Interactive Effects of Flaxseed Oil and Trastuzumab on the Growth of Breast Tumours Overexpressing HER2Mason, Julie 12 January 2011 (has links)
Flaxseed oil (FO), rich in α-linolenic acid, has been shown to inhibit breast cancer growth. One suggested mechanism is through modulation of HER2 expression and signalling. This study determined the effect of FO on the growth of established HER2-overexpressing breast tumours (BT-474) and its interaction with two doses of a primary anti-HER2 therapy, trastuzumab (TRAS), in athymic mice. FO alone had no effect on tumour size, cell proliferation and apoptosis. TRAS (2.5 and 5 mg/kg) reduced tumour size and cell proliferation but had no effect on apoptosis. TRAS (2.5 mg/kg) combined with FO reduced tumour size and cell proliferation and increased apoptosis compared to TRAS (2.5 mg/kg) alone and was just as effective as 5 mg/kg TRAS. TRAS (5 mg/kg) resulted in almost complete tumour regression with or without FO. In conclusion, FO has no effect on BT-474 tumour growth but can enhance the effectiveness of low dose TRAS.
Adams, Rose Anna
Since 1942, when Bittner reported the incidence of non-induced tumors occuring in mice, strains of laboratory mice producing mammary carcinomas have been used as tools in research. Although not ideal for human studies, the histological and morophological similarities of the human and mouse mammary glands make it an excellent model to study the development of breast cancer. This study was performed to develop a rapid and consistent classification system for mouse mammary tissue, and compare various tumors to this system.Laboratory mice from the A and Balb/c strains were utilized in these studies. The three types of tumors developed in these mice were, non-induced, induced, and transplanted. Specimens of these tumors were collected and studied via light and electron microscopy for cellularchanges of tumor cells. These tumors were then classified according to the new system. These various tumors ranged from Class 0, which were normal cells, through gradual cellular changes to a Class IV, which were totally undifferentiated cells. host induced and non-induced tumors were Class III or IV, while the transplanted tumors were Class IV. This system facilitated the classification of mouse mammary tumors.
20 August 2012
Mijo emerged as an alternate project to fulfill my MFA thesis requirement when Foreign Puzzle my initial thesis project faced serious setbacks. Foreign Puzzle is an hour-long documentary about love, life, breast cancer, dance and the transcending power of the human spirit. In an attempt to unravel an individual's struggle with mortality, to understand a child's adaptation to a mother's illness and to document the healing power of creativity, I began filming Sharon Marroquin's life from September 2010. Unfortunately, when filming real people undergoing life threatening medical illness it is impossible to stick to a timeline. Sharon Marroquin, the central character in the film developed serious medical complications that pushed the deadline for Foreign Puzzle significantly. While, I was committed to the completion of the film Foreign Puzzle, I did not want to delay my graduation from film school by almost two years and hence was forced to come up with an alternate thesis project. I had an animation script ready to go into production. But, I was so deeply involved with the production of Foreign Puzzle that it became impossible to work earnestly on a completely new film. The only viable alternative was to make a short film from the footage filmed for Foreign Puzzle. For the film to work and function independently, it had to have a strong and distinct thematic strand and not seem like a trailer or a scene from a longer film. This report is an elaboration of the process that went into the creation and exhibition of Mijo and its influence on Foreign Puzzle. / text
Anti-tumor actions of vitamin E analog [alpha]-TEA alone and in combinations in human breast cancer cellsTiwary, Richa 30 January 2013 (has links)
Breast cancer is the second leading cause of mortality among women in the US. A contributing factor to such dire statistics is that conventional therapies are all too often compromised due to tumor relapse. Clearly there is an urgent need for agents that can circumvent resistance when combined with conventional therapies. RRR-α-tocopherol ether-linked acetic acid analog (α-TEA), a small bioactive lipid, exhibits in vitro and in vivo anticancer actions in a variety of cancers, including breast, prostate, and ovarian with little or no effect on normal cells and tissues, which potentially makes it an ideal chemotherapeutic agent. My studies investigated the anticancer actions of α-TEA alone and in combination with therapeutic agents using human breast cancer cell lines. Data show that: (i) Endoplasmic reticulum (ER) stress plays an important role in α-TEA induced apoptosis by enhancing DR5/caspase-8 pro-apoptotic signaling and suppressing anti-apoptotic factors c-FLIP and Bcl-2 via ER stress mediated JNK/CHOP/DR5/caspase-8 signaling, (ii) α-TEA plus tamoxifen act cooperatively to circumvent acquired and de novo tamoxifen resistance, resulting in cancer cell death by apoptosis. Mechanistically, the circumvention of tamoxifen resistance involved induction of DR5/caspase-8 pro-apoptotic mediators and suppression of anti-apoptotic factors c-FLIP and Bcl-2 via ER stress mediated JNK/CHOP/DR5/caspase-8 signaling. (iii) α-TEA alone or with tamoxifen circumvents tamoxifen resistance via disruption of membrane cholesterol rich lipid raft microdomains. Cholesterol blocked the ability of α-TEA + tamoxifen to circumvent tamoxifen resistance. (iv) α-TEA in combination with PI3K, MEK or mTOR inhibitors acted cooperatively to induce apoptosis, by down-regulation of IRS-1/PI3K mediators via JNK. (v) α-TEA plus doxorubicin or cisplatin enhanced apoptosis in p53 mutant human breast cancer cells via targeting p53-inducible genes in a p73-dependent manner; namely, via up-regulation of death receptor-5 (DR5), CD95/APO-1 (Fas), Bax and Noxa, as well as down-regulation of anti-apoptotic mediator Bcl-2. Data showed that p73 responses were downstream of c-Abl, JNK and Yap. (vi) FASN inhibitor alone or with Tamoxifen or α-TEA circumvents tamoxifen resistance, thereby, providing novel strategies for restoring tamoxifen sensitivity to tamoxifen resistant cancers. In summary data show, α-TEA alone and in combination with multiple clinically-relevant anticancer agents is a promising anticancer agent. / text
Investigation of the effects of alpha-TEA, MSA and t-RES alone and in combination on human MDA-MB-435 breast cancer cells in vitro and in vivoSnyder, Rachel Marie 28 August 2008 (has links)
Not available / text
28 August 2008
Not available / text
Comparison on clinical and pathological characteristics between screening detected and self discovery of breast cancer of a cohort ofHong Kong breast cancer patientsLau, Suk-sze., 劉淑思. January 2011 (has links)
published_or_final_version / Public Health / Master / Master of Public Health
Hung, Wai-ka., 熊維嘉.
This thesis consisted a series of sentinel node biopsy (SNB) studies in Chinese patients to evaluate its impact on the management of breast cancer. Pilot studies The first SNB pilot study was performed in 30 patients using the blue dye technique. Accuracy was verified by axillary lymph node dissection (ALND). The success rate was 83% and the false-negative rate was 25%. The second pilot study was performed in 50 patients using combined mapping with isotope and dye. The success rate was 94% with no false-negative. SNB is shown to be feasible and accurate in Chinese. The optimal mapping method Combined mapping was superior to the blue dye technique. This could be due to the mapping technique or improved experience. One hundred and twenty-three women were randomly assigned to either the blue dye or combined mapping. Combined mapping had a higher success rate than the blue dye technique (100% versus 86%). False-negative rates were similar (0% versus 4.5%). Combined mapping is the preferred method. Accuracy of frozen section (FS) FS was used intra-operatively to guide the need of ALND. In 260 SNB, FS was compared to serial section and immuno-histochemical staining. FS detected 53 of 86 patients with SN metastases with a false-negative rate of 38.4%. The false-negative rates for macro-, micro-metastases and isolated tumour cells (ITC) were 2.4%, 57.7% and 94.4%. FS was accurate to diagnose macro-metastases but not micro-metastases and ITC. Can we skip ALND in SN metastases? 139 patients with SNB and ALND were studied to identify predictive factors for non-SN metastases. 55 had metastatic SN but 38 (69%) had no residual metastases in non-SN. Tumours <3 cm, a single metastatic SN, micro-metastases and absence of extra-capsular spread were significant factors to predict no residual nodal disease. Non-SN metastases were found in 42%, 19% and 0% when SN contained macro-, micro-metastases and ITC. Based on risk of non-SN involvement, ALND is indicated for macro- and micro-metastases but not for ITC. Extended indication for ductal carcinoma in situ (DCIS) SNB may be useful for staging of patients with a pre-operative diagnosis of DCIS because invasive cancer is not infrequently found on pathological examination of resected specimens after surgical excision. One hundred and seven patients with DCIS on core biopsy underwent SNB. Thirty-two patients (29.9%) were upstaged to invasive cancer and 9 (28.1%) had SN metastases. Performing SNB reduced the re-operation rate from 29.9% to 1.9%. Palpable mass and radiological mass lesion were associated with upstage. Extended indication: Sentinel Node Occult Lesion Localisation (SNOLL) Radioisotope is used to localise non-palpable breast cancer and SN. Seventy-four patients with non-palpable breast cancers underwent SNOLL. Radioisotope was injected into cancer and gamma probe guided breast cancer and SN resection. Primary cancer was removed in 73 patients (99%) after the first-round excision and 82% had complete excision. Gamma probe identified SN in 82% and supplementary blue dye increased SN detection to 97%. SNB modified the practice of breast cancer surgery. It has a major impact on the diagnosis, staging and treatment of breast cancer. / published_or_final_version / Surgery / Master / Master of Surgery
Yiu, Yui-tsi, Dara., 姚睿祉.
Breast cancer patients consistently reported psychosocial adjustment difficulty in their sense of femininity after breast removal surgery. In view of this, the present study aimed to explore the effects of three femininity-related concepts on emotional reactions towards breast removal surgery – femininity schema, femininity loss appraisals, and femininity contingency of self-worth. 212 women without breast cancer history participated in this study. They completed a questionnaire which included a hypothetical scenario of breast removal. Results showed that women who considered the breast of a high relative importance in femininity schema, and depended their self-worth highly on sense of femininity, reported greater increase in negative emotions after hypothetical breast removal. This effect was mediated by femininity loss appraisals. Implications and future directions were discussed. / published_or_final_version / Clinical Psychology / Master / Master of Social Sciences
Tse, Yuen-yu, Belinda, 謝宛余
Objectives: Forkhead box protein P1 (FOXP1) is a transcription factor, and a member of the P-subfamily of forkhead box transcription factor and regulate transcription of a subset of genes that involved in various cellular events. It plays a critical role in regulating cell growth and proliferation, differentiation, embryogenesis, adult tissue homeostasis, and possibly tumorigenesis. Predominant nuclear localisation of FOXP1 protein is commonly expressed at low level in normal tissues and upregulated in proliferative cells. Studies have demonstrated that the loss of FOXP1 expression and cytoplasmic mis-localisation is significantly associated with various malignant cancers, including breast cancer. FOXP1 can act either as a tumor suppressor or as an oncogenic protein in cell-type specific functions. It has been shown to be a co-regulator of estrogen receptor alpha and can modify a specific subset of forkhead box transcription factor class O (FOXO)-target genes. We hypothesise that there is association between FOXP1 expression and patient survival, and explore the potential role of FOXP1 expression as a prognostic marker in breast cancer. Methods: One hundred and twenty breast cancer samples in tissue microarray blocks were examined for FOXP1 expression by immuno-histochemistry. Nuclear and cytoplasmic FOXP1 expression patterns were analysed with clinico-pathological parameters. Statistical analysis was performed using SPSS software to determine the correlation between FOXP1 expression and clinico-pathological parameters. The correlation between subcellular FOXP1 expression and survival was evaluated by COX regression analysis. Results: Nuclear or cytoplasmic FOXP1 expression showed no association with clinico-pathological parameters. However, our results showed that there was significant association with estrogen receptor and progesterone receptor when nuclear and cytoplasmic scores were combined as total FOXP1 score (p=0.022 and p=0.028 respectively). In univariate analysis, high nuclear and cytoplasmic FOXP1 expression had no significant correlation with poor survival, while high total FOXP1 expression was associated with poor overall and disease-specific survival (p=0.045). Tumor stage and lymph-node involvement were significantly related to poorer overall and disease-specific survival, while other clinico-pathological parameters did not. In breast cancer with advanced tumor grade and lymph-node involvement, overall and disease-specific survival are significantly associated with high FOXP1 expression (p=0.041 and p=0.015 respectively). Conclusion: Unlike previous reports, our findings show that increased nuclear and cytoplasmic FOXP1 expression were both observed and high total FOXP1 expression was associated with poorer survival, particularly in cases of advance tumor grade and with lymph node metastases. These finding are supported by a recent report that showed that FOXP1 can up-regulate its own expression by binding to the promoter of FOXP1 and promote cell survival of breast cancer cells by suppressing FOXO-induced apoptosis. It may be possible that FOXP1 expression is up-regulated in a positive feedback loop in breast cancer cells such that there is both increased nuclear transcriptional activity and cytoplasm localisation of FOXP1. Further investigation is necessary to understand the role of FOXP1 in the progression of breast cancer and determine its potential use as a prognostic marker. / published_or_final_version / Pathology / Master / Master of Medical Sciences
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