Can we identify the group of small invasive (T1a,b) breast cancers with minimal risk of axillary lymph node involvement? A pathohistological and DNA flow cytometric study

The goal of this study was to identify a group of small (≤1 cm) breast cancers (T1a,b) with a particularly low probability of axillary lymph node metastases, where routine axillary staging may be unnecessary.We retrospectively analyzed 152 T1a,b breast carcinomas with axillary dissection surgically removed at Clinical Hospital Center Split (Croatia) in the period from 1997 to 2006. The analysis included 40 T1a,b cancers with, and 112 T1a,b cancers without axillary lymph node metastases. The basic morphological features of cancers were investigated histologically, while hormone receptors and HER2/neu were investigated immunohistochemically with an additional CISH analysis of HER2/neu 2+ cases. The ploidy and S-phase fraction were determined by DNA flow cytometry. The association of the investigated features with the likelihood of axillary lymph node metastases was analyzed by univariate and multivariate analysis.The univariate analysis showed that lymph node metastases were associated with tumor size (T1a/T1b; p = 0.026), histological type (ductal/non-ductal; p = 0.014), lymphovascular invasion (p < 0.001), HER2/neu expression (p = 0.04), ploidy (p = 0.027), and combined values of ploidy and S-phase fraction (p = 0.025). The lymphovascular invasion was the only independent factor associated with axillary nodal metastases (p = 0.01). In the group of T1a,b cancers without lymphovascular invasion, HER2/neu expression (p = 0.021) and combined values of ploidy and S-phase fraction (p = 0.016) were independent factors associated with axillary lymph node metastases.This study showed that diploid T1a,b cancers with low S-phase fraction, which are also without lymphovascular invasion and HER2/neu amplification, represented the group of cancers with a low probability of axillary lymph node metastases.     

Notch3 signaling is associated with MUC5AC expression and favorable prognosis in patients with small intestinal adenocarcinomas

Background

Notch signaling plays diverse roles not only in physiologic processes, including development and differentiation but also in tumorigenesis, either as a tumor promoter or suppressor depending on the cellular context, level of expression and cross-talk with other signaling pathways. In this study we investigated the expression of Notch3 and MUC proteins and their clinicopathological significance in small intestinal adenocarcinoma (SIAC).

Methods

Surgically resected 191 SIACs and their clinical data were collected. Immunohistochemistry for Notch3, MUC2, MUC5AC, and MUC6 using tissue microarrays from formalin-fixed paraffin-embedded normal and matched tumor tissues was performed.

Results

Notch3 expression was found in 52 (29.9%) cases of the tumors. MUC2, MUC5AC, and MUC6 were expressed in 52 (27.5%), 51 (31.9%), and 42 (22.0%) cases of the tumor, respectively. Notch3 expression was correlated with the absence of lymphovascular invasion (p = 0.009), lower T stage (p = 0.038), and histological subtype of tubular adenocarcinoma (p = 0.01), respectively. MUC2 was correlated with large tumor size (p = 0.013) and mucinous and signet ring cell adenocarcinomas (p = 0.01). MUC5A was correlated with proximal tumor location (p < 0.0001) and tumor differentiation (p = 0.027). MUC6 was correlated with proximal tumor location (p < 0.0001) and lower pT stage (p = 0.009), and absence of lymphovascular invasion, respectively. A significant correlation was noted between Notch3 and MUC5AC expression (p = 0.019). Notch3 expression was a relatively favorable prognostic factor in SIACs by univariate (p = 0.05) and multivariate analysis (p = 0.08, Cox Hazard ratio 0.841).

Conclusion

Our findings indicate that Notch3 signaling, associated with MUC5AC expression, could be a more favorable prognostic factor in SIACs.     

Beclin 1 and bcl-2 expressions in bladder urothelial tumors and their association with clinicopathological parameters

Beclin 1 plays a critical role in the regulation of autophagy, apoptosis, differentiation, as well as in the development and progression of cancer. The aim of this study was to examine the expression of beclin 1 and bcl-2 in bladder urothelial tumors, and to investigate the relationship between these two markers and clinicopathological parameters. Our study included 84 bladder urothelial tumors and 10 non-tumoral bladder tissues. Immunohistochemistry was performed on tissue microarray (TMA) sections and was evaluated semiquantitatively on the basis of the percentage of positively stained cells (proportion) and staining intensity. A significant association was found between the expression score of beclin 1 and pT stages of the urothelial tumors (p = 0.012). Also, the level of beclin 1 expression inversely correlated with histological grade and pT stages (p = 0.009, r = −0.284; p = 0.001, r = −0.361, respectively). The bcl-2 expression level positively correlated with histological grade and pT stages of the urothelial tumors (p = 0.026, r = 0.243; p < 0.0001, r = 0.491, respectively). In addition, the level of beclin 1 expression tended to be inversely correlated with the bcl-2 expression level in urothelial tumors (p = 0.055, r = −0.210). According to our data, down-regulation of beclin 1 expression and also bcl-2 overexpression seem to play an important role in the progression and aggressiveness of bladder urothelial tumors.     

Trends in prostatic adenocarcinoma tumor volume by visual estimation in prostatectomy specimens

We retrospectively reviewed 1792 consecutive radical prostatectomies (RP) from 2003 to 2006 at a single institution to establish tumor volume reference values, to determine current trends in visually estimated prostate adenocarcinoma tumor volume, and to characterize cases with no residual cancer on RP. Tumor volumes were recorded and subsequently stratified as very low, 0–1%; low, 1.1–10%; intermediate, 10.1–20%; high, 20.1–50%; and very high, >50%, with incidences of 11.7%, 52.1%, 21.5%, 13.2%, and 1.5%, respectively. The incidence of very low volume tumors increased within the time period (p = 0.04). Seminal vesicle involvement was detected in 5.0% of cases and lymph node metastasis occurred in 1.4%. Volume categories statistically correlated with seminal vesicle invasion (p = 0) and lymph nodes metastases (p = 0). Eleven cases of no residual cancer (0.6%) were identified with a non-statically significant increase during the study (p = 0.07). The rising incidence of very low volume tumors should be considered by clinicians when discussing treatment options with patients. A discrete tumor volume should be provided for RP specimens as it may be an important prognostic factor.     

Immunohistochemical COX-2 overexpression correlates with HER-2/neu overexpression in invasive breast carcinomas: a pilot study

Cyclooxygenase-2 (COX-2) is a prostaglandin synthase that catalyzes the synthesis of prostaglandin G2 and H2. It has been shown that COX-2 plays an important role in tumorigenesis of different tumor types and it is thought to take part in breast carcinogenesis. In the present study, we aimed to investigate the relationship of immunohistochemical COX-2 expression with clinicopathological parameters, including HER-2/neu overexpression in invasive breast carcinoma (IBC).Our study population comprised 10 normal breasts, 25 ductal carcinomas in situ (DCIS), and 51 invasive breast carcinomas. Immunohistochemical overexpressions of COX-2 and HER-2/neu were investigated in sections of formalin-fixed, paraffin-embedded blocks by 3 observers.In normal breast, DCIS and IBC, the COX-2 overexpression rate was 0%, 84%, and 58.8%, respectively. In IBC, COX-2 overexpression had a significant relationship with HER-2/neu overexpression (p = 0.026) and a high histological grade (p = 0.026). COX-2 expression in both DCIS (n = 25) and IBC (n = 51) was significantly higher than in normal breast tissue (p < 0.0001). In addition, the COX-2 expression rate was significantly higher in DCIS than in IBC (p = 0.042).Our results indicated that COX-2 overexpression correlates with aggressive phenotypic features, such as HER-2/neu overexpression and high histological grade in IBC. Increased expression of COX-2 in both DCIS and IBC in comparison to normal breast could indicate a role in breast carcinogenesis. COX-2 overexpression may provide a clinically useful biomarker for estimating tumor aggressiveness.     

Significantly upregulated TACSTD2 and Cyclin D1 correlate with poor prognosis of invasive ductal breast cancer

The tumor-associated calcium signal transducer 2 (TACSTD2) gene has been reported to be highly expressed in many types of human epithelial cancers, and is associated with tumor metastasis and poor prognosis. The aims of the present investigation were to analyze the TACSTD2 and Cyclin D1 expression at the mRNA and protein levels and to assess its prognostic significance in invasive ductal breast cancer (IDC). The expressions of TACSTD2 and Cyclin D1 in IDC tissues were consistently higher than those in the tumor-adjacent non-malignant tissues by a one-step real-time polymerase chain reaction and immunohistochemistry (P < 0.001 and P = 0.023, respectively). The statistical analysis of clinicopathologic characteristics and immunohistochemistry by the χ² test showed that the high expression of TACSTD2 in IDC was correlated to histological grade (P = 0.023), P53 status (P = 0.042), Cyclin D1 status (P < 0.001), lymph node metastasis (P < 0.001), distant metastasis (P = 0.004) and TNM staging (P < 0.001). Kaplan–Meier survival and Cox regression analyses were performed to evaluate the prognosis of IDC. These analyses also showed that a high TACSTD2 expression (P = 0.003), a high Cyclin D1 expression (P = 0.041), and lymph node metastasis (P = 0.006) were independent prognosis factors. Collectively, our studies demonstrated that the high expression of TACSTD2 correlates with a poor prognosis in IDC.     

An immunohistochemical study of interleukin-8 (IL-8) in breast cancer

The use of prognostic markers for breast cancer is important for routine diagnosis and research. Interleukin-8 is a chemotactic cytokine produced by several cell types in response to inflammation, however, its expression, regulation and function are poorly understood. Recent studies have associated angiogenesis and inflammatory processes with tumor malignancy. The present study investigated the correlation between interleukin-8 expression and breast cancer prognosis. Interleukin-8 expression was assessed in 72 women with mammary neoplasia by immunohistochemistry and the results were statistically correlated with clinical-pathological findings. There was an inverse correlation between interleukin-8 expression and metastasis (p = 0.03) and/or local recurrence (p = 0.02). In the patient group that received post-surgery chemotherapy and radiotherapy, a lower interleukin-8 expression was found in those women that showed local recurrence (p = 0.01). Multivariate logistic regression showed estrogen receptor negativity, progesterone positivity and metastasis with increased risk of death (p < 0.05). The data reflect the complexity of the role of interleukin-8 in tumor microenvironment and support its classification as a possible prognostic marker, although more studies are necessary for its inclusion in clinical practice.     

Expression of HAb18G/CD147 and its localization correlate with the progression and poor prognosis of non-small cell lung cancer

This study was designed to investigate the association of HAb18G/CD147 expression and localization with clinicopathological parameters and prognosis in NSCLC. Two hundred and eight (208) specimens of surgically resected NSCLC were stained by immunohistochemistry utilizing mouse anti-human HAb18G/CD147 monoclonal antibody. High levels of HAb18G/CD147 expression were associated with male gender, smoking history, tumor position, distant metastasis status, and clinical stage (p < 0.05) in squamous cell carcinoma. In adenocarcinomas, HAb18G/CD147 expression was associated with male gender, tumor diameter, differentiation, lymph node status, distant metastasis status, and clinical stage (p < 0.05). HAb18G/CD147 expression with higher PU was predominantly localized in the tumor cell membranes rather than in cytoplasms. In squamous cell carcinomas, membranous localization of HAb18G/CD147 was linked to distant metastasis status and TNM stage (p < 0.05). Cytoplasmic localization of HAb18G/CD147 was associated with male gender and smoking history. In adenocarcinomas, membranous localization of HAb18G/CD147 correlated with tumor diameter, differentiation and distant metastasis (p < 0.05). Univariate analysis indicated that patients with high HAb18G/CD147 expression and membranous localization predicted poor prognosis in both squamous cell carcinomas and adenocarcinomas. Multivariate analysis showed that lymph node status (HR = 1.762, 95%CI 1.105–2.811, p = 0.017), distant metastasis status (HR = 3.789, 95%CI 2.196–6.539, p = 0.000), expression (HR = 6.632, 95%CI 2.457–17.904, p = 0.000), and localization (HR = 0.520, 95%CI 0.341–0.794, p = 0.002) were good or excellent independent predictors of patient survival. HAb18G/CD147 is a biomarker characterizing progression and survival of NSCLC. More importantly, its cellular localizations should be considered in the analysis of clinicopathological characteristics and prognostic factors in NSCLC.     

Overexpression of EZH2 and loss of expression of PTEN is associated with invasion, metastasis, and poor progression of gallbladder adenocarcinoma

Overexpression of EZH2 and inactivation or loss of PTEN expression was observed in invasive and metastatic tumors. However, their expressions and clinical significances in gallbladder cancer (GBC) have rarely been reported. In this study, we investigated EZH2 and PTEN expression in an extensive collection of human gallbladder cancer samples and benign lesions of gallbladder using immunohistochemistry. Overexpression of EZH2 was detected in 53.7% of gallbladder adenocarcinomas associated with poor differentiation, lymph node metastasis, and invasion, while loss of PTEN expression was identified in 51.8% of adenocarcinomas with high grade, metastatic, and invasive tumors. Univariate Kaplan-Meier analysis showed that overexpression of EZH2 (p = 0.013) and loss of PTEN expression (p = 0.008) were significantly associated with decreased overall survival. Multivariate Cox regression analysis revealed that overexpression of EZH2 (p = 0.011) or loss of PTEN expression (p = 0.009) is a predictor of poor prognosis in gallbladder adenocarcinoma. Our study suggests that overexpression of EZH2 and loss of PTEN expression might be closely related to the carcinogenesis, progression, clinical biological behavior, and prognosis of gallbladder adenocarcinoma.     

Novel method for transdiaphragmatic pressure measurements in mice

The diaphragm muscle (DIAm) is responsible for breathing and determines the ability to generate both ventilatory and non-ventilatory behaviors. Size limitations of the mouse make transdiaphragmatic pressure (Pdi) measurement using a dual balloon system untenable. Adult C57BL/6J mice (n = 8) and C57BL/6 × 129 (n = 9), underwent Pdi measurements using solid-state pressure catheters spanning the thoracic and abdominal surfaces of the DIAm. Measurements were conducted during eupnea, hypoxia (10% O₂)–hypercapnia (5% CO₂), chemical airway stimulation (i.e., sneezing), spontaneously occurring deep breaths, sustained tracheal occlusion, and bilateral phrenic nerve stimulation. There was a difference in the Pdi generated across the range of ventilatory and non-ventilatory behaviors (p = 0.001). No difference in Pdi across behaviors was evident between mouse strains (p = 0.161). This study establishes a novel method to determine Pdi across a range of DIAm behaviors in mice that may be useful in evaluating conditions associated with reduced ability to perform expulsive, non-ventilatory behaviors.     

Doctor, what's wrong with me? Factors that delay the diagnosis of colorectal cancer

Objective

To examine the influence of patient and physician communication factors on diagnostic delay (DD).

Methods

242 patients diagnosed with colorectal cancer (CRC) in the past 6 months who experienced symptoms prior to diagnosis were administered a 2-h semi-structured qualitative interview to assess communication with health care provider and ease of access to care, among other factors. Patient-provided information was verified via review of medical records.

Results

The factors associated with DD > 2 months included lower income (OR = 0.56, p = 0.03), having regular physician prior to receiving a cancer diagnosis (OR = 2.52, p = 0.03), having a physician who used temporizing communication strategies during the consultation (OR = 2.41, p = 0.02), receiving an initial alternate diagnosis (OR = 3.36, p = 0.02), experiencing referral delay (OR = 3.61, p = < 0.001), and experiencing follow-up delay of any kind (OR = 3.32, p = 0.01).

Conclusion

Excellent communication skills that appropriately probe for relevant social and economic patient information, assist patients in distinguishing and elaborating on symptoms, and provide clear rationale and instructions for future steps, will speed along the diagnosis process and could be the difference between early and late stage CRC.

Practice implications

Increased understanding of physician communication and practice styles that contribute to DD could have a positive impact on decreasing the morbidity and mortality from this disease.     

Risperidone alters food intake, core body temperature, and locomotor activity in mice

Risperidone induces significant weight gain in female mice; however, the underlying mechanisms related to this effect are unknown. We investigated the effects of risperidone on locomotor activity, core body temperature, and uncoupling protein (UCP) and hypothalamic orexin mRNA expression. Female C57BL/6J mice were acclimated to individual housing and randomly assigned to either risperidone (4 mg/kg BW day) or placebo (PLA). Activity and body temperature were measured over 48-hour periods twice a week for 3 weeks. Food intake and body weights were measured weekly. UCP1 (BAT), UCP3 (gastrocnemius), and orexin (hypothalamus) mRNA expressions were measured using RT-PCR. Risperidone-treated mice consumed more food (p = 0.050) and gained more weight (p = 0.0001) than PLA-treated mice after 3 weeks. During the initial 2 days of treatment, there was an acute effect of treatment on activity (p = 0.046), but not body temperature (p = 0.290). During 3 weeks of treatment, average core body temperatures were higher in risperidone-treated mice compared to controls during the light phase (p = 0.0001), and tended to be higher during the dark phase (p = 0.057). Risperidone-treated mice exhibited lower activity levels than controls during the dark phase (p = 0.006); there were no differences in activity during the light phase (p = 0.47). UCP1 (p < 0.01) and UCP3 (p < 0.05) mRNA expressions were greater in risperidone-treated mice compared to controls, whereas, orexin mRNA expression was lower in risperidone-treated mice (p < 0.01). These results suggest that risperidone-induced weight gain in mice is a consequence of increased energy intake and reduced activity, while the elevation in body temperature may be a result of thermogenic effect of food intake and elevated UCP1, UCP3, and a reduced hypothalamic orexin expression.     

Downregulation of GLTSCR2 expression is correlated with breast cancer progression

Glioma tumor-suppressor candidate region gene2 (GLTSCR2) is a recently identified nucleolus-localized protein participating in the regulation of cell cycle progression and apoptosis. Down-regulation of GLTSCR2 in several types of cancers and increased transforming activity in GLTSCR2-downregulated cancer cells indicated its tumor suppressive potential. The aim of this study was to evaluate GLTSCR2 expression in breast cancer and to investigate the question of whether reduced expression of GLTSCR2 may have any pathological significance in breast cancer development or progression. In this study, we performed quantitative RT-PCR and immunohistochemistry to evaluate the expression of GLTSCR2 and relevance with clinicopathological factors in the invasive ductal carcinoma (IDC). GLTSCR2 expression was reduced in 48% of IDC (n = 426) by a semi-quantitative scoring system using tissue microarray. GLTSCR2 mRNA was significantly reduced by 0.16 fold in 15 out of 17 (88%) cases of IDC. Reduction of GLTSCR2 was significantly correlated with increased histological grade (p < 0.005), increased tumor size (p < 0.001), axillary lymph node involvement (p < 0.001) and decreased disease free survival (p < 0.025). In addition, we show that upregulation of GLTSCR2 decreases the invasive potential of breast cancer cells. Taken together, our data suggest that GLTCR2 may play a role in the tumorigenesis, progression and biological behavior in breast cancer.     

A cross-sectional study of elderly Asian and European women with primary operable breast cancer aged 70 and older. Are there differences?

Background

Breast cancer (BC) is becoming a disease of the elderly. Additionally, BC-incidence is rising in Asia. The aim of this study was to explore clinico-pathological characteristics and differences of breast cancer in elderly Asian/Han-Chinese compared to Caucasian/Austrian women.

Methods

A total number of 630 consecutive primary operable, unilateral breast cancer cases, 70 years and older, were analyzed. Histo-pathological findings and biological characteristics of 198 Caucasian/Austrian were compared with 432 Asian/Han-Chinese. Pearson's chi-square test was used to assess differences in the analyzed populations.

Results

A significantly higher rate of triple-negative BC (p = 0.027) was diagnosed among the Chinese geriatric population. More estrogen-receptor positive BC was detected in the Caucasian study group (p < 0.001). No statistically significant differences were detected based on tumor size, axillary lymph-node status, nor HER2-receptor expression.

Conclusion

This study will help us gain additional ethnic-specific insight into the biological characteristics of breast cancer in the elderly Caucasian/Austrian and Asian/Han-Chinese populations.     

Presence and extent of estrogen receptor-alpha expression in patients with simple steatosis and NASH

Loss of estrogen receptor-alpha (ER-α) in the liver is associated with hepatic steatosis and inflammation. We conducted a study in order to investigate the presence and extent of ER-α expression in NASH, and its relationship with histological findings. Fifty-four patients with histologically confirmed NASH, 12 patients with simple steatosis (SS), and 6 patients with normal liver tissue (NLT) were included. NASH activity score and fibrosis score were calculated according to biopsy findings. Liver biopsy specimens were immunohistochemically stained for ER-α expression. Nuclear ER-α expression percentage (staining index) was calculated. Mean staining index was significantly different across the NASH, SS, and NLT groups (6.3 ± 9.9 vs. 22.1 ± 26.4 vs. 44.2 ± 24.8, respectively, p < 0.001 for all comparisons). Staining index was significantly higher in women than in men (19.4 ± 22.2 vs. 7.9 ± 15.3, respectively, p = 0.003). Staining index negatively correlated with serum ALT (r = −0.240; p = 0.04), fasting plasma glucose (r = −0.261; p = 0.027), and fibrosis score (r = −0.312; p = 0.011). As a conclusion, hepatic nuclear ER-α expression percentage (staining index) is lower in patients with NASH when compared to SS and NLT groups. Staining index is negatively correlated with serum ALT levels, plasma glucose, and fibrosis score. Further studies are required to clarify the significance of ER-α expression in NASH.     

Prognostic importance of PAI-1 in node negative breast cancer patients--results after 10 years of follow up

The serine protease urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play key roles in the proteolytic cascade involved in physiological and pathological degradation of the extracellular matrix.The aim of this study was to determine the prognostic importance of PAI-1 expression in tumor cells in node-negative breast cancer patients that did not receive adjuvant chemotherapy. We used immunohistochemistry (IHC) as a detection method. The study retrospectively included 133 ductal invasive breast cancer patients from the Clinical Hospital Center Zagreb, Croatia, surgically treated in a two-year interval (1998-1999) with 10 years of follow up.The Cox proportional hazard regression test with stepwise variable selection was used to calculate the relative effect of investigated data on patients’ prognosis. Univariate analysis showed that all investigated factors, such as lymph node involvement (p = 0.025), tumor grade (p < 0.001), estrogen receptor status (p = 0.011), vascular invasion (p = 0.001), HER2 overexpression (p < 0.001), and proliferative index (p < 0.001), had a statistically significant influence on patients’ OS. Multivariate statistical analysis showed that only HER-2 (p < 0.001) can be considered an independent, statistically significant poor prognostic factor.In patients with negative lymph nodes that did not receive adjuvant chemotherapy, we found a significant correlation in overall survival (p = 0.009), which is favorable for PAI-1 negative tumors.In conclusion, it seems that PAI-1 in primary breast cancer tissue correlates with disease aggressiveness and has a strong prognostic impact on primary breast cancer, and is a strong prognostic factor for node-negative patients that did not receive chemotherapy.     

Serum cytokine profile in hepatitis C virus carriers presenting cryoglobulinaemia and non-organ-specific autoantibodies

This work investigated the serum cytokine profile (IL-2, IL-4, IL-5, IL-10, IFN-γ and BAFF) of hepatitis C virus (HCV) carriers with autoimmunity. Forty-seven HCV carriers and 28 healthy controls were evaluated. Cytokine levels were measured by ELISA. Patients and controls presented similar levels of IL-2, IL-4, IL-5, IL-10, IFN-γ and BAFF (p > 0.05). Cryoglobulinaemic HCV carriers had increased IL-2 (p = 0.013), IL-5 (p = 0.018) and BAFF (p = 0.050). IFN-γ level was decreased in HCV carriers with rheumatoid factor in comparison with those that were RF-seronegative (p = 0.035). Patients with β2GPI IgA antibodies when were compared with those without this autoantibody, had more serum IL-2 (p = 0.009), IL-5 (p = 0.018) and BAFF (p = 0.039). Interleukin-2 was increased in HCV carriers with positive ANA when they were compared with ANA-seronegative carriers (p = 0.044). Interleukins IL-4 and IL-10 were not associated with autoimmunity (P > 0.05). In HCV carriers, IL-2 was correlated with IL-5 (p < 0.0001) and IFN-γ (p = 0.015), and IL-5 with IFN-γ (p = 0.015). We concluded that the serum profile of cytokines in HCV carriers presenting autoimmune markers may be mainly represented by increased IL-2, IL-5 and BAFF.     

Striatum brain-derived neurotrophic factor levels are decreased in dystrophin-deficient mice

Brain dystrophin is enriched in the postsynaptic densities of pyramidal neurons specialized regions of the subsynaptic cytoskeletal network, which are critical for synaptic transmission and plasticity. Lack of dystrophin in brain structures have been involved with impaired cognitive functions. The brain-derived neurotrophic factor (BDNF) is a regulator of neuronal survival, fast synaptic transmission, and activity-dependent synaptic plasticity. The present study investigated BDNF protein levels by Elisa analysis in prefrontal cortex, cerebellum, hippocampus, striatum and cortex tissues from male dystrophic mdx (n = 5) and normal C57BL10 mouse (n = 5). We observed that the mdx mouse display diminution in BDNF levels in striatum (t = 6.073; df = 6; p = 0.001), while a tendency of decrease in BDNF levels was observed in the prefrontal cortex region (t = 1.962; df = 6; p = 0.096). The cerebellum (t = 1.258; df = 7; p = 0.249), hippocampus (t = 0.631; df = 7; p = 0.548) and cortex (t = 0.572; df = 7; p = 0.586) showed no significant alterations as compared to wt mouse. In conclusion, we demonstrate that only striatum decreased BDNF levels compared with wild-type (wt) mouse, differently to the other areas of the brain. This dystrophin deficiency may be affecting BDNF levels in striatum and contributing, in part, in memory storage and restoring.     

Obesity is associated with a poorer prognosis in women with hormone receptor positive breast cancer

Objective

Whether moderate to severe obesity (body mass index (BMI) ≥ 30 to <40 kg/m²) contributes to breast cancer recurrence and mortality remains uncertain.

Subjects and methods

1199 women, recruited within 12 months of their diagnosis of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) invasive breast cancer completed an enrolment questionnaire and an annual follow-up questionnaire every 12 months for another 5 years. The impact of obesity on time to either local or distant recurrence or new breast cancer, or death due to breast cancer was determined by Cox regression. Women in the most extreme categories of BMI (<18.5 and ≥40) were excluded from the analysis.

Results

Of the 1155 included women, mean age, 58.4 ± 11.6 years, 53.8% had Stage 1 disease and 88.9% received oral adjuvant endocrine therapy (OAET) within 2 years of diagnosis. The likelihood of an event was significantly associated with moderate to severe obesity (HR = 1.71, 95%CI, 1.12–2.62, p = 0.014), disease beyond Stage 1 (HR = 2.87, 95% CI 1.73–4.75, p < 0.001), OAET (HR = 0.26, 95%CI 0.14–0.46, p < 0.001), mastectomy (HR = 3.28, 95%CI 1.98–5.44, p < 0.001) and radiotherapy (HR = 2.12, 95%CI 1.24–3.63, p = 0.006). For Stage 1 disease, only moderate to severe obesity (HR 3.23, 95%CI 1.48–7.03, p = 0.003) and OAET use (HR 0.41, 95%CI 0.17–0.98, p = 0.046) were significantly associated with an event.

Conclusion

Moderate to severe obesity is associated with a poorer invasive breast cancer prognosis; this is also true for women with Stage 1 disease, and is independent of age and treatment.     

CD45RA expression on HCMV-specific effector memory CD8+ T cells is associated with the duration and intensity of HCMV replication after transplantation

In this cross-sectional study on 42 solid organ transplant recipients, the association of kinetics of human cytomegalovirus (HCMV) replication and EMRA HCMV-specific CD8+ T cells was investigated. Correlation was observed between the duration of HCMV replication after transplantation and CD45RA+CD27− (r = 0.609; p = 0.004), CD45RA+ CD28− (r = 0.579; p = 0.008) or CD45RA+CCR7− (r = 0.488; p = 0.029) HCMV-specific CD8+ T cells percentages. In the multivariate regression analyses, CD45RA+CD27−, CD45RA+CD28− or CD45RA+CCR7− HCMV-specific CD8+ T cells percentages increased 5.58% (p = 0.001), 5.35% (p = 0.001) or 4.49% (p = 0.012), respectively, with every 10-day increase in the duration of HCMV replication. Moreover, CD45RA+CD27− or CD45RA+CD28− frequencies increased 4.16% (p = 0.024) or 3.58% (p = 0.049), respectively, with every unity increase in log₁₀ genomes/mL. These observations support the major association between the frequency of EMRA HCMV-specific CD8+ T cells and the duration of post-transplant HCMV replication episodes in solid organ transplantation recipients.