Direct activation of HSF1 by macromolecular crowding and misfolded proteins.

Stress responses play a vital role in cellular survival against environmental challenges, often exploited by cancer cells to proliferate, counteract genomic instability, and resist therapeutic stress. Heat shock factor protein 1 (HSF1), a central transcription factor in stress response pathways, exhibits markedly elevated activity in cancer. Despite extensive research into the transcriptional role of HSF1, the mechanisms underlying its activation remain elusive.

RNA-related DNA damage and repair: The role of N7-methylguanosine in the cell nucleus exposed to UV light.

Background: Chemical modifications in mRNAs, tRNAs, rRNAs, and non-coding RNAs stabilize these nucleic acids and regulate their function. In addition to regulating the translation of genetic information from mRNA to proteins, it has been revealed that modifications in RNAs regulate repair processes in the genome.

Methods: Using local laser microirradiation, confocal microscopy, dot blots, and mass spectrometry we studied the role of N7-methylguanosine (m7G), which is co-transcriptionally installed in RNA.

Small change - big consequence: The impact of C15-C16 double bond in a D‑ring of estrone on estrogen receptor activity.

Estrogen receptor alpha (ER) is a key biomarker for breast cancer, and the presence or absence of ER in breast and other hormone-dependent cancers decides treatment regimens and patient prognosis. ER is activated after ligand binding - typically by steroid. 2682 steroid compounds were used in a molecular docking study to identify novel ligands for ER and to predict compounds that may show anticancer activity.

DNA Demethylation Switches Oncogenic ΔNp63 to Tumor Suppressive TAp63 in Squamous Cell Carcinoma.

The gene encodes two major protein variants; TAp63 contains a p53-like transcription domain and consequently has tumor suppressor activities whereas ΔNp63 lacks this domain and acts as an oncogene. The two variants show distinct expression patterns in normal tissues and tumors, with lymphocytes and lymphomas/leukemias expressing TAp63, and basal epithelial cells and some carcinomas expressing high levels of ΔNp63, most notably squamous cell carcinomas (SCC). Whilst the transcriptional functions of TAp63 and ΔNp63 isoforms are known, the mechanisms involved in their regulation are poorly understood.

p53 Binds Preferentially to Non-B DNA Structures Formed by the Pyrimidine-Rich Strands of GAA·TTC Trinucleotide Repeats Associated with Friedreich's Ataxia.

Expansions of trinucleotide repeats (TNRs) are associated with genetic disorders such as Friedreich's ataxia. The tumor suppressor p53 is a central regulator of cell fate in response to different types of insults. Sequence and structure-selective modes of DNA recognition are among the main attributes of p53 protein.

p53 Specifically Binds Triplex DNA In Vitro and in Cells.

Triplex DNA is implicated in a wide range of biological activities, including regulation of gene expression and genomic instability leading to cancer. The tumor suppressor p53 is a central regulator of cell fate in response to different type of insults. Sequence and structure specific modes of DNA recognition are core attributes of the p53 protein.

Impact of cadmium, cobalt and nickel on sequence-specific DNA binding of p63 and p73 in vitro and in cells.

Site-specific DNA recognition and binding activity belong to common attributes of all three members of tumor suppressor p53 family proteins: p53, p63 and p73. It was previously shown that heavy metals can affect p53 conformation, sequence-specific binding and suppress p53 response to DNA damage. Here we report for the first time that cadmium, nickel and cobalt, which have already been shown to disturb various DNA repair mechanisms, can also influence p63 and p73 sequence-specific DNA binding activity and transactivation of p53 family target genes.

Redox state of p63 and p73 core domains regulates sequence-specific DNA binding.

Cysteine oxidation and covalent modification of redox sensitive transcription factors including p53 are known, among others, as important events in cell response to oxidative stress. All p53 family proteins p53, p63 and p73 act as stress-responsive transcription factors. Oxidation of p53 central DNA binding domain destroys its structure and abolishes its sequence-specific binding by affecting zinc ion coordination at the protein-DNA interface.

[Comparison of two surgical methods for treatment of idiopathic thoracic scoliosis - anterior versus posterior approaches].

Purpose Of The Study: The aim of this retrospective randomised study is a comparison of two surgical approaches (anterior versus posterior) for the treatment of idiopathic thoracic scoliosis by corrective spondylodesis with segmental instrumentation in adolescents aged 13 to 20 years.

Material And Methods: The study included patients with right-sided idiopathic thoracic scoliosis (Cobb's angle, 40°-70°; Lenke type I). The group of patients treated from the posterior approach by fusion and segmental instrumentation, involving the use of a hybrid, tworod system or screws only, comprised 31 girls with an average age of 14.

Modulation of gene expression in U251 glioblastoma cells by binding of mutant p53 R273H to intronic and intergenic sequences.

Missense point mutations in the TP53 gene are frequent genetic alterations in human tumor tissue and cell lines derived thereof. Mutant p53 (mutp53) proteins have lost sequence-specific DNA binding, but have retained the ability to interact in a structure-selective manner with non-B DNA and to act as regulators of transcription. To identify functional binding sites of mutp53, we established a small library of genomic sequences bound by p53(R273H) in U251 human glioblastoma cells using chromatin immunoprecipitation (ChIP).

[Simple bony fusion or instrumented hemivertebra excision in the surgical treatment of congenital scoliosis].

Purpose Of The Study: In a retrospective study, to analyze long-term radiographic results of two surgical procedures used to treat congenital scoliosis.

Material And Methods: A total of 685 patients with congenital scoliosis were treated at the Department of Orthopaedic Surgery, Bohunice Teaching Hospital in Brno, between 1976 and 2007. Of these, 102 patients, with an average age of 6.

Growing clinical evidence for the interaction of the p53 genotype and response to induction chemotherapy in advanced non-small cell lung cancer.

Objective: The objective of this study is to establish clinical evidence that the p53 genotype can serve as a predictive marker for response to cisplatin-based induction therapy.

Methods: Patients with advanced non-small cell lung cancer who had received neoadjuvant chemotherapy in the context of a prospective phase II trial were analyzed for the p53 genotype of their tumors. Response to induction therapy was then correlated to the p53 genotype as assessed by complete direct DNA sequencing.

[Neuromuscular deformity of the pelvis and its surgical treatment].

Purpose Of The Study: To evaluate the efficacy of surgical treatment in pelvic deformities associated with neuromuscular spine deformity, using radiographic parameters and clinical outcome analysis. In the lumbo-pelvic region, spinal deformity is most frequently combined with pelvic obliquity, lumbar hyperlordosis, hip deformity and leg-length discrepancy. Pelvic deformities include an excessive posterior or anterior pelvic tilt, obliquity or rotation and windblown hip syndrome.

[Surgical options in the treatment of myeloma of the spine].

Myeloma of the spine seriously affects the stability of the spine and can lead to compression of nerve structures. Instability of the spine caused by pathological vertebral fracture without compression of the nerve structures can be addressed conservatively using an external orthesis. Surgery is indicated in patients whose survival prognosis is 3-6 months in a situation of existing or imminent spinal collapse or nerve damage.

Performance characteristics of seven neuron-specific enolase assays.

Background/aims: The determination of neuron-specific enolase (NSE) is relatively frequently requested in the differential diagnosis of small-cell lung carcinoma and non-small-cell lung carcinoma. The individual results of different immunoassays are often not comparable, which has been confirmed by long-term external quality assessments. In this study, we assessed the possible sources of these differences.

[Radical surgery in tumors of the thoraco-lumbar spine].

Purpose Of The Study: In this retrospective study, the outcomes of anterior and posterior approaches, performed either simultaneously or consecutively, in the radical surgical treatment of tumors of the thoracolumbar spine were compared in terms of surgery duration, intra-operative blood loss, neurological findings and complications.

Material: A total of 547 patients with malignant tumors of the spine were treated between 1981 and 2001. Of these, the thoracolumbar spine was affected in 422 cases.

[Replacement of the vertebral body with an expansion implant (Synex)].

Purpose Of The Study: This paper describes replacement of the vertebral body with the expansion implant Synex. Usually, autologous bone graft is used to replace the vertebral body. In patients with bone cancer or multiple injuries to the spine, cement filling is preferred whereas, in other indicated cases, implants are inserted, of which Harms' titanium cage has been the most common one.

[The action of cisplatin on the developing meso- and metanephros of chick embryos].

Injection of various doses of cisplatin to 2-14-day chick embryos showed that within 2-8 days of incubation cisplatin produces total toxic effect, the number of dead embryos being dependent on a dose of the drug. Within 9-16 days of incubation, i.e.