The Clinical and Molecular Spectrum of Trichorhinophalangeal Syndrome Types I and II in a Turkish Cohort Involving 22 Patients.

OBJECTIVE: Trichorhinophalangeal syndrome is a rare autosomal dominant disorder characterized by distinctive craniofacial and skeletal abnormalities. This study aimed to delineate the trichorhinophalangeal syndrome phenotype and to compare the clinical and molecular findings between trichorhinophalangeal syndrome types I and II. MATERIALS AND METHODS: A total of 22 trichorhinophalangeal syndrome patients aged 0.9-45 years from 17 families were enrolled. Nineteen patients were diagnosed with trichorhin ophalangeal syndrome I and 3 with trichorhinophalangeal syndrome II. Genetic analyses were made by TRPS1 sequencing and/or chromosomal microarray analyses. RESULTS: A novel frameshift variant (c.531_532del), a known missense variant, and whole-gene deletions were the pathogenic TRPS1 variants detected in trichorhinophalangeal syndrome I. Three trichorhinophalangeal syndrome II patients had large deletions with variable breakpoints involving the TRPS1-EXT1 interval. All patients had the typical craniofacial findings of trichorhinophalangeal syndrome such as a pear-shaped nose, long philtrum, and thin upper lip, as well as cone-shaped epiphyses. Sparse hair and eyebrows (20/22), short metacarpals and metatarsals (20/22), and small hands (19/22) were common. While craniofacial and limb abnormalities were similar in trichorhinophalangeal syndrome I and II, 3 of 19 trichorhinophal angeal syndrome I patients had mild, and 2 of 3 trichorhinophalangeal syndrome II patients had severe intellectual disability. Three trichorhinophalangeal syndrome II patients including the patient with the EXT1 deletion beginning from exon 2 had exostoses. In trichorhinophal angeal syndrome II, although microdeletion sizes and facial or skeletal features were not correlated, patients with larger deletions had severe intellectual disability. CONCLUSION: This study has expanded the existing knowledge on the phenotype-genotype spectrum in trichorhinophalangeal syndrome. We suggest including the EXT1 gene partially in the minimal critical region for trichorhinophalangeal syndrome II.

Tumor-selective new piperazine-fragmented silicon phthalocyanines initiate cell death in breast cancer cell lines.

A new silicon phthalocyanine with piperazine-furan ring and its quaternized form were synthesized. All compounds were analyzed by spectroscopic techniques (FT-IR, 1H-NMR, MS, and UV-vis), and the absorbance characteristics of silicon phthalocyanines were evaluated with the expected strong typical absorption bands in the far-red spectrum. The cytotoxic effects of these phthalocyanines induced by photodynamic therapy (PDT) were determined in a dose-dependent manner. Following cytotoxicity analysis, flow cytometric research of cell death was performed. The formation of reactive oxygen species (ROS) was determined by confocal microscopy. High levels of cytotoxicity and decreased viable cell population have been detected in cancer cells after treatment. In addition, ROS formation was observed in PDT treated cancer cells. However, low levels of cell death and ROS formation were observed in non-tumorigenic cells. According to western blot data, PDT-mediated treatment was found to provide different expression patterns of the cleaved PARP1 protein. The presented study demonstrates that PDT-mediated treatment of newly synthesized phthalocyanines has significant anti-cancer effects on breast cancer cells and may induce different cell death pathways.

Caffeic acid phenethyl ester induces apoptosis in colorectal cancer cells via inhibition of survivin.

Colorectal cancer is one of the most common types of cancer. Drug resistance and drug-induced damage of healthy tissues are major obstacles in cancer treatment. Therefore, to develop efficient anticancer therapy, it is necessary to find compounds that affect tumor cells, but do not exhibit toxicity to healthy cells. Caffeic acid phenethyl ester (CAPE) has been demonstrated to have anticancer properties in many types of cancer. In this study, the cytotoxic and apoptotic effects of CAPE on the RKO colorectal cancer cell line and CCD 841-CoN normal colorectal cell line was investigated. In addition, changes in the survivin expression were determined. According to the results, CAPE decreased cell viability in the RKO cell line in a dose-dependent manner. Likewise, CAPE induced apoptotic cell death in approximately 40% of the RKO cells. Furthermore, CAPE treatment increased the Serine 15 (Ser15) and Serine 46 (Ser46) phosphorylation of p53, while decreased the survivin expression. The results suggested that CAPE induced apoptosis by regulating p53 phosphorylation, leading to inhibition of the survivin expression. In accordance with the results, it is suggested that CAPE might be evaluated as an alternative drug in cancer therapy and further investigation is needed within this scope.