Inhibition of the ATR kinase enhances 5-FU sensitivity independently of nonhomologous end-joining and homologous recombination repair pathways.

The anticancer agent 5-fluorouracil (5-FU) is cytotoxic and often used to treat various cancers. 5-FU is thought to inhibit the enzyme thymidylate synthase, which plays a role in nucleotide synthesis and has been found to induce single- and double-strand DNA breaks. ATR Ser/Thr kinase (ATR) is a principal kinase in the DNA damage response and is activated in response to UV- and chemotherapeutic drug-induced DNA replication stress, but its role in cellular responses to 5-FU is unclear.

BRCA2 protects mammalian cells from heat shock.

Purpose: Heat shock induces DNA double-strand breaks (DSBs) in mammalian cells. Mammalian cells are capable of repairing DSBs by utilising the homologous recombination (HR) pathway. Breast cancer susceptibility gene 2 (BRCA2) is known to regulate the HR pathway.

Homologous recombination preferentially repairs heat-induced DNA double-strand breaks in mammalian cells.

Purpose: Heat shock induces DNA double-strand breaks (DSBs), but the precise mechanism of repairing heat-induced damage is unclear. Here, we investigated the DNA repair pathways involved in cell death induced by heat shock.

Materials And Methods: B02, a specific inhibitor of human RAD51 (homologous recombination; HR), and NU7026, a specific inhibitor of DNA-PK (non-homologous end-joining; NHEJ), were used for survival assays of human cancer cell lines with different p53-gene status.

The BRCA2 gene is a potential molecular target during 5-fluorouracil therapy in human oral cancer cells.

5-Fluorouracil (5-FU) is widely used in clinical cancer therapy. It is commonly used either alone or in combination with other drugs and/or radiation for head and neck, and other types of cancers. 5-FU induces DNA double-strand breaks (DSBs).

Depression of p53-independent Akt survival signals in human oral cancer cells bearing mutated p53 gene after exposure to high-LET radiation.

Although mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status in cancer cells. Recently, it has been suggested that the induction of p53-independent apoptosis takes place through the activation of Caspase-9 which results in the cleavage of Caspase-3 and poly (ADP-ribose) polymerase (PARP). This study was designed to examine if high-LET radiation depresses serine/threonine protein kinase B (PKB, also known as Akt) and Akt-related proteins.

Disk position and temporomandibular joint structure associated with mandibular setback in mandibular asymmetry patients.

Objective: To determine the changes in articular disk position and the temporomandibular joint (TMJ) structure in patients who had an asymmetric setback of the mandible performed by a bilateral sagittal split ramus osteotomy with manual positioning of the condyle.

Materials And Methods: Twenty-two patients with skeletal Class III malocclusion being treated at Nara Medical University Hospital were evaluated using clinical examination and pre- and postoperative magnetic resonance images of their TMJs.

Results: Changes in articular disk position after asymmetric setback surgery were not statistically significant, although a tendency of anterior displacement in the fossa was noted.

Protein microarray analysis of apoptosis-related protein expression following heat shock in human tongue squamous cell carcinomas containing different p53 phenotypes.

Purpose: Hyperthermia is useful in the treatment of human head and neck cancers, because it is relatively easy to regulate temperatures when compared to tumors located in deep organs. In this study, attention was focused on p53 as a possible predictive indicator for the efficacy of hyperthermic cancer therapy.

Methods: Two kinds of cell lines were used.

[Clinical trial of chemotherapy by superselective intra-arterial infusion of nedaplatin (CDGP) and 5-FU with concurrent radiotherapy for advanced oral cancer].

Nedaplatin (CDGP) is one of the platinum-derivatives to further improve the anti-tumor effect and to reduce adverse effects of cisplatin, such as renal toxicity. The present study evaluated the efficacy and adverse events of chemotherapy by superselective intra-arterial infusion of CDGP and 5-FU combined with concurrent radiotherapy in patients with advanced squamous cell carcinoma of the oral cavity. Sixteen patients were treated with CDGP plus 5-FU in combination with concurrent irradiation of 40.

[Anesthetic management of a patient with congenital plasminogen activator inhibitor-1 deficiency].

Congenital plasminogen activator inhibitor-1 (PAI-1) deficiency is an extremely rare disorder characterized by a bleeding diathesis due to hyperfibrinolysis as a result of decreased PAI-1 activity. A 21-year-old male with congenital PAI-1 deficiency underwent wisdom teeth extraction of the mandible under general anesthesia using propofol, nitrous oxide, sevoflurane, fentanyl, and vecuronium. No complications including prolonged bleeding and rebleeding after the operation were observed because hemostatic management was successful by using intravenous tranexamic acid.