Relationship between Dose Prescription Methods and Local Control Rate in Stereotactic Body Radiotherapy for Early Stage Non-Small-Cell Lung Cancer: Systematic Review and Meta-Analysis.

Variations in dose prescription methods in stereotactic body radiotherapy (SBRT) for early stage non-small-cell lung cancer (ES-NSCLC) make it difficult to properly compare the outcomes of published studies. We conducted a comprehensive search of the published literature to summarize the outcomes by discerning the relationship between local control (LC) and dose prescription sites. We systematically searched PubMed to identify observational studies reporting LC after SBRT for peripheral ES-NSCLC. The correlations between LC and four types of biologically effective doses (BED) were evaluated, which were calculated from nominal, central, and peripheral prescription points and, from those, the average BED. To evaluate information on SBRT for peripheral ES-NSCLC, 188 studies were analyzed. The number of relevant articles increased over time. The use of an inhomogeneity correction was mentioned in less than half of the articles, even among the most recent. To evaluate the relationship between the four BEDs and LC, 33 studies were analyzed. Univariate meta-regression revealed that only the central BED significantly correlated with the 3-year LC of SBRT for ES-NSCLC (p = 0.03). As a limitation, tumor volume, which might affect the results of this study, could not be considered due to a lack of data. In conclusion, the central dose prescription is appropriate for evaluating the correlation between the dose and LC of SBRT for ES-NSCLC. The standardization of SBRT dose prescriptions is desirable.

SMARCA4-deficient lung tumour that presented with haemoptysis and progressed rapidly.

The case of a heavy ex-smoking man in his early 70s who presented with haemoptysis and died following rapid progression is presented. The tumour excised by surgery was mostly composed of monotonous large rhabdoid cells showing prominent nucleoli and eosinophilic cytoplasm. On immunohistochemistry with SMARCA4 (BRG-1), the tumour cells showed significant loss of expression. The tumour was diagnosed as a SMARCA4-deficient thoracic sarcoma. This is a disease that progresses rapidly and has a poor prognosis. However, the search for specific treatments using synthetic lethality is underway. Clinical and pathological characteristics can be identified with examination of more cases, and when the tumour is suspected, it is necessary to actively perform immunohistochemical examination.

Inflammatory myofibroblastic tumors of the breast with simultaneous intracranial, lung, and pancreas involvement: ultrasonographic findings and a review of the literature.

We encountered a case of inflammatory myofibroblastic tumor (IMT) of the breast with simultaneous intracranial, lung, and pancreas involvement. Here, we present the clinical imaging results and report the significance of sonographic findings of breast IMT along with a review of the literature. A 16-year-old girl with a history of subarachnoidal hemorrhage was admitted to our hospital due to tonic-clonic seizure. Computed tomography (CT) and magnetic resonance imaging (MRI) showed multiple intracranial, lung, and pancreas mass lesions and a solitary mass lesion in the right breast. Breast ultrasonography showed a circumscribed oval-shaped hypoechoic mass with a central hyperechoic region. Power Doppler sonography revealed an unusual spiral-shaped flow signal. Breast tumorectomy was performed for definitive diagnosis, and pathological analysis indicated IMT. A literature review indicated that ultrasonographic findings of IMT of the breast are nonspecific, as in other systems or organs. It would be difficult to make a diagnosis of IMT of the breast preoperatively due to its rarity and the lack of specificity of clinical imaging findings. In addition, it is better to consider the possibility of IMT of the breast especially in younger patients without an obvious family history of hereditary breast cancer.

Paravertebral block for video-assisted thoracoscopic surgery: analgesic effectiveness and role in fast-track surgery.

BACKGROUND: Appropriate postoperative analgesia is crucial in fast-track surgery, which is a multimodal therapeutic strategy that aims toward enhanced postoperative recovery and shortened hospital stay. Paravertebral block (PVB) has been reported to be as effective as thoracic epidural blockade (TEB), but PVB is not often employed for video-assisted thoracoscopic surgery (VATS) for 2 reasons. First, TEB is still the gold standard for thoracic surgery, and second, thoracoscopic insertion of a PVB catheter is challenging. METHODS: In this retrospective observational study, 185 patients who underwent VATS and thoracoscopic paravertebral catheterization were analyzed. Postoperatively, the patients were continuously administered a local anesthetic (0.5% bupivacaine hydrochloride or 0.2% ropivacaine hydrochloride). Additionally, they were given an oral non-steroidal anti-inflammatory drug (NSAID) as needed. Intramuscular/intravenous pentazocine was administered as a rescue medication. The effect of pain control was measured in terms of the frequency of NSAID taken orally and the necessity for a rescue drug on postoperative days (POD) 0, 1, 2, and 3. RESULTS: The mean age of the 185 patients included in the study was 67 years (Confidence Interval: 66-69). The mean frequency of NSAID use was 0.67 (0-3), 1.59 (0-4), 1.43 (0-4), and 1.33 (0-4) on POD 0, 1, 2, and 3, respectively. 32 (17.3%) and 3 patients (1.6%) were administered a rescue medication on POD 0 and 1, respectively. The most common postoperative complication was nausea/vomiting, which occurred in 17 patients (9.1%). CONCLUSIONS: PVB may greatly contribute to enhanced recovery after thoracic surgery owing to effective analgesia and fewer side effects.

[Nutritional treatment for bronchopleural fistula-promising effect of arginine as a pharmaconutrient].

Pharmaconutrition, which is a supportive nutritional care of surgical patients, has been proven to shorten hospital stay, decrease the incidence of infection, and reduce hospital costs in selected groups of patients. Arginine, one of the most essential pharmaconutrients, has also been proven to enhance would healing process. In severely malnourished patients like bronchopleural fistula with resultant empyema, aggressive nutritional approach should be mandatory. And management of the fistula is also important in stabilizing the ongoing infection. Our hypothesis was that basic nutritional support enhanced with arginine would be effective in not only improving the general condition including nutritional status but also in healing the fistula. We report a case of major bronchopleural fistula in which arginine-supplemented diet as well as aggressive nutritional support could accelerate the postoperative recovery after open thoracic window, ultimately leading to the healing of the fistula.

Regulation of soybean seed germination through ethylene production in response to reactive oxygen species.

BACKGROUND AND AIMS: Despite their toxicity, reactive oxygen species (ROS) play important roles in plant cell signalling pathways, such as mediating responses to stress or infection and in programmed cell death, at lower levels. Although studies have indicated that hydrogen peroxide (H(2)O(2)) promotes seed germination of several plants such as Arabidopsis, barley, wheat, rice and sunflower, the role of H(2)O(2) in soybean seed germination is not well known. The aim of this study therefore was to investigate the relationships between ROS, plant hormones and soybean seed germination. METHODS: An examination was made of soybean seed germination, the expression of genes related to ethylene biosynthesis, endogenous ethylene contents, and the number and area of cells in the root tip, using N-acetylcysteine, an antioxidant, to counteract the effect of ROS. KEY RESULTS: H(2)O(2) promoted germination, which N-acetylcysteine suppressed, suggesting that ROS are involved in the regulation of soybean germination. H(2)O(2) was produced in the embryonic axis after imbibition. N-Acetylcysteine suppressed the expression of genes related to ethylene biosynthesis and the production of endogenous ethylene. Interestingly, ethephon, which is converted to ethylene, and H(2)O(2) reversed the suppression of seed germination by N-acetylcysteine. Furthermore, morphological analysis revealed that N-acetylcysteine suppressed cell elongation at the root tip, and this suppression was also reversed by ethephon or H(2)O(2) treatments, as was the case in germination. CONCLUSIONS: In soybean seeds, ROS produced in the embryonic axis after imbibition induce the production of endogenous ethylene, which promotes cell elongation in the root tip. This appears to be how ROS regulate soybean seed germination.

[Perioperative nutritional support with immune-enhancing diet for surgical closure of open thoracic window].

Immunonutrition, which is a therapeutic approach to modulate acute surgical or medical conditions, has been proven to decrease surgical site complications in patients undergoing major elective surgery for upper gastrointestinal and esophageal malignancy. For immunonutrition to be carried out effectively, specific nutrients called pharmaconutrients are quite important. In our case, to enhance the perioperative nutritional status of the patient, special formulas supplemented with specific pharmaconutrients, which are arginine and omega-3 fatty acids, were orally administered. The open thoracic window for chronic empyema caused by postoperative bronchopleural fistula was successfully closed. Perioperative immunonutrition is likely to have beneficial effect in decreasing postoperative infectious complications in high-risk malnourished thoracic surgical patients.

Efficient protein transduction method using cationic peptides and lipids.

Cationic peptides termed protein transduction domains (PTDs) have been shown to cross biological membranes efficiently. However, proteins transduced by PTDs become entrapped within the endosomal vesicles and are not delivered into organelles. We have developed a novel protein delivery system to enhance the proton sponge effect, which results in rupture of the endosomes, by using a mixture of Wr-T transporter peptide and a commercially available cationic lipid reagent. This peptide and cationic lipid reagent mixture efficiently delivers a variety of cargo proteins into living cells by releasing them from the endosomes.

The ethylene signal mediates induction of GmATG8i in soybean plants under starvation stress.

In higher plants, autophagy-related genes (ATGs) appear to play important roles in development, senescence, and starvation responses. Hormone signals underlying starvation-induced gene expression are involved in the expression of ATGs. An effect of starvation stress on the expression of ATGs and ethylene-related genes in young seedlings of soybean (Glycine max [L.] Merr. cv. Fukuyutaka) was analyzed. Reverse transcription-polymerase chain reaction (RT-PCR) showed that the expression levels of GmATG8i and GmATG4 increase in a starvation medium, but at a null or marginal level in a sucrose/nitrate-rich medium. The expression of GmACC synthase and GmERF are also upregulated in the starvation medium. In addition, immunoblot revealed that ethylene insensitive 3 (Ein3), an ethylene-induced transcription factor are accumulated in seedlings subjected to severe starvation stress. These results indicate that starvation stress stimulates the expression of GmATG8i and ethylene signal-related genes. Since the ethylene signal is involved in senescence and various environmental stresses, it is possible that starvation stress-induced autophagy is partly mediated by the ethylene signaling.

Diagnostic value of 18F-dihydroxyphenylalanine positron emission tomography for growth hormone-producing pituitary adenoma.

A 55-year-old woman with signs of acromegaly was referred to our hospital. Endocrinological examinations showed that she had high levels of growth hormone (GH; 5.54 ng ml(-1); normal range: 0.66-3.68 ng ml(-1)) and insulin-like growth factor-I (IGF-I; 508 ng ml(-1); normal range: 37-266 ng ml(-1)) levels, incomplete suppression of serum GH following a 75-gram oral glucose tolerance test (oGTT; trough GH 3.66 ng ml(-1)), and paradoxical GH responses to a TRH provocation test (peak GH 38.9 ng ml(-1)). Dynamic magnetic resonance imaging (MRI) suggested the presence of an intrasellar mass lesion (5.9 x 2.8 mm) in the left part of her pituitary gland (Fig. 1a, upper panel). F-18 fluorodeoxyglucose (FDG) positron emission tomographic (PET) imaging clearly showed focal but remarkable FDG uptake (Fig. 1a, lower panel), consistent with the localization of the tumor suspected on MRI. The tumor was removed by transsphenoidal surgery. Subsequent histological analysis confirmed the diagnosis of a GH-producing pituitary adenoma. After removal, serum IGF-I levels decreased to a normal range (178 ng ml(-1)), and serum GH was appropriately suppressed during oGTT (trough GH 0.30 ng ml(-1)), suggesting that complete resection was obtained [1]. While postsurgical changes made it difficult to detect any residual lesion on MRI (Fig. 1b, upper panel), abnormal FDG uptake was not seen on FDG-PET after surgery (Fig. 1b, lower panel). PET scans are reported to be a valuable tool for the detection of pituitary adenomas [2-4]. This case clearly showed that FDG-PET is also useful for re-evaluation of the disease after surgery. PET scans are recommended for patients with equivocal pituitary mass lesions on conventional MRI, and for follow-up examinations after surgery.

High glucose induces transactivation of the alpha2-HS glycoprotein gene through the ERK1/2 signaling pathway.

AIM: Alpha2-Heremans Schmid glycoprotein (AHSG), also known as fetuin-A, is secreted from the liver and inhibits tyrosine kinase activity of the insulin receptor. Hyperglycemia in type 2 diabetes is not only a secondary manifestation of insulin resistance, but could also be responsible for directly inducing insulin resistance in target tissues. In this study, we examined the effect of high glucose (HG) on AHSG gene transcription in the human hepatoma cell line HepG2. METHODS: AHSG transcriptional activity and protein expression were evaluated using reporter gene assays and Western blot analysis, respectively. RESULTS: D-glucose, but not L-glucose or mannitol, dose-dependently enhanced AHSG promoter activity. HG (25 mM) also increased AHSG protein expression. No protein kinase C inhibitors (bisindolylmaleimide, Ro-31-8220), an inhibitor of hexosamine biosynthesis pathway (6-diazo-5-oxo-L-norleucine), or a superoxide radical scavenger (tempol) affected HG-induced transactivation. MAPK/ERK kinase inhibitors (PD98059, U0126), but not the JNK inhibitor (SP600125) or p38 inhibitor (SB203580), significantly inhibited promoter activation by HG. CONCLUSION: Our data suggest that HG enhances AHSG transcription through activation of the ERK1/2 signaling pathway. Increased AHSG expression in the liver may be a cause of glucose toxicity in the diabetic state.

Pitavastatin induces PON1 expression through p44/42 mitogen-activated protein kinase signaling cascade in Huh7 cells.

It has been shown that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors have pleiotropic effects and that human serum paraoxonase (PON1) inhibits the oxidative modification of low-density lipoprotein. We investigated the effects of pitavastatin on PON1 gene promoter activity and PON1 protein expression through the activation of mitogen-activated protein (MAP) kinase signaling cascades in cultured Huh7 cells. Both PON1 gene promoter activity and PON1 protein expression were elevated by pitavastatin stimulation. Pitavastatin phosphorylated p44/42 MAP kinase. The effects of pitavastatin on PON1 promoter activity and PON1 protein expression were attenuated by PD98059. The cotransfection of Sp1 expression vector increased PON1 promoter activity, and mithramycin suppressed pitavastatin-enhanced PON1 promoter activity. The latter activity was attenuated by cotransfection with the expression vector of sterol regulatory element-binding protein-2 (SREBP-2) with mutated p44/42 MAP kinase specific phosphorylation sites. Pitavastatin increased the Sp1-PON1 DNA complex and this effect was attenuated by PD98059. These observations suggest that pitavastatin phosphorylates p44/42 MAP kinase and then activates the transcription of PON1 gene and increases the PON1 protein expression in Huh7 cells. Furthermore, we speculate that pitavastatin affects both the phosphorylation of SREBP-2 and the Sp1 binding to PON1 DNA through the activation of p44/42 MAP kinase signaling cascade.

A promoter polymorphism of the alpha2-HS glycoprotein gene is associated with its transcriptional activity.

alpha2-Heremans Schmid glycoprotein (AHSG), also designated fetuin-A, is an abundant plasma protein that is expressed in hepatocytes. AHSG/fetuin-A has diverse biological functions including regulation of calcium homeostasis and inhibition of insulin receptor tyrosine kinase activity. The aim of this study was to detect single nucleotide polymorphisms (SNPs) of the AHSG gene that can be involved in regulation of AHSG/fetuin-A expression. By a cycle sequencing method, two common SNPs in the promoter region of AHSG gene, -799A/T (rs2248690, dbSNP ID) and -425G/T (rs2077119), were identified. A reporter gene assay using HepG2 cells showed that the -799A allele had significantly higher promoter activity compared with the -799T allele. The overexpression of c-Fos/c-Jun significantly repressed transcriptional activity and a gel shift assay showed that the -799T DNA fragment had a greater affinity for transcription factor AP-1 than the -799A. In 40 unrelated healthy subjects, serum AHSG/fetuin-A levels increased with the following order of genotypes: -799TT<-799AT<-799AA (mean+/-S.E.M.; 222.1+/-11.0, 291.8+/-8.1, and 349.0+/-13.0 microg/ml, respectively, P<0.001). In conclusion, SNP rs2248690 in the promoter region of the AHSG gene affects the AHSG gene transcription, possibly by producing different association with AP-1.

Proinflammatory cytokines but not acute phase serum amyloid A or C-reactive protein, downregulate paraoxonase 1 (PON1) expression by HepG2 cells.

The expression of paraoxonase1 (PON1) during inflammation has been investigated in vitro. The alteration of steady state PON1 mRNA in HepG2 cells by interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), was investigated relative to acute-phase serum amyloid A (A-SAA) mRNA. PON1 mRNA expression by HepG2 cells was decreased within three hours of stimulation by IL-1beta or TNF-alpha. Relative to PON1 mRNA expression, the pattern of steady state A-SAA mRNA expression was altered reciprocally and inversely by IL-1beta. These findings suggested that the decrease in serum PON activity after abdominal surgery in our previous clinical study may be ascribed to a decrease in steady state PON1 mRNA expression by liver with proinflammatory cytokines.