Promoting indigenous vegetables in urban agriculture & livelihoods : policy lessons from Sub-Saharan Africa

[From Introduction] Globally, the growth of urbanised areas continues at an exponential rate, and most spectacularly in the developing world. The global urban population will increase from 2.9 billion in 2000 to 5.0 billion by 2030. The mean rate of urban growth in non-OECD countries between 2000 and 2005 was just under 3% per annum, compared to 0.5 % for rural regions of the same countries (UN-Habitat 2006). Although the proportion of Africans currently living in urban areas is the lowest in the world (+ 40%), because of this low base it is not unsurprising that the rates of urbanisation are among the highest at approximately 4.3% per annum. Projections vary, but sometime in the mid- 2020s over 50% of Africa's population will be living in urban areas, as compared to just 15% in 1950 and 34% in 1994. As urbanisation takes place another important trend is revealed, namely the locus of poverty in Africa is slowly shifting from rural to urban areas. For example, it is estimated that more than 56% of the world's absolute or chronic poor will be concentrated in urban areas (WRI 1996). Since as much as 60-80% of the income of the urban poor is spent on the purchase of food (Maxwell et al. 2000), the issue of food supply, both its quantity and quality, is increasingly a central issue in poverty reduction debates and strategies. In rural areas, a common strategy to alleviate poverty is to call for measures to boost small-holder food production. Surprisingly, this is less common in urban poverty alleviation programmes, despite the widespread promise of urban and household agriculture in contributing to improved food security

Comparison of the pattern of metastatic spread of squamous cell cancer and adenocarcinoma of the uterine cervix

Retrospective review of medical records and autopsy findings in patients dying of squamous cell cancer or adenocarcinoma of the uterine cervix was undertaken to evaluate for possible differences in biologic behavior between these tumor types. Twenty-one patients with each tumor type were evaluated. Patients with adenocarcinoma were found to have a higher incidence of tumor involvement of the paraaortic lymph nodes (13/21 vs 6/20, P P P P P < 0.05) was also significantly more frequent in patients with adenocarcinoma. These findings suggest that this tumor may behave differently in regard to pattern of metastatic spread or response to therapy. The therapeutic implications of these findings deserve further study.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27919/1/0000342.pd

Malignant placental site trophoblastic tumor associated with placental abruption, fetal distress, and elevated CA-125

The second pregnancy of 27-year-old woman, gravida 2, para 2 was complicated by a low [alpha]-fetoprotein and symptoms of chronic placental abruption. She delivered by cesarean section at 35 weeks for fetal distress at which time a biopsy of the uterus revealed a placental site trophoblastic tumor (PSTT). She rapidly developed intraabdominal spread of the neoplasm which did not respond to chemotherapy and she died 10 weeks later. Her CA-125 was elevated to 5360 u/ml and this decreased after hysterectomy. This patient is reported to highlight a very malignant course of PSTT that was associated with a live-born male infant.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29752/1/0000090.pd

DNA Methylation Profiles of Ovarian Epithelial Carcinoma Tumors and Cell Lines

BACKGROUND:Epithelial ovarian carcinoma is a significant cause of cancer mortality in women worldwide and in the United States. Epithelial ovarian cancer comprises several histological subtypes, each with distinct clinical and molecular characteristics. The natural history of this heterogeneous disease, including the cell types of origin, is poorly understood. This study applied recently developed methods for high-throughput DNA methylation profiling to characterize ovarian cancer cell lines and tumors, including representatives of three major histologies. METHODOLOGY/PRINCIPAL FINDINGS:We obtained DNA methylation profiles of 1,505 CpG sites (808 genes) in 27 primary epithelial ovarian tumors and 15 ovarian cancer cell lines. We found that the DNA methylation profiles of ovarian cancer cell lines were markedly different from those of primary ovarian tumors. Aggregate DNA methylation levels of the assayed CpG sites tended to be higher in ovarian cancer cell lines relative to ovarian tumors. Within the primary tumors, those of the same histological type were more alike in their methylation profiles than those of different subtypes. Supervised analyses identified 90 CpG sites (68 genes) that exhibited 'subtype-specific' DNA methylation patterns (FDR<1%) among the tumors. In ovarian cancer cell lines, we estimated that for at least 27% of analyzed autosomal CpG sites, increases in methylation were accompanied by decreases in transcription of the associated gene. SIGNIFICANCE:The significant difference in DNA methylation profiles between ovarian cancer cell lines and tumors underscores the need to be cautious in using cell lines as tumor models for molecular studies of ovarian cancer and other cancers. Similarly, the distinct methylation profiles of the different histological types of ovarian tumors reinforces the need to treat the different histologies of ovarian cancer as different diseases, both clinically and in biomarker studies. These data provide a useful resource for future studies, including those of potential tumor progenitor cells, which may help illuminate the etiology and natural history of these cancers

Factors impacting genomic testing rates among epithelial ovarian cancer patients across a large community-based healthcare system

Background: Epithelial ovarian cancer (EOC) accounts for the highest mortality of all gynecological cancers. NCCN guidelines recommend germline and somatic testing for all women with invasive EOC. Despite this recommendation, there is a large diversity in the types of testing patients receive even within a single healthcare system. Reported data of genetic testing for epithelial ovarian cancer (EOC) patients is largely based on patients treated at academic medical centers or patients who participate in clinical trials. Purpose: This study sought to determine the rates of germline and somatic testing for epithelial ovarian cancer patients and identify factors that impact testing rates across a large community-based healthcare system over 5 states: WA, OR, CA, AK, and MT. The system is comprised of over 100,000 caregivers, 51 hospitals and 829 physician clinics. The aim was to identify barriers to testing such as region, hospital type, insurance status, racial/ethnic disparities, and stage of diagnosis. Methods: Clinical, pathologic, demographic and genomic testing information was obtained from the diverse dataset within the Providence St. Joseph Health Electronic Medical Records and the system-wide cancer registry for all patients with an EOC diagnosis (ICD C56.x) between January 2015 and January 2020. Structured genomic data was sourced from laboratory information systems and manual abstraction of molecular sequencing reports. This dataset encompasses patient population data among diverse hospital settings and urban/rural environments. Institution types were broken down into academic setting which contain a residency program (Academic), Commission on Cancer (CoC) accredited programs, or smaller community sites (Community) without CoC accreditation. Descriptive statistics and logical regression are utilized to summarize key findings. Results: Within this EOC cohort (3,007 patients), 34% (n=1,027 patients) completed some type of genomic testing (GT). The percentage of patients tested increased from 31% in 2015 to 46% in 2019, reflecting uptake of testing guidelines. The increase in GT rates was largely attributable to an increase in somatic tumor testing (14-39%); while germline testing rates were stable across the interval (25-33%). Patients were more likely to receive testing if they received care at an academic or CoC institution vs community institution (p=0.0001). Logistic regression analysis demonstrated the following factors impacted tested rates: institution type, insurance, and stage at diagnosis (p=0.001, p= 0.0019 and p \u3c 0.0001, respectively). Race/ethnicity did not contribute significantly to the model but did have a significant effect when analyzed independently. Conclusion: This study is the first to analyze practice patterns in GT for EOC across a broad community-based healthcare system servicing 5 states. The data highlight discrepancies in GT heavily influenced by practice setting, insurance status, and stage of diagnosis (likely reflecting payer coverage/ increased need for information in advanced stage disease). Significance: There is a need for a universally defined approach to testing to provide equitable access to evidence based cancer care. Presenting Author: Nicole Kretzer, MD, PhD, Obstetrics and Gynecology, First Hill Campus, [email protected]

Effects of personal characteristics on serum CA125, mesothelin, and HE4 levels in healthy postmenopausal women at high-risk for ovarian cancer.

OBJECTIVE: To evaluate if serum levels of candidate ovarian cancer biomarkers vary with individual characteristics of healthy women who are likely candidates for an ovarian cancer screening program. METHODS: We analyzed serum CA125, mesothelin, and HE4 levels in a sample of 155 healthy postmenopausal women at increased risk for developing ovarian cancer based on personal and family cancer history. Information on reproductive, family and medical histories, lifestyle factors, and anthropometry was collected by self-report. Twenty-two factors were examined using univariate and multiple linear regression models for the three biomarker levels. RESULTS: In the multivariate models, CA125 levels were significantly higher in women who had used talcum powder (P = 0.02) and were lower in women who were parous (P = 0.05). Mesothelin levels were significantly higher in older women (P = 0.01) and lower in heavier women (P = 0.03). HE4 levels were higher in older women (P = 0.001) and in women who began menstruating at an older age (P = 0.03). CONCLUSIONS: CA125, mesothelin, and HE4 levels in healthy, postmenopausal women at increased risk for ovarian cancer are significantly associated with a few ovarian cancer risk factors. Since the effects of these personal characteristics on these serum markers are not large, their incorporation in screening algorithms may be unnecessary. This is true especially if a longitudinal algorithm is used because the marker level at the previous screen reflects personal characteristics such as age, body mass index, and age of menarche. Understanding the influence of personal factors on levels of novel early detection markers in healthy, unaffected women may have clinical utility in interpreting biomarker levels

Continuous infusion of low-dose 5-fluorouracil and radiation therapy for poor-prognosis squamous cell carcinoma of the uterine cervix

Ten patients with squamous cell carcinoma of the cervix metastatic to periaortic lymph nodes were treated with external-beam radiation therapy and synchronous infusion of intravenous 5-fluorouracil (5-FU) chemotherapy at doses of 350 mg/m2/day. The overall response rate was 90% with four complete responses (CR) and five partial responses (PR). The median duration of response was 11.8 months for CRs and 3.6 months for PRs. Toxicity was tolerable, with gastrointestinal symptoms and myelosuppression being noted most frequently. No patient experienced life-threatening toxicity. Median survival was 7.6 months, with only one patient being alive and free of disease at 2 years. In this pilot study we were unable to demonstrate a beneficial effect of continuous infusion of low doses of 5-FU chemotherapy concurrent with radiation therapy when compared to conventional radiotherapy in patients with advanced squamous cell carcinoma of the cervix.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30181/1/0000566.pd

Proteomic Analysis of Ovarian Cancer Cells Reveals Dynamic Processes of Protein Secretion and Shedding of Extra-Cellular Domains

Background: Elucidation of the repertoire of secreted and cell surface proteins of tumor cells is relevant to molecular diagnostics, tumor imaging and targeted therapies. We have characterized the cell surface proteome and the proteins released into the extra-cellular milieu of three ovarian cancer cell lines, CaOV3, OVCAR3 and ES2 and of ovarian tumor cells enriched from ascites fluid. Methodology and Findings: To differentiate proteins released into the media from protein constituents of media utilized for culture, cells were grown in the presence of [ 13 C]-labeled lysine. A biotinylation-based approach was used to capture cell surface associated proteins. Our general experimental strategy consisted of fractionation of proteins from individual compartments followed by proteolytic digestion and LC-MS/MS analysis. In total, some 6,400 proteins were identified with high confidence across all specimens and fractions. Conclusions and Significance: Protein profiles of the cell lines had substantial similarity to the profiles of human ovarian cancer cells from ascites fluid and included protein markers known to be associated with ovarian cancer. Proteomic analysis indicated extensive shedding from extra-cellular domains of proteins expressed on the cell surface, and remarkably high secretion rates for some proteins (nanograms per million cells per hour). Cell surface and secreted proteins identified by indept