Hypothesis: primary antiangiogenic method proposed to treat early stage breast cancer

<p>Abstract</p> <p>Background</p> <p>Women with Down syndrome very rarely develop breast cancer even though they now live to an age when it normally occurs. This may be related to the fact that Down syndrome persons have an additional copy of chromosome 21 where the gene that codes for the antiangiogenic protein Endostatin is located. Can this information lead to a primary antiangiogenic therapy for early stage breast cancer that indefinitely prolongs remission? A key question that arises is when is the initial angiogenic switch thrown in micrometastases? We have conjectured that avascular micrometastases are dormant and relatively stable if undisturbed but that for some patients angiogenesis is precipitated by surgery. We also proposed that angiogenesis of micrometastases very rarely occurs before surgical removal of the primary tumor. If that is so, it seems possible that we could suggest a primary antiangiogenic therapy but the problem then arises that starting a therapy before surgery would interfere with wound healing.</p> <p>Results</p> <p>The therapy must be initiated at least one day prior to surgical removal of the primary tumor and kept at a Down syndrome level perhaps indefinitely. That means the drug must have virtually no toxicity and not interfere meaningfully with wound healing. This specifically excludes drugs that significantly inhibit the VEGF pathway since that is important for wound healing and because these agents have some toxicity. Endostatin is apparently non-toxic and does not significantly interfere with wound healing since Down syndrome patients have no abnormal wound healing problems.</p> <p>Conclusion</p> <p>We propose a therapy for early stage breast cancer consisting of Endostatin at or above Down syndrome levels starting at least one day before surgery and continuing at that level. This should prevent micrometastatic angiogenesis resulting from surgery or at any time later. Adjuvant chemotherapy or hormone therapy should not be necessary. This can be continued indefinitely since there is no acquired resistance that develops, as happens in most cancer therapies.</p

Enhanced surgery-induced angiogenesis among premenopausal women might partially explain excess breast cancer mortality of blacks compared to whites

AbstractThere is excess breast cancer mortality for African-Americans (AA) compared to European-Americans (EA) of 1.5–2.2 fold that first appeared in 1970s and has been worsening since. This disparity may not be explained solely by reduced access to medical care. We proposed that surgery to remove a primary tumor induces angiogenesis of distant dormant micrometastases in 20% of premenopausal node-positive patients. This hypothesis helps explain the reduced benefit of mammography for women aged 40–49. Interestingly, for AA the average age at diagnosis is 46 while for EA it is 57. The resultant increased proportion of AA premenopausal breast cancer suggests a possible explanation for the AA/EA excess mortality. Early detection, which began in the 1970s, is more effective in postmenopausal women than in premenopausal women. Since AA breast cancer is mostly premenopausal and EA breast cancer is mostly postmenopausal, it might be anticipated that starting in the 1970s because of surgery-induced early mortality, outcome would be superior for EA compared to AA

Verbal and nonverbal indices of learning during problem-based learning (PBL) among first year medical students and the threshold for tutor intervention

Background: During problem-based learning (PBL), students brainstorm on a problem, generate hypotheses and formulate learning objectives. Certain verbal and non-verbal expressions are used by students in response to specific learning issues. Aims: This study examines the use of these expressions as indices of the learning taking place and the tutors’ threshold to intervene. Methods: Common verbal expressions used by students during PBL were identified and scored on a Likert scale to indicate the learning taking place. These expressions were categorised into the following groups of learning interactions: exploratory questioning, cumulative reasoning and handling conflicts relating to learning. The tutor's threshold for intervention was also scored on a Likert scale. Means for each learning interaction and observed non-verbal expressions were used to construct bar charts for comparison. Results: When the learning interactions involve exploratory questioning or cumulative reasoning, students tend to score high on learning and tutors have high threshold for intervention. When the learning interactions involve handling conflicts relating to knowledge, students score high on learning, but teachers have a low threshold for intervention. Conclusion: Verbal and non-verbal expressions from students during PBL are useful indices of learning and can be used to help tutors decide when and when not to intervene

A theme issue by, for, and about Africa [1] (multiple letters)

SCOPUS: le.jinfo:eu-repo/semantics/publishe

A theme issue by, for, and about Africa [1] (multiple letters)

SCOPUS: le.jinfo:eu-repo/semantics/publishe