoletin-horse radish peroxidase (HRP) assay. Western blotting and mitochondrial membrane potential transition analysis were performed in order to define the mechanical basis of apoptosis. Results : The viability of the cells was decreased by a combination treatment of $As_2O_3$ and sulindac, and the cells were protected using antioxidants in a dose-dependent manner. The increased $H_2O_2$ generation by the combination treatment was inhibited by antioxidants. The combination treatment induced changes in the mitochondrial transmembrane potential as well as the expression of the Bcl-2 family proteins, and increased cytochrome c release into the cytosol. However, the antioxidants inhibited the effects of the combination treatment. Conclusion : Combination treatment with $As_2O_3$ and sulindac induces apoptosis in NCI-H157 human lung carcinoma cells via ROS generation with a mitochondrial dysfunction.

Anti-inflammatory Activity of Antimicrobial Peptide Protaetiamycine 2 Derived from the Protaetia brevitarsis seulensis (흰점박이꽃무지 유래 항균 펩타이드 프로테티아마이신 2의 항염증활성)

  • Lee, Joon Ha;Baek, Minhee;Lee, Hwa Jeong;Kim, In-Woo;Kim, Sun Young;Seo, Minchul;Kim, Mi-Ae;Kim, Seong Hyun;Hwang, Jae Sam
    • Journal of Life Science
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    • v.29 no.11
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    • pp.1218-1226
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    • 2019
  • The white-spotted flower chafer Protaetia brevitarsis seulensis is a medicinally beneficial and important edible insect species. We previously performed an in silico analysis of the Protaetia brevitarsis seulensis transcriptome to identify putative antimicrobial peptides and then tested their antimicrobial and hemolytic activities. These peptides had potent antimicrobial activities against bacteria and yeast without inducing hemolysis. In the present study, the cationic antimicrobial peptide, protaetiamycine 2, was selected for further assessment of its anti-inflammatory properties in mouse macrophage Raw264.7 cells. Protaetiamycine 2 treatment of Raw264.7 cells suppressed LPS-induced nitric oxide production and reduced the expression of inducible nitric oxide synthase and cyclooxygenase-2, as determined by real-time PCR and western blotting. The expression of proinflammatory cytokines ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$) was also attenuated through the MAPKs and $NF-{\kappa}B$ signaling. We also confirmed that protaetiamycine 2 bound to bacterial cell membranes by a specific interaction with LPS. Collectively, these data obtained from LPS-induced Raw264.7 cells indicated that protaetiamycine 2 could have both antimicrobial and anti-inflammatory properties.

Abdominal Obesity in Relation to the Incidence of Type 2 Diabetes Mellitus and Impaired Fasting Glucose among some Korean Adults: A Retrospective Cohort Study (복부비만이 제2형 당뇨병 및 공복혈당장애 발생에 미치는 영향: 후향적 코호트 연구)

  • Ryu, Seung-Ho;Beck, Sung-Ho;Kim, Dong-Il;Suh, Byung-Seong;Kim, Woon-Sool;Sung, Ki-Chul;Chang, Yoo-Soo
    • Journal of Preventive Medicine and Public Health
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    • v.37 no.4
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    • pp.359-365
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    • 2004
  • Objectives : This study was performed to determine whether an increase in abdominal obesity is an independent risk factor for impaired fasting glucose and type 2 DM. Methods : Among 24,212 adults over 30 years who undertook comprehensive medical screening examinations from Jan to Dec 1999, in a university hospital in Seoul, a total of 11,183 subjects were selected who had no DM at baseline and who were followed up more than once by Dec 2002. The average follow up period was 2.4 (${\pm}0.5$) years. DM was defined as having a fasting glucose level $\geq$ 126mg/dl, and impaired fasting glucose as showing a fasting glucose level between 110 and 125 mg/dl. Body weight, height and waist circumference (WC) were simultaneously measured with blood sampling. The relative risks (RRs) for DM and impaired fasting glucose by WC were calculated using Cox proportional hazard model. Ageadjusted rates were estimated by direct standardization using a reference population of 2000 from 30 to 80 years. Results : The average age of the subjects was 41.7 (${\pm}7.0$) years; males 41.2 (${\pm}6.5$) and females 45.6 (${\pm}9.2$). RRs for type 2 DM by WC with the reference group of WC < 80cm were as follows: 2.66 (95%, CI $0.55{\sim}12.8$) for WC of $80{\sim}89cm$ in men, 5.92 (95%, CI $1.08{\sim}32.3$) for WC $\geq$ 90 cm in men, and 2.64 (95%, CI $0.23{\sim}29.8$) for WC of $80{\sim}89cm$ in females. RRs for impaired fasting glucose by WC were 3.03 (95%, CI $2.18{\sim}4.22$) for WC $80{\sim}89cm$ in men, 6.10 (95%, CI $4.25{\sim}8.75$) for WC $\geq$ 90cm in men, and 1.56 (95%, CI $0.43{\sim}5.67$) for WC $80{\sim}89cm$ in women, and 8.08 (95%, CI $2.22{\sim}29.4$) for WC $\geq$ 90cm in females. These results remained significant after adjustment for age, BMI and fasting glucose concentrations at baseline in both sexes. Annual increment of more than 1 cm in WC was associated with the development of DM and impaired fasting glucose independently of age, sex, BMI, or presence of abdominal obesity. Conclusion : In Korean adults, abdominal obesity increased the risk for the development of type 2 diabetes and impaired fasting glucose. This result supports many other prospective studies suggesting abdominal obesity as a risk factor for type 2 diabetes.

Analysis of Prognostic Factors in Glioblastoma Multiforme (다형성 교모세포증 환자의 예후인자 분석)

  • Chang Sei Kyung;Suh Chang Ok;Lee Sang Wook;Keum Ki Chang;Kim Gwi Eon;Kim Woo Cheol
    • Radiation Oncology Journal
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    • v.14 no.3
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    • pp.181-189
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    • 1996
  • Purpose : To find the more effective treatment methods that improving the survival of patients with glioblastoma multiforme(GBM), we analyze the prognostic factors and the outcome of therapy in patients with GBM. Materials and Methods : One hundred twently-one patients with a diagnosis of GBM treated at Severance Hospital between 1973 and 1993 were analyzed for survival with respect to patients characteristics, that is, duration of symptom, age, and Karnofsky performance status, as well as treatment related variables such as extent of surgery and radiotherapy. Results : The median survival time(MST) and 2-year overall survival rate (OSR) of the patients with GBM were 13 months and $20.8\%$, respectively. Duration of symptom, age, Karnofsky performance status(KPS), radiotherapy, and extent of surgical resection were associated with improved survial in a univariate analysis. Patients whose duration of symptom was longer than 3 months, had the 2-year OSR of $47.2\%$(p=0.0082), who were younger than age 50, $32.9\%$(p=0.0003) In patients with a KPS of 80 or higher, the 2-rear OSR was $36.9\%$(p=0.0422). Patients undergoing radiotherapy had the 2-year OSR of $22.9\%$(p=0.0030), and surgical resection of $23.3\%$ (p<0.000). A Cox regression model confirmed a significant correlation of duration of symptom, age, radiotherapy, and extent of surgical resection with survival, excluding KPS(P=0.8823). The 2-year OSR were $22.3\%$ and $19.4\%$, combined with chemotherapy or without, respectively(p=0.6028). The duration of symptom of 3 months or shorter, 50 years of age or older, and undergoing stereotactic biopsy only were considered as risk factors, then patients without any risk factors had the MST of 29 months and 2-year OSR of $53.9\%$ compared to 4 months and $0\%$ for Patients who had all 3 risk factors. Most of all treatment failures occurred in the primary tumor site($80.4\%$). Conclusion : The duration of symptom, age, radiotherapy, and extent of surgical resection were a prognostically significant indeuendent variables. To get a better survival, it seems to be reasonable that the study design which improves the local control rates is warranted.

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Photoprotection and Anti-inflammatory Effects of Chinese Medical Plants (약용식물추출물의 광보호 효과와 항염증 효과 연구)

  • Jin-Hwa, Kim;Sung-Min, Park;Gwan-Sub, Sim;Bum-Chun , Lee;Hyeong-Bae, Pyo
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.30 no.2
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    • pp.227-233
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    • 2004
  • Chronic exposure to solar radiation, particularly ultraviolet (UV) light, causes a variety of adverse reactions on human skin, such as sunburn, photoaging and photocarcinogenesis. Free radicals and reactive oxygen species (ROS) caused by UV exposure or other environmental facts play critical roles in cellular damage. And, repeated-UV irradiation activated the expression of the matrix metalloproteinase (MMP) and induced skin irritation. Therefore, the development of effective and safe photoprotectants that can reduce and improve the skin damage has been required. The purpose of this study was to investigate the photo-protective effect of several chinese medical plants (Juniperus chinensis) on the UV -induced skin cell damages. We tested free radical and superoxide scavenging effect in vitro. Fluorometric assays of the proteolytic activities of MMP-1 (collagenase) were performed using fluorescent collagen substrates. UVA induced MMP-1 synthesis and activity were analyzed by enzyme-linked immunosorbent assay (ELISA) and gelatin-based zymography in skin fibroblasts. We also examined anti-inflammatory effects by the determination test of proinflammatory cytokine, interleukin 6 in HaCaT keratinocytes. Expression of prostaglandin E$_2$ (PGE$_2$) after UVB irradiation was measured by competitive enzyme immunoassay(EIA) using PGE$_2$ monoclonal antibody. In the human skin we tested anti-irritation effect on the SLS-induced damage skin after appling the extract containing emulsion. We found that Juniperus chinensis extract had potent radical scavenging effect by 98% at 100$\mu\textrm{g}$/mL. The extract of Juniperus chinensis showed strong inhibitory effect on MMP-1 activities by 97% at 100 $\mu\textrm{g}$/mL and suppressed the UVA induced expression of MMP-1 by 79% at 25$\mu\textrm{g}$/mL. This extract also showed strong inhibition on MMP-2 activity in UVA irradiated fibroblast by zymography. In the test of proinflammatory cytokines of human keratinocytes Juniperus chinensis extract decreased expression of interleukin 6 about 30%. The amount of PGE$_2$ by HaCaT keratinocytes was significantly increased at the doses of above 10 mJ/$\textrm{cm}^2$ of UVB (p < 0.05). At the concentrations of 3.2-25$\mu\textrm{g}$/mL of this extract, the production of PGE$_2$ by HaCaT keratinocytes (24 h after 10mJ/$\textrm{cm}^2$ UVB irradiation) was significantly inhibited in culture supernatants (p < 0.05). In SLS-induced skin irritation model in vivo, we found to reduce skin erythema and improve barrier recovery after appling Juniperus chinensis extract containing emulsion when compared to irritated non-treated and placebo-treated skin. Our results suggest that Juniperus chinensis extract can be effectively used for the prevention of UV and SLS-induced adverse skin reactions and applied as anti-aging and anti-irritation cosmetics.

Comparison of Outcomes after Curative Resection of Primary Lung Cancer between 50 Year or Younger and 70 Year or Older Patients (50세 이하와 70세 이상 원발성 폐암 환자에서의 근치적 수술 후 성적 비교)

  • Lee, Jae-Ik;Kim, Keun-Woo;Park, Kook-Yang;Park, Chul-Hyun;Jeon, Yang-Bin;Choi, Chang-Hyu
    • Journal of Chest Surgery
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    • v.42 no.2
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    • pp.206-213
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    • 2009
  • Background: Previous series have suggested that younger patients with primary lung cancer exhibit a more aggressive disease course with a worse prognosis, as compared to older patients, although this issue is still debatable. Material and Method: We reviewed the medical records of 79 patients (32 patients 50 years and younger (Group I) and 47 patients 70 years and older (Group II)) who underwent curative resection for primary lung cancer between July 2000 and June 2008. Result: The median age of the patients was 46.5 years in Group I and this was 73 years in Group II. The older patients were more likely to have major comorbidities (44% versus 77%, respectively; p=0.003). Histological examinations identified that the minor histological types (excluding non-small cell lung cancer (NSCLC)) were predominantly found in the Group I patients (16% versus 2%, respectively; p=0.037). For the TNM staging of the NSCLC, with excluding the minor histologic types, a higher proportion of patients had stage III disease in Group I (33% versus 13%, respectively; p=0.038). There was no significant difference in major morbidity (16% versus 30%, respectively; p=0.148) and operative mortality (0% versus 4.3%; p=0.512) between the groups. The mean follow-up interval was 33 months (range: $1{\sim}98$ months) for patients in both groups. For the patients with NSCLC, the five-year overall survival rate was 52.3% for Group I and 53.7% for Group II (p=0.955). The rate of freedom from recurrence at five years was significantly lower for the Group I patients than for the Group II patients (39.4% versus 70.4%, respectively; p=0.027), and only being a member of Group I impacted recurrence, based on the Cox proportional hazard analysis (p=0.034). Of the patients who had recurrence, four patients in Group I underwent aggressive surgical treatment. All of these patients exhibited long-term survival (range: $46{\sim}87$ months). Conclusion: In our study, the early outcome and long-term survival were similar for the younger and older patients after curative resection of primary lung cancer. However, we think that younger patients require meticulous follow-up as they had a tendency to proceed to surgery with advanced stage disease, a higher recurrence rate than did the older patients and the survival rates were improved, even for the recurred cases, with early aggressive treatment.

The Role of Postoperative External Irradiation for the Incompletely Resected Meningiomas (불완전절제된 수막종에서 수술 후 방사선치료의 역할)

  • Kim Tae-Hyun;Yang Dae-Sik;Kim Chul-Young;Choi Myung-Sun
    • Radiation Oncology Journal
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    • v.18 no.2
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    • pp.85-91
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    • 2000
  • Purpose : The aim of this study is to look for the possible efficacy of postoperative external irradiation for incompletely resected meningiomas. Methods and Materials : From August 198: to January 1997, forty-four patients with intracranial meningioma were treated by postoperative external irradiation. Of the 44 meningiomas, 18 transitional, 13 meningotheliomatous, 6 hemangiopericytic, 4 atypical, 2 fibroblastic and 1 malignant meningioma were identified. We classified all patients into two groups by the histology. The benign group was consisted of the meningotheliomatous, transitional and fibroblastic types. The malignant group was consisted of the atypical, hemangiopericytic and malignat types. In the means of surgery, 37 patients were resected incompletely and 7 patients were managed by biopsy only. After surgery, all patients were received postoperative external irradiation. Radiotherapy was deliverd using Co-60 or 4 MV photon beam to a total dose of 50 to 65 Gy (mean dose 57.4 Gy) with a 1.8 to 2 Gy per fraction. The median follow-up was 48 months (range : 21 $\~$ 101 months). Multivariate analysis of the Influence by age, sex, location, histology and radiation dose on local control has been done using Cox's proportional hazard model. Results : 5-year local control rate was 93.8$\%$ for the benign histology and 51.8$\%$ for the malignant histology (p=0.0110) and overall local control rate at 5 years was 87.4$\%$. The analysis of the prognostic factors, such as age, sex, location, and radiation dose were not significant except for the histology. Conclusion : Adjuvant postoperative external irradiation appears to be significantly improved local control in the patients with incompletely resected meningiomas.

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Role of Shinorine derived from Microalgae in skin protection (미세조류 유래 Shinorine의 피부세포에서의 효능)

  • Jung, Hae Soo;Cho, Moon Jin;Seo, Hyo Hyun;Kulkarni, Atul;Suh, Seung Suk;Lee, Taek Kyun;Moh, Sang Hyun
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.15 no.7
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    • pp.4416-4422
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    • 2014
  • In the present study, mycosporine-like amino acids (MAAs)were extracted from in Chlamydomonas hedleyi, and their function was investigated regarding to protective capacity against UV radiation and a possibility to be developed into functional suncream including MAAs by using natural compounds. In particulr, we assessed UV protective ability and anti-inflammation of shinorine in human skin cells. As a result, shinorine can protect the skin against damage by the absorption of energy from UV radiation and functions as an anti-wrinkling substrate through a increase of collagen synthesis. These data suggest that shinorine can be utilized not only as a substrate to protect UV radiation, but anti-aging material in cosmetic products.

Gamma Knife Radiosurgery for Intracranial Meningioma (두개강내 수막종에 대한 감마나이프 방사선수술)

  • Shim, Kyu Won;Chang, Jong Hee;Choi, Jae Young;Chang, Jin Woo;Park, Yong Gou;Chung, Sang Sup
    • Journal of Korean Neurosurgical Society
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    • v.30 no.11
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    • pp.1263-1270
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    • 2001
  • Objective : To analyze the radiosurgical results of intracranial meningiomas after Gamma Knife radiosurgery (GKS) and to assess the possible factors related to the outcome and complications in treating meningiomas. Patients and Methods : We retrospectively reviewed the clinical and radiological data in 179 patients(194 lesions) treated with GKS for intracranial meningiomas between May 1992 and October 2000. Radiosurgical responses were categorized as shrinkage, stasis and enlargement, and we defined the shrunken and static group as a radio-logical control. A Cox proportional hazards model was used to evaluate the correlation between the radiosurgical outcomes and various factors such as location and size of tumor, age and gender of patients, relation to venous sinus, pre-GKS degree of edema, treatment modality, radiosurgical parameters, and pathologic findings. Results : Patients were grouped into skull base meningiomas(57.7%), non-skull base tumor including convexity, parasagittal, and falx meningiomas(37.1%), and others(5.2%) according to the location of tumors. The mean maximum dose and the margin dose of tumor was 30.0Gy(19-45Gy) and 15.1Gy(9.5-24.5Gy), respectively. The mean volume of the tumors was 9.4cc(0.003-45.0cc). The radiologic control rate was 97.1%. The radiation induced imaging change with or without neurologic deficit was the most common complication(23.6%). There were seen mostly in convexity, parasagittal, and falx meningiomas which were deeply embedded in cortex. Conclusion : GKS for intracranial meningioma seems to be safe and effective treatments. However, GKS should be considered very cautiously in non-skull base tumor such as convexity, parasagittal, or falx meningiomas with regards to patient's age and general condition, size and location of tumor, pattern of embedding into cortex, presenting symptoms and patient's preference.

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Breast Screening and Breast Cancer Survival in Aboriginal and Torres Strait Islander Women of Australia

  • Roder, David;Webster, Fleur;Zorbas, Helen;Sinclair, Sue
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.1
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    • pp.147-155
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    • 2012
  • Aboriginal and Torres Strait Islander people comprise about 2.5% of the Australian population. Cancer registry data indicate that their breast cancer survivals are lower than for other women but the completeness and accuracy of Indigenous descriptors on registries are uncertain. We followed women receiving mammography screening in BreastScreen to determine differences in screening experiences and survivals from breast cancer by Aboriginal and Torres Strait Islander status, as recorded by BreastScreen. This status is self-reported and used in BreastScreen accreditation, and is considered to be more accurate. The study included breast cancers diagnosed during the period of screening and after leaving the screening program. Design: Least square regression models were used to compare screening experiences and outcomes adjusted for age, geographic remoteness, socio-economic disadvantage, screening period and round during 1996-2005. Survival of breast cancer patients from all causes and from breast cancer specifically was compared for the 1991-2006 diagnostic period using linked cancer-registry data. Cox proportional hazards regression was used to adjust for socio-demographic differences, screening period, and where available, tumour size, nodal status and proximity of diagnosis to time of screen. Results: After adjustment for socio-demographic differences and screening period, Aboriginal and Torres Strait Islander women participated less frequently than other women in screening and re-screening although this difference appeared to be diminishing; were less likely to attend post-screening assessment within the recommended 28 days if recalled for assessment; had an elevated ductal carcinoma in situ but not invasive cancer detection rate; had larger breast cancers; and were more likely than other women to be treated by mastectomy than complete local excision. Linked cancer registry data indicated that five-year year survivals of breast cancer cases from all causes of death were 81% for Aboriginal and Torres Strait Islander women, compared with 90% for other women, and that the former had larger breast cancers that were more likely to have nodal spread at diagnosis. After adjusting for socio-demographic factors, tumour size, nodal spread and time from last screen to diagnosis, Aboriginal and Torres Strait Islander women had approximately twice the risk of death from breast cancer as other women. Conclusions: Aboriginal and Torres Strait Islander women have less favourable screening experiences and those diagnosed with breast cancer (either during the screening period or after leaving the screening program) have lower survivals that persist after adjustment for socio-demographic differences, tumour size and nodal status.