Response to sunitinib (Sutent) in chemotherapy refractory clear cell ovarian cancer

• Case describes a response to sunitinib in clear cell ovarian cancer. • Discussion of unique molecular characteristics of clear cell ovarian cancers; • Practical points regarding dosing and toxicity when using sunitinib discussed

A Study of Selected Characteristics of Committed Juvenile Delinquents in Omaha, Nebraska, 1955 and 1956

Any study dealing with the human variable is a difficult one. With all of his accomplishments in science and technology, man still remains one of the most unpredictable, least understood beings on this earth. It is the endeavor of this paper to shed a little more light on one aspect of human behavior, namely that of juvenile delinquency

The Masquerade : March - Two Step

https://digitalcommons.library.umaine.edu/mmb-ps/2178/thumbnail.jp

Novel ex vivo models of epithelial ovarian cancer: the future of biomarker and therapeutic research

Epithelial ovarian cancer (EOC) is a heterogenous disease associated with variations in presentation, pathology and prognosis. Advanced EOC is typified by frequent relapse and a historical 5-year survival of less than 30% despite improvements in surgical and systemic treatment. The advent of next generation sequencing has led to notable advances in the field of personalised medicine for many cancer types. Success in achieving cure in advanced EOC has however been limited, although significant prolongation of survival has been demonstrated. Development of novel research platforms is therefore necessary to address the rapidly advancing field of early diagnostics and therapeutics, whilst also acknowledging the significant tumour heterogeneity associated with EOC. Within available tumour models, patient-derived organoids (PDO) and explant tumour slices have demonstrated particular promise as novel ex vivo systems to model different cancer types including ovarian cancer. PDOs are organ specific 3D tumour cultures that can accurately represent the histology and genomics of their native tumour, as well as offer the possibility as models for pharmaceutical drug testing platforms, offering timing advantages and potential use as prospective personalised models to guide clinical decision-making. Such applications could maximise the benefit of drug treatments to patients on an individual level whilst minimising use of less effective, yet toxic, therapies. PDOs are likely to play a greater role in both academic research and drug development in the future and have the potential to revolutionise future patient treatment and clinical trial pathways. Similarly, ex vivo tumour slices or explants have also shown recent renewed promise in their ability to provide a fast, specific, platform for drug testing that accurately represents in vivo tumour response. Tumour explants retain tissue architecture, and thus incorporate the majority of tumour microenvironment making them an attractive method to re-capitulate in vivo conditions, again with significant timing and personalisation of treatment advantages for patients. This review will discuss the current treatment landscape and research models for EOC, their development and new advances towards the discovery of novel biomarkers or combinational therapeutic strategies to increase treatment options for women with ovarian cancer

Investigating the benefits of molecular profiling of advanced non-small cell lung cancer tumors to guide treatments.

In this study we utilized data on patient responses to guided treatments, and we evaluated their benefit for a non-small cell lung cancer cohort. The recommended therapies used were predicted using tumor molecular profiles that involved a range of biomarkers but primarily used immunohistochemistry markers. A dataset describing 91 lung non-small cell lung cancer patients was retrospectively split into two. The first group's drugs were consistent with a treatment plan whereby all drugs received agreed with their tumor's molecular profile. The second group each received one or more drug that was expected to lack benefit. We found that there was no significant difference in overall survival or mortality between the two groups. Patients whose treatments were predicted to be of benefit survived for an average of 402 days, compared to 382 days for those that did not (P = 0.7934). In the matched treatment group, 48% of patients were deceased by the time monitoring had finished compared to 53% in the unmatched group (P = 0.6094). The immunohistochemistry biomarker for the ERCC1 receptor was found to be a marker that could be used to predict future survival; ERCC1 loss was found to be predictive of poor survival

Acceptance and Commitment Therapy in a Low-Income Country in Sub-Saharan Africa: A Call for Further Research

A worsening trend of critical shortages in senior health care workers across low- and middle-income countries (LMICs) in sub-Saharan Africa has been documented for decades. This is especially the case in Ethiopia that has severe shortage of mental health professionals. Consistent with the WHO recommended approach of task sharing for mental health care in LMICs, Acceptance and Commitment Therapy (ACT), which is an empirically validated psychological intervention aimed at increasing psychological flexibility, may be delivered by trained laypersons who have a grassroots presence. In this paper, we discuss the need for and potential role of ACT to be delivered by health extension workers (HEWs) to address mental health care needs across Ethiopia. To this end, we also reviewed previous studies that have examined the effectiveness of ACT-based interventions in African countries including in Nigeria, Sierra Leone, Uganda, and South Africa. All studies revealed significant improvements of various mental health-related outcome measures such as decreased psychological distress and depressive symptoms, or increased subjective wellbeing and life satisfaction in the groups that received an ACT-based intervention. However, to date, there is no study that applied ACT in Ethiopia. Thus, more research is warranted to examine the effectiveness and, if proven successful, to scale up a task sharing approach of an ACT-based intervention being delivered by trained HEWs at a grassroots level, possibly paving the way for an innovative, sustainable mental health service in Ethiopia as well as other African LMICs

Association Between Sense of Coherence and Health Outcomes at 10 and 20 Years Follow-Up: A Population-Based Longitudinal Study in Germany

Background: The sense of coherence (SOC) is reported to influence health, but health may also have an impact on SOC. The objective of this study was to examine the longitudinal associations between SOC and selected self-reported and physician-assessed health outcomes over a period of 10 and 20 years and to determine the predominant direction of the associations. Methods: We conducted a population-based, longitudinal study, involving 392 participants (188 females and 204 males; mean age 43.01 years) who were followed for a median of 10 and 18 years. Analyses of variance were carried out to examine the longitudinal associations between SOC at baseline and health outcomes (i.e., self-rated health status, SHS; physical health status assessed by a physician, PHS; self-reported satisfaction with life, SWL) at follow-ups. The direction of associations was examined using a cross-lagged model on correlation coefficients. Results: There were significant group effects for SOC at baseline on SHS at 20-year follow-up (F = 4.09, p = 0.018, ηp(2) = 0.041), as well as on SWL at 10-year (F = 12.67, p < 0.01, ηp(2) = 0.072) and at 20-year follow-up (F = 8.09, p < 0.1, ηp(2) = 0.069). SHS (r = 0.238, p < 0.01), PHS (r = −0.140, p < 0.05) and SWL (r = 0.400, p < 0.01) predicted SOC at 10-year follow-up stronger than vice versa. The direction of associations between SOC and health parameters at 20-year follow-up was less consistent. Conclusions: The long-term associations between SOC and self-reported and physician-assessed health may be reciprocal in community-dwelling adults. More research is needed to examine the predictive power of health on SOC and whether interventions targeted at improving health parameters, may impact SOC

Size exclusion chromatography as a technique for the investigation of novel extracellular vesicles in cancer

Abstract: (1) Background: Cancer cells release extracellular vesicles that are a rich target for biomarker discovery and provide a promising mechanism for liquid biopsy. SEC is an increasingly popular technique which has been rediscovered for the purposes of EV isolation and purification from diverse biofluids. (2) Methods: A review was undertaken to identify all papers which described size exclusion as their primary EV isolation method in cancer research. (3) Results: 37 papers were identified and discussed which showcases the breadth of applications that EVs can be utilised, from proteomics, to RNA, and through to functionality. A range of different methods are highlighted, with Sepharose-based techniques predominating. (4) Conclusions: EVs isolated using SEC are able to identify cancer cells, highlight active pathways in tumourigenesis, clinically distinguish cohorts and remain functionally active for further experiments

Fast and Efficient Postsynthetic DNA Labeling in Cells by Means of Strain-Promoted Sydnone-Alkyne Cycloadditions

Fast and efficient: DNA strands, modified with the novel bioorthogonal reporters sydnones, undergo fast and efficient labeling with cyclooctynes and have the potential to become essential tools for imaging DNA and possibly RNA in cells. Sydnones are highly stable mesoionic 1,3-dipoles that react with cyclooctynes through strain-promoted sydnone-alkyne cycloaddition (SPSAC). Although sydnones have been shown to be valuable bioorthogonal chemical reporters for the labeling of proteins and complex glycans, nucleic acids have not yet been tagged by SPSAC. Evaluation of SPSAC kinetics with model substrates showed fast reactions with cyclooctyne probes (up to k=0.59 M$^{-1}$ s$^{-1}$), and two different sydnones were effectively incorporated into both 2’-deoxyuridines at position 5, and 7-deaza-2’-deoxyadenosines at position 7. These modified nucleosides were synthetically incorporated into single-stranded DNAs, which were successfully postsynthetically labeled with cyclooctyne probes both in vitro and in cells. These results show that sydnones are versatile bioorthogonal tags and have the premise to become essential tools for tracking DNA and potentially RNA in living cells

Wikipedia as an encyclopaedia of life

In his 2003 essay E O Wilson outlined his vision for an &#x201c;encyclopaedia of life&#x201d; comprising &#x201c;an electronic page for each species of organism on Earth&#x201d;, each page containing &#x201c;the scientific name of the species, a pictorial or genomic presentation of the primary type specimen on which its name is based, and a summary of its diagnostic traits.&#x201d; Although the &#x201c;quiet revolution&#x201d; in biodiversity informatics has generated numerous online resources, including some directly inspired by Wilson&#x27;s essay (e.g., &#x22;http://ispecies.org&#x22;:http://ispecies.org, &#x22;http://www.eol.org&#x22;:http://www.eol.org), we are still some way from the goal of having available online all relevant information about a species, such as its taxonomy, evolutionary history, genomics, morphology, ecology, and behaviour. While the biodiversity community has been developing a plethora of databases, some with overlapping goals and duplicated content, Wikipedia has been slowly growing to the point where it now has over 100,000 pages on biological taxa. My goal in this essay is to explore the idea that, largely independent of the efforts of biodiversity informatics and well-funded international efforts, Wikipedia (&#x22;http://en.wikipedia.org/wiki/Main_Page&#x22;:http://en.wikipedia.org/wiki/Main_Page) has emerged as potentially the best platform for fulfilling E O Wilson&#x2019;s vision