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"Lee, A H"
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The prognostic significance of B lymphocytes in invasive carcinoma of the breast
Although the favourable role of T lymphocyte populations in different tumour types is established, that of B cells is still a matter of debate and needs further clarification. The presence of tumour-infiltrating B cells may represent an antibody response against breast tumour antigens. We used immunohistochemistry to investigate the density and localisation of B lymphocytes infiltrating 1470 breast tumours and to identify any prognostic significance and relationship to various clinicopathological factors. Higher numbers of CD20
+
cells were found in the stroma away from the carcinoma (mean 12 cells) compared with either intratumoural or adjacent stromal compartments (mean 1 cell). The majority of tumours showed a diffuse pattern of B cells rather than aggregates. There was a positive correlation between higher numbers of total CD20
+
B cells and higher tumour grade (
r
s
= 0.20,
P
< 0.001), ER and PgR negativity (
P
< 0.001), and basal phenotype (
P
< 0.001) subclass. In univariate survival analysis, higher total number of infiltrating CD20
+
cells, irrespective of location, was associated with significantly better BCSS (
P
= 0.037) and longer DFI (
P
= 0.001). In multivariate analysis, total CD20
+
B cell count (HR = 0.75, 95% CI = 0.58–0.96 for BCSS and HR = 0.72, 95% CI = 0.58–0.89, for DFI), tumour size, nodal stage, grade, vascular invasion, HER-2 status, and total CD8
+
T cell count were independently associated with outcome. This suggests that humoral immunity, in addition to the cell mediated immunity, may be important in breast cancer. This should be considered in breast cancer immunotherapy and vaccine strategies.
Journal Article
Tumour-infiltrating macrophages and clinical outcome in breast cancer
BackgroundMacrophages constitute a major component of the leucocytic infiltrate of tumours. Human studies show an association between tumour-associated macrophages and tumours with poor prognostic features. In breast cancer, the presence of macrophages has been correlated with increased angiogenesis and poor prognosis but little information is available about the independent prognostic role of macrophages infiltrating breast carcinomas.Aims and methodsThis study used immunohistochemistry and tissue microarrays to assess the density and localisation of CD68 macrophages infiltrating 1322 breast tumours and to identify any relationship with clinicopathological factors and patient outcome.ResultsTumour-infiltrating macrophages were present in the majority of tumours with a predominantly diffuse pattern. The density of distant stromal macrophages (infiltrating stroma away from the carcinoma, median count 14 cells) was higher than intratumoural (median zero cells) and adjacent stromal macrophages (median three cells). Higher total macrophage number was associated with higher tumour grade (rs=0.39, p<0.001), ER and PgR negativity, HER-2 positivity and basal phenotype (p<0.001). In univariate survival analysis, higher numbers of CD68 macrophages were significantly associated with worse breast cancer-specific survival (p<0.001) and shorter disease-free interval (p=0.004). However in multivariate model analysis, the CD68 macrophage count was not an independent prognostic marker.ConclusionsMacrophages are heterogeneous with different subsets having different functions. The present study suggests that overall macrophage numbers are not related to prognosis in breast cancer. However, further studies are needed to investigate the potential role of different subsets of macrophages.
Journal Article
Soyfood and isoflavone intake and risk of type 2 diabetes in Vietnamese adults
Background/Objectives:
Animal studies have demonstrated that soy isoflavones exert antidiabetic effects. However, evidence regarding the association between soyfood intake, a unique source of isoflavones, and type 2 diabetes remains inconclusive. This study assessed the relationship between habitual intakes of soyfoods and major isoflavones and risk of type 2 diabetes in Vietnamese adults.
Subjects/Methods:
A hospital-based case-control study was conducted in Vietnam during 2013–2015. A total of 599 newly diagnosed diabetic cases (age 40–65 years) and 599 hospital-based controls, frequency matched by age and sex, were recruited in Hanoi, capital city of Vietnam. Information on frequency and quantity of soyfood and isoflavone intake, together with demographics, habitual diet and lifestyle characteristics, was obtained from direct interviews using a validated and reliable questionnaire. Unconditional logistic regression analyses were performed to examine the association between soy variables and type 2 diabetes risk.
Results:
Higher intake of total soyfoods was significantly associated with a lower risk of type 2 diabetes; the adjusted odds ratio (OR) for the highest versus the lowest intake was 0.31 (95% confidence interval (CI): 0.21–0.46;
P
<0.001). An inverse dose–response relationship of similar magnitude was also observed for total isoflavone intake (OR: 0.35; 95% CI: 0.24 to 0.49;
P
<0.001). In addition, inverse associations of specific soyfoods (soy milk, tofu and mung bean sprout) and major isoflavones (daidzein, genistein and glycitein) with the type 2 diabetes risk were evident.
Conclusions:
Soyfood and isoflavone intake was associated with a lower type 2 diabetes risk in Vietnamese adults.
Journal Article
Long-term outcome of primary non-surgical root canal treatment
Aim
The aim of this study is to examine the survival distributions of primary root canal treatment using interval-censored data and to assess the factors affecting the outcome of primary root canal treatment, in terms of periapical healing and tooth survival.
Materials and methods
About one tenth of primary root canal treatment performed between January 1981 and December 1994 in a dental teaching hospital were systematically sampled for inclusion in this study. Information about the patients' personal particulars, medical history, pre-operative status, treatment details, and previous review status of the treated teeth, were obtained from dental records. Patients were recalled for examination clinically and radiographically. Treatment outcomes were categorized according to the status for periapical healing and tooth survival. The event time was interval-censored and subjected to survival analysis using the Weibull accelerated failure time model.
Results
A total of 889 teeth were suitable for analysis. Survival curves of both outcome measures (periapical healing and tooth survival) declined in a non-linear fashion with time. Median survival of the treated teeth was 119 months (periapical healing) and 252 months (tooth survival). Age, tooth type, pre-operative periapical status, occlusion, type of final restoration, and condition of the tooth/restoration margin were significant factors affecting both periapical healing and tooth survival. Apical extent and homogeneity of root canal fillings had a significant impact towards periapical healing (
p
< 0.05), but not tooth survival.
Conclusion
The longevity of treated teeth based on tooth survival was considerably greater than that of periapical healing. Both outcome measures were affected by a number of socio-demographic, pre-, intra-, and post-operative factors.
Clinical relevance
Root canal-treated teeth may continue to function for a considerable period of time even though there may be radiographic periapical lesion present. Decision for extraction may be due to reasons other than a failure of the periapical tissues to heal.
Journal Article
Identification of novel myeloma-specific XBP1 peptides able to generate cytotoxic T lymphocytes: a potential therapeutic application in multiple myeloma
The purpose of these studies was to identify human leukocyte antigen (HLA)-A2
+
immunogenic peptides derived from XBP1 antigens to induce a multiple myeloma (MM)-specific immune response. Six native peptides from non-spliced XBP1 antigen and three native peptides from spliced XBP1 antigen were selected and evaluated for their HLA-A2 specificity. Among them, XBP1
184−192
, XBP1 SP
196−204
and XBP1 SP
367−375
peptides showed the highest level of binding affinity, but not stability to HLA-A2 molecules. Novel heteroclitic XBP1 peptides,
Y
ISPWILAV or
Y
LFPQLISV, demonstrated a significant improvement in HLA-A2 stability from their native XBP1
184−192
or XBP1 SP
367−375
peptide, respectively. Cytotoxic T lymphocytes generated by repeated stimulation of CD3
+
T cells with each HLA-A2-specific heteroclitic peptide showed an increased percentage of CD8
+
(cytotoxic) and CD69
+
/CD45RO
+
(activated memory) T cells and a lower percentage of CD4
+
(helper) and CD45RA
+
/CCR7
+
(naïve) T cells, which were distinct from the control T cells. Functionally, the cytotoxic T lymphocytes (CTL) demonstrated MM-specific and HLA-A2-restricted proliferation, interferon-γ secretion and cytotoxic activity in response to MM cell lines and importantly, cytotoxicity against primary MM cells. These data demonstrate the distinct immunogenic characteristics of unique heteroclitic XBP1 peptides, which induce MM-specific CTLs and highlights their potential application for immunotherapy to treat the patients with MM or its pre-malignant condition.
Journal Article