Estrogen receptor-α, progesterone receptor, and c-erbB/HER-family receptor mRNA detection and phenotype analysis in spontaneous canine models of breast cancer

Farruk M. Lutful Kabir,Patricia DeInnocentes,Payal Agarwal,Christopher P. Mill,David J. Riese 2nd,R. Curtis Bird 대한수의학회 2017 Journal of Veterinary Science Vol.18 No.2

Well characterized, stable, p16-defective canine mammary cancer (CMT) cell lines and normal canine mammary epithelial cells were used to investigate expression of the major breast cancer-specific hormone receptors estrogen receptor alpha (ER1) and progesterone receptor (PR) as well as luminal epithelial-specific proto-oncogenes encoding c-erbB-1 (epidermal growth factor receptor/EGFr), c-erbB-2/HER2, c-erbB-3, and c-erbB-4 receptors. The investigation developed and validated quantitative reverse transcriptase polymerase chain reaction assays for each transcript to provide rapid assessment of breast cancer phenotypes for canine cancers, based on ER1, PR, and c-erbB-2/HER2 expressions, similar to those in human disease. Roles for relatively underexplored c-erbB-3 and c-erbB-4 receptor expressions in each of these breast cancer phenotypes were also evaluated. Each quantitative assay was validated by assessment of amplicon size and DNA sequencing following amplification. Differential expression of ER1, PR, and c-erbB-2 in CMT cell lines clearly defined distinct human-like breast cancer phenotypes for a selection of CMT-derived cell lines. Expression profiles for EGFr family genes c-erbB-3 and c-erbB-4 in CMT models also provided an enriched classification of canine breast cancer identifying new extended phenotypes beyond the conventional luminal-basal characterization used in human breast cancer.

Lack of Detection of the Mouse Mammary Tumor-like Virus (MMTV) Env Gene in Iranian Women Breast Cancer using Real Time PCR

Tabriz, Hedieh Moradi,Zendehdel, Kazem,Shahsiah, Reza,Fereidooni, Forouzandeh,Mehdipour, Baharak,Hosseini, Zahra Mostakhdemin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5

Background: Mouse mammary tumor virus (MMTV) is the major cause of mammary tumors in mice. There is limited controversial evidence about the probable etiologic role of MMTV- like virus in human breast cancer. Materials and Methods: A total of 40 Formalin fixed paraffin embedded samples with diagnosis of breast cancer were collected in a period of 3 years from cancer institute of Iran. We selected both pre-menopausal and post-menopausal patients with different histologic grades and different ethnic groups. We evaluated presence of MMTV-like virus env gene through real time PCR method. Results: Forty patients (20 pre and 20 postmenopausal women) were evaluated with the mean age of 49.67. The average tumor size was 39 mm. None of the studied samples were positive for MMTV-like virus env gene target sequences. Conclusions: We found no evidence on the potential role of MMTV-like virus in the carcinogenicity of breast cancer among Iranian women.

Internal Mammary Lymph Node Irradiation after Breast Conservation Surgery : Radiation Pneumonitis versus Dose­Volume Histogram Parameters

Joo Young Kim(김주영),Ik Jae Lee(이익재),Ki Chang Keum(금기창),Yong Bae Kim(김용배),Su Jung Shim(심수정),Kyoungkeun Jeong(정경근),Jong Dae Kim(김종대),Chang Ok Suh(서창옥) 대한방사선종양학회 2007 Radiation Oncology Journal Vol.25 No.4

목 적: 방사선 폐렴과 체적­선량 히스토그램(dose­volume histogram, DVH) 변수들 사이의 연관성을 평가하고, 내유림 프절이 포함된 유방암의 방사선치료에서 방사선 폐렴을 방지할 수 있는 실제적인 지침을 제공하고자 한다. 대상 및 방법: 부분유방절제술을 받은 초기 유방암 환자 20명이 본 연구에 포함되었다. 전체 유방, 상부쇄골림프절,내유림프절에 총 28회 50.4 Gy가 조사되었다. 방사선 폐렴은 방사선 영상에서의 폐 변화(radiological pulmonary change; RPC)와 증상이 있는 방사선 폐렴(symptomatic radiation pneumonitis)에 의해 평가되었다. DVH 변수들은 grade<2 RPC와 grade≥2 RPC로 나누어 비교되었다. 이 때, DVH 변수들은 평균 폐 선량(mean lung dose), V10 (10 Gy 이상 받는 폐의 백분율 부피), V20, V30, V40, 그리고 정상 조직 합병증 확률(normal tissue complication probability, NTCP)이다. 결 과: 20명의 환자 중 9명(45%)에서 grade 2 RPC가 발생하였고, 11명(55%)에서는 발생하지 않았다. 1명의 환자에서 grade 1의 증상이 있는 방사선 폐렴이 발생하였다. 단변량 분석에서 DVH 변수 중, NTCP가 두 RPC grade 군 간에 유의한 차이를 보여주고 있다 (p<0.05). Fisher의 정확한 검증(exact test)은 NTCP값 45%가 RPC의 threshold level로서 적합함을 보여준다. 결 론: 본 연구는 NTCP가 유방암의 내유림프절 방사선치료 후 RPC 예측인자 중 한가지로 쓰일 수 있음을 보여준다. 임상적으로 이는 NTCP 45% 이상에서 RPC가 발생하기 용이함을 의미한다. Purpose: To evaluate the association between radiation pneumonitis and dose-volume histogram parameters and to provide practical guidelines to prevent radiation pneumonitis following radiotherapy administered for breast cancer including internal mammary lymph nodes. Materials and Methods: Twenty patients with early breast cancer who underwent a partial mastectomy were involved in this study. The entire breast, supraclavicular lymph nodes, and internal mammary lymph nodes were irradiated with a dose of 50.4 Gy in 28 fractions. Radiation pneumonitis was assessed by both radiological pulmonary change (RPC) and by evaluation of symptomatic radiation pneumonitis. Dose-volume histogram parameters were compared between patients with grade <2 RPC and those with grade ≥2 RPC. The parameters were the mean lung dose, V10 (percent lung volume receiving equal to and more than 10 Gy), V20, V30, V40, and normal tissue complication probability (NTCP). Results: Of the 20 patients, 9 (45%) developed grade 2 RPC and 11 (55%) did not develop RPC (grade 0). Only one patient developed grade 1 symptomatic radiation pneumonitis. Univariate analysis showed that among the dose-volume histogram parameters, NTCP was significantly different between the two RPC grade groups (p<0.05). Fisher’s exact test indicated that an NTCP value of 45% was appropriate as an RPC threshold level. Conclusion: This study shows that NTCP can be used as a predictor of RPC after radiotherapy of the internal mammary lymph nodes in breast cancer. Clinically, it indicates that an RPC is likely to develop when the NTCP is greater than 45%.

Analysis of Different Activation Statuses of Human Mammary Epithelial Cells from Young and Old Groups

Feng, Chen-Chen,Chen, Li-Na,Chen, Mei-Jun,Li, Wan,Jia, Xu,Zhou, Yan-Yan,He, Wei-Ming Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8

Human mammary epithelial cells have different proliferative statuses and demonstrate a close relationship with age and cell proliferation. Research on this topic could help understand the occurrence, progression and prognosis of breast cancer. In this article, using significance analysis of a microarray algorithm, we analyzed gene expression profiles of human mammary epithelial cells of different proliferative statuses and different age groups. The results showed there were significant differences in gene expression in the same proliferation status between elderly and young groups. Three common differentially expressed genes were found to dynamically change with the proliferation status and to be closely related to tumorigenesis. We also found elderly group had less status-related differential genes from actively proliferating status to intermediate status and more statusrelated differential genes from intermediate status than the young group. Finally, functional enrichment analyses allowed evaluation of the detailed roles of these differentially-expressed genes in tumor progression.

유방 질환의 X선 유방 촬영상에 관한 연구

한창열,전우기,김정숙 인제대학교 1989 仁濟醫學 Vol.10 No.2

유방의 동통 내지는 촉진되는 종괴를 주소로 내원한 환자 중 X선 유방 촬영술을 실시했었고 그 결과가 수술이나 세침흡인검사로써 그 병리조직학적 진단이 내려진 총 97예에 관하여 그들의 X선 유방 촬영상 소견을 분석하고 문헌 고찰과 함께 보고하는 바이다. The ideal diagnostic methods in breast diseases consist of the physical examination and complementary radiologic examination. In radiologic examination mammography is the most popular screening method and the only proven method capable of detecting nonpalpable breast cancers. From January 1st, 1987 through January 10th, 1988, 580pts. with complaints of various mammary problems were examined by mammography at Paik hospital, Inje University. The authors selected and analyzed the 97 cases had been pathologically proved through the operation or the fine needle aspiration biopsy. The results were as follows : 1.The malignant breast diseases were 25/97 (26%) 1) The most prevalent age group was 5th decade (40%) 2) The mammographic findings were smooth marginated mass (24%) 2.The benign breast diseases were 72/97 (74%) and all were infiltrating ductal carcinomas pathologically 1) The most common group is mammary dysplasia (53%), and followed by fibroadenoma (11%) 2) The prevalent age group in each case was 4th decade (47%) and 4th decade (64%) 3) In mammary dysplasia, the mammographic findings were poorly defined haziness (87%), mass mimicking lesion (8%) and coarse nodularities (5%) 4) In fibroadenoma, the mammographic findings were single mass (73%), Halo Sign (90%) and coarse nodular calcifications (18%) 3.The characteristic finding of calcification in benign and malignant diseases : 1) In benign breast mass, fibroadenoma or galactocele, a few number of coarse irregular sifted calcifications are distributed 2) In malignant breast mass multiple clustered miliary sized fine calcifications are distributed

Tumor therapy with Amanita phalloides (Death Cap): stabilization of mammary duct cancer

Isolde Riede 셀메드 세포교정의약학회 2011 셀메드 (CellMed) Vol.1 No.1

Molecular events that cause tumor formation enhance a number of HOX genes, called switch genes, coding for RNApolymeraseII transcription factors. Thus, in tumor cells, RNApolymeraseII is more active than in other somatic cells. Amanita phalloides contains amanitin which inhibits RNApolymeraseII. Partial inhibition with amanitin influences tumor cell - but not normal cell - activity. To widen the treatment spectrum, dilutions of Amanita phalloides, containing amanitin, are applied to a patient with mammary duct cancer. For monitoring tumormarkers, different doses of amanitin are applied. The former duplication time of tumor growth represented three months; however within a period of 18 months the patient can be stabilized without further growth of the tumor. There are also no severe symptoms, no liver damage and no continuous erythrocyte deprivation. This new principle of tumor therapy shows high potential to provide a medical treatment.

Breast Cancer Detection in a Screening Population: Comparison of Digital Mammography, Computer-Aided Detection Applied to Digital Mammography and Breast Ultrasound

조규란,서보경,우옥희,송성은,최정순,황신영,박은경,박아영,신혜선,정환훈 한국유방암학회 2016 Journal of breast cancer Vol.19 No.3

Purpose: We aimed to compare the detection of breast cancer using full-field digital mammography (FFDM), FFDM with computer-aided detection (FFDM+CAD), ultrasound (US), and FFDM+CAD plus US (FFDM+CAD+US), and to investigate the factors affecting cancer detection. Methods: In this retrospective study conducted from 2008 to 2012, 48,251 women underwent FFDM and US for cancer screening. One hundred seventy-one breast cancers were detected: 115 invasive cancers and 56 carcinomas in situ. Two radiologists evaluated the imaging findings of FFDM, FFDM+CAD, and US, based on the Breast Imaging Reporting and Data System lexicon of the American College of Radiology by consensus. We reviewed the clinical and the pathological data to investigate factors affecting cancer detection. We statistically used generalized estimation equations with a logit link to compare the cancer detectability of different imaging modalities. To compare the various factors affecting detection versus nondetection, we used Wilcoxon rank sum, chi-square, or Fisher exact test. Results: The detectability of breast cancer by US (96.5%) or FFDM+CAD+US (100%) was superior to that of FFDM (87.1%) (p=0.019 or p<0.001, respectively) or FFDM+ CAD (88.3%) (p=0.050 or p<0.001, respectively). However, cancer detectability was not significantly different between FFDM versus FFDM+CAD (p=1.000) and US alone versus FFDM+CAD+US (p=0.126). The tumor size influenced cancer detectability by all imaging modalities (p<0.050). In FFDM and FFDM+CAD, the nondetecting group consisted of younger patients and patients with a denser breast composition (p<0.050). In breast US, carcinoma in situ was more frequent in the nondetecting group (p=0.014). Conclusion: For breast cancer screening, breast US alone is satisfactory for all age groups, although FFDM+ CAD+US is the perfect screening method. Patient age, breast composition, and pathological tumor size and type may influence cancer detection during screening.

Evaluation Frequency of Merkel Cell Polyoma, Epstein-Barr and Mouse Mammary Tumor Viruses in Patients with Breast Cancer in Kerman, Southeast of Iran

Reza, Malekpour Afshar,Reza, Mollaie Hamid,Mahdiyeh, Lashkarizadeh,Mehdi, Fazlalipour,Hamid, Zeinali Nejad Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.16

Breast cancer is the most common cancer among women worldwide. Roles of the Epstein-Barr, Merkel cell polyoma and mouse mammary tumor viruses in breast carcinogenesis are still controversial although any relationship would clearly be important for breast cancer etiology, early detection and prevention. In the present study associations between EBV, MMTV and Merkel cell polyoma virus and breast cancer in 100 Iranian patients were evaluated using paraffin-embedded tissues. EBER RNA and expression of p53 and large T antigen were evaluated by real time PCR and CD34, p63, HER2, PR and ER markers were studied by immunohistochemistry. EBV was detected in 8/100 (8%), MMTV in 12/100 (12%), MPy in 3/100 (3%) and EBER RNA in 18/100 (18%) cases. None of the control samples demonstrated any of the viruses. p53 was suppressed in EBV, MPy and MMTV positive samples. The large T antigen rate was raised in MPy positive samples. Our results showed that EBV, MMTV and the Merkel cell polyoma virus are foundwith some proportion of breast cancers in our patients, suggesting that these viruses might have a significant role in breast cancer in Kerman, southeast of Iran.

The potential role of COX-2 in cancer stem cell-mediated canine mammary tumor initiation: an immunohistochemical study

Jian Huang,Di Zhang,Fuqiang Xie,Degui Lin 대한수의학회 2015 Journal of Veterinary Science Vol.16 No.2

Increasing evidence suggests that cancer stem cells (CSCs) are responsible for tumor initiation and maintenance. Additionally, it is becoming apparent that cyclooxygenase (COX) signaling is associated with canine mammary tumor development. The goals of the present study were to investigate COX-2 expression patterns and their effect on CSC-mediated tumor initiation in primary canine mammary tissues and tumorsphere models using immunohistochemistry. Patterns of COX-2, CD44, octamer-binding transcription factor (Oct)-3/4, and epidermal growth factor receptor (EGFR) expression were examined in malignant mammary tumor (MMT) samples and analyzed in terms of clinicopathological characteristics. COX-2 and Oct-3/4 expression was higher in MMTs compared to other histological samples with heterogeneous patterns. In MMTs, COX-2 expression correlated with tumor malignancy features. Significant associations between COX-2, CD44, and EGFR were observed in low-differentiated MMTs. Comparative analysis showed that the levels of COX-2, CD44, and Oct-3/4 expression varied significantly among TSs of three histological grades. Enhanced COX-2 staining was consistently observed in TSs. Similar levels of staining intensity were found for CD44 and Oct-3/4, but EGFR expression was weak. Our findings indicate the potential role of COX-2 in CSC-mediated tumor initiation, and suggest that COX-2 inhibition may help treat canine mammary tumors by targeting CSCs.

개 유선종양 내 종양줄기세포의 중요성

박서영(Seo-Young Park),백영빈(Yeong-Bin Baek),박상익(Sang-Ik Park),이창민(Chang-Min Lee),김성학(Sung-Hak Kim) 한국생명과학회 2021 생명과학회지 Vol.31 No.2

유선종양은 암컷 개에서 가장 흔한 암 중의 하나이며 종양 타입에 따라 조직학적으로 다양한 종류의 세포들이 존재한다. 특히, 복합 상피암종(complex carcinoma)의 경우 내강상피세포(luminal epithelium)와 근상피세포(myoepithelium)가 혼재되어 종양 내 세포 이형성(intra-tumoral heterogeneity)을 보인다. 하지만, 이러한 다양한 종양세포의 기원과 종양의 악성화에 미치는 영향에 대해서는 아직 밝혀진 바 없다. 최근, 여러 종류의 사람 종양에서 알려진 종양줄기세포는 종양 내 세포의 다양성(diversity)에 관여하고 악성화에도 기여할 수 있다고 보고되었다. 흥미롭게도 종양줄기세포는 자가재생능과 다분화능을 갖는 정상줄기세포와 동일한 능력을 가지고 있지만 종양 특이 유전자의 돌연변이와 줄기세포성격유지를 조절하는 신호전달체계에 문제가 있어 종양의 발생 시작부터 다른 조직으로의 전이에 관여하여 개체의 생존률에 직접적인 영향을 준다. 뿐만 아니라, 방사선 및 화학항암제에 대한 저항성을 보이기 때문에 종양 재발에 밀접하게 연관되어 있다. 본 리뷰 논문은 개 유선종양의 특성 및 종류, 종양줄기세포의 정의, 분리 방법, 임상학적 중요성에 대해서 정리하였다. Mammary gland tumors are one of the most common cancers in female dogs, and there are various types of cells depending on the tumor type. Complex carcinoma consists of a combination of luminal epithelial and myoepithelial cells with intra-tumoral heterogeneity. However, the origins of these tumor cells and their effects on the malignancies of tumors have not been identified. Recently, it has been reported that cancer stem cells, identified in several types of human tumors, are involved in tumor heterogeneity and may also contribute to malignancies such as tumor recurrence and metastasis. Interestingly, cancer stem cells share several abilities of self-renewal and cell differentiation into multiple types of cancer cells, but they have abnormal genetic mutation and signal transduction pathways to regulate the maintenance of stem cell characters. Moreover, it is known that these cell populations contribute to cell metastasis as well as cell resistance against chemo- and radio-therapeutics that promote tumor recurrence. The existence of cancer stem cells might explain the intra-tumoral heterogeneity and cancer aggressiveness during tumorigenesis in canine mammary gland tumors. This review summarizes the characteristics and types of canine mammary gland tumors, the definition of tumor stem cells, methods of isolation, and clinical significance.