Inactivation of the p16 gene by hypermethylation and loss of heterozygosity in adenocarcinoma of the lung

We investigated the aberrant promoter hypermethylation of p16, p15 and p14 genes and loss of heterozygosity (LOH) at 9p21-22 in 48 cases of adenocarcinoma of the lung. The frequencies of hypermethylation of genes were as follows: p16, 25.0%; p15, 22.9%; and p14, 18.8%. The frequency of LOH at chromosome 9p21-22 was 60.9%. The frequency of two-hit inactivation of the p16 gene by hypermethylation and LOH was 21.7%. Two-hit inactivation of the p16 gene showed loss of protein expression and was significantly correlated with tumor size, tumor grade and the Ki-67 labeling index. Hypermethylation of the p16 gene was not significantly correlated with hypermethylation of the p15 and p14 genes, both of which are close to the p16 gene locus, suggesting that hypermethylation of these genes occurs selectivity. In conclusion, biallelic inactivation of the p16 gene by hypermethylation and LOH might cause loss of p16 expression and play an important role in the development of adenocarcinoma of the lung. Therefore, controlling and monitoring for hypermethylation of the p16 gene may be partially useful for treatment and early diagnosis of adenocarcinoma of the lung.     

Effects of endurance training on myosin heavy-chain isoforms and enzyme activity in the rat diaphragm

We investigated the effects of endurance training (20 m/min, 60 min/day, 5 days/week) on myosin heavy-chain (MHC) isoforms and succinic dehydrogenase (SDH) activity in rat crural and costal diaphragms, and plantaris muscles. Although the 4-week endurance training produced significant (P<0.05) increases, both in SDH activity and the percentage of isoform HCIIa in the plantaris of the trained rat compared with the sedentary control rat, these alterations did not occur in either the crural or costal diaphragms. After 10 weeks of endurance training, trained animals had significantly (P<0.05) higher SDH activity in the costal diaphragm and the plantaris. Moreover, a significant (P<0.05) decrease occurred in the percentage of HCIIb in the costal diaphragm, and a significant (P<0.01) decrease in the percentage of HCIIb concomitant with a significant (P<0.05) increase of HCIIa resulted in the plantaris. However, the crural diaphragm did not show any significant changes after 10 weeks of endurance training. These results indicate that endurance training induces an alteration in the expression of an MHC phenotype, in addition to causing an increase in oxidative enzyme activity. However, the alterations in response to endurance training are apparently not uniform, varying between regions and/or kinds of muscles.     

Diagnostic impact of monitoring transcranial motor-evoked potentials to prevent ischemic complications during endovascular treatment for intracranial aneurysms

Neurosurgical Review - The present study aimed to determine the incidence of intraprocedural motor-evoked potential (MEP) changes and to correlate them with intraprocedural ischemic complications...     

Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.     

A cost-minimization analysis of measures against metallic dental restorations for head and neck radiotherapy

The aim of this study was to compare the estimated public medical care cost of measures to address metallic dental restorations (MDRs) for head and neck radiotherapy using high-energy mega-voltage X-rays. This was considered a first step to clarify which MDR measure was more cost-effective. We estimated the medical care cost of radiotherapy for two representative MDR measures: (i) with MDR removal or (ii) without MDR removal (non-MDR removal) using magnetic resonance imaging and a spacer. A total of 5520 patients received head and neck radiation therapy in 2018. The mean number of MDRs per person was 4.1 dental crowns and 1.3 dental bridges. The mean cost per person was estimated to be 121 720 yen for MDR removal and 54 940 yen for non-MDR removal. Therefore, the difference in total public medical care cost between MDR removal and non-MDR removal was estimated to be 303 268 800 yen. Our results suggested that non-MDR removal would be more cost-effective than MDR removal for head and neck radiotherapy. In the future, a national survey and cost-effectiveness analysis via a multicenter study are necessary; these investigations should include various outcomes such as the rate of local control, status of oral mucositis, frequency of hospital visits and efforts of the medical professionals.     

Enflurane reduces the excitation and inhibition of dorsal horn WDR neuronal activity induced by BK injection in spinal cats

The effects of enflurane (0.5%, 1.5% and 2.5%) on the excitation and inhibition of dorsal horn wide dynamic range (WDR) neuronal activity induced by bradykinin (BK) injection was studied in spinal cats. Extracellular activity was recorded in the dorsal horn from single WDR neurons responding to noxious and non-noxious stimuli applied to the cutaneous receptive fields on the left hind paw foot pads of decerebrate, spinal cord transected (L_1–2) cats. When 10µg of BK was injected into the femoral artery ipsilateral to the recording site as the noxious test stimulus, 24 of 26 WDR neurons (92%) gave excitatory responses and 2 (8%) gave inhibitory resposes. On the other hand, when the injection of 10µg of BK into the femoral artery contralateral to the recording site was used as the noxious test stimulus, 7 of 12 WDR neurons (58%) gave inhibitory responses, 3 (25%) gave excitatory responses, and 2 (17%) showed no response. The excitatory neuronal activity in WDR neurons was not depressed by 0.5% or 1.5% enflurane but was depressed significantly by 2.5%. However, the inhibitory neuronal activity in WDR neurons was significantly depressed by 0.5%, 1.5% and 2.5% enflurane. We have found that enflurane reduces the excitation as well as the inhibition of dorsal horn WDR neuronal activity induced by BK injection. These results suggest that the reduction of excitatory and inhibitory responses produced by noxious stimulation is likely to be the fundamental basis of the enflurane-induced anesthetic state in terms of WDR neurons.(Nagasaka H, Nakajima T, Takano Y et al.: Enflurane reduces the excitation and inhibition of dosal horn WDR neuronal activity induced by BK injection in spinal cats. J Anesth 4: 102–109, 1990)     

Nondomain biopolymers: Flexible molecular strategies to acquire biological functions

A long-standing assumption in molecular biology posits that the conservation of protein and nucleic acid sequences emphasizes the functional significance of biomolecules. These conserved sequences fold into distinct secondary and tertiary structures, enable highly specific molecular interactions, and regulate complex yet organized molecular processes within living cells. However, recent evidence suggests that biomolecules can also function through primary sequence regions that lack conservation across species or gene families. These regions typically do not form rigid structures, and their inherent flexibility is critical for their functional roles. This review examines the emerging roles and molecular mechanisms of “nondomain biomolecules,” whose functions are not easily predicted due to the absence of conserved functional domains. We propose the hypothesis that both domain- and nondomain-type molecules work together to enable flexible and efficient molecular processes within the highly crowded intracellular environment.     

Ovarian tumor complicated by a colo-ovarian fistula

Although a fistula is a rare complication of ovarian tumor, we encountered four patients with cole-ovarian fistulas in three years. The first case was demonstrated by following barium enema by the extravasation of barium from the sigmoid colon, and by a gas-containing lesion in the tumor observed on computed tomography. Mature cystic teratoma was the pathological diagnosis in two cases. A mixed germ cell tumor and a serous cystadenoma of low malignant potential were diagnosed in the other two cases. The etiology and differential diagnosis of cole-ovarian fistula are reviewed.     

A case with breast cancer under the nipple who underwent breast conserving treatment

Although breast conserving treatment (BCT) has become the standard therapy for early breast cancer, breast removal is still recommended for patients with a tumor beneath the nipple or with Paget’s disease. We have employed transposition of a latissimus dorsi myocutaneous (LD-MC) flap after wide local excision of a tumor with the nipple-areola complex. A new nipple-areola complex was reconstructed on the LD-MC flap after breast irradiation. Utilizing reconstructive techniques, BCT will likely become the treatment of choice for more patients with early breast cancer.