Obtaining Adequate Surgical Margins in Breast-Conserving Therapy for Patients with Early-Stage Breast Cancer: Current Modalities and Future Directions

Inadequate surgical margins represent a high risk for adverse clinical outcome in breast-conserving therapy (BCT) for early-stage breast cancer. The majority of studies report positive resection margins in 20% to 40% of the patients who underwent BCT. This may result in an increased local recurrence (LR) rate or additional surgery and, consequently, adverse affects on cosmesis, psychological distress, and health costs. In the literature, various risk factors are reported to be associated with positive margin status after lumpectomy, which may allow the surgeon to distinguish those patients with a higher a priori risk for re-excision. However, most risk factors are related to tumor biology and patient characteristics, which cannot be modified as such. Therefore, efforts to reduce the number of positive margins should focus on optimizing the surgical procedure itself, because the surgeon lacks real-time intraoperative information on the presence of positive resection margins during breast-conserving surgery. This review presents the status of pre- and intraoperative modalities currently used in BCT. Furthermore, innovative intraoperative approaches, such as positron emission tomography, radioguided occult lesion localization, and near-infrared fluorescence optical imaging, are addressed, which have to prove their potential value in improving surgical outcome and reducing the need for re-excision in BCT

New Trends in Heart Regeneration: A Review

In this review, we focus on new approaches that could lead to the regeneration of heart muscle and the restoration of cardiac muscle function derived from newly-formed cardiomyocytes. Various strategies for the production of cardiomyocytes from embryonic stem cells, induced pluripotent stem cells, adult bone marrow stem cells and cardiac spheres from human heart biopsies are described. Pathological conditions which lead to atherosclerosis and coronary artery disease often are followed by myocardial infarction causing myocardial cell death. After cell death, there is very little self-regeneration of the cardiac muscle tissue, which is replaced by non-contractile connective tissue, thus weakening the ability of the heart muscle to contract fully and leading to heart failure. A number of experimental research approaches to stimulate heart muscle regeneration with the hope of regaining normal or near normal heart function in the damaged heart muscle have been attempted. Some of these very interesting studies have used a variety of stem cell types in combination with potential cardiogenic differentiation factors in an attempt to promote differentiation of new cardiac muscle for possible future use in the clinical treatment of patients who have suffered heart muscle damage from acute myocardial infarctions or related cardiovascular diseases. Although progress has been made in recent years relative to promoting the differentiation of cardiac muscle tissue from non-muscle cells, much work remains to be done for this technology to be used routinely in translational clinical medicine to treat patients with damaged heart muscle tissue and return such individuals to pre-heart-attack activity levels

IN-VIVO PROTEIN-SYNTHESIS IN DEVELOPING HEARTS OF NORMAL AND CARDIAC MUTANT AXOLOTLS (AMBYSTOMA-MEXICANUM)

Recessive mutant gene c in axolotls causes a failure of the hearts of affected embryos to function. The mutant hearts (c/c) lack organized sarcomeric myofibrils. The present study was undertaken to determine the overall pattern of in vivo protein synthesis and subsequent accumulation of the newly synthesized proteins for a 24-h period in normal (+/+ or +/c) and cardiac mutant (c/c) axolotl hearts at various stages of development. Additionally, selected cytoskeletal/myofibrillar proteins were analyzed in detail for their synthesis during heart development. For such analyses, the hearts were radiolabeled with S-35-methionine for 24 h and subjected to SDS-PAGE and autoradiography. Quantitative densitometric analyses of the bands show that, even though the overall protein pattern is similar in normal and mutant heart tissues, a general reduction in the synthesis of the proteins in mutant hearts is observed even at the earlier stages of development (stages 35-36 and 37-38), Synthesis and accumulation of most of the proteins is significantly inhibited in mutant hearts at later stages (stages 41-42), Tropomyosin synthesis in mutant hearts is at a level of only 72.6% of that in normal embryonic hearts at stage 35. The synthesis and the accumulation of the tropomyosin in mutant hearts decreases further with increasing age until the protein essentially stops being synthesized by stage 41

CLONING, SEQUENCING AND EXPRESSION OF AN ISOFORM OF CARDIAC C-PROTEIN FROM THE MEXICAN AXOLOTL (AMBYSTOMA-MEXICANUM)

C-protein, a myosin binding protein, is thought to regulate and stabilize thick filaments during assembly of sarcomeric A-bands. Multiple isoforms of C-protein have been characterized in avian and mammalian systems. We now report the isolation and the nucleic acid sequence of a partial C-protein cDNA clone from an axolotl heart cDNA expression library in lambda gt11. The clone was isolated by screening the library with a heterologous monoclonal anti-C-protein antibody (MF1). Sequence comparison revealed that CPRO(Axocard)1 has an average sequence identity of 62-68% at the nucleic acid and 72-78% at the amino acid levels respectively to human and chicken sequences. We could not detect any significant differences at the levels of expression of the cardiac isoform of C-protein (CPRO(Axocard)1) in normal and non-beating heart tissues of the double-recessive cardiac lethal mutant (c/c) axolotl, Ambystoma mexicanum. This is the first report of a C-protein sequence from an amphibian species. (C) 1995 Academic Press, Inc