Background: Accurate evaluation of axillary lymph node (ALN) involvement is mandatory before treatment of primary breast cancer. The aim of this study is to compare preoperative diagnostic accuracy between positron emission tomography/computed tomography with 18 Ffluorodeoxyglucose ( 18 F-FDG PET/CT) and axillary ultrasonography (AUS) for detecting ALN metastasis in patients having operable breast cancer, and to assess the clinical management of axillary 18 F-FDG PET/CT for therapeutic indication of sentinel node biopsy (SNB) and preoperative systemic chemotherapy (PSC).
Cell-cycle response monitored by the Ki67 labeling index correlates with metabolic response monitored by tumor SUV(max). Monitoring of tumor SUV(max) using FDG PET/CT may be feasible to predict cell-cycle response to neoadjuvant endocrine therapy of primary breast cancer.
Chemokine receptor CXCR4 is known to be crucially involved in tumor progression, but the role of its ligand, stromal cell-derived factor-1 (SDF-1), remains unclear. The present study was conducted to clarify the clinicopathological and prognostic impact of SDF-1 expression in invasive breast cancers. Expression of SDF-1 mRNA and protein was examined in five breast cancer cell lines with or without estradiol treatment. In 52 surgically resected breast cancers, the level of SDF-1 mRNA in frozen samples and the pattern of SDF-1 protein immunoreactivity in formalin-fixed paraffin-embedded tissue sections were compared. In another cohort of 223 breast cancers, the correlation between SDF-1 immunoreactivity and clinicopathological parameters was examined using a tissue microarray. Estradiol treatment markedly increased the expression of SDF-1 mRNA and protein in the estrogen receptor (ER)-positive cell lines, MCF-7 and T47D. Among the 52 resected breast cancers, those with a cytoplasmic-dominant pattern of SDF-1 expression showed higher SDF-1 mRNA levels (median 27.4) than those with a membrane-dominant or negative pattern (median 13.6, P = 0.0017). Accordingly, the cytoplasmic-dominant pattern was defined as "high SDF-1 expression," and other patterns were defined as "low SDF-1 expression." Among the cohort of 223 tumors, "high SDF-1 expression" was detected in 158 (70.9%) and was significantly correlated with ER positivity (P < 0.0001), HER2 negativity (P = 0.021), and lower grade (P < 0.0001). Univariate analysis demonstrated that "high SDF-1 expression" was a significant indicator of better clinical outcome in both the entire patient cohort (P = 0.017) and the 133 patients with ER-positive tumors (P = 0.036), but not in the 90 patients with ER-negative tumors. Multivariate analysis showed that SDF-1 status was an independent factor related to overall survival in patients with ER-positive tumors (P = 0.046). SDF-1 status is a significant prognostic factor and may be clinically useful for assigning adjuvant therapy to patients with ER-positive invasive breast cancers.
Background
The function of sPLA2 is site dependent. In tissue, sPLA2 regulates eicosanoid production; in the blood, sPLA2 primes neutrophils; and in the intestinal lumen sPLA2 provides innate bactericidal immunity as a defensin-related protein. Since parenteral nutrition (PN) with lack of enteral stimulation primes leukocytes while suppressing intra-luminal mucosal immunity, we hypothesized that 1) PN would diminish luminal sPLA2 activity, but increase sPLA2 activity in small intestinal (SI) tissue and serum and 2) stress would accentuate these changes.
Methods
Mice received Chow, Complex Enteral Diet (CED), intragastric PN (IG-PN), or PN in Experiment 1, and Chow, Chow + Stress, PN, and PN + Stress in Experiment 2. Tissue, intestinal luminal fluid, and portal and systemic serum were analyzed for sPLA2 activity. IgA was measured in luminal fluid as a marker of acquired mucosal immunity.
Results
Expt1
Luminal fluid sPLA2 activity was greatest in Chow and decreased in CED (p=0.0001), IG-PN (p=0.0002), and PN (p=0.0001) with PN lower than CED (p<0.002) or IG-PN (p<0.0001). Compared to Chow, serum sPLA2 activity dropped after CED (p = 0.042), IG-PN (p<0.0001), and PN (p=0.0004). Serum sPLA2 was higher in portal than systemic serum (p=0.04).
Expt2
PN lowered luminal fluid sPLA2 activity vs Chow (p<0.0001). Stress lowered luminal sPLA2 activity in Chow (p<0.0001), without a change with PN. Following stress, luminal IgA increased in Chow (p=0.0025) but not PN (p=0.18). Serum sPLA2 activity was unchanged after Chow but increased in PN (p<0.03).
Conclusions
Parenteral nutrition with lack of enteral stimulation attenuates sPLA2 activity in intestinal fluid consistent with a suppressed innate mucosal defense. Stress suppresses luminal fluid sPLA2 activity in Chow, but not the IgA response: PN impairs both. Stress significantly elevates serum sPLA2 in PN fed mice consistent with the known increased neutrophil priming with PN. PN reduces innate bactericidal immunity of the gut but up-regulates serum pro-inflammatory products after stress.
In the absence of enteral nutrient delivery, gut-associated lymphoid tissue (GALT) mass and function are reduced. The purpose of this study was to examine whether exogenous interleukin (IL)-7 treatment reverses intravenous (IV)-total parenteral nutrition (TPN)-induced changes in GALT, immunoglobulin (Ig) A levels, and gut barrier function. Eighty-nine mice were randomized to chow, TPN, or TPN + IL-7 (1 microg/kg, administered IV twice a day) and treated for 5 days. The entire small intestine was harvested and lymphocytes were isolated from Peyer's patches (PPs), intraepithelial (IE) spaces, and the lamina propria (LP). Small intestinal and bronchoalveolar IgA levels were measured. Proximal and distal small intestinal levels of IgA-stimulating (IL-10) and IgA-inhibiting (IFNgamma) cytokines were determined with enzyme-linked immunoabsorbant assay. Moreover, 1 x 10 live Pseudomonas aeruginosa were delivered by gavage and survival was observed. TPN decreased total cell yields from PPs, IE spaces, and the LP compared with the chow group. IL-7 treatment restored cell numbers. PP CD4+, PP CD8+, IE gammadeltaTCR+, and LP CD4+ cell numbers were higher in the TPN + IL-7 group than in the TPN group. Secretory IgA levels were lower in the TPN and TPN + IL-7 than in the chow group. In the distal small intestine, IFNgamma levels were similar in the three groups, whereas IL-10 levels were reduced in the TPN and TPN + IL-7 groups relative to the chow group. Survival times were reduced in the TPN compared with the chow group, but IL-7 treatment significantly improved survival. Thus, exogenous IL-7 does not improve secretory IgA levels, nor are there any remarkable effects on levels of gut IgA-mediating cytokines. However, IL-7 treatment during TPN reverses TPN-induced GALT atrophy and improves survival in a gut-derived sepsis model.
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