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.     

Imbalance in serum soluble CD30/CD30L and CD40/CD40L systems are associated with ovarian tumors

The aim of the study was to examine the concentrations of the soluble receptors and their ligands of CD30/CD30L and CD40/CD40L systems in the serum of women with ovarian tumor and in the ovarian cyst fluid of women with Cystadenoma serosum. The study included 120 women with ovarian tumors. As a control, sera were obtained from 60 healthy female volunteers. Concentrations of the sCD30, sCD30L, sCD40 and sCD40L in the serum and the ovarian cyst fluid were measured by ELISA enzyme-linked immunosorbent assay. Concentrations of both sCD30 and sCD30L in serum of women with ovarian tumors were significantly higher than in control (p < 0.0001). The highest serum receptor and its ligand levels were observed in women with ovarian cancer (p < 0.0001). Moreover, results showed significantly increased levels of sCD40 and sCD40L serum in women with ovarian tumors, as compared to the control group (p < 0.0001). The highest concentration of sCD40 in the serum of women with ovarian cancer and sCD40L in serum of women with Teratoma maturum (p < 0.0001) were observed. Impaired apoptosis among women with ovarian tumors is associated with the impairments of soluble CD30/CD30L and CD40/CD40L systems. Measurement of studied parameter concentrations in serum of women with ovarian tumors has been suggested to be a potential tool in monitoring of inflammatory. Evaluation of sCD30, sCD30L and sCD40 might be an early diagnostic marker in patients with the ovarian cancer. Concentrations of the studied parameters in the ovarian cyst fluid higher than the serum values suggest local suppression of the immune response. However, the final evaluation of the importance of measurement of serum levels of them requires further investigation.     

Human leukocyte antigen G is associated with esophageal squamous cell carcinoma progression and poor prognosis

Human leukocyte antigen G (HLA-G) is a non-classical HLA class I molecule thought to play a key role in maternal-fetal tolerance and cancer immune evasion. This study aimed to investigate the HLA-G expression in lesion sections and plasma sHLA-G levels of primary esophageal squamous cell carcinoma (ESCC) patients and its clinical significance in diagnosis and prognosis of ESCC. 60 ESCC patients and 28 healthy controls were recruited, and the positive expression of HLA-G in ESCC lesions and adjacent normal tissues were 70% (42/60) and 8.6% (5/60) (P < 0.05), respectively, while no expression was found in normal controls. HLA-G1 and HLA-G5 were determined to be dominating isoforms measured by RT-PCR. There was a significant difference in plasma sHLA-G levels between patients with ESCC (15.04 U/ml, range 4.33–250.00 U/ml) and healthy controls (6.81 U/ml, range 0–29.27 U/ml) (P < 0.01). The plasma IL-10 level was higher in ESCC patients than the controls (23.86 pg/ml vs. 12.81 pg/ml, P < 0.01). HLA-G expression in lesion tissues was correlated with cancer cell differentiation (P = 0.033), lymph node metastasis (P = 0.035) of ESCC. However, no obvious correlations were demonstrated between the plasma sHLA-G levels and the clinicopathological parameters. There was a significant correlation between sHLA-G and IL-10 expression (r = 0.353, P = 0.006) in patients with Esophageal squamous cell carcinoma. HLA-G positive expression showed poorer prognosis of ESCC. HLA-G positive expression might serve as a potential marker in the diagnosis or prediction of ESCC.     

Evaluation of O6-methylguanine-DNA methyltransferase by immunohistochemistry: Best clinical and research practices

O6-Methyguanine-DNA methyltransferase (MGMT) repairs DNA damage and acts as a tumor suppressor in normal cells by preventing DNA mutations. Several antibodies against MGMT are used for immunohistochemical assessment of this marker and no universal standard is adopted.We evaluated the immunohistochemical expression of MGMT with 5 commercially available primary antibodies in 59 invasive breast carcinomas.A tissue microarray was constructed using 59 invasive breast carcinoma samples. Five primary antibodies against MGMT were used for immunohistochemistry, including clones MT3.1, SPM287, and MT23.2. Heat-induced antigen retrieval and polymer-based immunohistochemistry were performed. Stains were analyzed by microscopy and automated digital slide technology. qRT-PCR was performed for all tumors.Clone SPM287 had the highest sensitivity (p < 0.001), and clone MT3.1 had the lowest sensitivity (p < 0.001). Clone MT23.2 generated higher levels of cytoplasmic staining, which was not observed with the other antibodies (p < 0.001). Fifty-six samples (94.9%) showed hypoexpression of MGMT compared with normal breast, as measured by qRT-PCR (p < 0.001). Only clone SPM287 correlated significantly with the qRT-PCR results (p = 0.027).Antibody clone SPM287 is the most sensitive and specific antibody for the immunohistochemical evaluation of MGMT, rendering it a reliable and effective reagent for research and clinical practice in breast cancer.     

Circulating estradiol defines the tumor phenotype in menopausal breast cancer patients

Objective

To correlate circulating hormone levels with the clinical and biological features of the tumors in menopausal breast cancer patients.

Design

Circulating hormone levels were measured in 161 previously untreated menopausal breast cancer patients within 72 h of their planned surgery. The obtained hormone levels were correlated with tumor size, histological and nuclear grade, histological score, axillary nodal status, DNA-ploidy and Ki67-, c-erb-B2-, p53, Bax-, VEGF- and Nup88-expression.

Results

The only statistically significant correlations found between circulating hormone levels and all tested variables were an inverse one between estradiol and the expression of the apoptosis-associated Bax gene (p = 0.009), and again an inverse correlation between estradiol and the expression of c-erb-B2 (p = 0.04). When comparing hormone levels with each other, a significant correlation between estradiol and progesterone (p < 0.0001), an inverse one between estradiol and FSH (p = 0.04) and a direct one between LH and prolactin (p = 0.001) were found.

Conclusion

Higher circulating estradiol levels in postmenopausal breast cancer patients are associated with molecular features usually defining a biologically less aggressive tumor phenotype.     

Overexpression of steroid receptor coactivator-3 in bone cancers: An in vivo immunohistochemical study with tissue microarray

Bone tissue is steroid-responsive and profoundly regulated by steroids and/or their receptors. Bone cancers (either primary or metastatic) belong to the most dangerous tumors. Previous studies have demonstrated overexpression of steroid receptor coactivator-3 (SRC-3) in many cancers, such as breast cancer, prostate cancer, thyroid cancer, functioning in the regulation of cancer cell proliferation, invasion, and metastasis. However, so far, the expression and function of SRC-3 in bone cancers have not yet been clarified. In this study, nickel-intensified immunohistochemistry was conducted using a commercial tissue microarray (with 94 cases of bone cancer tissue and 10 normal bone tissues), and the 4-scoring system was employed to evaluate the expression levels of SRC-3 immunoreactivity. The results showed that in normal bone tissue, levels of SRC-3 are almost negative (score = 0), the total positivity (score = 1–3) of SRC-3 immunoreactivities in bone cancers was 74.47%. There were no significant differences in gender, status (malignant or benign) or (mean) age (p > 0.05). The percentage of positivity was 77.78% in osteogenic tumors, 58.82% in cartilage tumors, 70% in giant cell tumors, 100% in hematopoietic tumors, 77.78% in miscellaneous lesions, and 75% in miscellaneous tumors. Age related differences of SRC-3 immunoreactivities were detected in cartilage tumors and giant cell tumors (p < 0.05). The above results clearly demonstrated a high frequency of overexpression of SRC-3 immunoreactivities in different bone cancers, indicating its potential roles in the prognosis and treatment of these cancers.     

The association between indirect bilirubin levels and liver fibrosis due to chronic hepatitis C virus infection

We proposed to evaluate the association between serum indirect bilirubin levels and liver fibrosis in patients with chronic hepatitis C (CHC) genotype 1b. Biopsy proven CHC genotype 1b patients’ demographics, clinical and histopathological characteristics were evaluated. Logistic regression analysis was done to evaluate the clinical, laboratory and demographic features of the histologically proven liver fibrosis in CHC patients. A total of 112 biopsy proven CHC genotype 1b patients were enrolled into the study. Liver fibrosis scores were measured by using Ishak fibrosis scores and were divided into two groups; fibrosis scores ≤2 were categorized as mild fibrosis, 82 patients (73.2%), whereas fibrosis scores >2 were categorized as advanced fibrosis group, 30 patiens (26.8%). Patients with advanced fibrosis had lower indirect bilirubin levels than the mild fibrosis group (0.28 ± 0.02 mg/dl vs. 0.44 ± 0.032 mg/dl, p < 0.001, respectively). Indirect bilirubin level was negatively correlated with advanced fibrosis scores (r = −0.416 and p < 0.001). In multivariate logistic regression analysis, low indirect bilirubin level was an independent predicting factor of advanced liver fibrosis (OR: 0.001, 95% CI: 0.0–0.005, p < 0.001). There is an inverse relationship between indirect bilirubin levels and advanced liver fibrosis caused by CHC genotype 1b.     

Circulating IL-35 in pancreatic ductal adenocarcinoma patients

IL-35 is a novel inhibitory cytokine that is mainly produced by regulatory T-cells (Tregs) and is required for Treg-mediated immunosuppression. However, the plasma levels of IL-35 in patients with pancreatic ductal adenocarcinoma (PDAC) have never been investigated. In this study, we found that plasma IL-35 levels more significantly increased in PDAC patients than in normal controls (134.53 ± 92.45 pg/mL vs. 14.26 ± 6.56 pg/mL). IL-35 mRNA levels were positively correlated with plasma IL-35 levels (EBI3, R = 0.925, p < 0.01; p35, R = 0.916, p < 0.01). Furthermore, IL-35 expression levels were associated with lymph node metastasis (p = 0.001) and late tumor stage (p = 0.002). For the resected patients, high IL-35 expression levels were associated with large tumor size (p < 0.01), higher TNM classification T staging (p < 0.05), and late tumor stage (p < 0.05). In conclusion, circulating IL-35 in PDAC patients significantly increased, suggesting that regulating the expression of IL-35 may provide a new possible target for the treatment of PDAC patients, especially for the resectable ones.     

Using the Internet for information about breast cancer: A questionnaire-based study

Objectives

To identify the proportion of breast cancer patients that used the Internet for breast cancer information; to classify patterns of use based on patient demographics; and to evaluate whether using the Internet for this purpose was beneficial or problematic. Also to recognize whether a specific demographic group was more likely to experience problems when using the Internet for breast cancer information.

Methods

A 10-item questionnaire was given to patients who attended the breast unit at the University Hospital of South Manchester between May and June 2011 following breast cancer treatment within the last 5 years.

Results

200 questionnaires were completed. 50.5% of patients had used the Internet for breast cancer information, with younger (p < 0.001) patients with a higher household income (p < 0.001) being most likely to do so. The majority (73%) found it beneficial; however 31% had experienced problems. Ethnicity affected the likelihood of experiencing problems with white patients encountering fewer problems (25%) than non-white patients (64%) (p = 0.008).

Conclusion

A significant proportion of breast cancer patients will encounter difficulties when using the Internet for breast cancer information, particularly those from ethnic minorities.

Practice implications

Health professionals need to include a discussion about Internet use in consultations with breast cancer patients.     

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.     

Glutathione transferase pi (GSTpi) expression in breast cancer: an immunohistochemical and molecular study

Breast cancer is the most frequent cancer in women worldwide. Prognostic markers are important for diagnosis, allowing therapeutic strategies to be defined more efficiently. The expression of the glutathione S-transferase pi isoenzyme (GSTpi) in tumor cells has been evaluated as a predictor of prognosis and in response to cytotoxic treatments. Its immunoexpression was assessed in 63 women diagnosed with invasive ductal carcinoma in a retrospective study. The results were statistically correlated with clinicopathological parameters of patients. The results showed that high GSTpi expression was related to p53-positive tumors, grade III histology, large tumor size and death (p < 0.05). The 37 patients who received adjuvant treatment, checked separately, showed high expression of GSTpi in relation to local recurrence, metastasis and death (p < 0.05). In addition, high levels of GSTpi expression were significantly associated with a shorter overall survival (p < 0.05). To confirm this suspicion, GSTpi gene expression was checked by Real-time PCR in neoplastic mammary cells cultured and subjected to treatment with doxorubicin. Our results suggest that high levels of GSTpi may be related to the development of resistance to chemotherapy in these tumors, the response of these tumors to treatment and the clinical course of the patients involved.     

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.     

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.     

Serum paraoxonase and arylesterase activities in patients with pulmonary tuberculosis

Background: The aim of the present study was to determine serum paraoxonase and arylesterase activities in tuberculosis, nontuberculosis pulmonary disease and healthy subjects. Materials and methods: In this case-control study we determined the serum paraoxonase and arylesterase activities in 36 patients with pulmonary tuberculosis, 38 nontuberculosis pulmonary disease and 49 healthy controls. Results: The results showed that serum paraoxonase (PON) activity was significantly lower in patients with pulmonary tuberculosis (61.10 ± 51.62 IU/L) than healthy controls (98.79 ± 68.79 IU/L) (p < 0.05). In addition we found that the level of PON activity was significantly lower in patients with nontuberculosis pulmonary disease (67.49 ± 47.88 IU/L) than normal individuals (p < 0.05). There was no significant differences regarding PON activity between patients with pulmonary tuberculosis and nontuberculosis pulmonary disease (p > 0.05). The arylesterase activity was significantly lower in patients with pulmonary tuberculosis than nontuberculosis pulmonary disease and normal subjects (p < 0.05). Discussion: The lower paraoxonase and aryesterase activities in pulmonary tuberculosis patients compared to healthy subjects might be due to imbalance of oxidant/antioxidant systems in pulmonary tuberculosis patients which needs more clarification.     

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.     

Communication matters: The impact of communication and participation in decision making on breast cancer patients’ depression and quality of life

Objective

This study explored the impact of breast cancer patients’ experiences of physician–patient communication and participation in decision making on patient depression and quality of life three and six months after primary treatment.

Methods

Participants were 135 German breast cancer patients, recruited within a week after the beginning of treatment. Women were asked to complete a self-administered questionnaire at baseline and three and six months later.

Results

Patients who rated their level of information at baseline as high were less depressed after three (p = .010) and six months (p < .001) and experienced higher quality of life after three (p < .001) and six months (p = .049). Patients who participated as much as they had wanted were more satisfied with the decision making process (p < .001) and had lower depression scores three months later (p = .005). The level of participation itself (passive, collaborative, active) and the treatment type had no impact.

Conclusion

The findings reveal the significance of physician–patient communication and stress the meaning of baseline depression for later adjustment.

Practice implications

A high level of information and tailoring the involvement in decision making to patients’ desired level can help patients to better cope with their illness. Physicians should assess and treat depression early in cancer treatment.     

Association of angiotensin-converting enzyme functional gene I/D polymorphism with amnestic mild cognitive impairment

The relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and serum ACE activity, as well as amnestic mild cognitive impairment (aMCI), was investigated. The study recruited 90 aMCI patients and 90 matched healthy controls. All subjects underwent an extensive assessment of cognitive function. The ACE gene I/D genotype was determined by polymerase chain reaction. Serum ACE activity was measured using a spectrophotometric technique. The scores obtained by the aMCI patients on the neuropsychological tests were significantly lower than those of the control subjects (all p < 0.01). The genotype (χ² = 11.510) and allele (χ² = 6.945) frequencies of the ACE gene were significantly different between the aMCI and the control groups (all p < 0.01). The DD genotype (23%) and D-allele (57%) frequencies in the aMCI patients were higher than those in the controls (16% vs. 43%). ACE genotype was correlated with delayed recall in Auditory Verbal Memory Test, delayed recall in Complex Figure Test, Category Fluency Test, and Symbol Digit Modalities Test in all subjects, in which the carriers of the DD and DI genotypes obtained lower scores than those of the II genotype (p < 0.05). A significant difference in the serum ACE level was observed among the three genotypes (DD > DI > II) in both the aMCI and the control groups (all p < 0.01). D-allele may be a genetic risk factor for the development of aMCI to Alzheimer's disease. A high serum ACE level possibly plays an important role in the incidence of aMCI.     

Does the use of shared decision-making consultation behaviors increase treatment decision-making satisfaction among Chinese women facing decision for breast cancer surgery?

Objective

To assess the extent to which breast surgical consultations used shared decision making (SDM), identify factors associated with use of SDM, and assess if using SDM increases decision-making satisfaction.

Methods

Two hundred and eighty-three video-recorded diagnostic-treatment decision consultations between breast surgeons and women with breast cancer were assessed using the Decision Analysis System for Oncology (DAS-O) coding system designed for assessing SDM behaviors. Women completed a questionnaire at pre-consultation, one-week post-consultation and one-month post-surgery. Patient outcomes included decision conflict, patient satisfaction with medical consultation, and decision regret.

Results

Overall, the level of SDM behaviors was low. The extent of SDM behavior within consultation was related to greater consultation duration (p < 0.001), more than one treatment being offered (p < 0.001), and fewer questions raised by patients/companions (p < 0.05). While use of SDM consultation did not influence post-consultation decision conflict, it increased satisfaction with information given and explained, patients’ feelings of trust and confidence in their surgeons, and reduced post-surgical decision regret.

Conclusion

These breast surgical consultations mostly adopted informed treatment decision-making approaches. Using SDM improved patient consultation and decision satisfaction.

Practice implications

The study findings highlight a need to reinforce the importance of SDM in consultations among breast surgeons.     

Smad4/Smad7 balance: A role of tumorigenesis in gastric cancer

Smad signaling pathway plays an important role in tumorigenesis and progression in cancer (Halder, S.K., Rachakonda, G., Deane, N.G., Datta, P.K., 2008. Smad7 induces hepatic metastasis in colorectal cancer. Br. J. Cancer 99, 957-965). The protein level of Smad is associated with growth, inhibition, and metastasis in different cancers. It is unclear if the differentiation, metastasis and apoptosis are reduced by Smad expression pattern in gastric cancer. To determine the effect of Smad on gastric cancer cells, we investigated the relationship of Smad4/Smad7 expression, and differentiation, metastasis, and apoptosis in different gastric cancer. The results show that Smad4 expression in the gastric cancer tissue was dramatically lower than that in the peritumoral tissue. A lower expression of Samd4 was significantly lower in the poorly differentiated tissue than that in the well and middle differentiated tissues (P < 0.01). In contrast, Smad7 expression in gastric cancer tissues was significantly higher than that in the peritumoral tissue. Smad7 was overexpressed in poorly differentiated tissue, also higher than those in the middle, and well differentiated tissues (P < 0.05). The Smad4 or Smad7 expression obviously related with the lymphatic metastasis in gastric cancer. There were 45 cases with lymphatic metastasis in all 78 patients. Smad4 expression in the cases with lymphatic metastasis was lower than the cases without metastasis (P < 0.01), whereas Smad7 expression in the cases with lymphatic metastasis was much higher than the case without metastasis (P < 0.01). To better understand the mechanisms involved in tumorigenesis of gastric cancer, we established SGC7901 gastric cancer cell lines transduced with Smad4 or Smad7 plasmid DNA. Apoptosis and survival of cancer cells was induced after Smad4 and Smad7 transduction. This effect is concentration and time dependent. Thus, this study provides a mechanism by which a balance between Smad4 and Smad7 in human gastric cancer is critical for differentiation, metastasis, and apoptosis of tumor cells.     

CSF hypocretin-1 concentrations correlate with the level of fatigue in multiple sclerosis patients

Considering the multiplicity of symptoms associated with multiple sclerosis (MS), there is possibility that hypocretin system function might be involved in the pathogenesis of the disease. The current study aimed to investigate the hypocretin-1 levels in cerebrospinal fluid (CSF) of MS patients in relation to different neurological deficit measures including: Ambulation Index (AI), Expanded Disability Status Scale (EDSS), Fatigue Severity Scale (FSS), and Epworth Sleepiness Scale (ESS) in relapse-onset MS patients. 53 subjects were included into the study: 38 patients with a diagnosis of MS and 15 healthy controls. Among MS patients, 25 had relapsing-remitting and 13 secondary progressive MS. CSF hypocretin-1 levels did not differ between MS patients and healthy controls (p > 0.05). A positive correlation between hypocretin-1 level and fatigue level was found in MS patients (p < 0.05) and this effect was even stronger in the MS subgroup suffering from fatigue (p = 0.01). Hypocretin system seems to be generally unchanged in MS but a positive correlation between hypocretin-1 level and fatigue may indicate involvement of some compensatory mechanisms stimulating the production of the neuropeptide in MS patients.