Murine Model for Contact Sensitization

A method combining murine ear swelling and lymph node cell proliferation was evaluated as a quantitative measurement of delayed-contact sensitization. The method involves one and/or four occluded, abdominal induction applications; use of pertussis toxin as an adjuvant; topical challenge to the ear; baseline and postchallenge ear measurements; and measurement of ¹²⁵I incorporation in axillary lymph nodes after injection of 5-[¹²⁵I]iodo-2'-deoxyuridine ([¹²⁵I]UdR). The inclusion of vehicle-induced/test chemical-challenged control groups permits objective recognition of positive responses by statistical analysis. This model—intended for use in screening for the sensitization potential of topical therapeutics—was evaluated with the known sensitizers tetracaine, naloxone, and oxazolone and with the irritant sodium dodecyl sulfate. Axillary lymph node cell proliferation measured by ¹²⁵I incorporation was a more sensitive measurement of contact sensitization than ear swelling. It was essential to perform both one and four inductions because tetracaine gave the greatest lymph node response after one induction, whereas naloxone produced a sensitization response only after four inductions. Ear swelling response to tetracaine increased after four inductions; however, ear swelling response was not observed after either one or four inductions of naloxone. After one or four inductions of the strong sensitizer, oxazolone, lymph node and ear swelling responses were observed. As expected, no significant ear swelling or lymph node response to sodium dodecyl sulfate was observed after one or four inductions. This method allows quantitative evaluation of contact sensitization by two separate measurements, thereby increasing the potential of identifying sensitizers missed by other methods.     

Measurement of lymph node function from the extraction of immunoglobulin in lymph

Abstract

Background. We aimed to measure the extraction fraction of human immunoglobulin G (HIG) by the 1st echelon lymph node (sentinel node) following intradermal injection in patients with breast cancer undergoing axillary lymph node dissection (ALND) and examine its association with node size and presence and extent of nodal metastatic disease. Materials and methods. HIG labelled with either In-111 (n = 21) or Tc-99m (n = 9) was injected intradermally at the areolar. ALND was performed 2–4 h later. All lymph nodes were isolated and individually counted in a well-counter. The counts in the ‘hottest’ (1st echelon) node were expressed as a fraction of total counts in all the resected nodes. Since counts in the least hot nodes barely exceeded background, this fraction represents extraction fraction for the 1st echelon node. Presence of disease was noted in each 1st echelon node and the extent quantified as percentage replacement with disease. Results. Median extraction fraction in 1st echelon nodes with no or low (<1%) disease burden (n = 21) was 68 (range 23–93)%, significantly higher (p<0.05) than in diseased 1st echelon nodes (n = 9), in which it was 44 (21–66)%. There was, however, no association between extraction fraction in diseased nodes and disease extent. In nodes with no/low disease, extraction fraction was similar for the two radiolabels. There was no association between extraction fraction and node size. Conclusion. Nodal extraction fraction of HIG is a novel physiological measurement. It is reduced as a result of metastatic invasion. In the absence of disease, it shows no correlation with node size.     

Epstein–Barr virus positivity among surgically resected intramucosal gastric cancer

Epstein–Barr virus‐associated gastric cancer (EBV‐GC) accounts for approximately 8% of gastric cancers. However, little is known regarding intramucosal EBV‐GC. The present study aimed to evaluate endoscopic and clinicopathological characteristics of intramucosal EBV‐GC. Pathological data of 172 patients with 173 intramucosal gastric cancers who received gastrectomy with lymph node dissection were obtained for review. EBV‐encoded small RNA in situ hybridization (EBER‐ISH) was carried out using a tissue microarray block. Eight intramucosal early gastric cancers (4.6%) were EBER‐ISH positive in which no cases had any lymph node metastasis. Macroscopic types were either depressed or flat, dominant histology was mixed type of moderate and poorly differentiated adenocarcinoma. In detail, histological features of “lace pattern” or “lymphocyte infiltration into the stroma or cancer nests” were observed.     

Acyl-CoA thioesterase 8 is a specific protein related to nodal metastasis and prognosis of lung adenocarcinoma

Metastasis is a major cause of cancer recurrence or death. This study attempted to quantitatively identify different proteins in metastatic lung adenocarcinoma. The N/T quotient [number of metastatic lymph nodes (n)/tumor diameter (cm)] was used to select samples with an extreme metastatic phenotype. Among the six fresh frozen lung adenocarcinoma specimens, the three showing the highest N/T quotient represented the metastatic group, and others with the greatest tumor diameters without metastasis represented the non-metastatic group. After 2-dimensional electrophoresis, the significantly different protein spots were selected by image analysis and analyzed with MALDI-TOF mass spectrometry. Acyl-CoA thioesterase 8 isoform c (ACOT8) was one of most overexpressed proteins in the metastatic group, and it was validated by Western blot and immunohistochemical staining on 108 paraffin-embedded tumor samples. High ACOT8 expression was correlated with lymph node metastasis (p = 0.002), recurrence (p = 0.034), predominant histologic subtypes (p = 0.007), and higher stage (p = 0.005). In multivariate analysis, high ACOT8 expression was significantly associated with increased risks of lymph node metastasis (p = 0.009) and cancer-related death (p = 0.030), independent of clinical factors. ACOT8 may be a candidate prognostic biomarker and therapeutic target of lung adenocarcinoma.