Tumor Angiogenesis: Insights and Innovations

Angiogenesis is a vital process resulting in the formation of new blood vessels. It is normally a highly regulated process that occurs during human development, reproduction, and wound repair. However, angiogenesis can also become a fundamental pathogenic process found in cancer and several other diseases. To date, the inhibition of angiogenesis has been researched at both the bench and the bedside. While several studies have found moderate improvements when treating with angiogenesis inhibitors, greater success is being seen when the inhibition of angiogenesis is combined with other traditional forms of available therapy. This review summarizes several important angiogenic factors, examines new research and ongoing clinical trials for such factors, and attempts to explain how this new knowledge may be applied in the fight against cancer and other angiogenic-related diseases

Radioactive Iodine Therapy Decreases Recurrence in Thyroid Papillary Microcarcinoma

Background. The most appropriate therapy for papillary microcarcinoma (PMC) is controversial. Methods. We reviewed the therapy and outcome of 407 patients with PMC. Results. Three hundred-eighty patients underwent total thyroidectomy, and 349 patients received I-131 therapy. The median followup was 5.3 years. Forty patients developed recurrent disease. On univariate analysis, development of disease recurrence was correlated with histological tumor size > 0.8 cm (P = 0.0104), age < 45 years (P = 0.043), and no I-131 therapy (P < 0.0001). On multivariate analysis, histological tumor size > 0.8 cm, positive lymph nodes, and no I-131 therapy were significant. The 5-year RFS for patients treated with I-131 was 95.0% versus 78.6% (P < 0.0001) for patients not treated with I-131. Patients with lymph node metastasis who did not receive I-131 had a 5-year RFS of 42.9% versus 93.2% (P < 0.0001) for patients who received I-131. Conclusions. Recommend I-131 remnant ablation for patients with PMC, particularly patients with lymph node metastasis

BRAF mutation is not predictive of long-term outcome in papillary thyroid carcinoma

The BRAF mutation occurs commonly in papillary thyroid carcinoma (PTC). Previous investigations of its utility to predict recurrence-free survival (RFS) and disease-specific survival (DSS) have reported conflicting results and its role remains unclear. The purpose of this retrospective study was to determine the incidence of the BRAF mutation and analyze its relationship to clinicopathologic risk factors and long-term outcomes in the largest, single-institution American cohort to date. BRAF mutational status was determined in 508 PTC patients using RFLP analysis. The relationships between BRAF mutation status, patient and tumor characteristics, RFS, and DSS were analyzed. The BRAF mutation was present in 67% of patients. On multivariate analysis, presence of the mutation predicted only for capsular invasion (HR, 1.7; 95% CI, 1.1–2.6), cervical lymph node involvement (HR, 1.7; 95% CI, 1.1–2.7), and classic papillary histology (HR, 1.8; 95% CI 1.1–2.9). There was no significant relationship between the BRAF mutation and RFS or DSS, an observation that was consistent across univariate, multivariate, and Kaplan–Meier analyses. This is the most extensive study to date in the United States to demonstrate that BRAF mutation is of no predictive value for recurrence or survival in PTC. We found correlations of BRAF status and several clinicopathologic characteristics of high-risk disease, but limited evidence that the mutation correlates with more extensive or aggressive disease. This analysis suggests that BRAF is minimally prognostic in PTC. However, prevalence of the BRAF mutation is 70% in the general population, providing the opportunity for targeted therapy

Differential endothelial cell gene expression by African Americans versus Caucasian Americans: a possible contribution to health disparity in vascular disease and cancer

<p>Abstract</p> <p>Background</p> <p>Health disparities and the high prevalence of cardiovascular disease continue to be perplexing worldwide health challenges. This study addresses the possibility that genetic differences affecting the biology of the vascular endothelium could be a factor contributing to the increased burden of cardiovascular disease and cancer among African Americans (AA) compared to Caucasian Americans (CA).</p> <p>Methods</p> <p>From self-identified, healthy, 20 to 29-year-old AA (n = 21) and CA (n = 17), we established cultures of blood outgrowth endothelial cells (BOEC) and applied microarray profiling. BOEC have never been exposed to <it>in vivo </it>influences, and their gene expression reflects culture conditions (meticulously controlled) and donor genetics. Significance Analysis of Microarray identified differential expression of single genes. Gene Set Enrichment Analysis examined expression of pre-determined gene sets that survey nine biological systems relevant to endothelial biology.</p> <p>Results</p> <p>At the highly stringent threshold of False Discovery Rate (FDR) = 0, 31 single genes were differentially expressed in AA. <it>PSPH </it>exhibited the greatest fold-change (AA > CA), but this was entirely accounted for by a homolog (<it>PSPHL</it>) hidden within the <it>PSPH </it>probe set. Among other significantly different genes were: for AA > CA, <it>SOS1, AMFR, FGFR3; and for AA < CA, ARVCF, BIN3, EIF4B. </it>Many more (221 transcripts for 204 genes) were differentially expressed at the less stringent threshold of FDR <.05. Using the biological systems approach, we identified shear response biology as being significantly different for AA versus CA, showing an apparent tonic increase of expression (AA > CA) for 46/157 genes within that system.</p> <p>Conclusions</p> <p>Many of the genes implicated here have substantial roles in endothelial biology. Shear stress response, a critical regulator of endothelial function and vascular homeostasis, may be different between AA and CA. These results potentially have direct implications for the role of endothelial cells in vascular disease (hypertension, stroke) and cancer (via angiogenesis). Also, they are consistent with our over-arching hypothesis that genetic influences stemming from ancestral continent-of-origin could impact upon endothelial cell biology and thereby contribute to disparity of vascular-related disease burden among AA. The method used here could be productively employed to bridge the gap between information from structural genomics (for example, disease association) and cell function and pathophysiology.</p

What Can Be Learnt about Disease Progression in Breast Cancer Dormancy from Relapse Data?

Breast cancer patients have an anomalously high rate of relapse many years-up to 25 years-after apparently curative surgery removed the primary tumour. Disease progression during the intervening years between resection and relapse is poorly understood. There is evidence that the disease persists as dangerous, tiny metastases that remain at a growth restricted, clinically undetectable size until a transforming event restarts growth. This is the starting point for our study, where patients who have metastases that are all tiny and growth-restricted are said to have cancer dormancy. Can long-term follow-up relapse data from breast cancer patients be used to extract knowledge about the progression of the undetected disease? Here, we evaluate whether this is the case by introducing and analysing four simple mathematical models of cancer dormancy. These models extend the common assumption that a random transforming event, such as a mutation, can restart growth of a tiny, growth-restricted metastasis; thereafter, cancer dormancy progresses to detectable metastasis. We find that physiopathological details, such as the number of random transforming events that metastases must undergo to escape from growth restriction, cannot be extracted from relapse data. This result is unsurprising. However, the same analysis suggested a natural question that does have a surprising answer: why are interesting trends in long-term relapse data not more commonly observed? Further, our models indicate that (a) therapies which induce growth restriction among metastases but do not prevent increases in metastases' tumourigenicity may introduce a time post-surgery when more patients are prone to relapse; and (b), if a number of facts about disease progression are first established, how relapse data might be used to estimate clinically relevant variables, such as the likely numbers of undetected growth-restricted metastases. This work is a necessary, early step in building a quantitative mechanistic understanding of cancer dormancy

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS