Introduction. Although combination therapy with herbal medicine and probiotics is gaining popularity for controlling diarrhea-dominant irritable bowel syndrome (D-IBS) symptoms, few studies have investigated its clinical effects. Materials and Methods. Fifty-three patients with D-IBS were randomly allocated into 1 of the following 4 groups: herbal medicine (Gwakhyangjeonggisan; GJS) plus probiotics (Duolac7S; DUO), GJS plus placebo DUO, placebo GJS plus DUO, and placebo GJS plus placebo DUO. The study period consisted of a 2-week run-in, 8 weeks of administration, and 2 weeks of follow-up. The primary outcomes were weekly adequate relief (AR) of overall IBS symptoms and the proportion of responders (PR) during the administration period. The secondary outcomes included individual IBS symptoms, stool assessment, and quality of life. Changes of intestinal microbiota and intestinal permeability were also analyzed. Results and Discussion. Weekly AR was not different among the 4 groups throughout the treatment period. However, the 3 treatment groups exhibited significant improvements in PR compared to the findings in the placebo group. In the intestinal microbiota assessment, herbal medicine and probiotics synergistically increased beneficial bacteria counts. Conclusion. Combination therapy with herbal medicine and probiotics appears to relieve overall IBS symptoms by synergistically increasing beneficial intestinal microbe counts.

PurposeThe objectives of this study were to assess the potential value of Ki-67 in predicting response to neoadjuvant chemotherapy in breast cancer patients and to suggest a reasonable cutoff value for classifying Ki-67 expression.MethodsThis study included 74 breast cancer patients who underwent surgery after anthracycline-based neoadjuvant chemotherapy between 2007 and 2012. We analyzed the clinical and immunohistochemical characteristics using core biopsy specimens obtained before neoadjuvant chemotherapy to determine their correlations with the response to chemotherapy.ResultsA clinical complete response was observed in 6 patients (8.1%); a clinical partial response, in 44 patients (59.5%); and clinical stable disease, in 24 patients (32.4%). A pathologic complete response (pCR) was observed in 10 patients (13.5%). In univariate analysis, estrogen receptor (ER) negativity (p=0.031), human epidermal growth factor receptor 2 (HER2) positivity (p=0.040), and high Ki-67 expression (p=0.036) were predictive factors for a pCR. In multivariate analysis, Ki-67 was the only independent predictor of a pCR (p=0.049). The analysis of Ki-67 values revealed that 25% was a reasonable cutoff value for predicting the response to chemotherapy. In subgroup analysis, a higher Ki-67 value (≥25%) was a significant predictive factor for the response to neoadjuvant chemotherapy, especially in ER-negative and HER2-positive breast cancer patients.ConclusionKi-67 expression in breast cancer tissue may be an effective factor for predicting the response to neoadjuvant chemotherapy. We suggest that a 25% level of Ki-67 expression is a reasonable cutoff value for predicting a response to chemotherapy. Moreover, Ki-67 is a useful predictive factor for pCR, especially in patients with ER-negative and HER2-positive breast cancer.

We analyzed breast cancer subtypes using Korean Breast Cancer Society Registration Program data to compare clinical features and prognosis for triple-negative breast cancer (TNBC). A cohort of 26,767 breast cancer patients were divided in four groups: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+ HER2+), HER2+ (ER-, PR-, HER2+), and triple-negative (ER-, PR-, HER2-). Clinicopathologic factors were evaluated. The luminal A (14,437 patients, 53.9%) subtype was the largest in our study. Compared with luminal A subtype, TNBC correlated with younger age, more aggressive characteristics and poor overall survival and breast cancer-specific survival. The hazard rate showed a peak at 24 months for the TNBC subtype, but after 60 months, risk was similar to that of the luminal A subtype. Higher T, N stage and histologic grade, and lymphatic and vascular invasion showed poor prognosis in TNBC patients, but on multivariate analysis only histologic grade and ki-67 status were related. Young age was related to poor prognosis in the luminal A subtype, however, age was not related to prognosis in the TNBC subtype. Of the 5,586 TNBC patients, 282 patients (7.11%) expired within 3 years of diagnosis. T and N stage and grade were significantly associated with prognosis on multivariate analysis. TNBC subtype is characterized by younger age with poorer outcome. However, younger age is not related to prognosis, and mortality risk decreases to that of the luminal A subtype, which is known to have the best prognosis after a few years.

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Until recently, fermentation was the only processing used to improve the functionality of wheat germ. The release of 2,6-dimethoxy-1,4-benzoquinone (DMBQ) from hydroquinone glycosides during the fermentation process is considered a marker of quality control. Here, we treated wheat germ extract with citric acid (CWG) to release DMBQ and examined the anti-inflammatory activity of this extract using a lipopolysaccharide-activated macrophage model. Treatment of wheat germ with citric acid resulted in detectable release of DMBQ but reduced total phenolic and total flavonoid contents compared with untreated wheat germ extract (UWG). CWG inhibited secretion of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-6, and IL-12 and the synthesis of cyclooxygenase-2, while UWG only decreased IL-12 production. CWG and UWG induced high levels of anti-inflammatory IL-10 and heme oxygenase-1. CWG specifically inhibited phosphorylation of NF-κB p65 and p38 kinase at 15 min after LPS stimulation. Our study showed that citric acid treatment enhanced the anti-inflammatory activity of wheat germ extract.

PurposePatients with recurrent breast cancer usually die of their disease, even after radical surgery and adjuvant therapies which could reduce the odds of dying. Many studies analyzed and compared patients who died of recurrent disease with those that died without recurrent disease. However, less attention has been paid to evaluating factors associated with the timing of recurrence. Thus, the objective of this study is to investigate the correlation between various factors and the timing of recurrence.MethodsWe retrospectively reviewed the data of 95 recurrent breast cancer patients who underwent curative surgery to determine the prognostic factors such as menopausal status, operation method, stage, nodal status, histologic grade, nuclear grade, extensive intraductal carcinoma component, hormone receptor, p53, c-erbB-2, Ki-67, and molecular subtype. We had attempted to compare the recurrent patients within 2 years after operation and adjuvant chemotherapies as the early recurrence with those over 2 years as the late recurrence.ResultsHistologic grade (p=0.005), nuclear grade (p<0.001), p53 (p=0.022), and Ki-67 (p<0.001) were significant different factors that influenced the systemic recurrence between early recurrence and late recurrence. In stage I/II, histologic grade (p=0.001), nuclear grade (p<0.001), and Ki-67 (p=0.005) were significant factors that influenced the systemic early recurrence. In stage III, nuclear grade (p=0.024), and Ki-67 (p=0.001) were significant factors that influenced the systemic early recurrence. But subtypes (p=0.189, p=0.132, p=0.593, p=0.083) are not associated with the timing of recur rence.ConclusionIn systemic recurrent breast cancer patients, the risk factors such as histologic grade, nuclear grade, p53 and Ki-67 are also associated with the timing of recurrence. We sug gest that these patients should be proper treated and be closely followed up.

PurposeThe aim of this retrospective study was to investigate whether there are prognostically different subgroups among patients with pathologic N3 (pN3) breast cancer.MethodsThe records of 220 patients who underwent surgery for pN3 breast cancer from January 2006 to September 2012 were reviewed. All patients received adjuvant therapy according to standard protocols. The primary outcome was disease-free survival (DFS).ResultsPatients were followed for a median time of 68.3 months after their primary surgery (range, 10–122 months), during which time 75 patients (34.1%) had developed disease recurrence and 48 patients (21.8%) had died. The DFS and overall survival were 67.8% and 86.1%, respectively, at 5 years. Multiple logistic regression analysis showed that young age (<35 years, p=0.009), high serum neutrophil/lymphocyte ratio (>3.0) (p=0.020), high nodal ratio (number of metastatic lymph nodes divided by number of removed nodes) (>0.65) (p=0.062), and molecular phenotype (p=0.012) were significantly associated with tumor recurrence. Tumor biological subtype was the most significant predictor of recurrence. The 5-year DFS rates in patients with hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative, HR+HER2+, HR–HER2+, and triple negative subtypes were 82%, 63%, 58%, and 37%, respectively.ConclusionClinical outcomes of patients with extensive nodal metastasis were heterogeneous in terms of prognosis. Tumor biological subtype was the most important prognostic factor for pN3 disease. The prognosis of patients with HR+HER2– subtype in pN3 breast cancer was similar to that of patients with stage II breast cancer.

Inflammatory bowel disease (IBD) is a chronically relapsing inflammatory disorder of the gastrointestinal tract. Most IBD treatments are unsatisfactory; therefore, various dietary supplements have emerged as promising interventions. Laminaria japonica (LJ) is an edible seaweed used to regulate digestive symptoms. Probiotics have been reported to improve digestive problems and their simultaneous administration with seaweeds has been shown to produce synergistic therapeutic effects. Here, we investigated the effect of LJ combination with probiotics on dextran sodium sulfate-induced colitis model in mice. Aqueous LJ extracts (LJE) at doses from 100 to 300 mg/kg and probiotics at a dose of 300 mg/kg were orally administered for 7 days. Body weight, colon length, histological score, macroscopic damage, and the levels of cytokines IFN-γ, IL-1β, IL-6, IL-10, IL-12 (P40), IL-12 (P70), IL-17, and TNF-α were assessed. LJE alone caused a significant improvement of colitis signs such as colon length, histological score, and IL-1β and IL-6 production. LJE and probiotics demonstrated a synergistic effect by the histological score and levels of IL-1β, IL-6, and IL-12 (P40) but not IFN-γ, IL-10, and IL-12 (P70). In conclusion, LJE was effective in inducing protection against colitis in mice and acted synergistically with probiotics.