A rare case of cardiac fibroma diagnosis in Gorlin-Goltz syndrome with information on management.

Gorlin-Goltz syndrome is a rare autosomal dominant disease characterized by odontogenic keratocysts and basal cell carcinoma as well as ophthalmic and neurological implications. The following article presents the case of a 20-year-old female with Gorlin-Goltz syndrome incidentally found to have a cardiac mass. An ECG showed diffuse T-wave inversions in the lateral leads despite a lack of any acute coronary symptoms in the patient. Echocardiogram, cardiac MRI and CT scan confirmed a nonvascularized, smoothly marginated mass arising from the left ventricular apex without any hemodynamic compromise. A whole-body PET scan further demonstrated localized hyperactivity associated with a cardiac fibroma without any evidence of metastasis. The cardiac fibroma was surgically excised for definitive management to prevent the possibility of sudden cardiac death and congestive heart failure.

Cardiac fibroma presents as a benign tumor of the heart. Although tumors of the heart are uncommon, patients who have Gorlin­Goltz syndrome are at a higher risk of developing these fibromas. In the following article, the authors discuss the presence of this rare cardiac fibroma in a 20-year-old female patient with Gorlin­Goltz syndrome. The patient's tumor was found incidentally during a CT scan after she presented with symptoms of flank pain. A follow-up was later conducted with cardiology and cardiac surgery. Several tests were performed to scan the exact tumor location in the heart. Finally, the tumor was removed, and the patient recovered after surgery. Later, the patient was diagnosed with depression and needed medicine to cope with emotional trauma from multiple surgeries.

Using gene expression data to direct breast cancer therapy: evidence from a preclinical trial.

The heterogeneity both within and between breast cancers presents a significant clinical challenge for both diagnosis and therapy. This heterogeneity is present at all levels of analysis in breast cancer, ranging from genomic to metabolomic. A function of this heterogeneity is that numerous signaling networks are activated, and while treatment of one arm may be initially effective, this allows the tumor to be poised to evolve a resistance mechanism. Here we review the classification of breast cancers and discuss therapy of hormone positive, HER2 positive, and triple negative breast cancers. Model systems for breast cancer are examined allowing for a preclinical trial using a personalized medicine approach to be tested. This preclinical trial was based solely on cell signaling pathway activation and effectively and specifically blocked tumor growth in a preclinical model system.

A single mutant, A276S of p53, turns the switch to apoptosis.

The tumor suppressor protein p53 induces apoptosis, cell cycle arrest, and DNA repair along with other functions in a transcription-dependent manner [Vousden, K. H. Cell 2000, 103(5), 691-694]. The selection of these functions depends on sequence-specific recognition of p53 to a target decameric sequence of gene promoters [Kitayner, M.; et al. Mol. Cell 2006, 22(6), 741-753]. Amino acid residues in p53 that directly bind to DNA were analyzed, and the replacement of A276 in p53 with selected amino acids elucidated its importance in promoter transcription. For most apoptotic and cell cycle gene promoters, position 9 of the target decameric sequence is a cytosine, while for DNA repair gene promoters, thymine is found instead. Therefore, selective binding to the cytosine at the ninth position may transcribe apoptotic gene promoters and thus can induce apoptosis and cell cycle arrest. Molecular modeling with PyMOL indicated that substitution of a hydrophilic residue, A276S, would prefer binding to cytosine at the ninth position of the target decameric sequence, whereas substitution of a hydrophobic residue (A276F) would fail to do so. Correspondingly, A276S demonstrated higher transcription of PUMA, PERP, and p21(WAF1/CIP1)gene promoters containing a cytosine at the ninth position and lower transcription of GADD45 gene promoter containing a thymine at the ninth position compared to wild-type p53. Cell cycle analysis showed that A276S maintained similar G1/G0 phase arrest as wild-type p53. Additionally, A276S induced higher apoptosis than wild-type p53 as measured by DNA segmentation and 7-AAD assay. Since the status of endogenous p53 can influence the activity of the exogenous p53, we examined the activity of A276S in HeLa cells (wild-type endogenous p53) in addition to T47D cells (mutated and mislocalized endogenous p53). The same apoptotic trend in both cell lines suggested A276S can induce cell death regardless of endogenous p53 status. Cell proliferation assay depicted that A276S efficiently reduced the viability of T47D cells more than wild-type p53 over time. We conclude that the predicted preferred binding of A276S to cytosine at the ninth position better transactivates a number of apoptotic gene promoters. Higher induction apoptosis than wild-type p53 makes A276S an attractive candidate for therapy to eradicate cancer.