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Background: To investigate the association between pretreatment blood neutrophil-to-lymphocyte ratio (NLR) and clinical outcomes for advanced-stage cancer patients treated with immunotherapy.Methods: We conducted a comprehensive literature search to assess the relationship between pretreatment blood NLR and overall survival (OS) or progression-free survival (PFS) in advanced-stage cancer patients treated with immunotherapy. Published data including hazard ratios (HRs) and related 95% confidence interval (CI) were extracted. Pooled estimates of treatment outcomes were calculated using RevMan 5.3.5.Results: Twenty-seven studies with 4647 patients were included in the current study. The pooled results suggested that high pretreatment blood NLR was correlated with significant shorter OS (HR = 1.98, 95% CI 1.66-2.36, P < 0.001) and PFS (HR = 1.78, 95% CI 1.48-2.15, P < 0.001). Subgroup analysis stratified by study targets revealed that anti-VEGF/VEGFR therapy (HR = 2.04, 95% CI 1.61-2.60, P < 0.001) and immune checkpoints blockade (HR = 2.16, 95% CI 1.86-2.51, P < 0.001) were significantly associated with inferior OS while other targets (HR = 1.63, 95% CI 0.89-2.99, P = 0.120) were not associated with OS. There was no correlation between distinct NLR cutoff values and OS (rPearson = 0.218, P = 0.329) or PFS benefit (rPearson = − 0.386, P = 0.140). Of note, HRs of PFS showed significant correlation with HRs of OS (rPearson = 0.656, P = 0.015).Conclusion: Elevated pretreatment blood NLR was a promising prognostic and predictive biomarker for advanced-stage cancer patients treated with immunotherapy. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the concordance of measurements for early postpartum endometrial thickness between magnetic resonance imaging (MRI) and transcutaneous diagnostic medical sonography (DMS) as well as its implications. The measurements of early postpartum endometrial thickness were reviewed across 51 postpartum women who underwent MRI and transcutaneous DMS. Additionally, 30 women with a normal menstrual cycle formed a control group, and their data were compared. The results indicated that the endometrial thickness at early postpartum was 4.63 ± 0.62 mm on MRI and 8.18 ± 4.70 mm on DMS, with a comparative significant difference (P < .001). The endometrial thickness of the control group was 10.02 ± 1.71 mm on MRI and 10.17 ± 1.81 mm on DMS with no comparative significant difference (P = .124). This cohort study questions whether the hyperechoic zone in the early postpartum uterine cavity represents the actual endometrial thickness. Care should be taken by sonographers in labeling the hyperechoic zone in the early postpartum stage as endometrium. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) accounts for 10-25% of all breast tumors. This makes it more difficult to treat, so triple-negative cancers often require targeted therapies. We studied the prevalence of TNBC in a hospital-based study and compared the clinicopathological characteristics of triple-negative and non-triple-negative breast tumors. One hundred three patients were included in the study that underwent modified radical mastectomy. The procedure of immunostaining was performed using formalin-fixed, paraffin-embedded tissue sections. These sections were stained immunohistochemically for ER, PR, and HER2 neu by using ready-to-use monoclonal antibody detection system with 3′-3′ diaminobenzidine hydrochloride (DAB) as chromogen. Of all 103 patients, 35 (34%) were triple negative. The average age of patients of TNBC and non-TNBC group was found as 44.16 and 40.73 years, respectively. Patients of post-menopausal state were higher than premenopausal in TNBC (22/35; 62%) and non-TNBC groups (45/68; 66%). Further, TNBC patients reported at clinically early stages I and II (18/35; 51.4%) while non-TNBC patients predominantly reported at later stages III and IV (44/68; 64.7%). It was also observed that breast tumor size in majority of the patients in both groups lies between 2 to 5 cm (TNBC = 23/35; 65.7% and non-TNBC = 35/68; 51.5%). Lymph node metastases were present in 51.5% (18/35) cases in TNBC patients and 64.7% (44/68) cases in non-TNBC group. Despite the limitation of less number of breast cancer cases, we analyzed that TNBC tumors have aggressive clinical values than non-TNBC, though having no statistically significant difference between the prognostic clinical parameters of two groups. [ABSTRACT FROM AUTHOR]

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Introduction: The aim of this study is to determine of risk factors in patients with brain metastases, and prognostic factors affecting survival of patients by using the Cox proportional hazards model. Methods: This descriptive - analytic retrospective study was performed on 197 patients with brain metastases who referred to Shahid Ramezanzadeh Radiation Center, Yazd, Iran. Several risk factors in these patients were analyzed by the Cox model. Survival times were estimated by Kaplan - Meier and significant difference between the survivals distributions of sub groups were compared with the log-rank test. The data were analyzed by R and SPSS soft wares. Results: The Kaplan-Meier estimate of patients overall survival were 27% at 12 months and 12% at 24 months. By the log - rank test we founded that there was significant difference between the patients survival in subgroups of variables, such as: age at diagnosis, outside brain diseases (primary tumor), type of treatment, response to radiotherapy and re-radiation therapy (P<0.05). Cox model analysis indicated that the survival of patients with brain metastases influenced by the outside brain diseases (primary tumor) and response to radiotherapy variables. Conclusion: According to this result, control of the primary tumor and appropriate by radiation therapy seems to be effective to increase patients Lifetime. Also, it is more appropriate to use the Cox model in medical studies because of its easy for interpretation and not limited to use the type of covariates. [ABSTRACT FROM AUTHOR]

Objective: The study aims to explore the relationship between expressions of HER2 and JAK/STAT3-SOCS3 signaling pathway and clinicopathological features and prognosis of ovarian cancer (OC).Methods: A total of 136 OC patients were collected. Immunohistochemistry was applied to measure the expressions of STAT3, p-STAT3, SOCS3, HER2 and p-HER2 in the tumor tissues and adjacent normal tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expressions of HER2, SOCS3 and STAT3 and western blotting was applied for protein expressions of HER2, p-HER2, SOCS3, STAT3 and p-STAT3 in the tumor tissues and adjacent normal tissues. Flow cytometry was used for the cell apoptosis in the blank, afatinib (A), ruxolitinib (R) and afatinib + ruxolitinib (A + R) groups. Follow-up was performed to explore relationship of HER2, SOCS3, and STAT3 expressions with survival time of OC patients.Results: HER2, p-HER2, STAT3, and p-STAT3 expressions were higher while SOCS3 expression was lower in the tumor tissues. The positive expressions of STAT3, HER2, p-HER2 and p-STAT3 were lower while the positive expression of SOCS3 was higher in the adjacent normal tissues. The expressions of HER2, SOCS3, and p-STAT3 were associated with clinical stage and lymph node metastasis (LNM), and STAT3 expression has correlation with histological grade and LNM. The mRNA and protein expressions of HER2, STAT3 and p-STAT3 in the tumor tissues were higher than those in the adjacent normal tissues, but SOCS3 expression was significantly decreased. The positive expressions of HER2, p-HER2 and STAT3, the negative expression of SOCS3 and pathological stages were important risk factors for the prognosis of patients with OC.Conclusion: Our study showed that the expressions of HER2, STAT3, and SOCS3 are associated with the progression of OC, and higher expressions of HER2 and STAT3 and lower expression of SOCS3 predict poor prognosis of OC. [ABSTRACT FROM PUBLISHER]

The ability to accurately detect and analyze rare cells in a cell population is critical not only for the study of disease progression but also for next flow cytometry systems in clinical application. Here, we report the development of a prototype device, the ‘Rare cell sorter’, for isolating and recovering single rare cells from whole blood samples. On this device, we utilized an open-channel microfluidic chip for rare cell isolation. And the advantage of open-channel allows us to recover the isolated rare cell directly from the chip. We set the circulating tumor cell (CTC) as a target cell. For the clinical experiment, CTCs were isolated from blood samples collected from patients with metastatic breast cancer and healthy volunteers. There was a significant difference in the number of CTCs between the patients with metastatic breast cancer and healthy volunteers. To evaluate the damage to cells during isolation and recovery, we performed an RNA integrity assay using RNA extracted from CTCs recovered from the chip and found that our process for single CTC isolation and recovery is mild enough for gene analysis of CTCs. [ABSTRACT FROM AUTHOR]

Reviews on circulating biomarkers in breast cancer usually focus on one single biomarker or a selective group of biomarkers. An overview summarizing the discovery and evaluation of all blood-based biomarkers in metastatic breast cancer is lacking. This systematic review aims to identify the available evidence of known blood-based biomarkers in metastatic breast cancer, regarding their clinical utility and state-of-the-art position in the validation process. The initial search yielded 1078 original studies, of which 420 were assessed for eligibility. A total of 320 studies were included in the final synthesis. A Development, Evaluation and Application Chart (DEAC) of all biomarkers was developed. Most studies focus on identifying new biomarkers and search for relations between these biomarkers and traditional molecular characteristics. Biomarkers are usually investigated in only one study (68.8%). Only 9.8% of all biomarkers was investigated in more than five studies. Circulating tumor cells, gene expression within tumor cells and the concentration of secreted proteins are the most frequently investigated biomarkers in liquid biopsies. However, there is a lack of studies focusing on identifying the clinical utility of these biomarkers, by which the additional value still seems to be limited according to the investigated evidence. [ABSTRACT FROM AUTHOR]

Background: The presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with increased mortality in several malignancies. Here, we quantify the effect of NLR on survival in patients with breast cancer, and examine the effect of clinicopathologic factors on its prognostic value.Methods: A systematic search of electronic databases was conducted to identify publications exploring the association of blood NLR (measured pre treatment) and overall survival (OS) and disease-free survival (DFS) among patients with breast cancer. Data from studies reporting a hazard ratio (HR) and 95% confidence interval (CI) or a P value were pooled in a meta-analysis. Pooled HRs were computed and weighted using generic inverse variance. Meta-regression was performed to evaluate the influence of clinicopathologic factors such as age, disease stage, tumor grade, nodal involvement, receptor status, and NLR cutoff on the HR for OS and DFS. All statistical tests were two-sided.Results: Fifteen studies comprising a total of 8563 patients were included. The studies used different cutoff values to classify high NLR (range 1.9-5.0). The median cutoff value for high NLR used in these studies was 3.0 amongst 13 studies reporting a HR for OS, and 2.5 in 10 studies reporting DFS outcomes. NLR greater than the cutoff value was associated with worse OS (HR 2.56, 95% CI = 1.96-3.35; P < 0.001) and DFS (HR 1.74, 95% CI = 1.47-2.07; P < 0.001). This association was similar in studies including only early-stage disease and those comprising patients with both early-stage and metastatic disease. Estrogen receptor (ER) and HER-2 appeared to modify the effect of NLR on DFS, because NLR had greater prognostic value for DFS in ER-negative and HER2-negative breast cancer. No subgroup showed an influence on the association between NLR and OS.Conclusions: High NLR is associated with an adverse OS and DFS in patients with breast cancer with a greater effect on disease-specific outcome in ER and HER2-negative disease. NLR is an easily accessible prognostic marker, and its addition to established risk prediction models warrants further investigation. [ABSTRACT FROM AUTHOR]

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Background: The aim of this study was to evaluate the efficacy of vinorelbine-based regimens as first-, second- and more-line therapies in advanced breast cancer (ABC) and to analyze the best timing of vinorelbine treatment. Methods: A total of 71 ABC patients were retrospectively reviewed. Of these, 35 patients were treated with vinorelbine-based regimens as first-line chemotherapy, and 36 patients were treated with vinorelbine-based regimens as second-line or more-line therapy. The primary end point of the study was progression-free survival (PFS). Results: No difference was found in baseline characteristics between the two groups (p > 0.1 for all comparisons). There was a significant difference in the objective response rate (ORR; p = 0.006) and clinical benefit rate (CBR; p = 0.013) between the first-line group and the second- or more-line groups. In the vinorelbine firstline group, the ORR was 68.6% (24 patients), and in the second-line or more-line groups the ORR was 36.1% (13 pa-tients). A significant difference in PFS between the first-line group and the second-line or more-line groups was also observed (p = 0.030). The median PFS in the overall population was 6.3 ± 1.32 months (95% CI 3.69-8.90). The median PFS was 11.1 ± 3.76 months (95% CI 3.73-18.47) in the first-line group compared with 5.2 ± 1.35 months (95% CI 2.54-7.85) in the second-line or more-line groups. In patients treated with vinorelbine-trastuzumab combination as the first-line therapy, a complete response was observed in 1 patient (12.5%) and partial response in 5 patients (62.5%), giving an ORR of 75.0%. Progressive disease was observed in 1 patient (12.5%), and stable disease in 1 patient (12.5%), leading to a CBR of 87.5%. The median PFS was 13.8 ± 2.75 months (95% CI 8.42-19.18), and median OS was 37.0 ± 11.6 months (95% CI 14.18-59.82). No significant difference was found in overall survival (OS) between the groups (p = 0.612). Conclusion: For ABC patients, no significant difference in median OS was found between the early use and delayed use of vinorelbine-based regimens, but the short-term efficacy and PFS of vinorelbine-based regimens were significantly better in the early use group than in the delayed use group. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The present study measured social support perceptions and hope levels of uro-oncology patients diagnosed with cancer and examined how they vary according to sociodemographic variables. METHODS: Research was conducted on 143 uro-oncology patients in Konya, Turkey, using a sociodemographic information form, the Multidimensional Scale of Perceived Social Support (MSPSS) and the Hope Scale. RESULTS: Patient mean multidimensional perceived social support score was quite high at 62.14±14.99, and mean hope level score was 20.62±4.50. Hope level score was significantly higher in male patients. It was also higher for patients with dependents and for patients who believed their cancer was treatable. Perceived social support levels of patients with dependents and patients who believed their cancer was treatable were also significantly higher. CONCLUSION: Hope levels of uro-oncology patients are affected positively by high levels of perceived social support. Women, patients with dependents, and patients who develop a positive attitude toward their cancer treatment were more hopeful than others. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer is one of the most common causes of cancer death in women worldwide. The Glasgow Prognostic Score (GPS), a cumulative prognostic score based on C-reactive protein and albumin, indicates the presence of a systemic inflammatory response. The GPS has been adopted as a powerful prognostic tool for patients with various types of malignant tumors, including breast cancer. The aim of this study was to assess the value of the GPS in predicting the response and toxicity in breast cancer patients treated with chemotherapy. Patients and Methods: Patients with metastatic breast cancers in a progressive stage for consideration of chemotherapy were eligible. The clinical characteristics and demographics were recorded. The GPS was calculated before the onset of chemotherapy. Data on the response to chemotherapy and progression-free survival (PFS) were also collected. Objective tumor responses were evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). Toxicities were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTC) version 3.0 throughout therapy. Results: In total, 106 breast cancer patients were recruited. The GPS was associated with the response rate (p = 0.05), the clinical benefit rate (p = 0.03), and PFS (p = 0.005). The GPS was the only independent predictor of PFS (p = 0.005). The GPS was significantly associated with neutropenia, thrombocytopenia, anorexia, nausea and vomiting, fatigue, and mucositis (p = 0.05-0.001). Conclusions: Our data demonstrate that GPS assessment is associated with poor clinical outcomes and severe chemotherapy-related toxicities in patients with metastatic breast cancer who have undergone chemotherapy, without any specific indication regarding the type of chemotherapy applied. [ABSTRACT FROM AUTHOR]

This comprehensive review provides information on epidemiology, size, grade, cerebral localization, clinical symptoms, treatments, and factors associated with longer survival in 14,599 patients with brain metastasis from breast cancer; the molecular features of breast cancers most likely to develop brain metastases and the potential use of these predictive molecular alterations for patient management and future therapeutic targets are also addressed. The review covers the data from 106 articles representing this subject in the era of modern neuroimaging (past 35 years). The incidence of brain metastasis from breast cancer (24 % in this review) is increasing due to advances in both imaging technologies leading to earlier detection of the brain metastases and introduction of novel therapies resulting in longer survival from the primary breast cancer. The mean age at the time of breast cancer and brain metastasis diagnoses was 50.3 and 48.8 years respectively. Axillary node metastasis was noted in 32.8 % of the patients who developed brain metastasis. The median time intervals between the diagnosis of breast cancer to identification of brain metastasis and from identification of brain metastasis to death were 34 and 15 months, respectively. The most common symptoms experienced in patients with brain metastasis consisted of headache (35 %), vomiting (26 %), nausea (23 %), hemiparesis (22 %), visual changes (13 %) and seizures (12 %). A majority of the patients had multiple metastases (54.2 %). Cerebellum and frontal lobes were the most common sites of metastasis (33 and 16 %, respectively). Of the primary tumors for which biomarkers were recorded, 37 % were estrogen receptor (ER)+, 41 % ER−, 36 % progesterone receptor (PR)+, 34 % PR−, 35 % human epithelial growth factor receptor 2 (HER2)+, 41 % HER2−, 27 % triple negative and 18 % triple positive (TP). Treatment in most patients consisted of a multimodality approach often with two or more of the following: whole brain radiation therapy (52 %), chemotherapy (51 %), stereotactic radiosurgery (20 %), surgical resection (14 %), trastuzumab (39 %) for HER2 positive tumors, and hormonal therapy (34 %) for ER and/or PR positive tumors. Factors that had an impact on prognosis included grade and size of the tumor, multiple metastases, presence of extra-cranial metastasis, triple negative or HER2+ biomarker status, and high Karnovsky score. Novel therapies such as application of agents to reduce tumor angiogenesis or alter permeability of the blood brain barrier are being explored with preliminary results suggesting a potential to improve survival after brain metastasis. Other potential therapies based on genetic alterations in the tumor and the microenvironment in the brain are being investigated; these are briefly discussed. [ABSTRACT FROM AUTHOR]

The differential diagnosis of acute community-acquired meningitis is of paramount importance in both therapeutic and healthcare-related economic terms. Despite the routinely used markers, novel, easily calculated, and rapidly available biomarkers are needed particularly in resource-poor settings. A promising, exponentially studied inflammatory marker is the neutrophil-to-lymphocyte ratio (NLR), albeit not assessed in meningitis. The aim of this study was to investigate the utility of the NLR in the differential diagnosis of acute meningitis. Data on cerebrospinal fluid (CSF) and blood leukocyte parameters from more than 4,000 patients diagnosed with either bacterial or viral meningitis in Greece during the period 2006-2013 were retrospectively examined. The diagnostic accuracy of the NLR and neutrophil counts in CSF and blood were evaluated by receiver operating characteristic curves. The discrimination ability of both the NLR and neutrophil counts was significantly higher in CSF than in blood. The optimal cutoff values of the NLR and neutrophil counts were 2 in CSF vs 8 in blood, and 287 cells in CSF vs 12,100 cells in blood, respectively. For these values, sensitivity, negative predictive value, and odds ratio were statistically significantly higher in CSF than blood for both markers. Logistic regression analysis showed that the CSF NLR carries independent and additive information to neutrophil counts in the differential diagnosis of acute meningitis. This study is the first one to assess NLR in acute meningitis, providing promising results for its differential diagnosis. [ABSTRACT FROM AUTHOR]

Objective: Metastatic breast cancer (MBC) remains the main cause of cancer-related death, and the clinical significance and prognostic role of circulating tumor cells (CTCs) in metastatic breast cancer are still controversial. Here, we conducted a meta-analysis to clarify the correlation between CTCs and the clinicopathological features and prognosis of MBC. Methods: We performed a comprehensive search of Pubmed and the ISI Web of Science through December 2014. Only articles that focused on MBC patients and detected CTCs using the CellSearch system were included. The associations between CTCs and survival rate and clinicopathological parameters, including molecular pattern, metastatic region and treatment response, were evaluated. Results: This meta-analysis included 24 studies (3701 MBC patients), 13 prospective studies and 11 retrospective studies. We found that CTCs were more frequently detected with HER2 + primary tumors (pooled RR = 0.73, 95 % CI = 0.63-0.84). Additionally, higher CTC numbers indicated a worse treatment response (RR = 0.56, 95 % CI = 0.40-0.79), poorer PFS (RR = 0.64, 95 % CI = 0.56-0.73) and poorer OS (RR = 0.69, 95 % CI = 0.64-0.75) in MBC patients. Conclusion: Based on these results, we propose that HER2 positivity could be a significant risk factor for the presence of CTCs. Additionally, CTCs have a significant prognostic value for MBC patients. Therefore, CTCs should be continually monitored to guide the treatment of MBC patients, especially those with HER2 + primary tumors. [ABSTRACT FROM AUTHOR]

Inflammation may initiate and promote breast cancer development, and be associated with elevated circulating levels of inflammation markers. A total of eight 130 initially healthy women, participated in the population-based Tromsø study (1994-2008). Pre-diagnostic high-sensitivity C-reactive protein (hs-CRP) was assessed. During 14.6 years of follow-up, a total of 192 women developed invasive breast cancer. These cases were followed for additional 7.2 years. Detailed medical records were obtained. We observed an overall positive dose-response relationship between pre-diagnostic hs-CRP and breast cancer risk (hazard ratio (HR) = 1.06, 95 % CI 1.01-1.11). Postmenopausal women with above median levels of hs-CRP (>1.2 mg/l) had a 1.42 (95 % CI 1.01-2.00) higher breast cancer risk compared to postmenopausal women with hs-CRP below median. Postmenopausal women, who were hormone replacement therapy non-users, and were in the middle tertile (0.8-1.9 mg/l), or highest tertile of hs-CRP (>1.9 mg/l), had a 2.31 (95 % CI 1.31-4.03) and 2.08 (95 % CI 1.16-3.76) higher breast cancer risk, respectively, compared with women in the lowest tertile. For each unit increase in pre-diagnostic hs-CRP levels (mg/l), we observed an 18 % increase in disease-free interval (95 % CI 0.70-0.97), and a 22 % reduction in overall mortality (95 % CI 0.62-0.98). Our study supports a positive association between pre-diagnostic hs-CRP and breast cancer risk. In contrast, increased pre-diagnostic hs-CRP was associated with improved overall mortality, but our findings are based on a small sample size, and should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: Nearly 50% of gastric cancer patients are diagnosed with advanced gastric cancer (AGC). Therapy is palliative but results in ill effects. The median overall survival (OS) of AGC patients is often <12 months. It is unclear if the early initiation of therapy in all AGC patients is beneficial. Methods: A retrospective analysis of AGC patients in our database was carried out. The patients were divided into two groups: asymptomatic or symptomatic. We sought to assess whether the delay of systemic therapy was harmful in asymptomatic patients. Results: A total of 135 patients were analyzed. Most patients were symptomatic (68%), males (67%), and had low ECOG scores (0-1; 85%). In univariate analyses, ECOG performance status 0 (p = 0.005), delayed initiation of therapy (p = 0.03), and lack of symptoms (p = 0.03) were associated with a longer OS. The multivariate model for OS identified only ECOG performance status as an independent prognosticator of longer OS (p = 0.02). Asymptomatic patients who had delayed (≥4 weeks) systemic therapy had an OS rate of 77% at 1 year compared to 58% for patients treated within 4 weeks (p = 0.47). Conclusion: Symptomatic AGC patients had a poor outcome compared to asymptomatic AGC patients. Treatment delay in asymptomatic patients had no detrimental effect on OS, suggesting that the timing of therapy can be based on patient selection. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is the most common female cancer in the world. Triple negative breast cancer (TNBC) is a recently identified biological variant with aggressive tumor behavior and poor prognosis. Data of hormonal status from the Indian population is scarce due to financial constraints in performing immunohistochemistry evaluation. The present study aims to prospectively analyze receptor status of all breast cancer patients and identify TNBC and compare their clinical profile and short term survival with other non-TNBC group. Materials and methods: All cytologically and histopathologically confirmed cases of carcinoma breast were prospectively enrolled. In a longitudinal study at tertiary care hospital in central India based on the hormonal status, they were further divided into TNBC and other groups. Comparison of risk factors, clinical profile and short-term survival was carried out. Results: A total 85 patients were enrolled and of them 37 (43.7%) were TNBC. On comparing risk factors ie, age, age at menarche, total reproductive age, age at first child birth, and menopausal status - no statistical significance was observed between the TNBC and non-TNBC groups. But on comparison of clinical profile TNBC tumors were significantly large with majority of patients presenting as locally advanced breast cancer (83%). No statistical difference was observed in axillary lymph node status between two groups. TNBC tumors were histologically more aggressive (grade 3) compared to other groups. No statistically significant difference was observed in short term overall survival but all three deaths were observed in the TNBC group only and two local recurrences after surgery were observed in the TNBC group. Conclusion: TNBC forms a large proportion of carcinoma breast patients in a central Indian scenario and needs more research to identify appropriate treatment planning considering aggressive histology and advanced presentation. [ABSTRACT FROM AUTHOR]

Background:Peripheral blood-derived inflammation-based scores such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have recently been proposed as prognostic markers in solid tumours. Although evidence to support these markers as unfavourable prognostic factors is more compelling in gastrointestinal cancers, very little is known of their impact on breast cancer. We investigated the association between the NLR and PLR, and overall survival after breast cancer.Methods:Data from the University of Malaya Medical Centre Breast Cancer Registry was used. Of 2059 consecutive patients diagnosed from 2000 to 2008, we included 1435 patients with an available pre-treatment differential blood count (∼70%). Patients were stratified into quintiles of the NLR/PLR. Multivariable Cox regression was used to determine the independent prognostic significances of the NLR/PLR.Results:Compared with the first quintile of the NLR, women in quintile 5 were younger, had bigger tumours, nodal involvement, distant metastases and higher tumour grades. Higher NLR quintiles were significantly associated with poorer survival with a 5-year relative survival ratio (RSR) of 76.4% (95% CI: 69.6-82.1%) in quintile 1, 79.4% (95% CI: 74.4-83.7%) in quintile 2, 72.1% (95% CI: 66.3-77.3%) in quintile 3, 65.6% (95% CI: 59.8-70.8%) in quintile 4 and 51.1% (95% CI: 43.3-58.5%) in quintile 5. Following adjustment for demography, tumour characteristics, treatment and the PLR, the adjusted hazard ratio (HR) for quintile 5 vs quintile 1 was 1.50 (95% CI: 1.08-1.63); Ptrend=0.004. Results were unchanged when the NLR was analysed as a dichotomous variable using different cutoff points. Although patients in PLR quintile 5 had lower survival than in quintile 1 (5-year RSR: 53.2% (95% CI: 46.9-59.2%) vs 77.0% (95% CI: 70.9-82.2%)), this association was not significant after multivariable adjustment. However, a PLR >185 was significantly associated with poorer survival; adjusted HR: 1.25 (95% CI: 1.04-1.52).Conclusions:Both the NLR and PLR are independently associated with an increased risk of mortality in breast cancer. Their added value in the prognostication of breast cancer in clinical practice warrants investigation. [ABSTRACT FROM AUTHOR]

The prognostic significance of tumor-infiltrating lymphocytes and immune signals has been described previously in triple-negative breast cancer (TNBC). Furthermore, recent studies have shown that immunologic parameters are relevant for the response to neoadjuvant chemotherapy (NAC) in breast cancer as well as for outcomes after adjuvant chemotherapy. However, immune signals are variable, and which signals are important is largely unknown. We, therefore, evaluated the expression of immune-related genes in TNBC treated with NAC. We retrospectively evaluated biopsy tissue from 55 patients with primary TNBC treated with NAC (anthracycline, cyclophosphamide, and docetaxel) against the NanoString nCounter GX Human Immunology Panel (579 immune-related genes). Higher expression of cytotoxic molecules, T cell receptor signaling pathway components, cytokines related to T helper cell type 1 (Th1), and B cell markers was associated with a pathologic complete response (pCR). Higher expression of NFKB1, MAPK1, TRAF1, CXCL13, GZMK, and IL7R was significantly associated with pCR, higher Miller-Payne grade, and lower residual cancer burden class. Expression of NFKB1, TRAF1, and CXCL13genes, in particular, was significantly correlated with a longer disease-free survival rate. Conversely, patients those who failed to achieve a pCR showed increased expression of genes related to neutrophils. Higher expression of cytotoxic molecules, T cell receptor signaling pathway components, Th1-related cytokines, and B cell markers is correlated with pCR and survival in TNBC patients treated with NAC. Our results suggest that the activation status of neutrophils may provide additional predictive information for TNBC patients treated with NAC. [ABSTRACT FROM AUTHOR]

A range of prognostic cellular indices of the systemic inflammatory response, namely the neutrophil-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), combination of platelet count and neutrophil-lymphocyte ratio (COP-NLR) and prognostic nutritional index (PNI), have been developed and found to have prognostic utility across varied malignancies. The current study is the first to examine the prognostic value of these six inflammatory scores in patients with resectable colorectal liver metastases (CRLM). Data from 302 consecutive patients undergoing surgery for resectable CRLM were evaluated. The prognostic influence of clinicopathological variables and the inflammatory scores NLR, dNLR, PLR, LMR, COP-NLR and PNI upon overall survival (OS) and cancer-specific survival (CSS) were determined by log-rank analysis and univariate and multivariate Cox regression analyses. High preoperative NLR was the only inflammatory variable independently associated with shortened OS (HR 1.769, 95 % CI 1.302-2.403, P < 0.001) or CSS (HR 1.927, 95 % CI 1.398-2.655, P < 0.001) following metastasectomy. When NLR was replaced by dNLR in analyses, high dNLR was independently associated with shortened OS (HR 1.932, 95 % CI 1.356-2.754, P < 0.001) and CSS (HR 1.807, 95 % CI 1.209-2.702, P = 0.004). The inflammatory scores PLR, LMR, COP-NLR and PNI demonstrated no independent association with either overall or cancer-specific survival in the study population. Our findings support high preoperative NLR and dNLR as independent prognostic factors for poor outcome in patients undergoing CRLM resection, with prognostic value superior to other cellular-based systemic inflammatory scores. [ABSTRACT FROM AUTHOR]

An HPV infection is involved in the etiology of about 25 % of head and neck squamous cell carcinomas (HNSCC). It has been postulated that a strong antitumoral immune response in HPV-positive tumors represents an important underlying mechanism for their good response to therapy. Recently, the Warburg phenomenon has returned to the center of attention because it affects antitumoral immune response and response to therapy. Accumulation of tumor cell-derived lactate inhibits cytotoxic T cells, as these, analogous to cancer cells, depend on glycolysis and lactate secretion for fulfillment of energy needs. Sparse information exists on the Warburg effect in HNSCC. This study aimed to characterize the metabolic and immunological features of HPV-negative and HPV-positive HNSCC. An immunohistochemical analysis of oropharyngeal carcinomas showed an enhanced antitumoral immune response (CD8/CD4 ratio) together with increased levels of proteins involved in transmembranous metabolite transportation (GLUT1 and CD147) and respiratory metabolism (COX5B) in HPV-positive tumors as compared to HPV-negative tumors. mRNA and Western blot analyses of an HPV-positive and HPV-negative HNSCC cell line revealed metabolic characteristics similar to the in vivo situation. Additionally, the HPV-negative cell line showed stronger extracellular lactate accumulation. In contrast, the HPV-positive cell line presented with better adaption to lactic acidosis suggesting an ability to metabolize lactate. Our results indicate that HPV-positive and HPV-negative carcinomas do not only differ in terms of tumor immune microenvironment, but also in terms of tumor metabolism, characterized by an increased glucose and respiratory metabolism together with decreased lactate accumulation in HPV-positive HNSCC. Therefore, targeting metabolic pathways could represent a promising adjunct in the therapy of HPV-positive HNSCC. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives To assess the transvaginal ultrasonographic features of perineal masses in the lower urogenital tract in a cohort of 71 women. Methods Seventy-one women with perineal masses were referred consecutively for transvaginal ultrasonography. Two-dimensional ( 2D) ultrasound was used to scan the pelvic floor, including the urethra, vagina and rectum, and identify any possible areas of interest. A static three-dimensional ( 3D) sonographic reconstruction of the pelvic anatomy was created to further delineate the relation of the lesions with their neighboring structures. Ultrasound results were compared retrospectively with surgical pathology outcome when possible. Results Seventy-nine cystic, cystic-solid or solid masses were detected on transvaginal 2D ultrasonography in the 71 women: in 44 patients, 47 anechoic cystic masses were identified and diagnosed as vaginal wall cysts; in 19 patients, 23 hyperechoic cystic masses were diagnosed as vaginal epidermoid cysts; in each of two patients, a hypoechoic cystic-solid mass showing blood-flow signals on color Doppler imaging was diagnosed as urogenital angiomyofibroblastoma; in each of three patients, a hypoechoic cyst was diagnosed as urethral diverticulum; and in three patients with a known history of gynecological malignancy, solid heterogeneous masses with blood flow signals on color Doppler imaging were diagnosed as metastatic cancer. In all patients, 3D ultrasonography delineated the anatomical relationship of these masses to the vagina, urethra and rectum. Conclusions Transvaginal 2D and 3D ultrasonography is an accurate, non-invasive, cost-effective diagnostic modality for the delineation of congenital, septic and neoplastic lower urogenital tract perineal masses in women. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

In the treatment of advanced or recurrent gastric cancer, the prolongation of survival depends on the use of second-line therapy, with paclitaxel (PTX) or irinotecan (CPT-11) as the key agents. The present study aimed to retrospectively investigate the safety and continuity of weekly PTX and CPT-11 monotherapy as second- or third-line treatment for advanced or recurrent gastric cancer. A total of 62 patients who had received PTX or CPT-11 for gastric cancer at the Ogaki Municipal Hospital (Ogaki, Japan) were retrospectively reviewed. Of the 47 patients who received PTX as second-line therapy, 13 (27.7%) received third-line therapy with CPT-11. Second-line PTX and third-line CPT-11 were discontinued due to progressive disease (PD) in 27 and 7 cases, respectively, and deterioration in the performance status (PS) in 20 and 4 cases, respectively. Only 1 case of discontinuation due to adverse events (AEs) was reported for third-line CPT-11. Furthermore, of the 15 patients who received CPT-11 as second-line treatment, 11 (73.3%) then received PTX as third-line treatment. Second-line CPT-11 and third-line PTX were discontinued due to PD in 9 and 6 cases, respectively, and deterioration in the PS in 4 and 5 cases, respectively, whereas there was only 1 case of discontinuation due to AEs for second-line CPT-11. Severe AEs for PTX and CPT-11 were infrequent; however, the frequency of diarrhea was high when PTX was administered as third-line therapy (63.6%), whereas the frequency of malaise was high when CPT-11 was administered as second- (73.3%) and third-line (76.9%) therapy. In conclusion, severe AEs due to PTX and CPT-11 as second- and third-line treatment for advanced or recurrent gastric cancer are infrequent and patients are generally able to continue treatment. However, the possibility of diarrhea with third-line PTX and malaise with second- and third-line CPT-11 treatment should be considered when planning chemotherapy. [ABSTRACT FROM AUTHOR]

The value for lymphocytic infiltration (LI) has been increasingly recognized for tumor assessment. In breast cancer, however, the overall significance of LI remains poorly defined, probably due to its heterogeneity. A large cohort of breast cancer was evaluated for the degree of LI and its association with traditional pathologic factors, biomarker expression, and cancer subtypes. The number of CD8 cytotoxic effector and FoxP3 regulatory T cell (Treg) was evaluated in those cases with high LI. High LI was associated with negative ER and PR but positive HER2 and EGFR expression ( p < 0.001 for all). In ER-positive cancers, high LI was associated with poor prognostic features including higher grade, the presence of necrosis, and lymphovascular invasion (LVI) ( p = 0.007 for LVI and <0.001 for the others). Conversely, LI correlated with smaller tumor size, a good prognostic feature ( p = 0.046) in HER2+ ER-cancers. These observations suggested LI may show opposite prognostic values in different breast cancer subgroups. Interestingly, when the phenotype of LI in these subgroups was evaluated, a strong positive association with intratumoral accumulation of Treg was found in ER-positive cancers ( p = 0.003, Rs = 0.319), while the opposite was observed in HER2+ ER-cancers ( p < 0.001, Rs = −0.427). Also, in ER-positive cancers, positive associations between peri- and intra-tumoral distribution were found with both CD8 and Tregs (CD8: p < 0.001, Rs = 0.547; Treg: p = 0.001, Rs = 0.460). Nonetheless, in HER2+ ER-cancers, such strong association was found with CD8 ( p < 0.001, Rs = 0.766) but not Tregs. The results may implicate a differential intratumoral migration of LI in different subtypes of breast cancer. In summary, the clinical value of LI in breast cancers could be subtype-dependent. In ER-positive cancers, high LI correlated with biologic parameters associated with poor prognosis, whereas in HER2 positive cancers, LI correlated with biologic parameters of favorable prognosis. [ABSTRACT FROM AUTHOR]

Several previous studies have suggested that patients with brain metastases should be treated with individualized approaches taking into account prognostic factors that influence survival. Whether or not radiotherapy represents overtreatment in patients with adverse prognostic features is currently being addressed in the randomized QUARTZ trial (best supportive care (BSC) vs. whole brain radiotherapy (WBRT)). However, inclusion is limited to patients with primary non-small cell lung cancer. Therefore, we analyzed a broader patient population with different primary tumors managed with BSC or WBRT (intended total dose 20 or 30 Gy). Survival was examined by uni- and multivariate analyses including matched pairs. Median overall survival of all 113 patients was 2 months. No significant difference between BSC and 20 Gy WBRT was observed. A slight but significant improvement was observed in the 30 Gy WBRT group (median 2.2 vs. 1.7 months). The magnitude of difference is not clinically meaningful. Subgroup analyses revealed that improved survival after 30 Gy WBRT was limited to patients with primary small cell lung cancer. In conclusion, these results confirm and extent interim results from the QUARTZ trial, suggesting that BSC is a reasonable choice in patients with limited survival expectation. Further efforts are necessary to improve identification of patients who are likely to benefit from WBRT, e.g. by refining available survival prediction tools, and to confirm that management of those with small cell lung cancer should include a less restricted use of WBRT. [ABSTRACT FROM AUTHOR]

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Background: Most breast cancer patients use complementary and alternative medicine (CAM), usually in parallel with their conventional treatments. This study was planned to determine the prevalence and determining factors for use of CAM by breast cancer patients undergoing chemotherapy. Patients and Methods: This descriptive study was carried out between October 2010 and May 2011, and included 96 patients at the Istanbul University Institute of Oncology. The Patient Characteristics form and Complementary and Alternative Medicine Scale were used for data collection. Descriptive and non-parametric tests were performed, and logistic regression analysis was used to predict factors affecting CAM use. Results: Praying was the most frequently used form of CAM, and most of the herbal supplements used by patients were harmless. Herbal use was higher among patients who had local disease (relative risk (RR) 4.48%, 95% confidence interval (CI) 1.12-17.95), and worship was more common among those who had not undergone surgery (RR 4.66%, 95% CI 1.64-13.20). Conclusion: The CAM approaches used by patients were found to be safe. However, sage and flax seed usage for estrogenand progesteronepositive patients and exercise for patients with spinal metastasis can be inappropriate approaches. It is important to question and inform patients about CAM use during treatment. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the response rate of gemcitabine and cisplatin as second-line combination chemotherapy in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes. Thirty-eight eligible women with measurable disease and anthracycline- and taxane-pretreated MBC were enrolled. The chemotherapy treatment consisted of gemcitabine (1,250 mg/m by intravenous infusion over 30 min on days 1 and 8) and cisplatin (75 mg/m by intravenous infusion over 1 h on day 1), which were administered every 21 days. Thirty-seven of 38 (97.4%) of patients were assessable for response. The objective response rate was 42.1% (95% CI, 26.4-57.8%) with 16 partial responses. The median time to progression (TTP) and overall survival (OS) for all patients were 5.4 months (95% CI, 2.7-8.1 months) and 13.9 months (95% CI, 9.4-18.4 months), respectively. The most frequent hematologic-related adverse events were grade 3/4 leucopenia and thrombocytopenia, observed in 10 patients (27.0%) and 11 (29.7%), respectively. Grade 3 stomatitis was observed in 3 (8.1%) patients. No grade 4 nonhematologic toxicity was observed in this study. No treatment-related deaths occurred during the study. In conclusion, the combination of gemcitabine and cisplatin is a safe and tolerable regimen as second-line combination for patients with anthracycline- and taxane-pretreated MBC. [ABSTRACT FROM AUTHOR]

The role of platinum-based compounds (PBCs) in the treatment of metastatic breast cancer (MBC) has been extensively studied. As single agents, high response rates have been observed in first-line therapy, while results in pretreated patients were discouraging. Regimens containing cisplatin/carboplatin together with taxanes showed the highest efficacy and safety as both first-line and second-line therapy. When administered with vinorelbine, the combination was also active and well tolerated in anthracycline- and taxane-pretreated patients. Combining PBCs with etoposide or nucleoside analogues showed moderate activity, yet high toxicity in the case of etoposide. The overall results for the combination with anthracyclines were disappointing. Addition of trastuzumab to PBC combinations showed remarkable activity and good tolerability in patients with HER2/neu overexpression. The use of cisplatin or carboplatin alongside novel targeted therapeutics for patients with triple-negative MBC seems promising and is being further evaluated. The use of PBCs against MBC requires careful patient selection and combination with the right chemotherapeutic agent. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The primary objective of this multicenter, open-label, randomized, parallel, phase II selection trial was to compare the objective tumor response to biweekly (every 2 weeks) gemcitabine/paclitaxel, gemcitabine/carboplatin, and gemcitabine/cisplatin as first-line treatment for metastatic breast cancer. Patients and methods: Eligible patients with stage IV disease who relapsed after anthracycline failure were randomly assigned in a 1:1:1 ratio to gemcitabine (2,500 mg/m) plus paclitaxel 150 mg/m ( n = 49); plus carboplatin, area under the curve = 2.5 mg/mL × min ( n = 47); or plus cisplatin 50 mg/m ( n = 51). Study therapy continued up until a maximum of 8 cycles and follow-up continued for 24 months. Results: All patients were analyzed for efficacy and one patient was excluded from the safety analyses. The objective response was 26.5% [95% confidence interval (CI) 14.9-41.1] for gemcitabine/paclitaxel, 17.0% (95% CI 7.6-30.8) for gemcitabine/carboplatin, and 15.7% (95% CI 7.0-28.6) for gemcitabine/cisplatin. The adjusted odds ratio for tumor response was 0.33 (95% CI 0.10-1.06), P = 0.063 for gemcitabine/carboplatin versus gemcitabine/paclitaxel; 0.26 (95% CI 0.08-0.86), P = 0.027 for gemcitabine/cisplatin versus gemcitabine/paclitaxel; and 0.77 (95% CI 0.24-2.52), P = 0.671 for gemcitabine/cisplatin versus gemcitabine/carboplatin. There were no significant differences in overall survival or progression-free survival ( P > 0.05). Grade 3 or 4 drug-related adverse events varied between groups and the majority of deaths (94.9%; 74/78) were related to disease progression. Conclusions: The gemcitabine-based treatments had comparable activity and tolerability. Similar survival characteristics and different toxicity profiles suggested that gemcitabine-platinum may be evaluated further in patients after anthracycline failure. [ABSTRACT FROM AUTHOR]

Background: An increasing proportion of patients are exposed to anthracyclines and/or taxanes in the adjuvant or neoadjuvant setting. Re-exposure in the metastatic stage is limited by drug resistance, thus evaluation of non-cross-resistant regimens is mandatory.Methods: Anthracycline-pretreated patients were randomly assigned to three gemcitabine-based regimens. Chemotherapy consisted of gemcitabine 1.000 mg m(-2) plus vinorelbin 25 mg m(-2) on days 1+8 (GemVin), or plus cisplatin 30 mg m(-2) on days 1+8 (GemCis), or plus capecitabine 650 mg m(-2) b.i.d. orally days 1-14 (GemCap), q3w. The primary end point was response rate.Results: A total of 141 patients were recruited on the trial. The overall response rates were 39.0% (GemVin), 47.7% (GemCis) and 34.7% (GemCap). Median progression-free survival was estimated with 5.7, 6.9 and 8.3 months, respectively. Corresponding median survival times were 17.5 (GemVin), 13.0 (GemCis) and 19.4 months (GemCap). Neutropenia ≥grade 3 occurred in 16.7% (Gem/Vin), 4.4% (GemCis) and 0% (Gem/Cap), whereas non-haematological toxicities were rarely severe except grade 3 hand-foot syndrome in 2.0% of the GemCap patients (per patient analysis).Conclusions: This randomised phase II trial has revealed comparable results for three gemcitabine-based regimens regarding treatment efficacy and toxicity. Gemcitabine-based chemotherapy appears to be a worthwhile treatment option for pretreated patients with metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Background/Aim: Insulin-like growth factor-I (IGF-I) is associated with survival, apoptosis and proliferation in MCF-7 cells. All-trans-retinoic acid (RA) is used as a cancer therapeutic, but the use of RA in cancer therapy is limited by the unpredictable resistance of cancer cells to drug action. Furthermore, the relationship of IGF-I with RA-induced decrement in cell viability has yet to be elucidated. Materials and Methods: MCF-7 cells were grown as confluent monolayers. To demonstrate the signaling pathways and roles of IGF-I, we suppressed endogenous target IGF-I with specific small interfering RNA treatment. Protein kinase C-δ and insulin receptor substrate 1 (IRS-1) protein levels were analyzed by Western blot. Radioimmunoassays were used to assess the concentration of endogenous IGF-I, and RT-PCR was used to assess IGF-I mRNA expression. Cell viability was analyzed with the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Results: We showed that RA treatment resulted in a dose- and time-dependent decrease in the secretion and synthesis of IGF-I. Subsequently, we found that suppression of IGF-I and IRS-1 protein decreased cell viability. In contrast, suppression of protein kinase C-δ and stimulation of IGF-I protected cells from RA-induced decrement in cell viability. The combination of RA treatment with IGF-I or IRS-1 small interfering RNA resulted in an additive decrease in cell viability. Conclusion: These results indicate that IGF-I plays an important role in the effect of RA and that suppression of IGF-I is implicated in the RA-induced inhibition of cell viability in MCF-7 cells. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: This phase II study was designed to evaluate the effects of vinorelbine (VRL) and capecitabine (CAP) as second-line combination chemotherapy in patients with advanced breast cancer (ABC) previously treated with anthracyclines and/or taxanes. Methods: Treatment consisted of VRL 25 mg/m2 administered on days 1 and 8 of a 21-day treatment cycle, along with oral CAP 825 mg/m2 twice daily for 14 days, followed by 7 days of rest. Results: 50 patients were enrolled and 48/50 (96.0%) patients were assessable for response. The median time to progression (TTP) and overall survival (OS) of the patients were 5.0 (95% confidence interval, CI, 2.1-7.9 months) and 12.0 months (95% CI, 8.0-16.0 months), respectively. The objective response rate was 26.0% (95% CI, 13.8-38.2%) with 1 confirmed complete response and 12 partial responses. The most frequent hematological adverse event was neutropenia of grade 3 and 4 in 5 (10.4%) and 2 patients (4.2%), respectively. Grade 3 stomatitis, asthenia, and diarrhea were observed in 1 (2.1%), 2 (4.2%) and 3 (6.3%) patients, respectively. Conclusion: The combination of VRL and CAP is feasible as second-line chemotherapy in patients with ABC previously treated with anthracyclines and/or taxanes, with efficacy being comparable to other available combination regimens. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Quinacrine has potential as a chemosensitizer when combined with chemotherapy, but its anti-cancer mechanisms remain unclear. The purpose of this study was to explore the capability of quinacrine to enhance the cytotoxic effects of cisplatin and the underlying mechanism involved. Methods: The potential role of quinacrine in enhancing the effects of cisplatin was investigated in Hela, SCC-VII, SACC-83 and C6 cancer cell lines with different pathologies. The inhibitory effects of quinacrine plus cisplatin on these cell lines were detected using a CCK-8 assay for viability and a TUNEL assay for apoptosis. The molecules involved in apoptotic signal translation, including cIAP-1, Bax, p53 and cleaved caspase-3, were detected by Western blot to investigate the underlying mechanism. Results: The CCK8 assay showed that quinacrine markedly enhanced the cytotoxicity of cisplatin in a dose-dependant manner in the 4 cancer cell lines. The TUNEL assay showed that treating the 4 cell lines for 24 h with cisplatin plus quinacrine significantly increased the percentage of apoptotic cells compared to treatment with single-agent treatment or untreated controls. Western blot analysis showed that quinacrine plus cisplatin significantly down-regulated cIAP-1 and up-regulated Bax and cleaved caspase-3 expression in Hela and SCC-VII cells compared with single-agent treatment. Conclusions: Quinacrine has the potential to be used as a chemotherapy adjuvant when combined with cisplatin. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article aims to provide an insight into some aspects of the catalyst strength and to propose future prospects of the research on the mechanical properties of solid catalysts. The study focused on several concepts including the brittle fracture which leads to the mechanical failure of the catalyst pellets, the measurement, and statistical properties of the catalyst strength data. The study concludes that an integrated research on catalyst mechanical properties should involve all the processes from catalyst manufacturing to industrial application, rather than only catalyst pellets itself.

We present a case report of a 73-year-old, postmenopausal woman with detailed history of breast cancer and oncology treatment including tamoxifen therapy. She presented at the clinic of gynecology and obstetrics with recurrent inflammation of the urinary and genital tract and suspicion of a cervical mass. She also presented occasional abdominal complaints and malodorous vaginal discharge. These symptoms were observed in the patient for several years. Before hospitalization she received many kinds of empirical, antimicrobial treatment such as chlorquinaldol, metronidazole, nifuratel, and nystatin. She did not receive further guidance from doctors about the causes of ailments and further diagnostic and treatment capabilities. In our clinic a detailed diagnostic process including ultrasound transvaginal examination and a minisurgical procedure revealed the presence of a vaginal foreign body (which turned out to be a plastic, shampoo bottle cap) surrounded by a mass of inflamed tissue mimicking a cervical tumor. All symptoms and complaints subsided after surgical removal of the foreign body and antibacterial therapy with metronidazole and cefuroxime. Our study draws attention to the need of thorough gynecological care including prophylaxis, especially in the case of complaints of an intimate nature. Even trivial, frequently occurring disorders can be dangerous and require proper and responsible doctor's supervision and management through the healing process. [ABSTRACT FROM AUTHOR]

Invasive lobular carcinomas are the second most common type (5% to 15%) of invasive breast carcinomas. The most frequent sites of breast cancer metastasis are the local and distant lymph nodes, brain, lung, liver, and bones; metastasis to the gastrointestinal system, especially to the stomach, is rare. When a mass is detected in an unusual place in a patient with invasive lobular carcinoma, it should be kept in mind that such a mass may be either a second primary carcinoma or the metastasis of an invasive lobular carcinoma. In this report, we present a case of gastric metastasis from triple-negative invasive lobular breast cancer. It is important to make an accurate diagnosis by distinguishing gastric metastasis from breast cancer in order to select the best initial treatment for systemic diseases of breast cancer. Considering our case, healthcare professionals should take into account that cases with invasive lobular breast cancer may experience unusual metastases. [ABSTRACT FROM AUTHOR]

Background: The expression of DNA fragmentation factor 45 (DFF45) and B-cell lymphoma 2 (BCL2) in glands of the normal human endometrium is related to phases of the menstrual cycle and decreases after menopause, whereas the expression of DNA fragmentation factor 40 (DFF40) is stable. Moreover, DF45, BCL2 and DFF40 underexpression has been reported in numerous malignancies, including uterine leiomyosarcomas. In this study, we aimed to investigate DFF45, BCL2 and DFF40 expression in endometrioid and non-endometrioid types of endometrial cancers (ECs). We also evaluated the correlations between DFF45, BCL2 and DFF40 expression levels and clinicopathological parameters and determined the value of these three proteins as prognostic markers of disease-free survival (DFS) and overall survival (OS).Methods: Immunohistochemistry was performed to evaluate DFF45, BCL2 and DFF40 expression in 342 cases of ECs. Student's t-test, the Mann-Whitney U-test, and the chi-squared test were used for the statistical analyses as appropriate. The Cox-Mantel test, Cox's proportional hazard model, and relative risk analyses were used to evaluate associations between DFF40, DFF45, and BCL2 expression and clinicopathological characteristics.Results: DFF40 and BCL2, but not DFF45, were significantly underexpressed in non-endometrioid and high-grade endometrioid ECs compared with low- and moderate-grade endometrioid ECs. Women with DFF40- and BCL2-negative tumors had higher risks of disease recurrence, lymph node involvement, lympho-vascular space infiltration, and deep myometrial invasion compared with women with DFF40- and BCL2-positive tumors. Additionally, women with DFF40- and BCL2-negative tumors had significantly lower OS and DFS than women with DFF40- and BCL2-positive tumors. A multivariable analysis of the model, including the clinicopathological characteristics and immunohistochemical results, showed that negative BCL2 expression, lymph node involvement, and high-stage and high-grade disease were independent predictors of OS, whereas negative BCL2 expression, lymph node involvement, and high-stage disease were independent predictors of DFS.Conclusions: Compared with low- and moderate-grade endometrioid ECs, non-endometrioid and high-grade endometrioid ECs showed significant DFF40 and BCL2 underexpression. The absence of DFF40 and BCL2 expression negatively affects DFS and OS. Further prospective studies are warranted to assess the potential utility of DFF40 and BCL2 as targets in the diagnosis or treatment of ECs. [ABSTRACT FROM AUTHOR]