56 research outputs found

    Letter from Annie Jiagge to Mildred Persinger, December 13, 1977

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    Understanding the Biology of Triple Negative Breast Cancer and Breast Cancer Stem Cells in Patients of Diverse Ethnicities

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    Triple negative breast cancer is one of the most aggressive breast cancer subtypes, for which there are no approved targeted therapies. In US alone, the incidence of TNBC is highest in women with African ancestry (AA); in western sub-Saharan Africa, single-institution studies show that TNBC constitutes 40- 80% of all breast cancer cases. There is an urgent need to find actionable targets in TNBC of all ethnicities, but especially in patients with African ancestry, whose tumors are suspected to be more aggressive. Here, we sought to better understand the biology of TNBC by finding genes and pathways that are differentially expressed in the stem cell population of patient derived xenografts (PDX) created with TNBC tumors from Ghanaian (GH), AA and White American (WA) women and the effect of these differentially expressed genes on the stem cell phenotype in these primary tumors. We first established an international, inter-institutional collaboration with a teaching hospital in Ghana (Komfo Anokye teaching hospital, KATH) for the acquisition of patients’ samples. From these samples, we created patient derived xenograft models that serve as a reneweable source of tumor tissue to study the cancer biology. Breast cancer stem cells, the small population of cells that have been shown to mediate breast tumor initiation, metastasis, and resistance to conventional therapy have also been reported to mediate the heterogeneity of TNBC and are especially abundant in TNBC in AA women. We therefore sought to understand the biology of these stem cells in our primary patient samples and their associated PDX models. We report here that, through our collaboration, we now have a better understanding of the diversity of the breast cancers that occur in Ghana and other parts of Africa, we have contributed to an improvement in the diagnosis and treatment of breast cancer patients and have contributed to enriching the human resource at the KATH in Ghana. We have successfully created a cohort of PDXs from TNBC patients in Ghana as well as African-American and White American patients. By sequencing the stem cells in these tumors, we have identified the aldehyde dehydrogenase (ALDH) expressing stem cell population to represent the stem cells in these aggressive tumors from this diverse population. We identified 14 genes that were simultaneously differentially expressed between the two-breast cancer stem cell sub-populations in (ALDH+ vs the CD44+/CD24-/EPCAM+) as well as ALDH+ vs bulk (p-value <0.001, FDR < 0.05 for both comparisons). The 3 most significant genes were matrix metalloproteinase 2 (MMP2) and Protocadherin 7 (PCDH7), both known to be involved in breast cancer metastasis and Probable carboxypeptidase X1 (CPXM1), a carboxylase. Inhibiting MMP2 expression in the PDX cells grown in suspension resulted in significant reduction in the ALDH+ cell population. Also, the ALDH+ and not the CD44+/CD24- cells formed spheres in serum free media. The WNT, MAPK and TGF-beta pathways known to mediate metastasis were all significantly up-regulated in the ALDH+ population with down regulation of biosynthetic pathways which were up-regulated in the CD44+/CD24- population. Further studies are ongoing on pathway modulation in ALDH1+ cells based on these findings. Together, these findings demonstrate the importance of international collaborations with mutual benefits. It also shows that TNBC, being a very heterogeneous disease, may be driven by a population of tumor cells that can be targeted to improve patient outcome.PHDCancer BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/136936/1/emawunyo_1.pd

    Dissemination of Scientific Information: Adopting a Strategic Approach for the Council for Scientific and Industrial Research (CSIR), Accra, Ghana

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    The paper examined the information dissemination processes by the thirteen institutes of the Council for Scientific and Industrial Research of Ghana. The CSIR core mandate is to coordinate and manage all the national Research projects. Research findings are usually disseminated to benefit the citizenry.The main objective of this study was to develop and recommend a strategic approach for disseminating the scientific information that is generated by the CSIR institutes.The study adopted a survey research design and mixed research methods which involve the combination of qualitative and quantitative approaches in one single study.The findings revealed that the STI generated by the CSIR vary from one institute to another, it takes between 6 months to 2 years to disseminate research findings to the general public a situation which is not acceptable.The results further revealed that the CSIR disseminates STI in various formats ranging from journal articles, technical reports, radio and television talk shows, manuals, books and conference proceedings and there is a limited use of emerging technologies namely, emails, internet based group discussions to communicate STI to the general public.The study finally recommends: the adoption of electronic information dissemination methods such as emails, social media platforms, group discussions, lists to target groups who are computer literates, The CSIR must develop a policy for STI dissemination; this will help the various institutes to follow the acceptable standards in STI dissemination, Repackaging of STI. The CSIR should repackage STI and use the appropriate format, media to disseminate the information to the various targeted groups and The various institutes should conduct frequent STI needs assessment/analysis to determine the STI needs of the users, this will help in determining which STI will be relevant and in what format

    Evaluation of Mid-Year Review of 2014 Seminars: A case study of the CSIR-Water Research Institute, Ghana

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    Scientific seminars are organized to provide forum for participants to discuss and also bring into the public domain current activities of an organization. To ascertain whether the seminars are achieving its aim, evaluation is usually done to assess the effectiveness. It is against this background that Water Research Institute of the Council for Scientific and Industrial Research organized 2014 mid-year seminar to review its research activities as well as communicate findings of research undertaken by its scientist for the year under review. Hence, the main thrust of this paper is to evaluate the success of 2014 mid-year review seminar. The evaluation for the purposes of quality assurance and future organization of similar seminars were conducted using descriptive statistics analysis of the evaluation questionnaire. The results of the study revealed that 71% of the participants were males while 29% of them were females. Most of the respondents were of the view that the topics presented were relevant and the overall performance of the seminar was good as it was in line with the objectives of the institute, that is, to generate and provide scientific information. Keywords: CSIR-Water Research Institute, Scientific Seminars, Scientific Informatio

    Is the HERV-K HML-2 Xq2133, an endogenous retrovirus mutated by gene conversion of chromosome X in a subset of African populations, associated with human breast cancer?

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    The human endogenous retroviruses HERV-K HML-2 have been considered a possible cause of human breast cancer (BrC). A HERV-K HML-2 fully intact provirus Xq21.33 was recently identified in some West African people. We used PCR technology to search for the Xq21.33 provirus in DNA from Nigerian women with BrC and controls. to see if Xq21.33 plays any role in predisposing to BrC. This provirus was detected in 27 of 216 (12.5%) women with BrC and in 22 of 219 (10.0%) controls. These results were not statistically significant. The prevalence of provirus in premenopausal control women 44 years or younger [18/157 (11.46%)} vs women with BrC [12/117 (10.26%)] showed no statistical difference. The prevalence of virus in postmenopausal control women \u3e 45 yrs. was 7.4% (4/54) vs 15.31% (15/98) in postmenopausal women with BrC. These changes were not statistically significant at \u3c.05, but the actual p value of \u3c.0.079, suggests that Xq21.33 might play some role in predisposing to BrC in postmenopausal women. Provirus was present in Ghanaian women (6/87), in 1/6 Pygmy populations and in African American men (4/45) and women (6/68), but not in any Caucasian women (0/109). Two BrC cell lines (HCC 70 and DT22) from African American women had Xq21.33. Env regions of the virus which differed by 2-3 SNPs did not alter the protein sequence of the virus. SNP at 5730 and 8529 were seen in all persons with provirus, while 54% had an additional SNP at 7596.Two Nigerian women and 2 Ghanaian women had additional unusual SNPs. Homozygosity was seen in (5/27) BrC and (2/22) control women. The genetic variation and homozygosity patterns suggested that there was gene conversion of this X chromosome associated virus. The suggestive finding in this preliminary data of possible increased prevalence of Xq21.33 provirus in post-menopausal Nigerian women with BrC should be clarified by a more statistically powered study sample to see if postmenopausal African and/or African American women carriers of Xq21.33 might show increased risk of BrC. The implication of finding such a link would be the development of antiretroviral drugs that might aid in preventing BrC in Xq21.33+ women

    Clinicopathologic characteristics of early-onset breast cancer: a comparative analysis of cases from across Ghana

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    BACKGROUND: Breast cancer is the commonest cancer diagnosed globally and the second leading cause of cancer-related mortality among women younger than 40 years. This study comparatively reviewed the demographic, pathologic and molecular features of Early-Onset Breast Cancer (EOBC) reported in Ghana in relation to Late Onset Breast Cancer (LOBC). METHODS: A descriptive, cross-sectional design was used, with purposive sampling of retrospective histopathology data from 2019 to 2021. Reports of core or incision biopsy, Wide Local Excision or Mastectomy with or without axillary lymph node dissection specimen and matched immunohistochemistry reports were merged into a single file and analysed with SPSS v. 20.0. Descriptive statistics of frequencies and percentages were used to describe categorical variables. Cross-tabulation and chi-square test was done at a 95% confidence interval with significance established at p \u3c 0.05. RESULTS: A total of 2418 cases were included in the study with 20.2% (488 cases) being EOBCs and 79.8% (1930 cases) being LOBCs. The median age at diagnosis was 34.66 (IQR: 5.55) in the EOBC group (\u3c 40 years) and 54.29 (IQR: 16.86) in the LOBC group (≥ 40 years). Invasive carcinoma-No Special Type was the commonest tumour type with grade III tumours being the commonest in both categories of patients. Perineural invasion was the only statistically significant pathologic parameter with age. EOBC was associated with higher DCIS component (24.8% vs 21.6%), lower hormone-receptor-positive status (52.30% vs 55.70%), higher proliferation index (Ki-67 \u3e 20: 82.40% vs 80.30%) and a higher number of involved lymph nodes (13.80% vs 9.00%). Triple-Negative Breast cancer (26.40% vs 24.30%) was the most predominant molecular subtype of EOBC. CONCLUSION: EOBCs in our setting are generally more aggressive with poorer prognostic histopathological and molecular features when compared with LOBCs. A larger study is recommended to identify the association between relevant pathological features and early onset breast cancer in Ghana. Again, further molecular and genetic studies to understand the molecular genetic drivers of the general poorer pathological features of EOBCs and its relation to patient outcome in our setting is needed
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