Changes in programmed death ligand 1 expression in non-small cell lung cancer patients who received anticancer treatments

Background

The expression of programmed death ligand 1 (PD-L1) is considered a predictive biomarker of anti-programmed death 1 (PD-1)/PD-L1 cancer therapies. However, changes in PD-L1 expression of tumor cells during clinical courses have not been fully evaluated. We evaluated changes in PD-L1 expression for non-small cell lung cancer (NSCLC) patients who received anticancer treatments during clinical courses.

Methods

In 76 NSCLC patients, PD-L1 expression was evaluated before and after anticancer treatment by immunohistochemical (IHC) analysis using an anti-PD-L1 antibody. We defined two cut-off points of PD-L1 expression (1 and 50%) and three corresponding IHC groups (A: 0%, B: 1–49%, and C: ≥50%). IHC group B and C were considered to be positive expression, and we defined the difference of IHC group between pre- and post-treatment as ‘major change’ in PD-L1 expression.

Results

Before anticancer treatment, PD-L1 expression was observed in 38/76 (50%) patients, and was significantly less common in patients harboring mutations in the epidermal growth factor receptor gene (EGFR) than in those without (P?=?0.039). After anticancer treatment, PD-L1 expression was observed in 36/76 (47%) patients. Major increases in PD-L1 expression were seen in 11 (14%), and major decreases in 18 (24%) patients. Among 13 patients harboring EGFR mutations treated with EGFR tyrosine-kinase inhibitor (EGFR-TKI), five (38%) showed major increases.

Conclusion

Major changes of PD-L1 expression in tumor cells were observed in 38% of NSCLC patients who received anticancer treatments. And, treatments with EGFR-TKI may increase PD-L1 expression in NSCLC patients harboring EGFR mutations.

     

Pathology and images of radiation-induced hepatitis: a review article

Recent advances in highly conformal radiotherapies greatly extend the indications for radiotherapy of liver tumors. However, because of poor tolerance to hepatic radiation, estimation of the intensity of irradiation of the liver is important, particularly for a cirrhotic liver. Knowledge of radiation-induced hepatitis is important for understanding how to optimize hepatic radiation therapy. Pathological changes of the irradiated liver, which include perivenular fibrosis, sinusoidal obstruction, and damage to Kupffer cells and hepatocytes, can be visualized using clinical imaging techniques. This review article discusses and illustrates the pathological and radiological changes of hepatic tumors and the surrounding parenchyma of the irradiated liver.     

Rebiopsy for patients with non‐small‐cell lung cancer after epidermal growth factor receptor‐tyrosine kinase inhibitor failure

Although third‐generation epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKI) can overcome T790M‐mediated resistance in non‐small‐cell lung cancer (NSCLC), rebiopsy to confirm T790M status is occasionally difficult. We aimed to investigate the current tendency and the limitations of rebiopsy in clinical practice. This study included 139 consecutive NSCLC patients with EGFR mutations, who had experienced progressive disease (PD) after EGFR‐TKI treatment. We retrospectively reviewed patient characteristics, tumor progression sites and rebiopsy procedures. Of 120 patients (out of the original 139) who were eligible for clinical trials, 75 (63%) underwent rebiopsy for 30 pleural effusions, 32 thoracic lesions, four bone, two liver, and seven at other sites. Rebiopsy procedures included 30 thoracocentesis, 24 transbronchial biopsies, 13 computed tomography (CT)‐guided needle biopsies and 8 other procedures. Of the 75 rebiopsied patients, 71 (95%) were pathologically diagnosed with malignancy; and 34 (45%) had available tissue samples for EGFR analyses. Of the 75 biopsied patients, 61 (81%) were analyzed for EGFR mutation, using tissue or cytology samples; T790M mutations were identified in 20 (33%) of the 61 patients. Of the 120 patients, 45 (38%) did not undergo rebiopsy, because of inaccessible tumor sites (n = 19), patient refusal (n = 6) or decision of physician (n = 10). In conclusion, among patients with EGFR mutations who had PD after EGFR‐TKI treatment, 63% underwent rebiopsy. Most rebiopsy samples were diagnosed with malignancy. However, tissue samples were less available and T790M mutations were identified less frequently than in previous studies. Skill and experience with rebiopsy and noninvasive alternative methods will be increasingly important.     

Suppression of thyroid function during ingestion of seaweed "Kombu" (Laminaria japonoca) in normal Japanese adults

The effect of ingesting seaweed "Kombu" (Laminaria japonica) on thyroid function was studied in normal Japanese adults. Ingesting 15 and 30 g of Kombu (iodine contents: 35 and 70 mg) daily for a short term (7-10 days) significantly increased serum thyrotropin (TSH) concentrations, exceeding the normal limits in some subjects. The serum free thyroxine (FT(4)) and/or free 3,5,3'-triiodothyronine (FT(3)) concentrations were slightly decreased within the normal limits. During long term daily ingestion of 15 g of Kombu (55-87 days), the TSH levels were elevated and sustained while the FT(4) and FT(3) levels were almost unchanged. Urinary excretion of iodine significantly increased during ingestion of Kombu. These abnormal values returned to the initial levels 7 to 40 days after discontinuing the ingestion of Kombu. Based on these findings that thyroid function was suppressed during ingestion of Kombu, though the effect was reversible, we recommend Japanese people avoid ingesting excessive amounts of seaweed.     

Guadinomines, Type III secretion system inhibitors, produced by Streptomyces sp. K01-0509. II: physico-chemical properties and structure elucidation

The structures of guadinomines, new inhibitors of a bacterial Type III secretion system produced by Streptomyces sp. K01-0509, were elucidated by spectroscopic studies including various NMR experiments. Guadinomines A, B, C(1), C(2) and D consist of a carbamoylated cyclic guanidinyl moiety, an alkyl chain moiety and an L-Ala-L-Val moiety in common, while guadinomic acid is a smaller molecule consisting of a carbamoylated cyclic guanidinyl moiety and a hydroxyl hexanoate moiety.     

Misreporting of total energy intake in older men and women.

Misreporting of total energy intake occurs frequently in dietary studies. Relatively few studies have been performed in older individuals who may be vulnerable to obesity and its associated health risks. In the present study, we examined misreporting of total energy intake by comparing self-reported food intake, measured by 3-day food diaries, to energy expenditure, measured with the doubly labeled water technique, in a relatively large sample of older men (n = 39) and women (n = 43). An additional objective was to identify potential predictors of misreporting, including body composition, fitness as assessed by peak VO2, and sociodemographic characteristics such as gender, living arrangement, education, and income. In general, men and women underreported total energy intake. The magnitude of the underreporting, as measured by percent difference between reported intake and measured total energy expenditure, was comparable between the sexes. Body mass index, waist circumference, and fat mass were significant correlates of underreporting of total energy intake, with heavier individuals underreporting more than leaner individuals. Among the demographic variables, living arrangement was a significant determinant of misreporting of total energy intake in older people. Individuals in marriage-like living arrangements underreported their total energy intake to a greater extent than married individuals. However, the magnitude of misreporting by those living alone did not differ from that of married individuals. The results of the present study highlight the need to examine misreporting of total energy intake in older individuals, who are more prone to obesity and its health risks.     

The utility of total lipid core burden index/maximal lipid core burden index ratio within the culprit plaque to predict filter-no reflow: insight from near-infrared spectroscopy with intravascular ultrasound

Filter-no reflow (FNR) is a phenomenon wherein flow improves after the retrieve of distal protection. Near-infrared spectroscopy with intravascular ultrasound (NIRS–IVUS) enables lipid detection. We evaluated the predictors of FNR during PCI using NIRS–IVUS. Thirty-two patients who underwent PCI using the Filtrap® for acute coronary syndrome (ACS) were enrolled. The culprit plaque (CP) was observed using NIRS–IVUS. Total lipid-core burden index (T-LCBI) and maximal LCBI over any 4-mm segment (max-LCBI4mm) within CP were evaluated. T-LCBI/max–LCBI4mm ratio within CP was calculated as an index of the extent of longitudinal lipid expansion. The attenuation grade (AG) and remodeling index (RI) in CP were analyzed. AG was scored based on the extent of attenuation occupying the number of quadrants. The patients were divided into FNR group (N?=?8) and no-FNR group (N?=?24). AG was significantly higher in FNR group than in no-FNR group (1.6?±?0.6 vs. 0.9?±?0.42, p?=?0.01). RI in FNR group tended to be greater than in no-FNR group. T-LCBI/max–LCBI4mm ratio within the culprit plaque was significantly higher in FNR group than in no-FNR group (0.50?±?0.10 vs. 0.33?±?0.13, p?<?0.01). In multivariate logistic regression analysis, AG?>?1.04 (odds ratio [OR] 18.4, 95% confidence interval [CI] 1.5–215.7, p?=?0.02) and T-LCBI/max–LCBI4mm ratio?>?0.42 (OR 14.4, 95% CI 1.2–176.8, p?=?0.03) were independent predictors for the occurrence of FNR. The use of T-LCBI/max–LCBI4mm ratio within CP might be an effective marker to predict FNR during PCI in patients with ACS.     

Flexivirga alba gen. nov., sp. nov., an actinobacterial taxon in the family Dermacoccaceae

A novel actinobacterial strain ST13(T) isolated from soil near wastewater treatment facilities of an electroplating plant was subjected to a polyphasic taxonomic study. Cells of this organism were non-sporulating, and were irregular coccoid to comma shaped. The peptidoglycan of strain ST13(T) contained glutamic acid, serine, alanine, glycine and lysine, and represented the peptidoglycan type A4α. The whole-cell sugars contained ribose, glucose, galactose, rhamnose and mannose. The predominant menaquinone was MK-8(H(4)). The major fatty acid was iso-C(16:0). The polar lipid contained phosphatidylglycerol. The DNA G+C content was 67.4 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain ST13(T) fell within the radius of the family Dermacoccaceae, and its closest neighbor was Luteipulveratus mongoliensis MN07-A0370(T) (95.1%). However, strain ST13(T) did not make a coherent clade with members of the recognized organisms. On the basis of the phylogenetic and phenotypic characteristics of this actinobacterium, a novel genus and species, Flexivirga alba gen. nov., sp. nov., is proposed. The type strain of F. alba is ST13(T) (= NBRC 107580(T) = DSM 24460(T)).